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Patients found to have presumed germline pathogenic variants (PGPVs) during comprehensive genomic profiling (CGP) require genetic counseling (GC) referrals. We retrospectively investigated the outcomes of patients with PGPVs. Among 159 patients who underwent CGP, we recommended GC for the 16 patients with PGPVs (3 with [FG group] and 13 without [G Group] a family/personal history of hereditary cancer) as well as for the 8 patients with no PGPVs, but a history (F group); 2 (67%), 5 (38%), and 3 (38%) patients received GC in the FG, G, and F groups, respectively. Germline testing results were positive in 1 and 2 patients of the FG and G groups, respectively. Among the patients recommended for GC, 58% did not receive GC due to lack of interest, poor performance status, or death. CGP contributes to the identification of germline variants in patients without a history of hereditary cancer. However, the proportion of patients who undergo GC should be improved.

Background It is unclear what interventions can sustain long-term higherphysical activity (PA) to improve breast cancer outcomes. Thus, this study aimed to evaluate the long-term effects of interventions on PA after breast cancer treatment. Methods This was an open-label randomized controlled trial for patients with stage 0-III breast cancer evaluating the efficacy of exercise and educational programs on long-term PA compared with usual care. The primary endpoint was proportion of patients with recreational PA (RPA) ≥5 metabolic equivalents(METs)/week at 1 year after registration. Results From 01/03/2016 to 15/03/2020, breast cancer patients were registered in the control (n = 120), education (n = 121), or exercise (n = 115) group. There were no significant differences in proportion of RPA ≥5 METs/week at 1 year between the exercise and control groups (54% and 53%, P = 0.492) and between the education and control groups (62% and 53%, P = 0.126). Significant difference in reductions from baseline at 1 year were noted on body weight (P = 0.0083), BMI (P = 0.0034), and body fat percentage (P = 0.0027) between education and control groups. Similarly, the exercise group showed significant difference in reduction in body fat percentage (P = 0.0038) compared to control group. Conclusions Although there were no significant effects on RPA 1 year after exercise and educational programs for breast cancer survivors, both interventions reduced body composition. Future studies on PA should investigate appropriate interventions to improve overall survival. Trial registration UMIN000020595 at UMIN Clinical Trial Registry Date of first registration: 01/03/2016

Chemotherapy is often difficult to treat human epidermal growth factor receptor 2 (HER2)-positive metastatic recurrent breast cancer in the elderly, and no standard treatment has been established at this point. We experienced a case in which trastuzumab (Tmab) + anastrozole (ANA) was ineffective (progressive disease; PD) in elderly HER2-positive breast cancer with postoperative multiple liver metastases, but T-DM1 was significantly effective (complete response; CR), and treatment could be continued safely. An 82-year-old woman was referred to our department with a right breast mass. A close examination revealed right breast cancer cT1bN0M0 cStage I, and total mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological result was pT1bN0M0 pStage I (luminal HER2 type). The patient was elderly and had no adjuvant treatment after the operation. Approximately 2 years after the operation, multiple liver metastases were observed, and treatment with ANA and Tmab was started. Four months later, MRI showed that the number of multiple liver metastases increased. The patient was diagnosed with PD, and the anti-HER2 drug was changed from trastuzumab to trastuzumab emtansine (T-DM1). The dose was reduced due to vomiting (grade 3). Two months later, MRI showed that the multiple liver metastases shrank and became obscure after 5 months. After that, T-DM1 was continued, and the disease did not worsen. In elderly people with difficulty in administering chemotherapy, T-DM1 may have a safe and sufficient therapeutic effect by adjusting the dose and managing side effects appropriately.

BACKGROUND: The identification of factors that are related to return to work after surgery for breast cancer could help healthcare professionals accurately identify patients at risk of return to work-related difficulties in order to provide them with appropriate support during breast cancer management. OBJECTIVE: The aim of this study was to identify factors related to return to work in breast cancer patients three months after axillary lymph node dissection. METHODS: Seventy-three women who were working before the surgery were evaluated. Age, body mass index, level of lymph node dissection, marital status, children, co-resident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion, upper limb function (Disabilities of the Arm, Shoulder and Hand; DASH), and work were evaluated. Patients who had returned to work constituted the return to work group, and those who had not returned to work constituted the no return to work group. RESULTS: Of the patients, 36 returned to work at three months. Logistic regression analysis including the five variables showed that shoulder flexion range of motion and DASH were significantly associated with return to work (p

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients.

Background The multinational BREAKOUT study (NCT03078036) sought to determine the prevalence of germline BRCA1/2 (gBRCA1/2) and somatic BRCA1/2 (sBRCA1/2) mutations and mutations in other homologous recombination repair (HRR) genes in women with HER2-negative metastatic breast cancer (MBC) starting first-line chemotherapy. Methods Genetic testing for gBRCA, sBRCA, and HRR gene mutations was performed in patients who started first-line chemotherapy for MBC in the last 90 days (341 patients across 14 countries) who were not selected based on risk factors for gBRCA mutations. We report data from the Asian cohort, which included patients in Japan (7 sites), South Korea (10 sites), and Taiwan (8 sites). Results Of 116 patients screened, 104 patients were enrolled in the Asian cohort. The median age was 53.0 (range 25–87) years. gBRCA1/2, gBRCA1, and gBRCA2 mutations were detected in 10.6% (11/104), 5.8% (6/104), and 4.8% (5/104) of patients, respectively; none had mutations in both gBRCA1 and gBRCA2. gBRCA1/2 mutations were detected in 10.0% (6/60) and 11.6% (5/43) of patients with hormone receptor-positive and triple-negative MBC, respectively. HRR gene mutations were tested in 48 patients without gBRCA mutations, and 5 (10.4%) had at least one HRR mutation in sBRCA, ATM, PALB2, and CHEK2. Conclusion We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC. Study registration NCT03078036.

Background Risk-reducing mastectomy is one option for women with hereditary breast and ovarian cancer to reduce the risk of breast cancer. Patients and methods We analyzed data of the Japanese Organization of Hereditary Breast and Ovarian Cancer on women who were diagnosed as hereditary breast and ovarian cancer by BRCA germline genetic testing between 2010 and 2019 to reveal the rate and likelihood of risk-reducing mastectomy. Results There were 412 women with BRCA1, 271 with BRCA2 and 4 with both female pathogenic variants. Ninety (13.1%) received risk-reducing mastectomy. The rates of risk-reducing mastectomy were statistically significantly higher in women with BRCA1 pathogenic variants than BRCA2, in women who had breast cancer than those who did not, in women with a breast cancer family history than in those without, in mothers than in those without children, in women who were receiving surveillance with MRI than those who were not and in women who received risk-reducing salpingo-oophorectomy than in those who did not on univariate analyses. The ages when they received the genetic testing were statistically significantly younger in the women receiving risk-reducing mastectomy than those who did not receive it. The women with BRCA1 pathogenic variants, personal history of breast cancer, mothers, those receiving MRI surveillance and younger women were independently significantly more likely to receive risk-reducing mastectomy based on multivariate analysis. Conclusions The rate of risk-reducing mastectomy was not high in Japan; however, risk-reducing surgery was approved by the Japanese National Medical Insurance for hereditary breast and ovarian cancer patients with breast and/or ovarian cancer in 2020, so this rate will increase.

Purpose Scalp cooling during chemotherapy infusion to mitigate alopecia for breast cancer patients is becoming widespread; however, studies regarding hair recovery after chemotherapy with scalp cooling are limited. We conducted a prospective study of hair recovery after chemotherapy with scalp cooling. Patients and methods One hundred and seventeen Japanese female breast cancer patients who completed planned (neo)adjuvant chemotherapy using the Paxman Scalp Cooling System for alopecia prevention were evaluated for alopecia prevention in our prospective study. We evaluated their hair recovery 1, 4, 7, 10, and 13 months after chemotherapy. Primary outcomes were grades of alopecia judged by two investigators (objective grades) and patients’ answers to the questionnaire regarding the use of a wig or hat (subjective grades). Results Of 117 patients, 75 completed scalp cooling during the planned chemotherapy cycles (Group A), but 42 discontinued it mostly after the first cycle (Group B). Objective and subjective grades were significantly better in Group A than in Group B throughout 1 year, and at 4 and 7 months after chemotherapy. When we restricted patients to those with objective Grade 3 (hair loss of > 50%) at 1 month, Group A exhibited slightly faster hair recovery based on the objective grades than Group B. There was less persistent alopecia in Group A than in Group B. Conclusions Scalp cooling during chemotherapy infusion for Japanese breast cancer patients increased the rate of hair recovery and had preventive effects against persistent alopecia.

In this study, we examined whether axillary web syndrome (AWS) in patients with breast cancer following axil-lary lymph node dissection affects range of motion (ROM), upper extremity function, and quality of life (QOL). The risk factors for AWS were also evaluated in a total of 238 consecutive breast cancer patients follow-ing axillary lymph node dissection. At 1, 2, and 3 months after surgery, there were no significant differences between the AWS group and the non-AWS group in upper-limb function or QOL. At 2 months after surgery, shoulder flexion and abduction ROM were significantly higher in the AWS group than in the non-AWS group (p < 0.05). Self-training time at home was not significantly different between the groups at 1, 2, or 3 months. Only age was a significant predictor of AWS at 1 month after surgery (p < 0.05). The AWS group in the present study did not have worse results for shoulder joint ROM, upper-limb function, and QOL than the non-AWS group. Younger age should be useful for predicting the development of AWS in the early postoperative period.

Purpose To evaluate the efficacies of cyclophosphamide, methotrexate, and fluorouracil (CMF) and tegafur–uracil (UFT) as adjuvant therapy in patients with resected stage I–IIIA breast cancer by immunohistochemistry (IHC)-based subtype and to determine the relationships between clinicopathological factors and long-term outcomes. Methods A pooled analysis of the randomized controlled N·SAS-BC 01 and CUBC studies was conducted. Expression of hormone receptors (HRs; estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and Ki67were assessed by IHC. Tumor-infiltrating lymphocytes (TILs) and nuclear/histological grades were determined by hematoxylin and eosin staining. Relapse-free survival (RFS) and overall survival (OS) were estimated by Kaplan–Meier analysis and hazard ratios were determined by Cox model adjusted for baseline tumor size and nodal status. Results A total of 689 patients (342 CMF and 347 UFT) were included in the analyses with a median follow-up of 11.1 years. There was no significant difference in RFS or OS between the two cohorts (RFS: 0.96 [95% confidence interval: 0.71–1.30], log-rank test p = 0.80; OS: 0.93 [0.64–1.35], p = 0.70). There was no difference in RFS or OS between the two cohorts for HR+/HER2− and HR+/HER2+ subtypes. RFS was significantly longer in patients treated with UFT compared with CMF in patients with HR−/HER2+ subtype (0.30 [0.10–0.88], p = 0.03). A high TILs level was associated with a better OS compared with low TILs level (p = 0.02). Conclusions This long-term follow-up study showed that RFS and OS were similar in patients with luminal-type breast cancer treated with CMF and UFT.

Background Breast-conserving surgery with radiotherapy is one of standard treatments for early breast cancer. However, it is regarded as an option to treat elderly patients with small hormone receptor-positive breast cancer with breast-conserving surgery and hormone therapy without radiotherapy. We conducted two sequential prospective studies to examine the feasibility of breast-conserving surgery without radiotherapy since 2002 and present the results. Patients and methods Primary female breast cancer patients who fulfilled the strict eligibility criteria were prospectively enrolled in two sequential studies named WORTH 1 and 2. The surgical materials were sliced in 5-mm intervals and all slices were examined microscopically. Postoperative radiotherapy was not allowed, but tamoxifen or anastrozole was administered for 5 years. Ipsilateral breast tumor recurrence (IBTR)-free survival was the primary outcome. Results The data of the two studies were combined (N = 321). The median follow-up period for IBTR was 94 months (4–192 months). Only three patients were treated with adjuvant chemotherapy. The 5- and 10-year IBTR-free rates were 97.0% and 90.5%, respectively. The age at operation and PR status affected IBTR rates independently. When we calculated IBTR-free rates of patients who were 65 years of age or older at the time of surgery and had PR-positive tumors, the 5- and 10-year IBTR rates were both 98.4%. Conclusions Our “5-mm-thick slice and 5-mm free-margin” method may be effective to select patients who can be treated by breast-conserving surgery and hormone therapy without radiotherapy.

BackgroundPrevious study results have suggested that local treatment of isolated lung metastases, may be beneficial and increase overall survival (OS) in highly selected patients. However, these were all retrospective studies. We designed this prospective cohort study to investigate the therapeutic and diagnostic clinical situation of oligometastatic breast cancer in the lung, as well as the prognosis outcomes of patients with this disease.MethodsWe enrolled patients with less than 3 lung nodules which suspected as oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were choice by each physician. The primary outcome was OS of patients with oligometastasis of breast cancer detected in the lung and secondary outcomes were the efficacy and safety of surgery for lung oligometastases. The study was in accordance with the relevant national/institutional guidelinesResultsBetween May 2015 and May 2019, 14 patients were enrolled at 5 centers. Resection of lung nodules (metastasectomy) was performed 11 (78.6%) of 14 patients and one was diagnosed with primary lung cancer. Metastasectomy were all performed employing video-assisted thoracic surgery (VATS) and achieved complete resection without perioperative complication. Systemic therapies such as chemotherapy, as well as endocrine and molecular target therapies were administered to all patients except one who declined all treatments offered. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%. Progression events occurred in 6 patients: 3 (30%) with and 3 (100%) without metastasectomy. Whereas 2 of 10 patients with metastasectomy survived 5 years without progression, progression events occurred all patients without metastasectomy within 1 year.ConclusionLung metastasectomy was worthwhile as a diagnostic evaluation and possibly provide long-term benefit in some patients. Phase 3 trials might be required to provide definitive evidence and to provide criteria for selecting patients. Trial registrationThis study was approved by the Institutional Review Board (IRB No. 960) of the Okayama University Hospital, Okayama, Japan, and was registered in the clinical trials database UMIN (UMIN000016999) on 31 March 2015. Written informed consent was obtained from all enrolled patients.

Scalp cooling during chemotherapy infusion has been recently reported to have moderate efficacy in the mitigation of chemotherapy-induced alopecia; however, there are few reports on Asian patients. We aimed to clarify the effects of scalp cooling in Japanese women. Female Japanese breast cancer patients who planned to receive (neo)adjuvant chemotherapy participated in this prospective study on the efficacy of scalp cooling using the Paxman Scalp Cooling System for alopecia prevention. The primary outcomes were the rates of patients with Grade 3 alopecia (defined as hair loss of > 50%) and the rates of patients who used a wig or hat to conceal hair loss 1 month after the last infusion of chemotherapy. The subjects were given a brief questionnaire regarding headaches, bad mood, fatigue, and chills shortly after each cooling. One hundred and forty-three patients participated in the study and used the cooling cap at least once. The mean and median ages of the subjects were 50.6 and 50, respectively (age range 28–76). One hundred and twenty-nine patients completed the planned chemotherapy of 4 to 8 cycles. Among them (7 patients were not evaluable), 74 patients (60.7%) had Grade 3 alopecia 1 month after chemotherapy. Of 80 patients who used the scalp cooling system throughout the planned chemotherapy (1 patient was not evaluable), 36 patients (45.6%) experienced Grade 3 alopecia. The efficacy of scalp cooling during chemotherapy infusion for hair loss mitigation in Asian women is similar to that in Caucasian women.

Background The effectiveness of a therapeutic strategy that switches chemotherapy, based on Ki-67 tumour expression after initial therapy, relative to that of standard chemotherapy, has not been evaluated. Methods Patients were randomly assigned to the control arm or the Ki-67 response-guided arm (Ki-67 arm). Primary tumour biopsies were obtained before treatment, and after three once-weekly doses of paclitaxel and trastuzumab to assess the interim Ki-67 index. In the control arm, paclitaxel and trastuzumab were continued for a total of 12 doses, regardless of the interim Ki-67 index. In the Ki-67 arm, subsequent treatment was based on the interim Ki-67 index. Ki-67 early responder is defined as the absolute Ki-67 value that was 30% compared with before treatment. Early Ki-67 responders continued to receive the same treatment, while early Ki-67 non-responders were switched to epirubicin plus cyclophosphamide. The primary endpoint was the pathological complete response (pCR) rate. Results A total of 237 patients were randomised. There was almost linear correlation between the Ki-67 reduction rate at interim assessment and the pCR rate. The pCR rate in Ki-67 early non-responders in the Ki-67 arm was inferior to that in the control arm (44.1%; 31.4–56.7; P = 0.025). Conclusions The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer. Clinical trial registration Clinical Trial Registration: UMIN-CTR as UMIN000007074.

Introduction Scalp cooling during chemotherapy infusion to mitigate hair loss for breast cancer patients is becoming popular in European and North American countries. But there is little prospective data regarding hair recovery after chemotherapy with scalp cooling. We reported on the results of hair loss prevention with scalp cooling during (neo)adjuvant chemotherapy with anthracyclines and/or taxanes for 122 Japanese breast cancer patients at the 2018 San Antonio Breast Cancer Symposium. Now we report on the prospective data of hair recovery of our 122 patients. Patients and Methods One hundred and twenty two Japanese breast cancer female patients who completed planned (neo)adjuvant chemotherapy used Paxman Scalp Cooling System for alopecia prevention and were evaluable for hair loss prevention in our prospective study. The scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. We evaluated their hair recovery 1, 4, 7, 10, and 13 months after completion of the chemotherapy. We took photographs of the heads of the patients from 5 directions, namely front, back, both sides, and top and asked the patients about the use of a wig or hat to conceal the hair loss using a questionnaire at the times mentioned above. Primary outcomes were grades of alopecia judged by two investigators (defined as Grade 0: 0% of hair loss, G1: 1~25 %, G2: 26~50%, G3: > 50%)(objective grade) and patients' answers to the questionnaire (defined as Grade 0: not at all, G1: sometimes, G2: almost always)(subjective grade). Among 122 patients 79 completed scalp cooling during the whole planned chemotherapy cycles, but 43 discontinued it mostly after the first cycle due to several reasons. We compared the objective and subjective grades of hair loss between the patients who had completed the scalp cooling (79 patients: Group A) and those who had discontinued it (43 patients: Group B). Results Objective grades 1 month after completion of the chemotherapy were Grade 0 in 6 patients (4.9 %), G1 in 13, G2 in 29, and G3 in 74, and subjective grades at 1 month were Grade 0 in 3 patients (2.5 %), G1 in 13, G2 in 105, and unknown in 1. The changes over time in objective grades were as follows; 4 months: G0 55 (47.0 %), G1 52, G2 9, G3 1, unknown 5, 7 months: G0 99 (85.3 %), G1 15, G2 1, G3 1, unknown 6, 10 months: G0 105 (89.7 %), G1 10, G2 1, G3 1, unknown 5, 13 months: G0 104 (92.0 %), G1 7, G2 1, G3 1, unknown 9. On the other hand, the changes in subjective grades were as follows; 4 months: G0 12 (10.3 %), G1 29, G2 76, unknown 5, 7 months: G0 53 (45.7 %), G1 22, G2 41, unknown 6, 10 months: G0 80 (68.4 %), G1 15, G2 22, unknown 5, 13 months: G0 93 (82.3%), G1 7, G2 13, unknown 9. When we compared Group A with Group B, the rates of objective G0 were statistically significantly higher in Group A than Group B, at 4, 10, and 13 months (4 months: 55.7% vs. 28.9%, P = 0.010, 10 months: 96.1% vs. 78.0%, P = 0.006, 13 months: 97.3% vs. 81.6%, P = 0.011) and the rate of subjective G0 was also statistically significantly higher in Group A than Group B at 7 months (53.2 % vs. 30.8 %, P = 0.022). When we restricted the data to those with objective Grade 3 at 1 month, Group A showed tendency of faster hair recovery in the objective grades than Group B. Conclusion It is concluded that scalp cooling during chemotherapy infusion for Japanese breast cancer patients made their hair recovery faster. Citation Format: Shozo Ohsumi, Sachiko Kiyoto, Yuichiro Miyoshi, Mina Takahashi, Seiki Takashima, Kenjiro Aogi, Sachie Shimizu, Miyuki Doi. Prospective study of hair recovery after (neo)adjuvant chemotherapy with scalp cooling in Japanese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-21.

Background: Two randomized controlled trials comparing the efficacy of oral tegafur-uracil (UFT) (2 years) with that of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) (6 courses) were conducted in patients with resected early breast cancer (N-SAS-BC01 trial [Watanabe et al, J Clin Oncol 2009] and CUBC trial [Park et al, Br J Cancer 2009]). Pooled analysis of these two randomized controlled trials using individual patient data has been published (Ohashi et al, Breast Cancer Res Treat 2010) and long-term follow-up data has also been reported (Yonemori et al, SABCS 2018). However, because the pathological factors evaluated in those studies are insufficient and based on old criteria, a re-evaluation using the current standard pathological factors is requited to use the data in the clinical practice. Methods: Paraffin-embedded sections of surgically excised tumor tissue were available for patients with resected stage I-IIIA breast cancer. The expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) and the Ki67 labeling index were assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and the grades of TILs were evaluated by hematoxylin and eosin (H&E) staining by pathology central review. The relationship of these pathological factors to relapse free survival (RFS) and overall survival (OS) was evaluated using long-term follow-up data. Hazard ratios were determined using the Cox model adjusted for clinical characteristics, namely tumor size and nodal status. Survival curves were estimated by the Kaplan-Meier method. This study is registered with the University Hospital Medical Information Network (UMIN), Japan (UMIN000022571). Results: Paraffin-embedded sections were available from 689 of the total of 1,057 (65.2%) patients (CMF, n=342; UFT n=347). The median follow-up time was 11.1 years (12.1 years in the N-SAS-BC 01 trial and 8.3 years in the CUBC trial). Baseline characteristics were similar in each group. The 10-year RFS and OS was 79.9%, 87.7% in the CMF arm, and 77.1%, 88.8% in the UFT arm, respectively. The hazard ratio (UFT vs. CMF) was 0.962 (95% CI 0.712-1.300) for RFS and 0.929 (95% CI 0.639-1.350) for OS. Table 1 shows the 10-year RFS and OS in each IHC-defined breast cancer subtype. 10-year OS in UFT arm and in CMF arm were similar in Hormone receptor (HR) + groups. Although this is not expected, there is a positive signal of benefit of UFT in HR-HER2+ group (RFS; hazard ratio 0.296 (95% CI 0.100-0.878)). High TILs were associated with better prognosis in all patient group (vs. low TILs: hazard ratio 0.347 (95% CI 0.140-0.855)), however in HR+ HER2- group, there was no association between TIL status and prognosis (High vs. low: hazard ratio 0.787 (95% CI 0.240-2.581)). TILs status could not predict the benefit of UFT in the subset analysis of all patient group and of each subtype group. Conclusion: This long-term follow-up study using randomized controlled trials shows that RFS and OS are similar in luminal type patients treated with UFT and CMF. Funding: Taiho Pharmaceutical CO., LTD. Table 1. 10-year RFS and OS in each IHC-defined breast cancer subtypeUFT (%)CMF (%)hazard ratio (UFT vs. CMF)10-year RFSHormone receptor (HR)+ HER2-76.7 (n=210)81.2 (n=210)1.034 (95%CI: 0.705-1.517)HR+ HER2+71.4 (n=26)73.7 (n=42)1.237 (0.499-3.069)HR- HER2+81.2 (n=29)68.4 (n=29)0.296 (0.100-0.878)HR- HER2-78.2 (n=73)84.7 (n=59)1.263 (0.596-2.675)10-year OSHR+ HER2-91.0 (n=210)89.5 (n=210)0.907 (0.551-1.491)HR+ HER2+83.9 (n=26)82.6 (n=42)0.993 (0.345-2.856)HR- HER2+90.9 (n=29)78.9 (n=29)0.335 (0.081-1.394)HR- HER2-84.6 (n=73)89.4 (n=59)1.455 (0.628-3.367) Citation Format: Shigehira Saji, Shinji Ohno, Norikazu Masuda, Hitoshi Tsuda, Futoshi Akiyama, Masafumi Kurosumi, Akihiko Shimomura, Nobuaki Sato, Shintaro Takao, Shozo Ohsumi, Yutaka Tokuda, Hideo Inaji, Toru Watanabe, Yasuo Ohashi. Pooled analysis of long-term outcome of patients enrolled in two trials comparing the efficacy of oral tegafur-uracil with CMF (N-SAS-BC01 and CUBC trials) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-17.

Background: It is critical that a large proportion of eligible patients should participate in clinical trials. However, recruitment into clinical trials requires informed consent and involves some difficult and complex problems. Therefore, it is important to know what factors affect the participation of eligible patients in clinical trials. Patients and Methods: Patients with metastatic breast cancer (MBC) who were eligible to participate in the SELECT BC or SELECT BC-CONFIRM trials were recruited to a prospective study accompanying them named SELECT BCFEEL. The SELECT BC and SELECT BC-CONFIRM trials were randomised controlled trials (RCTs) that compared taxanes or anthracyclines, respectively, with the oral regimen of S-1 in the first line setting for Japanese patients with MBC. The SELECT BC FEEL was conducted to identify factors affecting the rates at which informed consent was obtained, using a self-administered questionnaire we developed. The questionnaire included the following items: Physician recommendation, family or friend recommendation, satisfaction with the explanation about the trial, both from the doctor or clinical research coordinator and from printed matter, regimens used, understanding of the concept of the trial, benefit to future patients, relationship with the doctor, attitude toward random assignment, concerns about privacy, burden on the patient, and potential adverse effects. We also asked the patients their age, whether they received prior chemotherapy, and about the time needed to decide whether or not to participate, communication with their doctor or other patients, potential adverse effects they were concerned about, and other people's opinions that affected their decision. The patients were asked to answer most of the questions in 5-point Likert scales. To investigate the associations between patients’ decision regarding whether or not to participate in the RCTs and their responses to each question, the Chi-square test, the Mann-Whitney U test, and the t-test were used. P values of < 0.05 were considered statistically significant. Results: Two hundred and thirty-two patients participated in the present study. Data were missing for 3 patients, and they were excluded from the analyses. One hundred and eighty five participated in the RCT, but 44 did not. The patients who chose to participate in these RCTs were more likely to answer that they decided to participate because "My doctor wanted me to participate in this trial" (69.2% vs. 25.6%; P Conclusions: To enhance the consent rate in randomised trials of Japanese breast cancer patients, the concepts of the trials must be considered important and acceptable by the doctors and families of the patients. Citation Format: Yasuo Hozumi, Shozo Ohsumi, Hirofumi Mukai, Masato Takahashi, Hiromitsu Akabane, Youngjin Park, Eriko Tokunaga, Tsutomu Takashima, Takanori Watanabe, Yoshiaki Sagara, Tetsuji Kaneko, Yasuo Ohashi. Factors affecting enrolment in randomised controlled trials of Japanese patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-21-01.

Background In the global phase III IMpassion031 study, neoadjuvant atezolizumab plus nab-paclitaxel/anthracycline-based chemotherapy improved pathological complete response in patients with early stage triple-negative breast cancer. Here, we report primary analysis results from a subgroup of Japanese patients. Methods Patients with histologically documented, previously untreated, stage cT2–cT4, cN0–cN3, cM0 triple-negative breast cancer were randomized 1:1 to receive intravenous atezolizumab 840 mg or placebo every 2 weeks in combination with chemotherapy consisting of nab-paclitaxel intravenous 125 mg/m2 once a week, followed by doxorubicin intravenous 60 mg/m2 and cyclophosphamide intravenous 600 mg/m2 every 2 weeks. Patients then underwent surgery. Pathological complete response (ypT0/is ypN0) in the intention-to-treat and PD-L1-positive (≥1% PD-L1-expressing tumor-infiltrating immune cells) populations were co-primary endpoints. Results This subanalysis (data cutoff: 3 April 2020) included 36 patients from Japan (intention-to-treat; atezolizumab arm, n = 17; placebo arm, n = 19). Pathological complete response occurred in 41% (n = 7; 95% confidence interval, 18–67) of patients in the atezolizumab arm and 37% (n = 7; 95% confidence interval, 16–62) in the placebo arm. In the PD-L1-positive population, pathological complete response occurred in 50% (n = 5; 95% confidence interval, 19–81) of patients in the atezolizumab arm and 45% (n = 5; 95% confidence interval, 17–77) in the placebo arm. Treatment-related grade 3–4 adverse events occurred in 71% and 68% of patients in the respective arms. Conclusion Atezolizumab added to neoadjuvant chemotherapy numerically improved pathological complete response versus placebo in this small exploratory analysis of Japanese patients with early stage triple-negative breast cancer, a trend directionally consistent with the global study results. No new safety signals were identified.

Background This retrospective observational study validated nuclear grading criteria developed to identify a high-risk group with recurrence rate ≥20–30% and local pathology diagnosis used in a previous multi-institutional randomized N·SAS-BC 01 trial, where the efficacy of adjuvant chemotherapy regimens was evaluated in 733 high-risk node-negative invasive breast cancer patients. Methods Of 545 patients with long-term follow-up data (median 12.1 years), pathology slides, and local pathology diagnosis, 530 eligible patients were subjected to central pathology review (CPR) for histological type and nuclear grade (NG). Concordance in NGs was compared with local diagnosis. The 10/15-year recurrence-free survival (RFS) and overall survival (OS) rates stratified by NG and histological type were calculated. Results Local diagnoses were invasive ductal carcinoma (IDC)-NG2, IDC-NG3, invasive lobular carcinoma (ILC), and metaplastic carcinoma (MC) in 158/327/38/7 patients, respectively. The 10/15-year RFS rates were 87.2/82.6% for IDC-NG2 and 81.8/75.0% for IDC-NG3 (p = 0.061), and OS rates were 95.0/92.8% for IDC-NG2 and 90.8/85.7% for IDC-NG3 (p = 0.042). CPR graded 485 locally diagnosed IDCs as IDC-NG1/NG2/NG3/unknown in 98/116/267/4 patients, respectively. No significant difference was found among survival curves for the three NG groups. Although the agreement level between local and CPR diagnoses was low (κ = 0.311), both diagnoses identified a patient group with a 15-year recurrence rate ≥ 20%. The 10/15-year RFS rates were 79.4/63.5% for ILC and 68.6%/unknown for MC. Conclusions The N·SAS grading system identified a patient group with high-risk node-negative invasive breast cancer, suggesting that local diagnosis was performed efficiently in the N·SAS-BC 01 trial. Trial registration number: UMIN000022571. Date of registration: June 1, 2016.

Background Hereditary breast and ovarian cancer (HBOC) syndrome is a susceptibility syndrome for cancers, such as breast and ovarian cancer, and BRCA1/2 are its causative genes. Annual breast-enhanced magnetic resonance imaging (MRI) is recommended for BRCA1/2 mutation carriers aged over 25 years as a secondary prevention of breast cancer. However, breast MRI surveillance is rarely performed in Japan, and only four cases of breast cancer diagnosis triggered by MRI surveillance have been reported. Case presentation At our hospital, MRI triggered the diagnosis of breast cancer in four cancer-free BRCA1/2 mutation carriers. In one of our four cases, although MRI showed only a 3-mm focus, we could diagnose breast cancer by shortening the surveillance interval considering the patient’s high-risk for developing breast cancer. Conclusions Image-guided biopsy, including MRI-guided biopsy, depending on the size of the lesion, and shorter surveillance intervals are useful when there are potentially malignant findings on breast MRI surveillance for cancer-free patients with HBOC.

Introduction Recently scalp cooling during chemotherapy infusion has been reported to be quite effective to mitigate chemotherapy-induced alopecia. But data in Asian patients are quite limited. Patients and methods Japanese breast cancer female patients who planned to receive (neo)adjuvant chemotherapy were offered to participate in this prospective study of scalp cooling with Paxman Scalp Cooling System for alopecia prevention. The scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. Photographs of the head of the participants were taken from 5 directions, namely front, back, both sides, and top, on the day of chemotherapy infusion and 1 month after the last infusion. Two investigators consisting of a physician and a nurse judged the grade of alopecia by looking at the photographs according to the WHO classification. The primary outcomes were the rates of patients with Grade 3 alopecia (defined as hair loss of > 50%) and the rates of patients who used a wig or hat to conceal the hair loss one month after the last infusion of chemotherapy. This paper reports on the former outcome mainly. They were asked to answer a brief questionnaire regarding headache, fatigue, chill etc. shortly after each cooling. They could use the cooling cap for free on the first cycle of chemotherapy. But they were required to purchase it (about 1,130 US$) for the scalp cooling of the following cycles. Results One hundred forty three patients participated in the study and actually used the cooling cap at least once. The mean and median age of them are 50.6 and 50, respectively (28 - 76). One hundred twenty nine patients completed the planned chemotherapy of 4 to 8 cycles (89 Pts 4 cycles, 1 Pt 6 cycles, 39 Pts 8 cycles). Among them (7 patients were not evaluable), 74 patients (60.7 %) had Grade 3 alopecia 1 month after chemotherapy. In 80 patients who used the scalp cooling system throughout the planned chemotherapy (1 patient was not evaluable), 36 patients (45.6 %) experienced Grade 3 alopecia. On the other hand, among 49 patients who discontinued the cooling mostly after the 1st cycle (6 were not evaluable), 38 (88.3 %) had Grade 3 alopecia. When we restrict them to 33 (5 were not evaluable) who decided to discontinue the cooling by day10 of the first cycle of chemotherapy to exclude the patients who discontinued it because of less effect on alopecia prevention than they expected, 25 (89.3 %) experienced Grade 3 alopecia. Comparing the results of those who completed the cooling and patients who decided to discontinue it by day10 of the first cycle, the rates of Grade 3 alopecia (45.6 % vs. 89.3 %) were statistically significantly different in favor of the former (P = 0.0001). Most patients complained of some headache, chill, and pain of the jaw. Conclusion Scalp cooling with Paxman Scalp Cooling System during chemotherapy infusion in Asian women seems as effective for hair loss mitigation as in Caucasian women. Citation Format: Ohsumi S, Kiyoto S, Takahashi M, Hara F, Takashima S, Aogi K, Matsuda M, Yamamura N, Matsuda A, Yamauchi T, Doi M. Prospective study of scalp cooling for hair loss prevention in Japanese breast cancer women receiving (neo)adjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-13.

Background: Two randomized controlled trials comparing the efficacy of oral tegafur-uracil (UFT) (2 years) with that of classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (6 courses) were conducted in patients with resected early breast cancer. UFT is an oral fluoropyrimidine that combines tegafur, a prodrug of 5-fluorouracil, with uracil in a 1:4 molar ratio. One study was the N-SAS-BC01 trial (Watanabe et al, J Clin Oncol 2009), which was conducted in patients with high-risk node-negative breast cancer (n=733). The other was the CUBC trial (Park et al, Br J Cancer 2009), which was performed in patients with node-positive breast cancer (n=377). We reported the pooled analysis of these two randomized control trials using individual patient data (Ohashi et al, Breast Cancer Res Treat 2010). This pooled analysis showed that UFT was non-inferior to CMF in terms of inhibiting recurrence of estrogen receptor (ER)-positive early breast cancer. In addition, an exploratory subgroup analysis showed that UFT may be more effective in ER-positive patients who were 50 years or older. The present study was conducted to investigate the long-term efficacy of UFT or CMF in patients with early breast cancer. Methods: Long-term follow-up data for disease recurrence and survival were collected. Hazard ratios (HR) were determined using the Cox model stratified by study and adjusted for clinical characteristics, namely age, tumor size, nodal status, histological type, ER, and progesterone receptor (PgR). Survival curves were estimated by the Kaplan-Meier method. Hochberg multiplicity adjustment was applied in the previous pooled analysis, and non-inferiority of UFT versus CMF was shown in terms of relapse-free survival (RFS) in the ER-positive patient group. We investigated the non-inferiority of UFT in the same patient group with updated data. Restricted mean survival time (RMST) was calculated to consider the relative efficacy of UFT. This study is registered with JapicCTI-163321. Results: In total, 1,057 patients were analyzed (CMF, n=528; UFT n=529). The median follow-up time was 11.1 years (12.1 years in the N-SAS-BC 01 trial and 8.3 years in the CUBC trial). Table 1 shows the 10-year RFS and overall survival (OS) in all patients and ER-positive patients. The difference in RMST between arms at 20 years in terms of RFS was -2.7 months in all patients and 3.4 months in ER-positive patients. Table 2 shows the HR for RFS according to ER status and age. UFT (%)CMF (%)UFT to CMF; HR (95% CI)10-year RFSall patients74.477.11.02 (0.81–1.30)ER-positive patients75.075.10.91 (0.66–1.27)10-year OSall patients86.886.90.98 (0.72–1.34)ER-positive patients89.987.90.86 (0.54–1.37) Age Conclusion: This study shows that UFT was shown to be non-inferior to CMF in terms of RFS in ER-positive early breast cancer. This result is similar to that of the previous pooled analysis. Sponsor: Taiho Pharmaceutical Co., LTD Citation Format: Yonemori K, Ohsumi S, Takao S, Tokuda Y, Ito Y, Nakagami K, Takahashi M, Yoshidome K, Nakayama T, Yamaguchi Y, Ohashi Y, Inaji H, Watanabe T. Long-term follow-up of two randomized controlled trials (N-SAS-BC01 trial and CUBC trial) comparing oral tegafur-uracil (UFT) versus classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant therapy in early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-09.

Background In PALOMA-2, palbociclib–letrozole significantly improved progression-free survival (PFS) vs placebo–letrozole in women with estrogen receptor–positive, human epidermal growth factor receptor 2–negative (ER+/HER2–) advanced breast cancer (ABC) in the first-line setting. We evaluated the efficacy, safety, and pharmacokinetics of palbociclib in Japanese women in PALOMA-2. Methods In this phase 3 study, 666 postmenopausal women with ER+/HER2– ABC were randomized 2:1 to palbociclib (125 mg/day [3 weeks on/1 week off]) plus letrozole (2.5 mg daily) or placebo plus letrozole. A prespecified, exploratory, subgroup analysis of Japanese patients (n = 46) was conducted to compare results with those of the overall population. Results At the February 26, 2016 cutoff, median PFS among the 46 Japanese patients was 22.2 months (95%CI, 13.6‒not estimable) with palbociclib–letrozole vs 13.8 months (5.6‒22.2) with placebo–letrozole (hazard ratio, 0.59 [95%CI, 0.26−1.34]). The most common adverse events (AEs) were hematologic and more frequent among Japanese patients than the overall population (neutropenia: 93.8% [87.5% grade 3/4] vs 79.5% [66.4%]; leukopenia: 62.5% [43.8%] vs 39.0% [24.8%]); no Japanese patients had febrile neutropenia. Palbociclib dose reductions due to toxicity (mainly neutropenia) were more common in Japanese patients (62.5% vs 36.0%); few permanently discontinued due to AEs. Although mean palbociclib trough concentration was higher in Japanese patients vs non-Asians (95.4 vs 61.7 ng/mL), the range of individual values of the Japanese patients was within that of non-Asians. Conclusions These results from PALOMA-2 suggest that palbociclib–letrozole merits consideration as a first-line treatment option for postmenopausal Japanese patients with ER+/HER2‒ ABC. ClinicalTrials.gov: NCT01740427. Electronic supplementary material The online version of this article (10.1007/s10147-018-1353-9) contains supplementary material, which is available to authorized users.

The multinational BREAKOUT study (NCT03078036) sought to determine the prevalence of germline BRCA1/2 (gBRCA1/2) and somatic BRCA1/2 (sBRCA1/2) mutations and mutations in other homologous recombination repair (HRR) genes in women with HER2-negative metastatic breast cancer (MBC) starting first-line chemotherapy.Genetic testing for gBRCA, sBRCA, and HRR gene mutations was performed in patients who started first-line chemotherapy for MBC in the last 90 days (341 patients across 14 countries) who were not selected based on risk factors for gBRCA mutations. We report data from the Asian cohort, which included patients in Japan (7 sites), South Korea (10 sites), and Taiwan (8 sites).Of 116 patients screened, 104 patients were enrolled in the Asian cohort. The median age was 53.0 (range 25-87) years. gBRCA1/2, gBRCA1, and gBRCA2 mutations were detected in 10.6% (11/104), 5.8% (6/104), and 4.8% (5/104) of patients, respectively; none had mutations in both gBRCA1 and gBRCA2. gBRCA1/2 mutations were detected in 10.0% (6/60) and 11.6% (5/43) of patients with hormone receptor-positive and triple-negative MBC, respectively. HRR gene mutations were tested in 48 patients without gBRCA mutations, and 5 (10.4%) had at least one HRR mutation in sBRCA, ATM, PALB2, and CHEK2.We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC.NCT03078036.

Introduction The previous randomized phase 3 trial (SELECT BC) showed that S-1 as a first-line chemotherapy for metastatic breast cancer (MBC) is non-inferior to taxane with respect to overall survival. This study aimed to identify the usefulness of metabolism-related genes as predictive biomarkers for the response to S-1 compared with taxane using tumor tissue samples from the previous trial. Patients and Methods In this SELECT BC-EURECA study, 147 patients with human epidermal growth factor 2 (HER2)-negative MBC who received either S-1 or taxane were evaluated. Formalin-fixed paraffin-embedded specimens were collected, and 14 genes involved in the pyrimidine metabolic pathway, estrogen receptor, progesterone receptor, HER2, Ki67, and beta-tubulin were measured using reverse transcription polymerase chain reaction in microdissected tumor specimens. The expression of each gene was categorized as low, intermediate, and high by tertile values. Results Interaction tests to identify biomarkers for the response to S-1 compared with taxane, revealed the following as the top 3 biomarkers: RRM1 (P value = 0.24), GGH (P value = 0.25), and MTHFR (P value = 0.28). In the S-1 group, lower GGH and higher MTHFR expression were significantly correlated with better time to treatment failure. In the taxane group, there was no gene that was identified as a significant indicator of treatment failure. Conclusion This biomarker analysis from SELECT BC did not identify any predictive biomarkers for the response to S-1 compared with taxane. Future studies with larger sample size and information on not only mRNA, but also protein and DNA for broad functional analyses are needed.

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.

Background It is critical to obtain informed consent from eligible patients to complete clinical trials. We investigated the factors that affect the participation rates of eligible patients. Patients and methods Patients with metastatic breast cancer who were eligible for SELECT BC or SELECT BC-CONFIRM trials, randomized controlled trials conducted for patients with chemotherapy-naive metastatic breast cancer were recruited to prospective studies, SELECT BC-FEEL and SELECT BC-FEEL II, respectively. SELECT BC FEEL and SELECT BC-FEEL II were conducted to identify the factors affecting the rates at which informed consent was obtained, using a self-administered questionnaire we developed. Results In total, 232 patients participated in the studies. The patients who agreed to take part in the randomized trials were more likely than the refusers to answer that they decided to participate because: ‘My doctor wanted me to participate in this trial’ (P = 0.00000), ‘ My family or friends wanted me to participate in this trial’ (P = 0.00000), ‘Both treatment regimens used in the trial are suitable to me’ (P = 0.00383), ‘I know that the trial is conducted to determine which is a better treatment’ (P = 0.01196), and ‘ I think that my participation in the trial will contribute to the benefit to future patients with the same disease’ (P = 0.00756). Conclusions To enhance the consent rate in randomized trials of metastatic breast cancer patients, concepts of the trials must be considered important and acceptable not only by patients but also by doctors and their families.

Postoperative shoulder joint dysfunction has been observed at a certain rate after breast cancer surgery with axillary lymph node dissection. The purposes of this study were to verify the feasibility and effects of home-based exercise using a DVD and clarify the target of intensive intervention with physiotherapy by identifying the factors that cause postoperative shoulder dysfunction. The study comprised 237 female patients who underwent breast cancer surgery with axillary lymph node dissection, whose data were acquired until 3 months postoperatively. All patients were instructed to exercise at home using a DVD. Range of motion (ROM) of shoulder flexion and abduction and the disability of the arm, shoulder, and hand (DASH) score were measured before surgery, 1 week and 1, 2, and 3 months after surgery. As factors influencing the recovery of shoulder ROM at 3 months after surgery, the presence or absence of radiation and factors up to 1 month after surgery (age, body mass index, the relationship between operated side and dominant side of the hand, treatment modalities, and complications). Shoulder ROM and DASH scores had gradually recovered from 1 week to 3 months postoperatively. As the results of the multivariate analysis, the factors that were associated with the recovery of ROM of shoulder flexion at 3 months were the side of surgery corresponding to the dominant hand (negative factor) and the presence of paresthesia at 1 week postoperatively (positive factor) (p

Background The global observational BREAKOUT study investigated germline BRCA mutation (gBRCAm) prevalence in a population of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Methods Eligible patients had initiated first-line cytotoxic chemotherapy for HER2-negative MBC within 90 days prior to enrollment. Hormone receptor (HR)-positive patients had experienced disease progression on or after prior endocrine therapy, or endocrine therapy was considered unsuitable. gBRCAm status was determined using baseline blood samples or prior germline test results. For patients with a negative gBRCAm test, archival tissue was tested for somatic BRCAm and homologous recombination repair mutations (HRRm). Details of first-line cytotoxic chemotherapy were also collected. Results Between March 2017 and April 2018, 384 patients from 14 countries were screened and consented to study enrollment; 341 patients were included in the full analysis set (median [range] age at enrollment: 56 [25–89] years; 256 (75.3%) postmenopausal). Overall, 33 patients (9.7%) had a gBRCAm (16 [4.7%] in gBRCA1 only, 12 [3.5%] in gBRCA2 only, and 5 [1.5%] in both gBRCA1 and gBRCA2). gBRCAm prevalence was similar in HR-positive and HR-negative patients. gBRCAm prevalence was 9.0% in European patients and 10.6% in Asian patients and was higher in patients aged ≤ 50 years at initial breast cancer (BC) diagnosis (12.9%) than patients aged > 50 years (5.4%). In patients with any risk factor for having a gBRCAm (family history of BC and/or ovarian cancer, aged ≤ 50 years at initial BC diagnosis, or triple-negative BC), prevalence was 10.4%, versus 5.8% in patients without these risk factors. HRRm prevalence was 14.1% (n = 9/64) in patients with germline BRCA wildtype. Conclusions Patient demographic and disease characteristics supported the association of a gBRCAm with younger age at initial BC diagnosis and family history of BC and/or ovarian cancer. gBRCAm prevalence in this cohort, not selected on the basis of risk factors for gBRCAm, was slightly higher than previous results suggested. gBRCAm prevalence among patients without a traditional risk factor for harboring a gBRCAm (5.8%) supports current guideline recommendations of routine gBRCAm testing in HER2-negative MBC, as these patients may benefit from poly(ADP-ribose) polymerase (PARP) inhibitor therapy. Trial registration NCT03078036.

BACKGROUND: Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) ...