Search

Background: The participation rate for breast cancer screening remains to be suboptimal in Japan. Therefore, it is important to identify factors associated with non-participation and identify people at high risk for non-participation., Methods: We carried out a cross-sectional study using the data of women aged 40-74 years from the 2016 and 2019 Comprehensive Survey of Living Conditions. We selected candidate predictor variables from the survey sheets and conducted a multivariable logistic regression for non-participation in breast cancer screening for the past 2 years. In addition, using data from 2016, we created an integer risk score for non-participation and tested its predictive performance in 2019., Results: The proportion of participants in breast cancer screening in 2016 and 2019 were 46.7% (50,177/107,513) and 48.7% (49,498/101,716), respectively. In multivariable logistic regression analysis, age over 50 years, single/divorced/widowed, lower education level, lower household expenditure, being insured for National Health Insurance, employed to small/middle scale company, non-regularly employed, current smoker, never/quit drinking or middle/high-risk drinking, lower self-rated health status, higher Kessler Psychological Distress Scale score, non-participation in the annual health checkups for diseases other than cancer, not constantly visiting hospitals/clinics showed a positive association with non-participation. The 9-item risk score (age, marital status, education, health insurance plan, employment, smoking, drinking, non-participation in the annual health checkups for diseases other than cancer, and not constantly visiting hospitals/clinics) and 3-item risk score (age, health insurance plan, non-participation in the annual health checkups for diseases other than cancer) showed the area under the receiver operating characteristic curve of 0.744 and 0.720, respectively., Conclusion: We identified factors associated with non-participation in breast cancer screening. The simple risk score would be useful for public health sectors to identify people at risk for non-participation., (© 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Purpose: To clarify the characteristics, treatment trends, and long-term outcomes of patients with pregnancy-associated breast cancer (PABC)., Methods: PABC includes breast cancer diagnosed during pregnancy (PBC) and breast cancer diagnosed within 1 year after childbirth or during lactation (LBC). We compared clinical characteristics of 126 patients with LBC and 49 patients with PBC who underwent surgery at our hospital from 1946 to 2018. Survival was compared between patients with LBC and those with PBC in terms of breast cancer-specific disease-free survival (BC-DFS) and overall survival (OS)., Results: Patients with LBC were more likely to have family history, lymph node metastasis, lymphatic invasion, and to receive chemotherapy than patients with PBC. Patients with LBC showed poorer BS-DFS and OS than patients with PBC. Among patients with LBC, those treated after 2005 were older at surgery, had a smaller tumor size, received more systemic therapy, and had a more favorable prognosis than patients treated before 2004. Family history, breast cancer within 1 year after childbirth, and surgery before 2004 as well as cStage, lymph node metastasis, and lymphatic invasion were significantly associated with poor prognosis in patients with LBC. In the multivariate analysis for BC-DFS and OS among patients with PABC, LBC vs PBC did not remain as an independent prognostic factor while cStage remained., Conclusion: Patients with LBC had a poorer prognosis than those with PBC, most likely due to disease progression rather than biological characteristics. Early detection and optimization of systemic treatments are critical for improving the outcomes of patients with LBC., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies., Methods: We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype., Results: We analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered., Conclusions: Nab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774., (© 2021. The Author(s).)

Background: We conducted a prospective study with the intention to omit surgery for patients with ductal carcinoma in situ (DCIS) of the breast. We aimed to identify clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with DCIS., Patients and Methods: We retrospectively analyzed patients with DCIS diagnosed through biopsy between April 1, 2010 and December 31, 2014, from 16 institutions. Clinical, radiological, and histological variables were collected from medical records., Results: We identified 2,293 patients diagnosed with DCIS through biopsy, including 1,663 DCIS (72.5%) cases and 630 IDC (27.5%) cases. In multivariate analysis, the presence of a palpable mass (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2-2.6), mammography findings (≥ category 4; OR 1.8; 95% CI 1.2-2.6), mass formations on ultrasonography (OR 1.8; 95% CI 1.2-2.5), and tumor size on MRI (> 20 mm; OR 1.7; 95% CI 1.2-2.4) were independent predictors of IDC. Among patients with a tumor size on MRI of ≤ 20 mm, the possibility of postoperative upstaging to IDC was 22.1%. Among the 258 patients with non-palpable mass, nuclear grade 1/2, and positive for estrogen receptor, the possibility was 18.1%, even if the upper limit of the tumor size on MRI was raised to ≤ 40 mm., Conclusion: We identified four independent predictive factors of upstaging to IDC after surgery among patients with DCIS diagnosed by biopsy. The combined use of various predictors of IDC reduces the possibility of postoperative upstaging to IDC, even if the tumor size on MRI is larger than 20 mm.

Background: Owing to low incidence rates, population-based breast cancer screening is not recommended by many municipalities in Japan for women aged < 40 years. To evaluate the usefulness of screening in women aged < 40 years, we investigated the results of population-based breast cancer screening among young women performed in the Ibaraki Prefecture., Methods: Data regarding histological characteristics, recall rates, cancer detection rates, positive predictive values, tumor categories, and status of lymph node metastases were obtained from population-based screening data from Ibaraki Health Service Association Institute. The "number needing to be screened" (NNS) was determined; using Pearson's chi-squared test, these data were compared between women aged < 40 years and > 40 years., Results: The data of 428,560 women were evaluated. Cancer detection rates were significantly lower and the NNS and proportion of women with tumor category T2 or higher was significantly increased in women aged < 40 years than in those aged > 40 years (0.06% vs. 0.21%, 1505 vs. 281-439, and 28.9% vs. 6.3%, respectively; all, p < 0.05). The proportion of early-stage cancers was lower in women aged < 40 years than in those > 40 years, but this was not significant., Conclusions: These results suggest that population-based breast cancer screening should not be recommended for women aged < 40 years. To reduce the breast cancer-related mortality rate in young women and ensure efficient use of limited medical resources in Japan, a more efficient surveillance system, based on genetic propensity and family history, needs to be established.

Background: Breast cancer diagnosed during pregnancy (BCP) is uncommon, and thus there is limited evidence on its treatment. However, the incidence of BCP is increasing probably due to women having children at an older age. We aimed to clarify the practice patterns and limitations in treatment for BCP in Japan., Methods: A cross-sectional survey was developed for board-certified Japanese breast cancer specialists (n = 1583) to evaluate their knowledge, attitude, experience, and practice patterns regarding BCP. Survey items also included questions regarding potential barriers of practice toward patients diagnosed during pregnancy and respondents' background., Results: In March 2018, 492 (31.1%) breast oncologists responded to the survey. Among them, 234 (48%) respondents had the experience of treating at least one case of BCP. The accuracy of knowledge about BCP was evaluated by three items regarding BCP treatment from the latest Japanese Breast Cancer Society treatment guideline, and 265 (54%) were categorized to have "appropriate knowledge". Majority of the physicians (89%) have responded that patients should be treated in a center where both a cancer-treating team and obstetrician exist, and 48% responded that treating patients by the collaboration of cancer-treating team and obstetric team in different institutes is an alternative reasonable option., Conclusions: Interest, knowledge, and awareness of the guidelines appear to influence physician attitude, and thus it is urgently important to lay out educational materials and learning opportunities regarding BCP for breast specialists. A regional network of oncologists, obstetricians, and pediatricians to support the BCP patients should be developed.

Background: The poliovirus receptor (CD155) is expressed ubiquitously at low levels on both hematopoietic and nonhematopoietic cells, but its expression is upregulated in various tumor cells. An activating receptor DNAM-1 expressed on cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells binds to CD155 and mediates the cytotoxic activity of CTLs and NK cells against tumors. Unlike mouse tissues, human tissues express a soluble form of CD155 (sCD155), which is a splicing isoform of CD155 lacking the transmembrane region. We previously reported that the serum levels of sCD155 were higher in lung, gastrointestinal, breast, and gynecologic cancer patients than in healthy donors. Here, we focus on breast cancer patients., Methods: To analyze the association between serum level of sCD155 and clinicopathological parameters of breast cancer, we quantified sCD155 in the sera of 153 breast cancer patients by sandwich ELISA., Results: sCD155 levels in the sera of breast cancer patients were positively correlated with patient age, disease stage, and invasive tumor size. Moreover, they were higher in patients with estrogen receptor (ER)-negative cancers than in those with ER-positive tumors, and higher in those with Ki-67-high cancers than in those with Ki-67-low cancers., Conclusions: The serum level of sCD155 is correlated with high risk factors in breast cancer.

Background: An association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. The efficacy of TAM dose escalation appears limited in poor TAM metabolizers. Since the chlorine atom on the side chain of toremifene (TOR) prevents 4-hydroxylation by CYP2D6, its contribution to active conversion of TOR is minor. We examined the role of TOR and its dose escalation among poor TAM metabolizers., Methods: The pharmacokinetics (PK) and pharmacogenomics (PGx) of TAM and TOR were studied. Correlation between PK and CYP2D6 inhibitor use, smoking status, and PGx were examined by regression analysis. For patients showing low endoxifen levels, an intra-patient dose escalation of TOR was conducted, and TOR was increased from 40 to 120 mg for ≥ 24 weeks with PK sampling. Total activity was calculated as the sum of the concentration of each active metabolite adjusted by their respective in vitro activities., Results: Fifty and 11 of the 273 participating patients had endoxifen levels < 15 and < 7.5 ng/mL, respectively. The CYP2D6 genotype was the major determinant for TAM activity (p < 0.01). Smoking status (p = 0.07) and the CYP2C19 phenotype (p = 0.07), but not the CYP2D6 genotype (p = 0.61), showed marginally significant effects on TOR activity. TOR activity increased significantly with dose escalation, even among poor TAM metabolizers, and was maintained for ≥ 24 weeks., Conclusion: TOR might be a valid alternative to TAM in patients predicted to be poor TAM metabolizers.

Background: Dual blockade of HER2 promises increased pathological complete response (pCR) rate compared with single blockade in the presence of chemotherapy for HER2-positive (+) primary breast cancer. Many questions remain regarding optimal duration of treatment and combination impact of endocrine therapy for luminal HER2 disease., Methods: We designed a randomised phase II, five-arm study to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks) followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks) with/without prolongation of anti-HER2 therapy prior to chemotherapy (18 vs. 6 weeks), and with/without endocrine therapy in patients with HER2+ and/or oestrogen receptor (ER)+ disease. The primary endpoint was comprehensive pCR (CpCR) rate. Among the secondary endpoints, pCR (yT0-isyN0) rate, safety, and clinical response were evaluated., Results: In total, 215 patients were enrolled; 212 were included in the full analysis set (median age 53.0 years; tumour size = T2, 65%; and tumour spread = N0, 55%). CpCR was achieved in 101 (47.9%) patients and was significantly higher in ER- patients than in ER+ patients (ER- 63.0%, ER+ 36.1%; P = 0.0034). pCR with pN0 was achieved in 42.2% of patients (ER- 57.6%, ER+ 30.3%). No significant difference was observed in pCR rate between prolonged exposure groups and standard groups. Better clinical response outcomes were obtained in the prolongation phase of the anti-HER2 therapy. No surplus was detected in pCR rate by adding endocrine treatment. No major safety concern was recognised by prolonging the anti-HER2 treatment or adding endocrine therapy., Conclusions: This study confirmed the therapeutic impact of lapatinib, trastuzumab, and paclitaxel therapy for each ER- and ER+ subgroup of HER2+ patients. Development of further strategies and tools is required, particularly for luminal HER2 disease.

Cystoid macular edema (CME) is a rare complication of taxane-based chemotherapy. We encountered a patient who developed CME during treatment with nab-paclitaxel for metastatic breast cancer. Early detection of this disease enables continuation of appropriate treatment without reducing the quality of life for patients with end-stage disease. Physicians should be aware of this potential adverse effect, and should make changes to the treatment of patients as soon as possible.

Non-Hodgkin lymphoma (NHL) of the breast is a rare disease. Herein, we report a rare case of secondary involvement of the breast by NHL in a male patient and the ultrasound imaging findings. A 70-year-old man noticed an induration of the subareolar region of the right breast. He had been diagnosed as having mantle cell lymphoma 5 years before and treated with several series of chemoradiotherapy. On supine examination, palpation revealed bilateral breast enlargement, but detection of a lump was difficult. Ultrasonography showed a hypoechoic non-mass image-forming lesion in the subareolar region of the right breast. The final pathological diagnosis was recurrence of mantle cell lymphoma in the right breast. The diagnosis of malignant lymphoma of the breast by imaging modalities is difficult because there are no specific features. Breast lymphoma should be included with gynecomastia and breast cancer in the differential diagnosis of male patients with breast enlargement.

About 5-10 % of breast cancer cases are considered to be hereditary, and germ line mutations in the BRCA1 and BRCA2 genes have been proven to contribute to the development of hereditary breast and/or ovarian cancer syndrome (HBOC). Breast cancer diagnosed at a young age is an indication of a higher likelihood of HBOC. Risk assessment, genetic counseling, and BRCA1/BRCA2 mutation testing, especially for younger women with breast cancer, have started to be an integral element of practice due to advances in gene sequencing technologies and accumulating evidence for the clinical implications of BRCA mutation status for not only early breast cancer management, but also for the patient's own and their family's next cancer risk, and proactive steps toward a risk-reducing approach. As yet, the cancer genetic service system is immature in Japan. There are several problems to be solved to improve cancer genetic services in clinical practice for breast cancer.

Background: Fertility is one of the key aspects of quality of life for breast cancer patients of childbearing age. The objective of this study was to describe fertility-related practice for young breast cancer patients in Japan and to identify healthcare provider factors that contribute to physicians' behavior towards fertility preservation., Methods: A cross-sectional survey was developed in order for Japanese breast cancer specialists (n = 843) to self-evaluate their knowledge, attitude, and behavior regarding fertility preservation. Survey items included questions regarding knowledge of and attitude toward fertility issues in cancer patients, fertility-related practice, potential barriers for the discussion of fertility with patients, and responding physicians' socio-demographic background., Results: Four hundred and thirty-four (52%) breast oncologists responded to the survey. Female and younger oncologists (age less than 50 years) had significantly higher probability of referring patients to reproductive specialists. Physicians who had better knowledge score and positive attitudes toward fertility preservation were more likely to discuss potential fertility issues with cancer patients. This was significantly associated with consultation and referral to reproduction specialists when encountering fertility issues with cancer patients. Risk of recurrence, lack of collaborating reproductive specialists, and time constraints in the clinic were identified as major barriers to discussion of fertility preservation with breast cancer patients., Conclusion: Female and younger physicians as well as physicians working in a multidisciplinary environment had positive attitudes and behavior towards fertility preservation in breast cancer patients. The development of comprehensive and interdisciplinary programs for healthcare providers is necessary to meet the expectations and fertility needs of breast cancer patients.

Cancer development requires neovascularization. The level of angiogenic activity in breast cancer has been shown to be a determinant of disease progression and survival. Vascular endothelial growth factor (VEGF) is a one of the most essential pro-angiogenic growth factors expressed by most cancer-cell types and certain tumor stromal cells. Blocking the action of VEGF appears to be a promising anti-angiogenic approach to treat multiple types of solid tumors including breast cancer, and clinical trials using agents which target VEGF were launched beginning in the late 1990s. The effort reached fruition in 2005 with the first report of a large, prospective randomized trial of anti-VEGF therapy in patients with metastatic breast cancer (MBC), which demonstrated the benefit of adding the monoclonal antibody bevacizumab to the chemotherapeutic agent paclitaxel. The success of this trial provided proof of principle that inhibition of angiogenesis has the potential to enhance the effectiveness of treatment of this disease. Adjuvant therapy trials are in development with bevacizumab and numerous other anti-VEGF agents are now being tested in patients with breast cancer in various settings. Nevertheless, since bevacizumab monotherapy has minimal activity, a question for future therapeutic development of these agents in breast cancer relates to the interaction between anti-angiogenic strategies and cytotoxic therapies. Further research is still needed for complete understanding of the exact role of VEGF and angiogenesis in health and disease, to take best advantage and avoid the adverse effects of anti-angiogenic therapy.

Antibody therapy with trastuzumab has greatly impacted breast cancer treatment. Combination treatment with trastuzumab is regarded currently as a first-line therapy for metastatic breast cancers that overexpress Her-2. It has become routine practice to examine the status of Her-2 expression in primary tumors. The impact of this therapy might be as great as that of endocrine therapy from a historical point of view. A number of new approaches using trastuzumab for seeking individualized treatment are being tested in current clinical trials. We reviewed recent advances in trastuzumab treatment and discuss the future of antibody therapy for breast cancer.

Several recent studies have investigated the administration of docetaxel on a weekly basis. Here, we review the weekly use of docetaxel in breast cancer. To identify articles published on this topic we performed a computer-assisted MEDLINE search; additional references were found in the bibliographies of these articles. Several phase Tstudies of weekly docetaxel have provided encouraging data indicating that there is generally less myelosuppression than with the three week schedule in patients with a variety of advanced malignancies. Dose-limiting toxicities are reached at 43 to 50 mg/m(2), and the recommended dose ranges from 36 to 42 mg/m(2). Furthermore, five studies of weekly docetaxel in patients with metastatic breast cancer achieved 32 to 41% response rates using 25 to 40 mg/m(2) of docetaxel. Myelosuppression was mild, but fatigue was common and was the most common reason for dose reduction. In general, the planned dose intensity was equivalent to those used in standard three week schedules, and fatigue, asthenia, nail changes, excessive lacrimation (tearing), and fluid retention became more common with prolonged administration of docetaxel. Thus, weekly scheduling of docetaxel maintains efficacy and alters the toxicity profile, and the use of weekly docetaxel will become a promising alternative to three week dosing in the treatment of advanced breast cancer once randomized controlled studies confirm these results. However, there is still much to learn about the role of weekly docetaxel in adjuvant and neoadjuvant therapy.

Aromatase inhibition provides both paracrine/intracrine and endocrine treatment. Recent accumulated data clarified that 3rd generation aromatase inhibitors potently suppress intratumoral estrogen synthesis particularly in postmenopausal patients. In the 2nd-line treatment for metastatic breast cancer patients, aromatase inhibitors achieved results antitumor activity at least equal to and sometimes better than that of tamoxifen. In the first-line treatment for metastatic breast cancer patients, a recent pivotal study clearly demonstrated that aromatase inhibitor was superior to tamoxifen. Based upon these results, various adjuvant trials which compare aromatase inhibitors with tamoxifen and attempt to determine optimal combination therapies and treatment periods with aromatase inhibitors are currently being conducted. In addition, preliminary studies conducted in neoadjuvant setting indicated that aromatase inhibitors showed an extremely high response rate, which predicts a future paradigm, that neoadjuvant therapy using aromatase inhibitors singly or in combination may become standard for hormone-responsive and post-menopausal breast cancer patients.

Recent accumulated data have indicated that angiogenesis is a promising indicator to predict prognosis and response to treatment. In breast cancer, microvessel density (MVD), a semi-quantitative marker of neovascularization grade, has been suggested to provide independent prognostic value. In addition, the expression of both vascular endothelial growth factor (VEGF)and thymidine phosphorylase (TP), two angiogenesis regulatory molecules, were found to be closely associated with MVD, and with the effect of treatments. In particular, VEGF expression seems to be a phenotype resistant to endocrine therapy, whereas TP expression decreases sensitivity to chemotherapy containing fluorouracil. This review summarizes the current topics regarding the prognostic and predictive value of angiogenesis in primary breast cancer, and we discuss future applications of antiangiogenesis treatments in an adjuvant setting.