Search

Your search keyword '"Yamashita, J."' showing total 38 results
Start Over Author "Yamashita, J." Topic breast neoplasms
38 results on '"Yamashita, J."'

1. Elevated serum levels of sialyl Lewis X (sLe X ) and inflammatory mediators in patients with breast cancer.

Author

Cohen EN, Fouad TM, Lee BN, Arun BK, Liu D, Tin S, Gutierrez Barrera AM, Miura T, Kiyokawa I, Yamashita J, Alvarez RH, Valero V, Woodward WA, Shen Y, Ueno NT, Cristofanilli M, and Reuben JM

Subjects
Biomarkers, Biomarkers, Tumor, Breast Neoplasms mortality, Case-Control Studies, Cluster Analysis, Cytokines blood, Female, Humans, Neoplasm Staging, Prognosis, Proportional Hazards Models, Retrospective Studies, Survival Analysis, Breast Neoplasms blood, Breast Neoplasms diagnosis, Inflammation Mediators blood, Sialyl Lewis X Antigen blood
Abstract

Purpose: The carbohydrate sialyl Lewis X (sLe X ) mediates cell adhesion, is critical in the normal function of immune cells, and is frequently over-expressed on cancer cells. We assessed the association, differential levels, and prognostic value of sLe X and inflammatory cytokines/chemokines in breast cancer sera., Methods: We retrospectively measured sLe X and a panel of cytokines/chemokines in the sera of 26 non-invasive ductal carcinoma in situ (DCIS), 154 invasive non-metastatic breast cancer (non-MBC), 63 metastatic breast cancer (MBC) patients, and 43 healthy controls. Differences in sLe X and inflammatory cytokines among and between patient groups and healthy controls were assessed with nonparametric tests and we performed survival analysis for the prognostic potential of sLe X using a cut-off of 8 U/mL as previously defined., Results: Median serum sLe X was significantly higher than controls for invasive breast cancer patients (MBC and non-MBC) but not DCIS. In univariate analysis, we confirmed patients with serum sLe X  > 8 U/mL have a significantly shorter progression-free survival (PFS) (P = 0.0074) and overall survival (OS (P = 0.0003). Similarly, patients with high serum MCP-1 and IP-10 had shorter OS (P = 0.001 and P < 0.001, respectively) and PFS (P = 0.010 and P < 0.001, respectively). sLe X , MCP-1 and IP-10 remained significant in multivariate survival analysis., Conclusion: Elevated serum sLe X was associated with invasive cancer but not DCIS. High serum sLe X levels were associated with inflammatory mediators and may play a role in facilitating local invasion of breast tumor. Furthermore, serum MCP-1, IP-10 and sLe X may have prognostic value in breast cancer.

Published
2019
Full Text
View/download PDF

2. Neutrophil elastase and trastuzumab responsiveness.

Author

Harao M, Sato T, Fukutomi T, Yorozuya K, Takasugi M, Mohri Y, Mizumoto T, Takahashi S, and Yamashita J

Subjects
Antibodies, Monoclonal, Humanized, Antineoplastic Agents administration & dosage, Female, Humans, Prognosis, Trastuzumab, Treatment Outcome, Antibodies, Monoclonal administration & dosage, Biomarkers, Tumor metabolism, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Leukocyte Elastase metabolism, Models, Biological
Published
2007
Full Text
View/download PDF

3. First report of a fibro-adenoma in axillary mammary tissue of a renal transplant patient taking cyclosporin.

Author

Yarak S, Floriano M, Decico JE, Konishi CT, Michalany NS, Enokihara MY, and Tomimori-Yamashita J

Subjects
Adult, Breast Neoplasms pathology, Breast Neoplasms surgery, Cyclosporine, Diagnosis, Differential, Female, Fibroadenoma pathology, Fibroadenoma surgery, Humans, Immunocompromised Host, Immunosuppressive Agents, Axilla pathology, Breast Neoplasms diagnosis, Fibroadenoma diagnosis, Kidney Transplantation
Published
2007
Full Text
View/download PDF

4. Prognostic significance of immunoreactive neutrophil elastase in human breast cancer: long-term follow-up results in 313 patients.

Author

Akizuki M, Fukutomi T, Takasugi M, Takahashi S, Sato T, Harao M, Mizumoto T, and Yamashita J

Subjects
Breast Neoplasms mortality, Breast Neoplasms pathology, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Humans, Leukocyte Elastase immunology, Leukocyte Elastase physiology, Multivariate Analysis, Prognosis, Breast Neoplasms enzymology, Leukocyte Elastase analysis
Abstract

Objective: We have measured the concentration of immunoreactive neutrophil elastase (ir-NE) in the tumor extracts of 313 primary human breast cancers. Sufficient time has elapsed, and we are now ready to analyze its prognostic value in human breast cancer., Methods: ir-NE concentration in tumor extracts was determined with an enzyme-linked immunosorbent assay that enables a rapid measurement of both free-form ir-NE and the A1-protease inhibitor-complexed form of ir-NE. We analyzed the prognostic value of this enzyme in human breast cancer in univariate and multivariate analyses., Results: Patients with breast cancer tissue containing a high concentration of ir-NE had poor survival compared to those with a low concentration of ir-NE at the cutoff point of 9.0 microg/100 mg protein (P = .0012), which had been previously determined in another group of 49 patients. Multivariate stepwise analysis selected lymph node status (P = .0004; relative risk = 1.46) and ir-NE concentration (P = .0013; relative risk = 1.43) as independent prognostic factors for recurrence., Conclusions: Tumor ir-NE concentration is an independent prognostic factor in patients with breast cancer who undergo curative surgery. This enzyme may play an active role in tumor progression that leads to metastasis in human breast cancer.

Published
2007
Full Text
View/download PDF

5. Neutrophil elastase and cancer.

Author

Sato T, Takahashi S, Mizumoto T, Harao M, Akizuki M, Takasugi M, Fukutomi T, and Yamashita J

Subjects
Animals, Breast Neoplasms drug therapy, Breast Neoplasms physiopathology, Elastin metabolism, Humans, Leukocyte Elastase antagonists & inhibitors, Lung Neoplasms drug therapy, Lung Neoplasms physiopathology, Neoplasm Metastasis, Prognosis, Breast Neoplasms metabolism, Enzyme Inhibitors therapeutic use, Leukocyte Elastase metabolism, Lung Neoplasms metabolism
Abstract

This mini-review summarizes our recent experimental and clinical studies on neutrophil elastase (NE) and cancer based on our original view point. Neoplasms metastasize as a result of a complex series of events. This process requires various degradative enzymes including proteases. NE has broad substrate specificity under physiological conditions, and excessive NE results in digestion of not only elastin, but also other extracellular matrix proteins. Several cell lines from human breast cancer and human lung cancer produce immunoreactive NE. The amount of immunoreactive NE in tumor tissue is an independent prognostic indicator of patients with breast cancer and lung cancer. Furthermore, a specific NE inhibitor completely suppressed growth of cancer cells transplanted into severe combined immunodeficiency mice. The use of NE inhibitor would seem to be a promising way to prevent the invasion and metastasis of cancer.

Published
2006
Full Text
View/download PDF

6. Neutrophil elastase predicts trastuzumab responsiveness in metastatic breast cancer.

Author

Yamashita J, Akizuki M, Jotsuka T, Harao M, and Nakano S

Subjects
Antibodies, Monoclonal, Humanized, Breast Neoplasms enzymology, Clinical Trials as Topic, Female, Humans, Neoplasm Metastasis, Receptor, ErbB-2, Trastuzumab, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Leukocyte Elastase metabolism
Published
2006
Full Text
View/download PDF

7. Persistent evidence of circulating tumor cells detected by means of RT-PCR for CEA mRNA predicts early relapse: a prospective study in node-negative breast cancer.

Author

Jotsuka T, Okumura Y, Nakano S, Nitta H, Sato T, Miyachi M, Suzumura K, and Yamashita J

Subjects
Adult, Aged, Biomarkers, Tumor blood, Breast Neoplasms blood, Breast Neoplasms surgery, Carcinoembryonic Antigen blood, Carcinoembryonic Antigen genetics, Carcinoma, Ductal, Breast blood, Carcinoma, Ductal, Breast surgery, Female, Humans, Lymphatic Metastasis, Mastectomy methods, Middle Aged, Predictive Value of Tests, Prognosis, Prospective Studies, RNA, Messenger analysis, Reverse Transcriptase Polymerase Chain Reaction methods, Treatment Outcome, Biomarkers, Tumor immunology, Breast Neoplasms immunology, Carcinoembryonic Antigen immunology, Carcinoma, Ductal, Breast immunology, Neoplastic Cells, Circulating immunology
Abstract

Background: In 100 consecutive patients with node-negative breast cancer who underwent curative surgery, we prospectively tested whether detection of circulating tumor cells in peripheral blood by means of reverse transcription-polymerase chain reaction for carcinoembryonic antigen (CEA) messenger RNA (mRNA) could predict patient outcomes., Methods: We performed reverse transcription-polymerase chain reaction in blood samples taken before surgery and in repeat samples taken 2 to 3 weeks after surgery. Univariate and multivariate analyses of relapse-free survival were performed., Results: Patients with CEA mRNA in preoperative samples had poorer survival rates than those who had no detectable CEA mRNA. The worst survival rate was seen in those with CEA mRNA in both pre- and postoperative samples. Stepwise multivariate analysis selected CEA mRNA expression pattern (P=.001; relative risk=0.69) and histologic tumor grade (P=.002; relative risk=1.35) as independent prognostic factors for disease-free survival., Conclusions: Molecular detection of CEA mRNA in both pre- and postoperative blood samples is an independent, negative prognostic factor in patients with node-negative breast cancer undergoing curative surgery.

Published
2004
Full Text
View/download PDF

8. Immunohistochemical analysis of estrone sulfatase and aromatase in human breast cancer tissues.

Author

Yamamoto Y, Yamashita J, Toi M, Muta M, Nagai S, Hanai N, Furuya A, Osawa Y, Saji S, and Ogawa M

Subjects
Adult, Breast Neoplasms pathology, Carcinoma, Ductal pathology, Female, Humans, Menopause, Microcirculation, Middle Aged, Neoplasm Invasiveness pathology, Prognosis, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-mdm2, Receptors, Estrogen analysis, Stromal Cells pathology, Survival Rate, Thymidine Phosphorylase metabolism, Tumor Suppressor Protein p53 metabolism, Vascular Endothelial Growth Factor A metabolism, Aromatase metabolism, Biomarkers, Tumor analysis, Breast Neoplasms enzymology, Carcinoma, Ductal enzymology, Nuclear Proteins, Sulfatases metabolism
Abstract

We examined, by immunohistochemical analysis, the expression of aromatase and estrone sulfatase (E1-STS) which are the two major enzymes involved in in situ estrogen synthesis in breast cancer tissue. In the 83 cases examined, E1-STS, which hydrolyses estrone sulfate (E1S) to estrone (E1), was dominantly detected in tumor cells in 43 (59.0%) cases. Aromatase, which converts androgens to estrogens, was dominantly detected in stromal cells of the tumor. It was detected in 39 (47.0%) of the 83 cases. There was no significant correlation between the expression of these two enzymes and clinicopathological factors. We found a tendency for a correlation between aromatase expression and E1-STS expression in breast tumor (p=0.075). In terms of the possible use of these enzymes as prognostic indicators, patients who had aromatase in their tumor showed longer relapse-free survival than those lacking aromatase (p=0.045). Significant correlations between the expression of aromatase and the angiogenesis regulators, vascular endothelial growth factor and thymidine phosphorylase, were found (p=0.047 and p=0.046, respectively), though the presence of aromatase did not correlate with intratumoral microvessel density. This may indicate that aromatase is involved in vascular permeability and recruitment of endothelial cells rather than neovascularization. It may be useful to study the expression of aromatase and E1-STS using immunocytochemical analysis for understanding the tumor characteristics in breast cancer.

Published
2003

9. Metastasis of breast cancer to intracranial meningioma: case report.

Author

Watanabe T, Fujisawa H, Hasegawa M, Arakawa Y, Yamashita J, Ueda F, and Suzuki M

Subjects
Bone Neoplasms secondary, Brain Neoplasms diagnosis, Female, Humans, Liver Neoplasms secondary, Lung Neoplasms secondary, Meningioma diagnosis, Middle Aged, Neoplasms, Multiple Primary diagnosis, Brain Neoplasms pathology, Brain Neoplasms secondary, Breast Neoplasms pathology, Carcinoma, Ductal, Breast secondary, Meningioma pathology, Neoplasms, Multiple Primary pathology
Abstract

Metastasis of systemic cancer to intracranial tumors is a rare event. The authors report a case of 49-year-old woman with such occurrence, whose breast cancer metastasized to a preexisting parasagittal meningioma at a postoperative interval of 1.5 years. She was admitted to our hospital because of progressive right hemiparesis. Magnetic resonance imaging revealed newly emerged perifocal edema and inhomogeneous contrast enhancement of the meningioma. High choline/creatine ratio and lactate/lipid peak on proton magnetic resonance spectroscopy suggested malignancy. She underwent a tumor resection, and pathologic examination revealed intratumoral metastasis of breast cancer in a transitional meningioma. Immunoreactivity of E-cadherin was detected in both meningioma and breast cancer cells. It is suggested that abrupt appearance of symptoms, inhomogeneous enhancement, and perifocal edema of meningioma is a sign of intratumoral metastasis from systemic cancers.

Published
2002
Full Text
View/download PDF

10. Clinical significance of circulating cancer cells in peripheral blood detected by reverse transcriptase-polymerase chain reaction in patients with breast cancer.

Author

An XY, Egami H, Hayashi N, Kurusu Y, Yamashita JI, and Ogawa M

Subjects
Adult, Aged, Breast Neoplasms blood, Carcinoembryonic Antigen blood, Cell Line, Female, Humans, Middle Aged, Neoplasm Staging, Prognosis, RNA, Messenger blood, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Breast Neoplasms pathology, Neoplastic Cells, Circulating pathology
Abstract

Detection of breast cancer micrometastases based on specific genetic markers may provide useful information to justify appropriate therapeutic strategies. We examined the presence of a carcinoembryonic antigen (CEA) messenger RNA(mRNA) in the peripheral blood of 32 patients with varying stages of breast cancers by means of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay prior to and after the curative operation. CEA mRNA were detected in the peripheral blood samples from 12 (38%) out of 32 breast cancer patients prior to surgery. Among 12 CEA mRNA-positive patients prior to surgery, 4 (33.3%) relapsed from breast cancer within 2 years after surgery. Moreover, CEA mRNA was detected in the peripheral blood samples obtained prior to surgery in 3 out of 11 patients (27.2%) with a stage I disease. One out of three of these patients had a relapse in lung. There were four patterns of CEA mRNA expression, ( +, + ), (+, -), (-, + ), and (-, -) in the pre- and post-operative blood samples. In 12 CEA mRNA-positive patients submitted to surgical resection of the primary tumor, persistence of CEA mRNA expression was observed in five patients (+, +) within a month after surgical treatment. Three out of these 5 patients (60%) relapsed from breast cancer within 2 years after surgery. In 7 other patients (+, -), CEA mRNA expression was not detected within a month after tumor removal, and recurrence occurred in 1 out of the 7 patients (14%) within 2 years after surgery. In 19 patients, CEA mRNA expression was not detected in pre- or post-operative blood samples (-, -). There was a patient whose blood sample was negative for CEA mRNA before the operation, but changed to show a positive result after surgery (-,+). No recurrence was found in 20 of CEA mRNA-negative patients prior to surgery (-, +), (-, -). This study suggested that the presence of CEA mRNA expression in preoperative peripheral blood sample represent the progression of the disease, especially the risk of hematogenous metastasis in the patients in spite of their clinical stage, and the presence of CEA mRNA in the postoperative blood sample may represent the evidence of a residual disease. Thus consideration might be given for adding combined multi-modal therapy.

Published
2001
Full Text
View/download PDF

11. [Study on CAF + medroxyprogesterone acetate (MPA) therapy for advanced or recurrent breast cancer--comparison between MPA 600 mg and 1,200 mg. Kyushu CAFT Therapy Study Group (Third Study)].

Author

Mitsuyama S, Ohno S, Koga T, Takayama T, Yamashita J, Ogawa M, Shirouzu K, Sugimachi K, Nomura Y, and Ogawa N

Subjects
Adult, Aged, Body Weight drug effects, Breast Neoplasms mortality, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Administration Schedule, Female, Fluorouracil administration & dosage, Humans, Middle Aged, Neoplasm Recurrence, Local mortality, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Medroxyprogesterone Acetate administration & dosage, Neoplasm Recurrence, Local drug therapy
Abstract

To find the optimal dose of MPA for combined use with CAF therapy for advanced or recurrent breast cancer, a randomized comparative study with a MPA 1,200 mg group and 600 mg group was carried out multi-institutionally. The response rate of complete cases was 37.5% (12/32) in the 1,200 mg group and 36.6% (15/41) in the 600 mg group, showing no difference between the two groups. There were no differences in either the duration of response or the survival term. The major adverse effects and abnormal laboratory test values included alopecia, nausea and vomiting, general fatigue, anorexia and leukopenia, with no difference in incidence between the groups. Moon face, genital hemorrhage and body weight increase, which are thought to be caused by MPA, were found in both groups without a significant difference in incidence. The results of this study revealed no differences in effectiveness or safety between MPA 1,200 mg and 600 mg, suggesting that MPA for combined use with CAF is fully effective at a dose of 600 mg.

Published
1999

12. Medroxyprogesterone acetate treatment reduces serum interleukin-6 levels in patients with metastatic breast carcinoma.

Author

Yamashita J, Hideshima T, Shirakusa T, and Ogawa M

Subjects
Administration, Oral, Adult, Aged, Breast Neoplasms drug therapy, Female, Humans, Medroxyprogesterone Acetate administration & dosage, Medroxyprogesterone Acetate blood, Medroxyprogesterone Acetate therapeutic use, Middle Aged, Progesterone Congeners administration & dosage, Progesterone Congeners blood, Progesterone Congeners therapeutic use, Prospective Studies, Breast Neoplasms blood, Interleukin-6 blood, Medroxyprogesterone Acetate pharmacology, Neoplasm Proteins blood, Progesterone Congeners pharmacology
Abstract

Background: The serum interleukin (IL)-6 concentration was very low in patients with metastatic breast carcinoma who had received oral medroxyprogesterone acetate (MPA) treatment as compared with those who had not. Accordingly, the authors conducted a prospective study to determine whether MPA treatment reduces the serum level of IL-6 in patients with this disease., Methods: In 21 consecutive Japanese patients who were scheduled to receive oral MPA treatment at doses of 600, 800 or 1200 mg/day, serum concentrations of IL-6 were determined with a sensitive enzyme-immunoassay prior to the administration of MPA and again at 4 weeks after the treatment was started. In addition, plasma levels of MPA were determined by high-performance liquid chromatography (HPLC)., Results: Four weeks after the oral MPA therapy was started, serum IL-6 levels decreased in all 21 patients regardless of whether or not they responded to the treatment. Although the extent of decrease in the serum IL-6 (delta IL-6) did not correlate with the daily dose of MPA, it correlated closely with the plasma MPA level in these patients. Subjective improvement in appetite and weight gain were more frequent in the delta IL-6 > 3 pg/mL group compared with the delta IL-6 < or = 3 pg/mL group (80% vs. 45% and 70% vs. 45%, respectively). Similar results were obtained for improvement in patients' sense of well-being (100% vs. 55%)., Conclusions: Oral MPA treatment reduces serum IL-6 concentration in patients with metastatic breast carcinoma, but the decrease is not associated with response to MPA. This observation may indicate a potential of this agent for producing subjective improvement.

Published
1996

13. Immunohistochemical expression of the c-kit proto-oncogene product in human malignant and non-malignant breast tissues.

Author

Chui X, Egami H, Yamashita J, Kurizaki T, Ohmachi H, Yamamoto S, and Ogawa M

Subjects
Adult, Aged, Breast cytology, Breast Diseases metabolism, Breast Neoplasms pathology, Carcinoma pathology, Cytoplasm metabolism, Female, Humans, Immunoenzyme Techniques, Lymphatic Metastasis, Middle Aged, Papilloma metabolism, Proto-Oncogene Mas, Breast metabolism, Breast Neoplasms metabolism, Carcinoma metabolism, Proto-Oncogene Proteins c-kit metabolism
Abstract

The immunohistochemical expression of c-kit proto-oncogene product in 57 breast cancer tissues was studied using anti-c-kit proto-oncogene product antibody in comparison with 20 normal breast tissues and 58 benign breast tumours. In normal breast tissues, the c-kit proto-oncogene product was strongly expressed on cell membrane and/or cytoplasm of alveolar and ductal cells. The immunoreactive score (IRS) of c-kit proto-oncogene product in normal mammary epithelia was 6.22 +/- 2.11 (mean +/- s.d.). In benign breast diseases, the c-kit proto-oncogene product was detected heterogeneously with a reduced IRS (3.33 +/- 2.44). In breast cancer tissues, the expression of the immunoreactive c-kit proto-oncogene product was often deleted and the average IRS was significantly reduced compared to those of normal breast tissues or benign breast diseases tissues. Among benign diseases, the average IRS of intraductal papilloma was significantly reduced (1.34 +/- 1.70) and the staining intensity and pattern were found to be similar to those seen in breast cancer. The results in this study suggested that the c-kit proto-oncogene product is correlated with the growth control or the differentiation of normal breast epithelium. Also, the loss of the expression of this protein may indicate the change of the signal transduction in relation to malignant transformation in human mammary epithelium.

Published
1996
Full Text
View/download PDF

14. Prognostic significance of three novel biologic factors in a clinical trial of adjuvant therapy for node-negative breast cancer.

Author

Yamashita J, Ogawa M, and Sakai K

Subjects
Breast Neoplasms pathology, Carcinoma pathology, Chemotherapy, Adjuvant, Disease-Free Survival, Endothelins analysis, Female, Follow-Up Studies, Humans, Leukocyte Elastase, Mastectomy, Modified Radical, Mastectomy, Radical, Neoplasm Staging, Phospholipases A2, Prognosis, Prospective Studies, Risk Factors, Survival Rate, Tamoxifen therapeutic use, Urokinase-Type Plasminogen Activator analysis, Breast Neoplasms chemistry, Breast Neoplasms drug therapy, Carcinoma chemistry, Carcinoma drug therapy, Pancreatic Elastase analysis, Phospholipases A analysis, Tissue Plasminogen Activator analysis
Abstract

Background: Five products of human breast carcinoma cells, including membrane-associated phospholipase A2 (M-PLA2), polymorphonuclear leukocyte elastase (PMN-E), tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and endothelin-1 (ET-1), have been implicated in the processes of tumor cell invasion and metastasis in human breast carcinoma. However, the prognostic significance of these factors has not been assessed previously in node-negative breast carcinoma, in which adjuvant treatment is dependent on risk stratification., Methods: The five products of breast carcinoma cells were measured in 184 patients with node-negative breast carcinoma who were enrolled in the Kumamoto Adjuvant Chemo-Endocrine Therapy for Breast Cancer prospective randomized trial, and the predictive values of these factors for relapse-free and overall survival were evaluated., Results: M-PLA2, PMN-E, and t-PA were found to be significant independent predictors of relapse-free and overall survival, whereas u-PA and ET-1 were not independently predictive. Further statistical analyses showed that the predictive powers of M-PLA2, PMN-E, and t-PA were additive. A combination of these three factors identified a group of patients (approximately 50% of those who manifested node-negative breast carcinoma) with a favorable prognosis, regardless of the administration of adjuvant therapy., Conclusions: This study identified three biologic factors that are valuable predictors of survival in node-negative breast carcinoma. A combination of these biologic factors may allow identification of low-risk patients who could be spared adjuvant therapy.

Published
1995
Full Text
View/download PDF

15. [A strong predictor of breast cancer--hepatocyte growth factor (HGF)].

Author

Sakai K, Yamashita J, and Ogawa M

Subjects
Disease-Free Survival, Female, Humans, Middle Aged, Prognosis, Survival Rate, Breast Neoplasms chemistry, Breast Neoplasms mortality, Hepatocyte Growth Factor analysis
Abstract

We measured the hepatocyte growth factor (HGF) concentration in breast cancer tissue extracts and evaluated its association with survival. The HGF level was found to be the most important factor in survival, even more so than lymph node involvement. HGF may play an important role in the progression of human breast cancer.

Published
1995

16. Free-form neutrophil elastase is an independent marker predicting recurrence in primary breast cancer.

Author

Yamashita J, Ogawa M, and Shirakusa T

Subjects
Adult, Age Factors, Biomarkers, Tumor, Breast Neoplasms enzymology, Female, Humans, Leukocyte Elastase chemistry, Middle Aged, Multivariate Analysis, Pancreatic Elastase chemistry, Prognosis, Recurrence, Survival Analysis, alpha 1-Antitrypsin metabolism, Breast Neoplasms diagnosis, Leukocyte Elastase metabolism, Neutrophils enzymology, Pancreatic Elastase metabolism
Abstract

We have measured the immunoreactive neutrophil elastase (ir-NE) concentration in tumor extracts of 313 primary human breast cancers using an enzyme-linked immunosorbent assay recently developed and have evaluated its association with disease-free survival. This is a sensitive assay that enables rapid measurement of both free-form and alpha 1-proteinase inhibitor (alpha 1-PI)-complexed form of ir-NE. Breast cancer patients with high ir-NE concentrations had a significantly shorter disease-free survival (P = .013) than those with a low ir-NE concentration at the cutoff point of 9.0 micrograms/100 mg protein, which was determined in another group of 49 patients. In multivariate analysis, the ir-NE level was found to be an independent prognostic factor (relative risk = 2.2, P = .025) for disease recurrence in human breast cancer. Furthermore, when multivariate analysis was repeated with inclusion of each level of free-form and alpha 1-PI-complexed form, the former level was an independent predictor of recurrence (relative risk = 2.5, P = .015), whereas the latter was not independently predictive (P = .43). These results support the hypothesis that this enzyme may play an active role in the tumor progression that leads to metastasis in human breast cancer.

Published
1995
Full Text
View/download PDF

17. Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency.

Author

Yamashita S, Yamashita J, and Ogawa M

Subjects
Age Factors, Analysis of Variance, Blotting, Northern, Breast Neoplasms enzymology, Breast Neoplasms mortality, Breast Neoplasms surgery, Female, Follow-Up Studies, Humans, Middle Aged, Multivariate Analysis, Neoplasm Metastasis, Phospholipases A analysis, Phospholipases A2, Prognosis, RNA, Messenger analysis, RNA, Messenger biosynthesis, Receptors, Estrogen, Receptors, Progesterone analysis, Survival Analysis, Time Factors, Breast Neoplasms pathology, Gene Expression, Phospholipases A biosynthesis
Abstract

Membrane-associated phospholipase A2 (M-PLA2) is an enzyme that hydrolyses the sn-2 fatty acyl ester bond of phosphoglycerides. We measured M-PLA2 concentration in tissue extracts from 325 human breast cancers using a specific radioimmunoassay recently developed. Correlation analyses between the tissue concentration of M-PLA2 and clinicopathological factors showed that the enzyme level was significantly higher in patients with distant metastasis than in those without. In addition, M-PLA2 concentration was significantly higher in scirrhous carcinoma than in other histological types. No significant association was found between M-PLA2 concentration and age, menstrual status, tumour size, histological grade, vessel involvement or oestrogen receptor (ER) and progesterone receptor (PR) status. The expression of M-PLA2 mRNA was examined in a fibroadenoma, a stage IV breast cancer and its metastatic site of skin. Northern blot analysis showed a clear hybridisation band corresponding to M-PLA2 mRNA in both primary breast cancer and its metastatic site, while the fibroadenoma expressed a faint band corresponding to M-PLA2 mRNA. Breast cancer patients with high M-PLA2 concentrations exhibited significantly shorter disease-free and overall survival than those with low M-PLA2 concentration at the cut-off point of 5 ng 100 mg-1 protein, which was determined in a separate study. In multivariate analysis, M-PLA2 was found to be an independent prognostic factor for disease recurrence and death in human breast cancer. The possible significance of M-PLA2 expression in human breast cancer tissue is discussed.

Published
1994
Full Text
View/download PDF

18. Immunoreactive hepatocyte growth factor is a strong and independent predictor of recurrence and survival in human breast cancer.

Author

Yamashita J, Ogawa M, Yamashita S, Nomura K, Kuramoto M, Saishoji T, and Shin S

Subjects
Adult, Age Factors, Breast Neoplasms mortality, Breast Neoplasms pathology, Female, Humans, Lymphatic Metastasis, Mastectomy, Modified Radical, Mastectomy, Radical, Menopause, Middle Aged, Prognosis, Receptors, Estrogen, Receptors, Progesterone, Survival Analysis, Survival Rate, Time Factors, Biomarkers, Tumor analysis, Breast Neoplasms surgery, Hepatocyte Growth Factor analysis
Abstract

Hepatocyte growth factor (HGF) is a stromally derived modulator of epithelial cell proliferation and motility. In the present study, we have measured immunoreactive (ir)-HGF concentration in tumor extracts of 258 primary human breast cancers using an enzyme-linked immunosorbent assay and have evaluated its association with disease-free and overall survival. The median value of ir-HGF concentration was 11.0 ng/100 mg protein (range, 1.4-566.7 ng/100 mg protein). Correlation analyses between ir-HGF concentration and clinicopathological factors showed that the ir-HGF level was correlated only with tumor size (P = 0.05). No significant associations were found between ir-HGF content and age, menopausal status, nodal status, histological type, histological grade, vessel involvement, estrogen receptor, progesterone receptor, type of surgery, or postoperative adjuvant therapy. Breast cancer patients with high ir-HGF concentration had a significantly shorter relapse-free (P = 0.001) and overall survival (P = 0.001) rate when compared to those with low ir-HGF concentration at the cutoff point of 21.7 ng/100 mg protein, which was determined in another group of 82 patients. In multivariate analysis, ir-HGF level was found to be the most important independent factor in predicting relapse-free and overall survival, of greater import than lymph node involvement. The putative role of HGF in breast cancer growth and metastasis is hereby strengthened.

Published
1994

19. Production of immunoreactive polymorphonuclear leucocyte elastase in human breast cancer cells: possible role of polymorphonuclear leucocyte elastase in the progression of human breast cancer.

Author

Yamashita JI, Ogawa M, Ikei S, Omachi H, Yamashita SI, Saishoji T, Nomura K, and Sato H

Subjects
Breast Neoplasms blood, Breast Neoplasms pathology, Female, Humans, Leukocyte Elastase, Middle Aged, Pancreatic Elastase physiology, Retrospective Studies, Tumor Cells, Cultured, Breast Neoplasms enzymology, Neutrophils enzymology, Pancreatic Elastase biosynthesis, Pancreatic Elastase immunology
Abstract

Breast cancer cells are known to express various proteolytic enzymes, which make them invasive and favour their dissemination to distant sites. However, it is unclear whether breast cancer cells have the ability to produce polymorphonuclear leucocyte elastase (PMN-E). We measured immunoreactive (ir) PMN-E content in the conditioned medium of two breast cancer cell lines, MCF-7 and ZR-75-1, and two normal breast epithelial cell lines, HBL-100 and Hs 578Bst, using a highly specific and sensitive enzyme immunoassay. Furthermore, ir-PMN-E content was determined in tissue extracts from 62 human breast cancers. ir-PMN-E content in the culture medium of MCF-7 cells and ZR-75-1 cells increased as a function of time, regardless of the presence or absence of oestradiol. On the other hand, no detectable ir-PMN-E was secreted into the culture medium of HBL-100 and Hs 578Bst cells. ir-PMN-E was detectable in 59 of 62 tissue extracts prepared from human breast cancers, the concentration ranging from 0.12 to 19.17 micrograms per 100 mg of protein. When 62 breast cancer specimens were categorised into four groups in terms of clinical stage, ir-PMN-E content in breast cancer tissue was significantly higher in stage III (8.90 +/- 5.13 micrograms 100 mg-1 protein) and stage IV (12.19 +/- 5.44 micrograms 100 mg-1 protein) patients than in stage I (1.64 +/- 1.54 micrograms 100 mg-1 protein) and stage II (4.23 +/- 3.74 micrograms 100 mg-1 protein) patients. Breast cancer patients with high levels of ir-PMN-E showed significantly shorter disease-free survival and overall survival than those with low levels of ir-PMN-E at the cut-off point of 8.99 micrograms 100 mg-1 protein. In the multivariate analysis, ir-PMN-E content was found to be a significant prognostic factor for disease recurrence and death in human breast cancer.

Published
1994
Full Text
View/download PDF

20. Immunoreactive hepatocyte growth factor is present in tissue extracts from human breast cancer but not in conditioned medium of human breast cancer cell lines.

Author

Yamashita J, Ogawa M, and Beppu T

Subjects
Breast Neoplasms pathology, Culture Media, Conditioned chemistry, Enzyme-Linked Immunosorbent Assay, Female, Humans, Middle Aged, Tissue Extracts chemistry, Tumor Cells, Cultured, Breast Neoplasms metabolism, Hepatocyte Growth Factor metabolism
Abstract

Hepatocyte growth factor (HGF) is a novel mitogen for mature hepatocytes. In the present study, we have measured immunoreactive (ir)-HGF concentration in tumor extracts of 82 primary human breast cancers using an enzyme-linked immunosorbent assay (ELISA). Ir-HGF was detectable in all tissue extracts, the concentration ranging from 1.4 to 306.5 ng/100 mg protein (median value: 11.2 ng/100 mg protein). Correlation analyses between ir-HGF concentration and clinicopathological factors showed that the ir-HGF level was significantly higher in tumors with sizes of more than 5.0 cm compared with those less than 5.0 cm. In contrast, no detectable amount of ir-HGF was secreted into culture medium of two breast cancer cell lines, MCF-7 and ZR-75-1, suggesting that the cancer cell itself has no ability to produce ir-HGF.

Published
1993

21. Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer.

Author

Yamashita J, Ogawa M, Yamashita S, Nakashima Y, Saishoji T, Nomura K, Inada K, and Kawano I

Subjects
Bone Neoplasms secondary, Breast Neoplasms pathology, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Middle Aged, Prognosis, Receptors, Cell Surface metabolism, Retrospective Studies, Breast Neoplasms metabolism, Tissue Plasminogen Activator metabolism, Urokinase-Type Plasminogen Activator metabolism
Abstract

Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were positive for both receptors were found to contain the highest t-PA activity and antigen. This study provides provocative evidence suggesting a possible differential significance of t-PA and u-PA expression in human breast cancer.

Published
1993
Full Text
View/download PDF

22. Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells.

Author

Yamashita S, Yamashita J, Sakamoto K, Inada K, Nakashima Y, Murata K, Saishoji T, Nomura K, and Ogawa M

Subjects
Breast enzymology, Breast Diseases enzymology, Breast Neoplasms pathology, Cell Membrane enzymology, Humans, Lymphatic Metastasis, Middle Aged, Multivariate Analysis, Neoplasm Metastasis, Phospholipases A2, Prognosis, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Risk Factors, Survival Analysis, Breast Neoplasms enzymology, Phospholipases A metabolism
Abstract

Background: Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors., Methods: M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method., Results: Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M-PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates., Conclusions: M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.

Published
1993
Full Text
View/download PDF

23. Interleukin 6 stimulates the production of immunoreactive endothelin 1 in human breast cancer cells.

Author

Yamashita J, Ogawa M, Nomura K, Matsuo S, Inada K, Yamashita S, Nakashima Y, Saishoji T, Takano S, and Fujita S

Subjects
Cycloheximide pharmacology, Cytokines pharmacology, Dactinomycin pharmacology, Endothelins immunology, Endothelins metabolism, Estrogens pharmacology, Humans, Stimulation, Chemical, Tamoxifen pharmacology, Tumor Cells, Cultured drug effects, Breast Neoplasms metabolism, Endothelins biosynthesis, Interleukin-6 pharmacology
Abstract

To investigate the potential regulation of endothelin 1 production in human breast cancer cells, we measured the release of immunoreactive endothelin 1 (ir-ET-1) from the MCF-7 and ZR-75-1 breast cancer cell lines in response to various agents including estrogen and tamoxifen as well as several cytokines. ir-ET-1 was detected in conditioned medium of MCF-7 cells and ZR-75-1 cells by specific radioimmunoassay. Among the agents tested, estrogen, tamoxifen, tumor necrosis factor, gamma-interferon, interleukin (IL) 1, and transforming growth factor beta had no effect on ir-ET-1 secretion by these breast cancer cells. However, IL-6 (20 ng/ml) treatment of MCF-7 cells and ZR-75-1 cells caused maximal increases in the amount of ir-ET-1 secreted into the culture medium to 206 and 314% of basal values after 6 h, respectively. This effect of IL-6 on ir-ET-1 secretion was inhibited by actinomycin D and cycloheximide, indicating that IL-6 stimulates de novo synthesis of ir-ET-1 at a transcriptional level. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay in the conditioned medium from IL-6-treated cells revealed one major ir-ET-1 component corresponding to human standard ET-1. The present study demonstrates the potential for IL-6 to stimulate ir-ET-1 production in human breast cancer cells, which may participate in the process of acute phase reactant-like expression of this peptide and/or in the process of IL-6 enhanced breast cancer cell motility, the latter being recently clarified.

Published
1993

24. Breast cancer prognosis is poor when total plasminogen activator activity is low.

Author

Yamashita J, Ogawa M, Inada K, Yamashita S, Nakashima Y, Saishoji T, and Nomura K

Subjects
Female, Follow-Up Studies, Humans, Middle Aged, Prognosis, Retrospective Studies, Breast Neoplasms enzymology, Plasminogen Activators metabolism
Abstract

Plasminogen activator (PA) is a serine protease which exists in two forms: tissue-type (t-PA) and urokinase-type (u-PA). The total PA activity was measured in tumour extracts of 235 breast cancer patients who were followed for a median of 8.5 years after surgery. Patients were initially divided into three groups with low (< 60 units mg-1 protein), intermediate (60-300 unit mg-1 protein), or high (> 300 unit mg-1 protein) total PA activity in tumour extracts. The PA activity was not significantly associated with the recognised prognostic factors of age, menstrual status, tumour size, lymph node involvement, histologic type, grade of anaplasia, and/or vessel involvement. A significant association was found between total PA activity and the oestrogen receptor (ER) or progesterone receptor (PgR) status. Among receptor-positive tumours, a significantly greater proportion of patients had high PA activity in their tumour extracts. Breast cancer patients with low total PA activity had a significantly shorter disease-free and overall survival rate when compared to those with intermediate or high PA activity. In univariate and multivariate analyses, total PA activity (< 60 unit mg-1 vs > or = 60 unit mg-1 protein) was found to be a significant prognostic factor for disease-free and overall survival of about the same import as lymph node involvement. Furthermore, the combination of total PA activity and nodal status could be even more precise in predicting survival times and probabilities in individual patients. This retrospective study demonstrates the total PA activity is a valuable prognostic factor in determining prognosis in human breast cancer.

Published
1993
Full Text
View/download PDF

25. Abundant expression of immunoreactive endothelin 1 in mammary phyllodes tumor: possible paracrine role of endothelin 1 in the growth of stromal cells in phyllodes tumor.

Author

Yamashita J, Ogawa M, Egami H, Matsuo S, Kiyohara H, Inada K, Yamashita S, and Fujita S

Subjects
Adenofibroma pathology, Adolescent, Adult, Breast Neoplasms pathology, Chromatography, High Pressure Liquid, Female, Humans, Phyllodes Tumor pathology, Adenofibroma chemistry, Breast Neoplasms chemistry, Endothelins analysis, Phyllodes Tumor chemistry
Abstract

Immunoreactive endothelin 1 (irET-1) concentrations were measured in extracts prepared from 4 phyllodes tumors and 14 fibroadenomas. irET-1 was detectable in all tissue extracts by specific radioimmunoassay, and the mean concentration of irET-1 was 18-fold and 27-fold higher in tissue extracts from phyllodes tumors than in those from intracanalicular fibroadenomas and pericanalicular fibroadenomas, respectively. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay in the extracts from phyllodes tumors revealed one major irET-1 component corresponding to human standard ET-1. Furthermore, immunocytochemical staining for ET-1 revealed that numerous ET-1-immunoreactive cells were seen in the epithelial cells but not in the stromal cells, suggesting that ET-1 is synthesized by the epithelial component of phyllodes tumors. A possible paracrine role of ET-1 in the growth of this rare tumor which is characterized by its prominent stromal cellularity is discussed.

Published
1992

26. Tissue-type plasminogen activator is involved in skeletal metastasis from human breast cancer.

Author

Yamashita J, Inada K, Yamashita S, Nakashima Y, Matsuo S, and Ogawa M

Subjects
Bone Neoplasms enzymology, Breast Neoplasms enzymology, Fibrin metabolism, Fibrinolysis, Humans, Neoplasm Metastasis, Neoplastic Cells, Circulating, Spinal Neoplasms enzymology, Spinal Neoplasms secondary, Spine blood supply, Veins, Bone Neoplasms secondary, Breast Neoplasms pathology, Neoplasm Proteins physiology, Tissue Plasminogen Activator physiology
Abstract

This study was undertaken to determine if primary breast tumor plasminogen activator expression correlates with skeletal metastasis in breast cancer. Total plasminogen activator activity was significantly lower in tumors of patients with recurrence than in recurrence-free patients. Similarly, the primary tumors of patients with skeletal metastasis contained considerably less enzyme activity compared with those of patients surviving without skeletal metastasis. When patients with skeletal metastasis were categorized in terms of their recurrence pattern, those who had skeletal metastasis without other organ metastasis had significantly less tissue-type plasminogen activator antigen in their primary breast tumors than did those who had metastasis to other organs. Furthermore, a significantly lower level of tissue-type plasminogen activator antigen was found in primary tumors associated with axial bone metastasis than in those associated with appendicular bone metastasis. These results suggest that tissue-type plasminogen activator is involved in skeletal metastasis formation by its effects through the vertebral venous plexus.

Published
1992
Full Text
View/download PDF

27. A large amount of endothelin-1 is present in human breast cancer tissues.

Author

Yamashita J, Ogawa M, Inada K, Yamashita S, Matsuo S, and Takano S

Subjects
Adult, Aged, Breast chemistry, Breast Neoplasms pathology, DNA biosynthesis, Female, Humans, Middle Aged, Breast Neoplasms chemistry, Endothelins analysis
Abstract

Endothelin (ET)-1 concentration was measured in tissue extracts from 157 human breast cancers, 26 benign breast tumors and 10 normal breast tissues. ET-1 was detectable in all tissue extracts by specific radioimmunoassay, the concentration ranging from 0.12 to 11.95 pg/mg protein. ET-1 concentration was significantly higher in tissue extracts from breast cancer than in those from benign breast tumor or normal control tissue, suggesting that this peptide is synthesized by breast cancer cells. When 157 breast cancer specimens were categorized into 4 groups in terms of clinical staging, no significant difference was found among these clinical staging groups. Furthermore, no significant associations were observed between ET-1 concentrations and the age of patients, tumor size, lymphnode involvement, histological type or steroid hormone receptor status.

Published
1991

28. [Biological and clinical analysis of breast cancer in relation to hormone receptors].

Author

Akagi M, Iwaki J, Kimura M, Kihara S, Maeno M, Nishimura R, Araki K, Egami H, Yamashita J, Shigaki N, and Fujino N

Subjects
Breast Neoplasms pathology, Breast Neoplasms physiopathology, Female, Humans, Breast Neoplasms analysis, Receptors, Estrogen analysis, Receptors, Progesterone analysis
Abstract

We examined whether or not the presence of hormone receptors (ERC, PRC, and ERN) were related to morphological and functional features in breast cancers. Well-differentiated tumors were more frequently receptor positive while poorly differentiated tumors were generally receptor negative. And labelling index and receptor contents were negatively correlated. There was a significant inverse correlation between the receptor contents and numbers of intracellular organellas in ultrastructural features of breast cancer cells. In LMI tests by 3-M KCl cancer extracts, migration of leucocyte from patients with poorly differentiated tumors were more frequently inhibited than those well differentiated tumors. Patients with receptor positive tumors were more endocrine sensitive and had better prognosis.

Published
1983

29. [Estrogen dependent plasminogen activator in breast cancer cells; experimental and clinical studies].

Author

Yamashita J, Inada K, Matsuo S, Kawano I, Misumi A, and Akagi M

Subjects
9,10-Dimethyl-1,2-benzanthracene, Animals, Biomarkers, Tumor metabolism, Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Clinical Enzyme Tests, Estradiol pharmacology, Estrogen Antagonists pharmacology, Female, Humans, Mammary Neoplasms, Experimental chemically induced, Mammary Neoplasms, Experimental metabolism, Neoplasms, Hormone-Dependent diagnosis, Neoplasms, Hormone-Dependent enzymology, Neoplasms, Hormone-Dependent metabolism, Ovariectomy, Plasminogen Activators biosynthesis, Rats, Receptors, Estrogen metabolism, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured enzymology, Breast Neoplasms enzymology, Estrogens metabolism, Mammary Neoplasms, Experimental enzymology, Plasminogen Activators metabolism
Abstract

Hormonal regulation of plasminogen activator (PA) in rat mammary tumor induced by 7,12-dimethylbenz (a) anthracene (DMBA) was studied both in vivo and in vitro. PA activity in DMBA-tumor was markedly decreased by ovariectomy, and recovered in a dose-dependent fashion upon estradiol administration. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide and tamoxifen. Furthermore DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. This indicates that estrogen might regulate de novo synthesis of PA at a transcriptional level via an estrogen receptor system, and that this hormone might support the growth of DMBA-tumor into adjacent tissues by inducing PA in a direct manner via a route distinct from a prolactin pathway. To examine whether PA reflects the functional state of estrogen receptors in human breast cancer, the enzyme activities were determined in extracts prepared from 160 breast cancer specimens and compared on qualitative and quantitative bases with the levels of steroid receptors. The results strongly suggest that PA can be used as an effective functional marker for hormone dependence in human breast cancer.

Published
1989

30. Analysis of estrogen receptors in human breast cancer by assays using monoclonal antibodies and by the dextran-coated charcoal method.

Author

Fujino N, Sakamoto K, Shigaki N, Yamashita J, Kimura M, and Akagi M

Subjects
Charcoal, Dextrans, Humans, Immunohistochemistry, Antibodies, Monoclonal, Breast Neoplasms analysis, Receptors, Estrogen analysis
Abstract

Estrogen receptors (ER) were analyzed in 63 human breast cancers by immunocytochemical assay, and by enzyme-immunoassay, using monoclonal antibodies against human ER protein, and also by the dextran-coated charcoal method. The specific staining was observed only in the nucleus of cancer cells by the immunocytochemical assay, and the presence of nuclear staining by this assay was closely associated with the estimation of the cytosolic ER content by both the dextran-coated charcoal method and the enzyme-immunoassay. In the latter, the cytosolic ER content correspondingly increased with the nuclear ER content. Both the cytosolic and nuclear ER contents correlated well with those obtained by the dextran-coated charcoal method. Furthermore, the cytosolic ER contents obtained by the enzyme-immunoassay and the dextran-coated charcoal method correlated significantly with the age of the patient, but not with the nuclear ER contents. These above mentioned results suggest that ER is present mainly in the nucleus of breast cancer cells and that the cytosolic ER obtained by these two assays is the unoccupied one released from the nucleus.

Published
1987
Full Text
View/download PDF

31. Plasminogen activator as a functional marker for estrogen dependence in human breast cancer cells.

Author

Yamashita J, Horiuchi S, Kimura M, Nishimura R, and Akagi M

Subjects
Cell Nucleus analysis, Cytoplasm analysis, Female, Humans, Molecular Weight, Receptors, Estrogen analysis, Receptors, Progesterone analysis, Breast Neoplasms analysis, Estrogens physiology, Neoplasms, Hormone-Dependent analysis, Plasminogen Activators analysis
Abstract

To examine whether plasminogen activator reflects the functional state of estrogen receptors in human breast cancer, the enzyme activities were determined in extracts prepared from 160 breast cancer specimens and compared on qualitative and quantitative bases with the levels of steroid receptors, such as cytoplasmic estrogen receptor (ERC), progesterone receptor (PgR) and nuclear estrogen receptor (ERN). With any receptor, plasminogen activator activity was significantly higher in receptor-positive tumors than in receptor-negative tumors. When these breast tumors were categorized into 8 groups in terms of combinations of receptor status, breast cancers which were positive for all these receptors were found to contain the highest plasminogen activator activity. Furthermore, quantitative analyses demonstrated positive correlations of the enzyme activity with either ERC content (correlation coefficient +0.37, P less than 0.001) or PgR content (correlation coefficient +0.45, P less than 0.001). These results strongly suggest that plasminogen activator can be used as an effective functional marker for hormone dependence in human breast cancer.

Published
1986

32. Tamoxifen binding sites in human mammary cancers.

Author

Fujino N, Kimura M, Sakamoto K, Shigaki N, Yamashita J, and Akagi M

Subjects
Adenocarcinoma pathology, Adenocarcinoma, Scirrhous pathology, Binding Sites, Breast Neoplasms pathology, Carcinoma, Intraductal, Noninfiltrating pathology, Cell Line, Female, Humans, In Vitro Techniques, Adenocarcinoma analysis, Adenocarcinoma, Scirrhous analysis, Breast Neoplasms analysis, Carcinoma, Intraductal, Noninfiltrating analysis, Receptors, Estrogen analysis, Receptors, Progesterone analysis, Tamoxifen analysis
Abstract

Tamoxifen binding sites (TBS) were measured using 3H-tamoxifen, the objective being to evaluate the relationships among TBS and hormone receptors and/or clinical and pathological characteristics in malignant tissues from 60 patients with mammary cancer. TBS were detected in most (96.7 per cent) cancers in the breast tissues, and the mean content and affinity were 569 fmol/mg X protein with Kd: 1.98 nM. There was no significant correlation between TBS and the estrogen receptor and/or progesterone receptor, with respect to positivity or content. However, there was a significant correlation between TBS and histological grading, thereby indicating the differentiation and the proliferative activity in this tissue. The content of TBS was significantly higher in the group with a high grade of malignancy. The TBS content significantly increased in parallel with the degree of malignancy, as related to tubule formation, nuclear pleomorphism and mitotic activity. On the other hand, there was no significant correlation between TBS and age, tumor size, lymph node status or clinical stage. These results suggest the possibility that TBS may be associated with differentiation and cell-proliferation in breast cancer tissues.

Published
1986
Full Text
View/download PDF

33. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years

Author

Pan, H, Gray, R, Braybrooke, J, Davies, C, Taylor, C, Mcgale, P, Peto, R, Pritchard, Ki, Bergh, J, Dowsett, M, Hayes, Df, Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bartlett, J, Bergsten‐nordström, E, Bliss, J, Boccardo, F, Bradley, R, Brain, E, Cameron, D, Clarke, M, Coates, A, Coleman, R, Correa, C, Costantino, J, Cuzick, J, Davidson, N, Dodwell, D, Di Leo, A, Ewertz, M, Forbes, J, Gelber, R, Gnant, M, Goldhirsch, A, Goodwin, P, Hill, C, Ingle, J, Jagsi, R, Janni, W, Loibl, S, Mackinnon, E, Martin, M, Mukai, H, Norton, L, Ohashi, Y, Paik, S, Perez, E, Piccart, M, Pierce, L, Poortmans, P, Raina, V, Ravdin, P, Regan, M, Robertson, J, Rutgers, E, Slamon, D, Sparano, J, Swain, S, Tutt, A, Viale, G, Von Minckwitz, G, Wang, X, Whelan, T, Wilcken, N, Winer, E, Wolmark, N, Wood, W, Zambetti, M, Alberro, Ja, Ballester, B, Deulofeu, P, Fábregas, R, Fraile, M, Gubern, Jm, Janer, J, Moral, A, De Pablo Jl, Peñalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Solà, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Garaud, P, Collett, V, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hma, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Hupperets, Psgj, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Dal, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bramwell, Vh, Chen, Be, Gelmon, K, Goss, Pe, Levine, Mn, Parulekar, W, Pater, Jl, Shepherd, Le, Tu, D, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu‐zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett‐lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec’h, J, De La Lande, B, Mouret‐fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Boddington, C, Burrett, Ja, Cutter, D, Duane, F, Evans, V, Gettins, L, Godwin, J, James, S, Kerr, A, Liu, H, Mannu, G, Mchugh, T, Morris, P, Read, S, Wang, Y, Wang, Z, Albano, J, De Oliveira Cf, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Mouridsen, Ht, Fehm, T, Trampisch, Hj, Dalesio, O, De Vries Ege, Rodenhuis, S, Van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jgm, Treurniet‐donker, Ad, Van Putten Wlj, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Van De Velde Cjh, Cunningham, Mp, Brufsky, Am, Coleman, Re, Llombart, Ha, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Carrasco, E, Segui, Ma, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, De Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Galligioni, E, Leone, B, Vallejo, Ct, Zwenger, A, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, De Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Delaloge, S, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, Van De Velde Ao, Van Dongen Ja, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Bighin, C, Bruzzi, P, Del Mastro, L, Dozin, B, Pastorino, S, Pronzato, P, Sertoli, Mr, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro Mg, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, Ah, Kohno, N, Miyashita, M, Takao, S, Ahn, Jh, Jung, Kh, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, Gj, Christiaens, R, Neven, P, Paridaens, R, Van Den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, De La Huerta, R, Sainz, Mg, Ro, J, Camphausen, K, Danforth, D, Lichter, A, Lippman, M, Smart, D, Steinberg, S, D’Amico, C, Lioce, M, Paradiso, A, Ohno, S, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Redmond, C, Wickerham, L, Aihara, T, Hozumi, Y, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Venturini, M, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Reinertsen, Kv, Varhaug, Je, Gundersen, S, Hauer‐jensen, M, Høst, H, Nissen‐meyer, R, Mitchell, Ak, Robertson, Jfr, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Cocconi, G, Di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Hadji, P, A’Hern, R, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Clack, G, Van Poznak, C, Deshpande, N, Di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Ajs, Ewing, Gh, Firth, La, Krushen‐kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, Af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ahg, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Lemonnier, J, Martin, Al, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Deutsch, Gp, Kwong, Dlw, Pai, Vr, Senanayake, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Bell, R, Hinsley, S, Marshall, Hc, Pierce, Lj, Solomayer, E, Horsman, Jm, Lester, J, Winter, Mc, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Aft, R, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Other departments, CCA - Cancer Treatment and Quality of Life, Radiotherapy, Pan, Hongchao, Gray, Richard, Braybrooke, Jeremy, Davies, Christina, Taylor, Carolyn, Mcgale, Paul, Peto, Richard, Pritchard, Kathleen I, Bergh, Jona, Dowsett, Mitch, Hayes, Daniel F, De Laurentiis, Michelino, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Interne Geneeskunde

Subjects
0301 basic medicine, Oncology, medicine.medical_treatment, Kaplan-Meier Estimate, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Recurrence, Receptors, Neoplasm Metastasis, AMERICAN SOCIETY, Adjuvant, CLINICAL-PRACTICE GUIDELINE, Absolute risk reduction, Estrogen Antagonists, General Medicine, Estrogen Antagonist, CHEMOTHERAPY, Middle Aged, Prognosis, Neoplasm Metastasi, Local, POSTMENOPAUSAL WOMEN, Receptors, Estrogen, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Meta-analysis, Lymphatic Metastasis, Female, Human, Estrogen Antagonists/therapeutic use, Adult, Risk, medicine.medical_specialty, Prognosi, medicine.drug_class, DISCONTINUATION, Breast Neoplasms, Article, Drug Administration Schedule, LATE DISTANT RECURRENCE, 03 medical and health sciences, Breast cancer, Breast Neoplasms/drug therapy, Internal medicine, SCORE, medicine, Humans, SURGICAL ADJUVANT BREAST, Aged, Proportional Hazards Models, Chemotherapy, business.industry, Proportional hazards model, Lymphatic Metastasi, TAMOXIFEN THERAPY, ta3122, medicine.disease, Estrogen, RANDOMIZED-TRIALS, Discontinuation, Surgery, Neoplasm Recurrence, 030104 developmental biology, Proportional Hazards Model, Neoplasm Grading, Neoplasm Recurrence, Local, business
Abstract

Background The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. Methods In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. Results Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. Conclusions After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)

Published
2017

34. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Author

Alberro, JA, Ballester, B, Deulofeu, P, Fabregas, R, Fraile, M, Gubern, JM, Janer, J, Moral, A, de Pablo, JL, Penalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Sola, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Coles, CE, Haybittle, JL, Moebus, V, Leonard, CF, Calais, G, Garaud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, VJ, Holdaway, IM, Kay, RG, Mason, BH, Forbe, JF, Franci, PA, Wilcken, N, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, CF, Steger, GG, Stoeger, H, Canney, P, Yosef, HMA, Focan, C, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, JM, Philippson, C, Piccart, MJ, Masood, MB, Parker, D, Price, JJ, Lindsay, MA, Mackey, J, Martin, M, Hupperets, PSGJ, Bates, T, Blamey, RW, Chetty, U, Ellis, IO, Mallon, E, Morgan, DAL, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Pritchard, KI, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, RB, Abu-Zahara, HT, Karpov, A, Portnoj, SL, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, PJ, Manse, RE, Monypenny, IJ, Gordon, NH, Davis, HL, Cuzick, J, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, JB, Delozier, T, Griffon, B, Lesec'h, J Mace, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, JR, Meier, P, Shan, Y, Shao, YF, Wang, X, Zhao, DB, Howell, A, Swindell, R, Albano, J, de Oliveira, CF, Gervasio, H, Gordilho, J, Ejlertsen, B, Jensen, M-B, Mouridsen, H, Gelman, RS, Harris, JR, Hayes, D, Henderson, C, Shapiro, CL, Christiansen, P, Ewertz, M, Jensen, MB, Mouridsen, HT, Fehm, T, Trampisch, HJ, Dalesio, O, de Vries, EGE, Rodenhuis, S, van Tinteren, H, Comis, RL, Davidson, NE, Gray, R, Robert, N, Sledge, G, Solin, LJ, Sparano, JA, Tormey, DC, Wood, W, Cameron, D, Dixon, JM, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, JGM, Treurniet-Donker, AD, van Putten, WLJ, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Cunningham, MP, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, LJ, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Lupors, E, Namer, M, Carrasco, E, Segui, MA, Eierman, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loib, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, MC, Sacco, M, Valentini, M, McArdle, CS, Smith, DC, Stallard, S, Dent, DM, Gudgeon, CA, Hacking, A, Murray, E, Panieri, E, Werner, ID, De Salvo, GL, Del Bianco, P, Zavagno, G, Leone, B, Vallejo, CT, Zwenger, A, Galligioni, E, Lopez, M, Erazo, A, Medina, JY, Horiguchi, J, Takei, H, Fentiman, IS, Hayward, JL, Rubens, RD, Skilton, D, Scheurlen, H, Sohn, HC, Untch, M, Dafni, U, Markopoulos, C, Bamia, C, Fountzilas, G, Koliou, G-A, Manousou, K, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Canavese, G, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roche, H, Asselain, B, Salmon, RJ, Vilcoq, JR, Brain, E, de La Lande, B, Mouret-Fourme, E, Andre, F, Arriagada, R, Delaloge, S, Hill, C, Koscienly, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, JR, Benraadt, J, Kooi, M, van de Velde, AO, van Dongen, JA, Vermorken, JB, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelbe, RD, Goldhirsch, A, Lindtner, J, Price, KN, Regan, MM, Rudenstam, CM, Senn, HJ, Thuerlimann, B, Bliss, JM, Chilvers, CED, Coombes, RC, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, WD, Stewart, HJ, Stroner, P, Borovik, R, Hayat, H, Inbar, MJ, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro, MG, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, AH, Kohno, N, Miyashita, M, Takao, S, Ahn, J-H, Jung, KH, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, GJ, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Gazet, JC, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Host, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Firth, LA, Krushen-Kosloski, JL, Nissen-Meyer, R, Anderson, H, Killander, F, Malmstrom, P, Ryden, L, Arnesson, L-G, Carstense, J, Dufmats, M, Fohlin, H, Nordenskjold, B, Soderberg, M, Sundqvist, M, Carpenter, TJ, Murray, N, Royle, GT, Simmonds, PD, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, CK, Ravdin, PM, Bergh, J, Bondesso, T, Celebiogl, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Goransson, E, Iiristo, M, Johansson, U, Lenner, E, Lofgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadstrom, C, Janni, W, Maibach, R, Thurlimann, B, Hadji, P, Hozumi, J, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, AHG, Fyles, A, Meakin, JW, Panzarella, T, Bahi, J, Lemonnier, J, Martin, AL, Reid, M, Spittle, M, Bishop, H, Bundred, NJ, Forbes, JF, Forsyth, S, George, WS, Pinder, SE, Deutsch, GP, Kwong, DLW, Pai, VR, Peto, R, Senanayake, F, Boccardo, F, Rubagotti, A, Baum, M, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, JS, Carlomagno, C, De Laurentiis, M, De Placido, S, Schem, C, Williams, L, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Pierce, LJ, Basso, SMM, Lumachi, F, Solomayer, E, Horsman, JM, Lester, J, Winter, MC, Buzdar, AU, Hsu, L, Love, RR, Ahlgren, J, Garmo, H, Holmberg, L, Lindman, H, Warnberg, F, Asmar, L, Jones, SE, Aft, R, Gluz, O, Harbeck, N, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, BK, Chlebowski, RT, Caffier, H, Brufsky, AM, Llombart, HA, Asselain, B, Barlow, W, Bartlett, J, Bradley, R, Braybrooke, J, Davies, C, Dodwell, D, Gray, R, Mannu, G, Taylor, C, Peto, R, McGale, P, Pan, H, Wang, Y, Wang, Z, Department of Oncology, Clinicum, HUS Comprehensive Cancer Center, Medical Oncology, Cancer Research UK, and Pfizer Limited

Subjects
0301 basic medicine, Oncology, Time Factors, SURGERY, medicine.medical_treatment, menopause, chemotherapy, Mastectomy, Segmental, Rate ratio, THERAPY, aromatase inhibitors, CEA, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Breast, Neoplasm Metastasis, Randomized Controlled Trials as Topic, RISK, tamoxifen, breast tumor, CA15-3, axillary dissection, mastectomy, Middle Aged, Neoadjuvant Therapy, METHOTREXATE, 3. Good health, trastuzumab, Treatment Outcome, quadrantectomy, Chemotherapy, Adjuvant, axillary lymphnodes, 030220 oncology & carcinogenesis, Meta-analysis, SURVIVAL, Disease Progression, Female, Life Sciences & Biomedicine, axillary clearance, RADIOTHERAPY, medicine.drug, Adult, medicine.medical_specialty, Anthracycline, 3122 Cancers, Antineoplastic Agents, Breast Neoplasms, axillary nodes, sentinel node biopsy, 03 medical and health sciences, breast cancer, Breast cancer, SDG 3 - Good Health and Well-being, HER2, Internal medicine, Journal Article, medicine, cancer, Humans, Breast, breast cancer, breast diseases, cancer, malignancy, menopause, surgery, mastectomy, quadrantectomy, lumpectomy, axillary nodes, axillary lymphnodes, axillary dissection, axillary clearance, sentinel node biopsy, sentinel node, BRCA1, BRCA2, tamoxifen, aromatase inhibitors, breast tumor, osteoporosis, bisphosphonates, denosumab, trastuzumab, HER2, CEA, CA15-3, tumor marker, chemotherapy, endocrine therapy, Oncology & Carcinogenesis, RECURRENCE, bisphosphonates, Pathological, Neoplasm Staging, lumpectomy, Chemotherapy, Science & Technology, breast diseases, endocrine therapy, business.industry, denosumab, BRCA1, medicine.disease, BRCA2, osteoporosis, Radiation therapy, STIMULATING FACTOR, 030104 developmental biology, sentinel node, tumor marker, Methotrexate, Neoplasm Recurrence, Local, business, 1112 Oncology And Carcinogenesis, malignancy
Abstract

BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. METHODS: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). FINDINGS: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45). INTERPRETATION: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health. ispartof: LANCET ONCOLOGY vol:19 issue:1 pages:27-39 ispartof: location:England status: published

Published
2017

35. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials

Author

Mcgale, P., Taylor, C., Correa, C., Cutter, D., Duane, F., Ewertz, M., Gray, R., Mannu, G., Peto, R., Whelan, T., Wang, Y., Wang, Z., Darby, S., Albain, K., Anderson, S., Arriagada, R., Barlow, W., Bergh, J., Bergsten Nordström, E., Bliss, J., Burrett, J. A., Buyse, M., Cameron, D., Carrasco, E., Clarke, M., Coleman, R., Coates, A., Collins, R., Costantino, J., Cuzick, J., Davidson, N., Davies, C., Davies, K., Delmestri, A., Di Leo, A., Dowsett, M., Elphinstone, P., Evans, V., Forbes, J., Gelber, R., Gettins, L., Geyer, C., Gianni, L., Gnant, M., Goldhirsch, A., Godwin, J., Gregory, C., Hayes, D., Hill, C., Ingle, J., Jakesz, R., James, S., Janni, W., Kaufmann, M., Kerr, A., Liu, H., Mackinnon, E., Martín, M., Mchugh, T., Morris, P., Norton, L., Ohashi, Y., Paik, S., Pan, H. C., Perez, E., Piccart, M., Pierce, L., Pritchard, K., Pruneri, G., Raina, V., Ravdin, P., Robertson, J., Rutgers, E., Shao, Y. F., Sparano, J., Swain, S., Valagussa, P., Viale, G., Von Minckwitz, G., Winer, E., Wiang, X., Wood, Abe O, W., Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Cuzick, J, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesech, J, Brain, E, de La Lande, B, Mouret-Fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Wang, X, Zhao, Db, Chen, Zm, Pan, Hc, Howell, A, Swindell, R, Burrett, Ja, Clarke, M, Collins, R, Correa, C, Cutter, D, Darby, S, Davies, K, Elphinstone, P, Evans, V, Gettins, L, Godwin, J, Gray, R, Gregory, C, Hermans, D, Hicks, C, James, S, Kerr, A, Liu, H, Mackinnon, E, Lay, M, Mcgale, P, Mchugh, T, Morris, P, Peto, R, Taylor, C, Wang, Y, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Hayes, D, Henderson, C, Shapiro, Cl, Winer, E, Christiansen, P, Ewertz, M, Møller, S, Mouridsen, Ht, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Wood, W, Cameron, D, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Rutgers, E, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Carrasco, E, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Arriagada, R, Delaloge, S, Hill, C, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Goldhirsch, A, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Abe, O, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Whelan, T, Ohno, S, Anderson, S, Bass, G, Brown, A, Bryant, J, Costantino, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Paik, S, Redmond, C, Swain, S, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Perez, E, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Reinertsen, K, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Dowsett, M, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Businico, A, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Adolfsson, J, Bergh, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Janni, W, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Martin, Al, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., McGale, P, Taylor, C, Correa, C, Cutter, D, Duane, F, Ewertz, M, Gray, R, Mannu, G, Peto, R, Whelan, T, Wang, Y, Wang, Z, Darby, S, Biomedische Technologie, RS: GROW - Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Mcgale, P, DE LAURENTIIS, Michelino, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy

Subjects
medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, Rate ratio, Lower risk, Systemic therapy, Statistical significance, Medicine, Humans, Mastectomy, Randomized Controlled Trials as Topic, business.industry, Articles, General Medicine, Surgery, Radiation therapy, Axilla, Neoplasm Recurrence, medicine.anatomical_structure, Local, Meta-analysis, Lymphatic Metastasis, Lymph Node Excision, Female, Neoplasm Recurrence, Local, business, Breast Neoplasm, Human
Abstract

BACKGROUND: Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection.METHODS: We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status.FINDINGS: 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2pINTERPRETATION: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council.

Published
2016

36. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Author

EARLY BREAST CANCER TRIALISTS' COLLABORATIVE GROUP (EBCTCG), Darby, S., Mcgale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., Ewertz, M., Godwin, J., Gray, R., Pierce, L., Whelan, T., Wang, Y., Peto, R., Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bergh, J, Bliss, J, Buyse, M, Cameron, D, Carrasco, E, Clarke, M, Correa, C, Coates, A, Collins, R, Costantino, J, Cutter, D, Cuzick, J, Darby, S, Davidson, N, Davies, C, Davies, K, Delmestri, A, Di Leo, A, Dowsett, M, Elphinstone, P, Evans, V, Ewertz, M, Gelber, R, Gettins, L, Geyer, C, Goldhirsch, A, Godwin, J, Gray, R, Gregory, C, Hayes, D, Hill, C, Ingle, J, Jakesz, R, James, S, Kaufmann, M, Kerr, A, Mackinnon, E, Mcgale, P, Mchugh, T, Norton, L, Ohashi, Y, Paik, S, Pan, Hc, Perez, E, Peto, R, Piccart, M, Pierce, L, Pritchard, K, Pruneri, G, Raina, V, Ravdin, P, Robertson, J, Rutgers, E, Shao, Yf, Swain, S, Taylor, C, Valagussa, P, Viale, G, Whelan, T, Winer, E, Wang, Y, Wood, W, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec'h, J, Rambert, P, Mustacchi, G, Petruzelka, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Wang, X, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Burrett, Ja, Hermans, D, Hicks, C, Lay, M, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Johansen, H, Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Ejlertsen, B, Jensen, Mb, Møller, S, Carstensen, B, Palshof, T, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Tinterri, C, Bonadonna, G, Gianni, L, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, G, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Dafni, D, Fountzilas, G, Mavroudis, D, Klefstrom, P, Saarto, T, Gallen, M, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, Bourgier, C, Koscielny, S, Laplanche, A, Lê, Mg, Spielmann, M, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Janni, W, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Ohno, S, Anderson, A, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Mamounas, Ep, Redmond, C, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Martin, Al, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Ashley, S, Makris, A, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Green, S, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Adolfsson, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H, Mcgale, P, Correa, C, Taylor, C, Arriagada, R, Clarke, M, Cutter, D, Davies, C, Ewertz, M, Godwin, J, Gray, R, Pierce, L, Whelan, T, Wang, Y, Peto, R, Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, DE PLACIDO, Sabino, Carlomagno, Chiara, Darby, S, McGale, P, Interne Geneeskunde, RS: GROW - School for Oncology and Reproduction, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy

Subjects
Oncology, medicine.medical_specialty, Neoplasm Recurrence, Local - epidemiology, medicine.medical_treatment, Population, Breast Neoplasms, Mastectomy, Segmental, Breast cancer, breast cancer, Internal medicine, medicine, Breast-conserving surgery, Humans, education, skin and connective tissue diseases, radiotherapy, Randomized Controlled Trials as Topic, education.field_of_study, business.industry, Estrogen Antagonists - therapeutic use, Mortality rate, Age Factors, Estrogen Antagonists, General Medicine, Breast Neoplasms - mortality - therapy, medicine.disease, Surgery, Unilateral Breast Neoplasms, Radiation therapy, Clinical trial, meta-analysis, Tamoxifen, Receptors, Estrogen, Lymphatic Metastasis, Female, Radiotherapy, Adjuvant, Neoplasm Grading, Neoplasm Recurrence, Local, business, Mastectomy
Abstract

BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35.0% to 19.3% (absolute reduction 15.7%, 95% CI 13.7-17.7, 2p/=20%), intermediate (10-19%), or lower (, link_to_OA_fulltext

Published
2011

37. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials

Author

EBCTCG, Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, Jl, Davies, C., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, Hma, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, Mj, Masood, Mb, Parker, D., Price, Jj, Hupperets, Psgj, Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Baum, M., Cuzick, J., Houghton, J., Riley, D., Gordon, Nh, Davis, Hl, Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, Jb, Delozier, T., Mace-Lesec H, J., Rambert, P., Andrysek, O., Barkmanova, J., Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Alison, R., Boreham, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Peto, R., Wang, Y., Albano, J., Oliveira, Cf, Gervasio, H., Gordilho, J., Johansen, H., Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, Ic, Shapiro, Cl, Andersen, Kw, Axelsson, Ck, Blichert-Toft, M., Moller, S., Overgaard, J., Overgaard, M., Rose, C., Cartensen, B., Palshof, T., Trampisch, Hj, Dalesio, O., Vries, Ege, Rodenhuis, S., Tinteren, H., Comis, Rl, Davidson, Ne, Robert, N., Sledge, G., Tormey, Dc, Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, Jgm, Treurniet-Donker, Ad, Putten, Wlj, Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Hage, Ja, Velde, Cjh, Cunningham, Mp, Catalano, R., Creech, Rh, Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, Cs, Smith, Dc, Galligioni, E., Boccardo, F., Rubagotti, A., Dent, Dm, Gudgeon, Ca, Hacking, A., Erazo, A., Medina, Jy, Izuo, M., Morishita, Y., Takei, H., Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D., Graeff, H., Janicke, F., Meisner, C., Scheurlen, H., Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, Rj, Vilcoq, Jr, Rodrigo Arriagada, Hill, C., Laplanche, A., Le, Mg, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, MR, Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Velde, Ao, Dongen, Ja, Vermorken, Jb, Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, Rd, Goldhirsch, A., Lindtner, J., Price, Kn, Rudenstam, Cm, Senn, Hj, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Den Boegart, W., Martin, P., Romain, S., Hakes, T., Hudis, Ca, Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., La Huerta, R., Sainz, Mg, Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O Shaughnessy, J., Pierce, Lj, Steinberg, S., Venzon, D., Zujewski, J., Paradiso, A., Lena, M., Schittulli, F., Myles, Jd, Pater, Jl, Pritchard, Ki, Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Jonsson, H., Larsson, Lg, Lythgoe, Jp, Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, Ab, Varhaug, Je, Gundersen, S., Hauer-Jensen, M., Host, H., Nissen-Meyer, R., Blamey, Rw, Mitchell, Ak, Morgan, Dal, Robertson, Jfr, Di Palma, M., Mathe, G., Misset, Jl, Clark, Rm, Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, MR, Ueo, H., Falkson, Ci, A Hern, R., Ashley, S., Powles, Tj, Smith, Ie, Yarnold, Jr, Gazet, Jc, Cocoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, Ajs, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Foster, L., George, Wd, Stewart, Hj, Stroner, P., Malmstrom, P., Moller, Tr, Ryden, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjold, B., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Martino, S., Osborne, Ck, Ravdin, Pm, Glas, U., Johansson, U., Rutqvist, Le, Singnomklao, T., Wallgren, A., Maibach, R., Thurlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, Ahg, Meakin, Jw, Panzarella, T., Shan, Y., Shao, Yf, Wang, X., Zhao, Db, Chen, Zm, Pan, Hc, Bahi, J., Reid, M., Spittle, M., Deutsch, Gp, Senanayake, F., Kwong, Dlw, Bianco, Ar, Carlomagno, C., Laurentiis, M., Placido, S., Buzdar, Au, Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, Cc, Buchanan, Rb, Cross, M., Royle, Gt, Dunn, Ja, Hills, Rk, Lee, M., Morrison, Jm, Spooner, D., Litton, A., Chlebowski, Rt, Caffier, H., Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, and DE PLACIDO, Sabino

Subjects
Oncology, medicine.medical_specialty, Antineoplastic Agents, Hormonal, DEATHS, Ovariectomy, Antineoplastic Agents, Breast Neoplasms, Aged, Anthracyclines, Antineoplastic Combined Chemotherapy Protocols, Cause of Death, Chemotherapy, Adjuvant, Female, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Ovary, Randomized Controlled Trials as Topic, Receptors, Estrogen, Survival Rate, Tamoxifen, Medicine (all), Breast cancer, MammaPrint, Internal medicine, Receptors, medicine, Chemotherapy, TAMOXIFEN, skin and connective tissue diseases, Survival rate, Adjuvant, Gynecology, Hormonal, medicine.diagnostic_test, Oncotype DX Breast Cancer Assay, business.industry, General Medicine, medicine.disease, Estrogen, Neoplasm Recurrence, Local, Hormonal therapy, Oncotype DX, business, medicine.drug, Epirubicin
Abstract

Background Quinquennial overviews (1985–2000) of the randomised trials in early breast cancer have assessed the 5 year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxorubicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modern aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50–69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0·0001 for recurrence, 2p For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age ( These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1–2 years of tamoxifen versus none (33 000); and about 5 years versus 1–2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.

Published
2005

38. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials

Author

Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, J. L., Davies, C., Harvey, V. J., Holdaway, T. M., Kay, R. G., Mason, B. H., Forbes, J. F., Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, H. M. A., Focan, C., Lobelle, J. P., Peek, U., Oates, G. D., Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, M. J., Masood, M. B., Parker, D., Price, J. J., Hupperets, P. S. G. J., Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, R. B., Abu-Zahra, H. T., Portnoj, S. M., Baum, M., Cuzick, J., Houghton, J., Riley, D., Mansel, R. E., Gordon, N. H., Davis, H. L., Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, J. B., Delozier, T., Mace Lesec'h, J., Rambert, P., Petruzelka, L., Pribylova, O., Owen, J. R., Harbeck, N., Jänicke, F., Meisner, C., Meier, P., Howell, A., Ribeiro, G. C., Swindell, R., Burrett, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., Jackson, D., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Morris, P., Oulds, J., Peto, R., Taylor, C., Wang, Y., Albano, J., De Oliveira, C. F., Gervásio, H., Gordilho, J., Johansen, H., Mouridsen, H. T., Gelman, R. S., Harris, J. R., Henderson, I. C., Shapiro, C. L., Christiansen, P., Ejlertsen, B., Møller, S., Overgaard, M., Carstensen, B., Palshof, T., Trampisch, H. J., Dalesio, O., De Vries, E. G. E., Rodenhuis, S., Van Tinteren, H., Comis, R. L., Davidson, N. E., Robert, N., Sledge, G., Tormey, D. C., Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, J. G. M., Treurniet-Donker, A. D., Van Putten, W. L. J., Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Van Der Hage, J. A., Van De Velde, C. J. H., Cunningham, M. P., Catalano, R., Creech, R. H., Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Von Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., De Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, C. S., Smith, D. C., Galligioni, E., Boccardo, F., Rubagotti, A., Dent, D. M., Gudgeon, C. A., Hacking, A., Erazo, A., Medina, J. Y., Izuo, M., Morishita, Y., Takei, H., Fentiman, I. S., Hayward, J. L., Rubens, R. D., Skilton, D., Scheurlen, H., Von Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, R. J., Vilcoq, J. R., Arriagada, R., Hill, C., Laplanche, A., M. G., Lê, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, M. R., Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Van De Velde, A. O., Van Dongen, J. A., Vermorken, J. B., Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, R. D., Goldhirsch, A., Lindtner, J., Price, K. N., Rudenstam, C. M., Senn, H. J., Bliss, J. M., Chilvers, C. E. D., Coombes, R. C., Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., De Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Van Den Bogaert, W., Martin, P., Geniez, ROMAIN SYLVAIN JEAN, Hakes, T., Hudis, C. A., Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., De La Huerta, R., Sainz, M. G., Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O'Shaughnessy, J., Pierce, L. J., Steinberg, S., Venzon, D., Zujewski, J. A., Paradiso, A., De Lena, M., Schittulli, F., Myles, J. D., Pater, J. L., Pritchard, K. I., Whelan, T., Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, I. M., Palmer, M. K., Ingle, J. N., Suman, V. J., Bengtsson, N. O., Jonsson, H., Larsson, L. G., Lythgoe, J. P., Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, A. B., Varhaug, J. E., Gundersen, S., Hauer-Jensen, M., Høst, H., Nissen-Meyer, R., Blamey, R. W., Mitchell, A. K., Morgan, D. A. L., Robertson, J. F. R., Di Palma, M., Mathé, G., Misset, J. L., Clark, R. M., Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, M. R., Ueo, H., Falkson, C. I., A'Hern, R., Ashley, S., Powles, T. J., Smith, I. E., Yarnold, J. R., Gazet, J. C., Corcoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, A. J. S., Ewing, G. H., Firth, L. A., Krushen-Kosloski, J. L., Foster, L., George, W. D., Stewart, H. J., Stroner, P., Malmström, P., Möller, T. R., Rydén, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjöld, B., Söderberg, M., Carpenter, J. T., Albain, K., Crowley, J., Green, S., Martino, S., Osborne, C. K., Ravdin, P. M., Glas, U., Johansson, U., Rutqvist, L. E., Singnomklao, T., Wallgren, A., Maibach, R., Thürlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, A. H. G., Meakin, J. W., Panzarella, T., Shan, Y., Shao, Y. F., Wang, X., Zhao, D. B., Chen, Z. M., Pan, H. C., Bahi, J., Reid, M., Spittle, M., Deutsch, G. P., Senanayake, F., Kwong, D. L. W., Bianco, A. R., Carlomagno, C., De Laurentiis, M., De Placido, S., Buzdar, A. U., Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, C. C., Buchanan, R. B., Cross, M., Royle, G. T., Dunn, J. A., Hills, R. K., Lee, M., Morrison, J. M., Spooner, D., Litton, A., Chlebowski, R. T., Caffier, H., Clarke, M, Collins, R, Darby, S, Davies, C, Elphinstone, P, Evans, E, Godwin, J, Gray, R, Hicks, C, James, S, MacKinnon, E, McGale, P, McHugh, T, Peto, R, Taylor, C, and Wang, Y

Subjects
medicine.medical_specialty, Time Factors, medicine.medical_treatment, Breast Neoplasms, Rate ratio, Breast Conservation Treatment, Disease-Free Survival, Breast cancer, Cause of Death, Breast-conserving surgery, Medicine, Humans, Lung cancer, Aged, Probability, Randomized Controlled Trials as Topic, business.industry, Female, Middle Aged, Neoplasm Recurrence, Local, Medicine (all), General Medicine, medicine.disease, Surgery, Radiation therapy, Unilateral Breast Neoplasms, Neoplasm Recurrence, Local, business, Mastectomy
Abstract

Background In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (10%, 25 000 women). Findings About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44·6% versus 49·5% (absolute reduction 5·0%, SE 0·8, 2p These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30·5% versus 35·9% (reduction 5·4%, SE 1·7, 2p=0·0002; overall mortality reduction 5·3%, SE 1·8, 2p=0·005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54·7% versus 60·1% (reduction 5·4%, SE 1·3, 2p=0·0002; overall mortality reduction 4·4%, SE 1·2, 2p=0·0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1·18, SE 0·06, 2p=0·002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1·12, SE 0·04, 2p=0·001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1·27, SE 0·07, 2p=0·0001) and lung cancer (rate ratio 1·78, SE 0·22, 2p=0·0004). Interpretation In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Catalog

Books, media, physical & digital resources
See catalog results