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Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR− patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II–III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II–III at an older age, surveillance for preventing late cardiotoxicity is crucial.

BackgroundA rare subtype of breast cancer, atypical medullary carcinoma of the breast (AMCB), shows a highly adverse prognosis compared to medullary carcinoma of the breast (MBC). The current study aimed to establish a correlated nomogram for the identification of the prognostic factors of AMCB and MBC.MethodsKaplan–Meier and Cox regression analyses were applied to data acquired from the Surveillance, Epidemiology and End Results (SEER) database for 2004 to 2013 to analyse tumour characteristics and overall survival. Propensity score matching (PSM) analysis was performed to determine the overall survival (OS) among those with AMCB and MBC. A predictive nomogram was created, and the concordance index (C-index) was used to predict accuracy and discriminative ability.ResultsA total of 2,001 patients from the SEER database were diagnosed with MBC between 2004 and 2013, including 147 patients diagnosed with AMCB. The number of diagnoses gradually increased in both groups. Cox analysis of multivariate and Kaplan–Meier analysis showed that older age (HR = 3.005, 95% CI 1.906–4.739) and later stage were significantly associated with poor prognosis, while cancer-directed surgery was an independent protective factor (HR = 0.252, 95% CI 0.086–0.740). In the HR-negative stratification analysis, older age (HR = 2.476, 95% CI 1.398–4.385), later stage and histological type (HR=0.381, 95% CI 0.198-0.734) were found to be independent prognostic factors for low standard survival. The log-rank analysis demonstrated significantly worse prognostic factors for patients with AMCB than for those with MBC (P = 0.004). A nomogram (C-index for survival = 0.75; 95% CI 0.69–0.81) was established from four independent prognostic factors after complete identification.ConclusionsMBC is rare, and cancer-directed surgery, older age, and later stage are independently linked with prognosis. In the HR negative population, AMCB patients show a worse survival gain than those with MBC.

Background The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women. Methods We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHMmolar) and adjusted for creatinine and potential confounders. Results Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04–1.68) and 1.26 (95% CI 0.96–1.66) (Ptrend = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA ORT3 vs T1 = 2.66, 95% CI 1.39–5.12, Ptrend = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05–1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (ORabove vs below median = 1.59, 95% CI 1.01–2.48). Conclusions Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted.

Background Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. We aimed to evaluate the association between young-onset breast cancer and perinatal exposures and to explore etiologic heterogeneity in the relationship between associated perinatal factors and estrogen receptor status of the tumor. Methods We addressed this in a sister-matched case-control study. Cases were women who had been diagnosed with ductal carcinoma in situ or invasive breast cancer before the age of 50. Each case had a sister control who was free of breast cancer up to the same age at which her case sister developed the disease. The factors considered were self-reported and included the mother’s preeclampsia in that pregnancy, mother’s smoking in that pregnancy, gestational hypertension, prenatal diethylstilbestrol use, and gestational diabetes, as well as low birth weight (less than 5.5 pounds), high birth weight (greater than 8.8 pounds), short gestational length (less than 38 completed weeks), and being breastfed or being fed soy formula. Results In conditional logistic regression analyses, high birth weight (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.07–2.36) and preeclampsia (adjusted OR = 1.92, CI 0.824–4.5162) were positively associated with risk. The association with preeclampsia was stronger when the analysis was restricted to invasive breast cancer (OR = 2.87, CI 1.08–7.59). We also used case-only analyses to assess etiologic heterogeneity for estrogen receptor (ER)-positive versus estrogen receptor-negative cancer. Women who were born to a preeclamptic pregnancy and later developed young-onset breast cancer were at increased odds for the ER-negative type (OR = 2.27; CI 1.05–4.92). Conclusion These results suggest that being born to a preeclamptic pregnancy may increase risk for young-onset breast cancer, especially for the ER-negative subtype.

Background The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii) whether the survival impact of TIL measurements varies according to different adjuvant systemic therapies. Methods The WSG PlanB trial compared an anthracycline-free chemotherapy regimen (6x docetaxel/cyclophosphamide, TC) to an anthracycline-taxane sequence (4xEC followed by 4x docetaxel) in patients with intermediate-risk, HER2-negative early breast cancer (EBC). Patients with HR-positive HER2-negative EBC were further stratified to receive endocrine therapy alone vs. chemotherapy followed by endocrine therapy based on Recurrence Score results and nodal status. In this analysis, three independent observers quantified and categorized the presence of TILs among tumor samples from patients in PlanB. TIL measurements were correlated with clinical/pathological parameters and treatment outcome overall and according to the treatment arm. Results Disease-free survival (DFS) rates were significantly better (p = .04) in HR-negative patients with high vs. intermediate TIL levels and were higher in low vs. intermediate TIL patients, however with borderline significance only (p = .06). There were no significant differences among TIL categories in HR+ patients. High RS categories, HR-negative status, and high KI67 were independently and significantly associated with high TIL categories. There was no significant impact of TIL category on DFS in patients treated by endocrine therapy only; however, in patients receiving chemotherapy, DFS in the intermediate TIL category was lower than that in the other categories. Conclusion Although the presence of high TILs is associated with negative prognostic parameters such as high KI67 and HR-negative status among patients with HR-positive HER2-negative EBC, patients with high TILs show a favorable 5-year DFS in both HR-positive/HER2-negative and triple-negative breast cancer.

Goals: BRCA1/2 mutations are associated with bilateral breast cancer. The extent of concordance between synchronous bilateral breast cancer (SBBC) tumors with respect to hormone receptor expression and BRCA1/2 mutations is unknown. We investigated the distribution of BRCA1/2 mutations and bilateral estrogen receptor (ER) status in SBBC.Methods: A retrospective analysis was performed on 15,337 patients with primary breast cancer who underwent surgical treatment at the Fudan University Shanghai Cancer Center between 2007 and 2014. We included 163 patients with synchronous bilateral breast cancer who had germline BRCA1/2 mutations testing. BRCA1/2 pathogenic/likely pathogenic mutations and other clinicopathological characteristics were studied in further analyses.Results: Patients with SBBC developed breast cancer at an older age and had a higher rate of ER positivity than patients with UBC (p < 0.001, separately). In contrast, 14.1% of SBBC patients had carcinomas with a lobular component in either breast based on pathological reports (p < 0.001). Twelve patients had BRCA1 mutations, and 14 patients had BRCA2 mutations, while no patients had mutations in both genes. The BRCA1/2 mutation rate was higher in younger patients (23.4 vs. 11.1%, p = 0.036). SBBC patients with a family history of breast cancer or bilateral ER-negative disease had a higher frequency of BRCA1/2 mutations than the cohort without a history of these conditions. SBBC with a bilateral ER-discordant status had a very low frequency of BRCA1/2 mutations (5.6%). Patients with an ER-positive (concordant or discordant) status had better 3-year disease-free survival than patients with a concordant ER-negative status (HR = 0.324, 95% CI: 0.126–0.837, P = 0.020). However, the outcomes were similar during long-term follow-up. Pathological lymph node stage was the only prognostic factor for SBBC in both univariate and multivariate Cox analyses.Conclusions: Our study shows that Chinese women with SBBC have different characteristics from their UBC counterparts. SBBC patients with a younger age, family history of breast cancer, or bilateral ER-negative disease are more likely to have BRCA1/2 mutations. SBBC patients with a concordant ER-negative status had worse early outcomes. Our results suggest that there may be additional factors underlying the tumor biology and genetics of SBBC.

Aim: To correlate the relationship between the aggressiveness of breast cancer based on hormone receptor status with histopathological grading and staging of breast cancer. Methods. 193 patients of breast cancer were seen during a period of two years and 112 were included in the study. All the patients were subjected to appropriate surgery under general anesthesia and further treatment in the form of Chemotherapy/ Radiotherapy/ Hormonal therapy as indicated after obtaining the histopathological report. A biopsy was sent for detailed histopathological diagnosis including hormone receptor status. Observations were made and results were recorded. Patients were followed up as per the protocol. Results: Hormone receptor status was done in all the patients. 72 (64%) patients had ER/PR status positivity whereas 14 (13%) patients were ER/PR negative. All the cases were of infiltrating ductal carcinoma (IDC). Of these cases, 42 (37.5%) patients had IDC grade II and 70 (62.5%) patients had grade III. There was no grade I case in our study. Stage I cases comprised 2 (2%), Stage II 37 (33%), and Stage III 70 (62%) of patients. Whereas, 3 (3%) patients had stage IV disease or Metastatic breast cancer. Conclusion: Hormone receptors negative status in younger women in premenopausal status by itself is a poor prognostic factor. There is also a direct correlation between the hormone receptor (ER / PR) negativity and breast cancer aggressiveness with metastasis positive lymph node, larger tumor size, and higher histopathological gradation.

Breast cancers include a heterogeneous group of diseases with clinical behaviors that may vary according to the hormonal receptor status. However, limited knowledge is available on the role of breast cancer environmental and occupational risk factors in the onset of specific molecular disease phenotypes. Therefore, the aim of this review was to provide an overview on the possible correlation between occupational chemical exposures and breast cancers with a specific receptor pattern. Pubmed, Scopus, and ISI Web of Science databases were systematically reviewed to identify all the studies addressing chemical exposure in workplaces and risk of breast cancer classified according to the presence of estrogen and/or progesterone receptors. Some positive associations were reported between solvent, polycyclic aromatic hydrocarbon, organophosphoric insecticide, and synthetic fiber exposure and estrogen receptor-positive cases, while other investigations demonstrated a relationship with receptor-negative tumors or failed to detect any significant effect. Overall, further investigation should overcome limitations due to the self-reported information on work histories, the chemical classification in general categories, and the lack of environmental or biological monitoring exposure data. This may support the development of suitable and individually “tailored” occupational risk assessment and management strategies to protect the health of exposed workers, particularly those with hypersusceptibility conditions.

Introduction Reproductive history has been associated with breast cancer risk, but more knowledge of the underlying biological mechanisms is needed. Because of limited data on normal breast tissue from healthy women, we examined associations of reproductive history and established breast cancer risk factors with breast tissue composition and markers of hormone receptors and proliferation in a nested study within the Karolinska Mammography project for risk prediction for breast cancer (Karma). Materials and methods Tissues from 153 women were obtained by ultrasound-guided core needle biopsy as part of the Karma project. Immunohistochemical staining was used to assessed histological composition of epithelial, stromal and adipose tissue, epithelial and stromal oestrogen receptor (ER) and progesterone receptor (PR) status, and Ki-67 proliferation status. An individualised reproductive score including parity, number of pregnancies without birth, number of births, age at first birth, and duration of breastfeeding, was calculated based on self-reported reproductive history at the time of the Karma study entry. All analyses were adjusted for age and BMI. Results Cumulated reproductive score was associated with increased total epithelial content and greater expression of epithelial ER. Parity was associated with greater epithelial area, increased epithelial–stromal ratio, greater epithelial ER expression and a lower extent of stromal proliferation. Increasing numbers of pregnancies and births were associated with a greater epithelial area in the entire study set, which remained significant among postmenopausal women. Increasing numbers of pregnancies and births were also associated with a greater expression of epithelial ER among postmenopausal women. Longer duration of breastfeeding was associated with greater epithelial area and greater expression of epithelial PR both in the entire study set and among postmenopausal women. Breastfeeding was also positively associated with greater epithelial ER expression among postmenopausal women. Prior use of oral contraceptives was associated with lower epithelial–stromal ratio amongst all participants and among pre- and postmenopausal women separately. Conclusion Reproductive risk factors significantly influence the epithelial tissue compartment and expression of hormone receptors in later life. These changes remain after menopause. This study provides deeper insights of the biological mechanisms by which reproductive history influences epithelial area and expression of hormone receptors, and as a consequence the risk of breast cancer. Electronic supplementary material The online version of this article (10.1007/s10549-018-4768-0) contains supplementary material, which is available to authorized users.

Introduction The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. Material and methods A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. Results During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR– patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. Conclusions These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.

This is the peer reviewed version of the following article: Matejcic, M., De Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., ... Chajès, V. (2017). Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort. International Journal of Cancer, 140(6), 1246-1259. https://doi.org/10.1002/ijc.30536, which has been published in final form at https://doi.org/10.1002/ijc.30536. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4‐Q1 = 1.26; 95% CI 1.00–1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4‐Q1 = 1.29; 95% CI 1.02–1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

BACKGROUND: Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients. METHODS: We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients' OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis. RESULTS: In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS. CONCLUSIONS: Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease.

Item does not contain fulltext Hormone receptor (HR) status is an important prognostic factor for patients with metastatic breast cancer (MBC) and is also correlated with other prognostic factors, such as initial lymph node status, HER2-Neu status and age. The prognostic value of these other factors, however, is unknown when stratified by HR positive versus HR negative patients. The aim of this study was to evaluate prognostic factors for MBC survival in relation to HR status. Dutch women diagnosed with breast cancer in 2003-2006 treated with curative intent who developed MBC within 5 years of follow-up were selected from the Netherlands cancer registry (N = 2,001). Independent prognostic factors for survival after metastatic occurrence were determined by multivariable Cox survival analyses stratified by HR status. Interactions between HR status and prognostic factors were determined. Median survival for MBC patients with HR negative (HR-) tumours was 8 months, compared to 19 months for HR positive (HR+) patients. The prognostic value of lymph node status, HER2-Neu status, adjuvant endocrine treatment and first-line palliative chemotherapy was dependent on HR status. Initial lymph node status was independently associated with survival in HR- patients, but not in HR+ patients. HER2-Neu positive status was associated with better survival in both HR+ and HR- patients, although the association was stronger in HR- patients. Similarly, patients treated with first-line palliative chemotherapy fared better, especially HR- patients. HR+ patients had worse survival if they had received adjuvant endocrine treatment. This study shows that the prognostic value of various factors depends on HR status in MBC. This information may help physicians to determine individual prognostic profiles and therapeutic strategies for MBC patients.

Molecular subtyping of breast cancer is necessary for therapy selection and mandatory for all breast cancer patients. Metabolic alterations are considered a hallmark of cancer and several metabolic drugs are currently being investigated in clinical trials. However, the dependence of metabolic alterations on breast cancer subtypes has not been investigated on -omics scale. Thus, 204 estrogen receptor positive (ER+) and 67 estrogen receptor negative (ER−) breast cancer tissues were investigated using GC–TOFMS based metabolomics. 19 metabolites were detected as altered in a predefined training set (2/3 of tumors) and could be validated in a predefined validation set (1/3 of tumors). The metabolite changes included increases in beta-alanine, 2-hydroyglutarate, glutamate, xanthine and decreases in glutamine in the ER− subtype. Beta-alanine demonstrated the strongest change between ER− and ER+ breast cancer (fold change = 2.4, p = 1.5E − 20). In a correlation analysis with genome-wide expression data in a subcohort of 154 tumors, we found a strong negative correlation (Spearman R = − 0.62) between beta-alanine and 4-aminobutyrate aminotransferase (ABAT). Immunohistological analysis confirmed down-regulation of the ABAT protein in ER− breast cancer. In a Kaplan–Meier analysis of a large external expression data set, the ABAT transcript was demonstrated to be a positive prognostic marker for breast cancer (HR = 0.6, p=3.2E-15).Biological significanceIt is well-known for more than a decade that breast cancer exhibits distinct gene expression patterns depending on the molecular subtype defined by estrogen receptor (ER) and HER2 status. Here, we show that breast cancer exhibits distinct metabolomics patterns depending on ER status. Our observation supports the current view of ER+ breast cancer and ER− breast as different diseases requiring different treatment strategies.Metabolic drugs for cancer including glutaminase inhibitors are currently under development and tested in clinical trials. We found glutamate enriched and glutamine reduced in ER− breast cancer compared to ER+ breast cancer and compared to normal breast tissues. Thus, metabolomics analysis highlights the ER− subtype as a preferential target for glutaminase inhibitors.For the first time, we report on a regulation of beta-alanine catabolism in cancer. In breast cancer, ABAT transcript expression was variable and correlated with ER status. Low ABAT transcript expression was associated with low ABAT protein expression and high beta-alanine concentration. In a large external microarray cohort, low ABAT expression shortened recurrence-free survival in breast cancer, ER+ breast cancer and ER− breast cancer.

Einleitung: Seit einigen Jahren werden epigenetische Aspekte in der Karzinogenese diskutiert und untersucht. Eine wesentliche Rolle spielen hierbei Histondeacetylasen (HDAC), die durch eine verstärkte Deacetylierung von DNA-Histonen aber auch anderer Zellzyklus-relevanter Proteine und Transkriptionsfaktoren zu vermehrter Zellproliferation und Angiogenese, Entdifferenzierung und Metastasierung führen. Basierend auf der Hypothese der modulierenden Wirkung von HDAC in der Karzinogenese entstanden neue Therapiekonzepte. In In-Vitro- und In-Vivo-Untersuchungen konnte gezeigt werden, dass eine HDAC-Inhibition zur Wachstumshemmung maligner Zellen führt. Im Jahr 2006 wurde der HDAC-Inhibitor Suberoylanilid-Hydroxamsäure (SAHA) für die Behandlung des kutanen T-Zell-Lymphoms zugelassen. Derzeit kommen mehrere HDAC-Inhibitoren in der Therapie verschiedener Tumorentitäten im Rahmen von klinischen Studien zum Einsatz. In der vorliegenden Arbeit wurde das Expressionsverhalten der Isoformen HDAC1, 2 und 3 im Mammakarzinom untersucht. Dabei wurden der prognostische Charakter sowie die Korrelationen der HDAC- Expression mit wichtigen klinisch-pathologischen Parametern im Mammakarzinom analysiert. Ziel war die Identifikation einer Subgruppe, die ein potentiell höheres Ansprechen auf HDACi haben könnte. Material und Methoden: Die Analyse erfolgte mittels eines Tissue-Microarrays (TMA) aus Formalin-fixiertem- Paraffin-eingebettetem (FFPE) Gewebe von insgesamt 238 Patientinnen mit invasivem Mammakarzinom, diagnostiziert am Institut für Pathologie der Universitätsmedizin Charité in den Jahren 1985-1999. An diesem erfolgten immunhistochemische Untersuchungen für HDAC1, 2 und 3. Die gefärbten Schnitte wurden im Anschluss digitalisiert und mittels virtueller Mikroskopie ausgewertet. Ergebnisse: HDAC1 zeigte eine starke Expression in 68 (32,7%), eine schwache Expression in 69 (33,2%) und eine fehlende Expression in 71 (34,1%) Fällen. Hinsichtlich der HDAC2-Expression stellte sich folgendes Expressionsprofil dar: starke Expression in 51 (24,1%), schwache Expression in 69 (32,5%) und fehlende Expression in 92 (43,4%) Fällen. HDAC3 wies eine starke Expression in 71 (31,7%), eine schwache Expression in 73 (32,6%) und eine fehlende Expression in 80 (35,7%) Proben auf. HDAC1 korrelierte signifikant mit einem positiven Hormonrezeptorstatus (p, Introduction: During the last years epigenetic aspects in carcinogenesis have been discussed and alterations caused by histonedeacetylases (HDAC) might play an important role. HDAC lead through increased deacetylation of DNA-histones and other proteins of cellcyclus to proliferation, angiogenesis, lower grading and metastasis in cancer cells. Based on this effect of HDAC in carcinogenesis new therapies were developed. In vitro and in vivo it has been shown that HDAC inhibition could limit growth of cancer cells. In 2006 the HDAC inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) was first approved for therapy for cutaneous T-cell lymphoma. Actually different HDACi are investigated in different types of cancers. In this study the expression of the isoforms HDAC1, 2 and 3 in breast cancer was analyzed and correlated with relevant clinicopathological parameters. Furthermore, we examined a potential prognostic impact of the expression of these proteins to identificate a subgroup who might have better benefit of HDACi. Methods: A tissue micro array (TMA) was constructed by formalin-fixed paraffin embedded (FFPE) tissue samples from 238 patients with primary invasive breast cancer diagnosed in the years from 1985 - 1999 in the institute of pathology of Charité University hospital. An immunhistochemical staining of HDAC1, 2 and 3 was done. Finally the slides were digitized and evaluated by virtual microscopy. Results: HDAC1 showed strong expression in 68 (32,7%), intermediate expression in 69 (33,2%) and low expression in 71 (34,1%) cases. For HDAC2 strong expression could be observed in 51 (24,1%), intermediate expression in 69 (32,5%) and low expression in 92 (43,4%) cases. HDAC3 was strongly expressed in 71 (31,7%), intermediately expressed in 73 (32,6%) and low expressed in 80 (35,7%) samples. HDAC1 was highly expressed in hormone receptor positive tumors (n=203; p

Item does not contain fulltext Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (n = 2,949) or IDC (n = 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all P < 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR- subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER-PR- patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (3 years HR 1.07, 95 % CI 0.88-1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences. 01 augustus 2012

Yunchao Wang,1 Tao Sun,2 Donggui Wan,3 Lijun Sheng,4 Wei Li,5 Huayun Zhu,6 Yanping Li,1 Janice Lu1,7 1Department of Breast Cancer, Beijing Shijitan Hospital, Capital Medical University, Beijing, 2Department of Oncology, Liaoning Cancer Hospital and Institute, Shenyang, 3Department of Oncology, China-Japan Friendship Hospital, Beijing, 4Department of Oncology, Shandong Cancer Hospital, Jinan, 5Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, 6Department of Oncology, Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 7Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA Objectives: Trastuzumab, a humanized monoclonal antibody that binds human epidermal growth factor receptor 2 (HER2), dramatically improves the clinical outcomes of HER2-positive breast cancer. Emerging evidence implied that the clinical behavior and sensitivity to targeted agents in HER2-positive breast cancer differed by hormone receptor (HR) status. The objectiveof this study was to determine the effect of the HR status on survival benefit of HER2-positive metastatic breast cancer when treated with anti-HER2-targeted therapy in People’s Republic of China.Methods: Metastatic breast cancer patients with HER2-positive diseases across six cancer centers in People’s Republic of China were retrospectively analyzed in our study. Patients were classified into four groups according to HR/HER2 status and trastuzumab treatment: HER2+/HR+ patients with first-line trastuzumab treatment, HER2+/HR+ patients with no trastuzumab treatment, HER2+/HR- patients with first-line trastuzumab treatment, and HER2+/HR- patients with no trastuzumab treatment. Kaplan–Meier analysis, log-rank test, and multivariate analysis were performed during analysis.Results: A total of 295 patients were included in the final analysis. The median overall survival was 30 months (95% confidence interval: 27.521–32.479). Among patients with HER2+/HR- disease, significant survival benefit was observed when treated with trastuzumab (30 vs 21months, P=0.000). However, in patients with HER2+/HR+ disease, trastuzumab administration had a survival improvement trend but no significant statistical differences (36 vs 30months, P=0.258). In the multivariate analysis, HR status was an independent predictor of overall survival and trastuzumab treatment had significantly decreased risk of death in HER2+/HR- patients (hazard ratio =0.330).Conclusion: HR status is an independent predictor of overall survival in HER2-positive metastatic breast cancer patients and patients with HER2+/HR- subtype might be associated with more survival benefits when treated with trastuzumab-based regimens. Keywords: HER2-positive, metastatic breast cancer, hormone receptor status

Using archived tumours, those from 1984–1986 and 1996–1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival.

Aims and background This study was aimed at analyzing metastatic involvement in interpectoral (Rotter's) lymph nodes in relation to tumor location, size, grade and hormone receptor status in primary breast cancer. Methods The study included 172 female patients undergoing surgery for breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes were removed in all of the patients. Serum levels of the tumor marker CA 15-3 were determined before surgery and hormone receptor status after surgery. Results Rotter's lymph nodes were identified in 67% of the patients, with metastatic involvement being found in 20% of the Rotter's nodes. Metastatic involvement of Rotter's nodes in patients with negative and positive axillary lymph nodes was 4% and 35%, respectively. When we looked at the location of the tumor in patients with metastatic involvement of Rotter's nodes, we found that tumors located in the upper quadrants were more prone to metastasis to Rotter's nodes; there was a significant positive correlation between tumor location and positive Rotter's nodes (r = 0.953, P = 0.012). As regards tumor size, Rotter's nodes were identified in 15%, 20% and 30% of stage T1 (5 cm) tumors, respectively. Hormone receptor status showed no statistically significant difference in the expression of estrogen and progesterone receptors between patients with and those without positive Rotter's nodes. Of 35 Rotter's node-positive patients, 31.4% had elevated serum levels of CA 15-3; the level was significantly higher in Rotter's-positive patients compared to those with negative (or absent) Rotter's nodes. Conclusions The results show that one-fifth of breast cancer patients, or even one-third of those with positive axillary lymph nodes, are discharged with positive interpectoral lymph nodes that remain undiagnosed. As the nodes can be surgically removed without additional mutilation, exploration of Rotter's lymph nodes should be introduced into routine clinical practice.