A prospective analysis of two studies that used the 5-mm interval slices and 5-mm margin-free method for ipsilateral breast tumor recurrence after breast-conserving surgery without radiotherapy.

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.

Diagnostic performance of dedicated breast positron emission tomography.

BACKGROUND: Dedicated breast positron emission tomography (dbPET) has been developed for detecting smaller breast cancer. We investigated the diagnostic performance of dbPET in patients with known breast cancer. METHODS: Eighty-two preoperative patients with breast cancer were included in the study (84 tumours: 11 ductal carcinomas in situ [DCIS], 73 invasive cancers). They underwent mammography (MMG), ultrasonography (US), and contrast-enhanced breast magnetic resonance imaging (MRI) before whole-body PET/MRI (WBPET/MRI) and dbPET. We evaluated the sensitivity of all modalities, and the association between the maximum standard uptake value (SUVmax) level and histopathological features. RESULTS: The sensitivities of MMG, US, MRI, WBPET/MRI and dbPET for all tumours were 81.2% (65/80), 98.8% (83/84), 98.6% (73/74), 86.9% (73/84), and 89.2% (75/84), respectively. For 11 DCIS and 22 small invasive cancers (≤ 2 cm), the sensitivity of dbPET (84.9%) tended to be higher than that of WBPET/MRI (69.7%) (p = 0.095). Seven tumours were detected by dbPET only, but not by WBPET/MRI. Five tumours were detected by only WBPET/MRI because of the blind area of dbPET detector, requiring a wider field of view. After making the mat of dbPET detector thinner, all 22 scanned tumours were depicted. The higher SUVmax of dbPET was significantly related to the negative oestrogen receptor status, higher nuclear grade, and higher Ki67 (p < 0.001). CONCLUSIONS: The sensitivity of dbPET for early breast cancer was higher than that of WBPET/MRI. High SUVmax was related to aggressive features of tumours. Moreover, dbPET can be used for the diagnosis and oncological evaluation of breast cancer.

Identifying ductal carcinoma in situ cases not requiring surgery to exclude postoperative upgrade to invasive ductal carcinoma.

BACKGROUND: Prospective cohort studies are being conducted worldwide to identify a low-grade group of ductal carcinoma in situ (DCIS) that does not require surgery. However, to do this, it is necessary to predict which cases, diagnosed with preoperative DCIS, will be upgraded to invasive ductal carcinoma (IDC) after surgery. METHODS: In this study, we evaluated the frequency of IDC upgrades in patients who were preoperatively diagnosed with DCIS at Showa University using the criteria of ongoing clinical trials. We divided our cases into those that could be enrolled in the ongoing trial and those that could not. Moreover, we evaluated whether CNB, which is allowed only in Japanese clinical trials, is related to the IDC mixture. RESULTS: There were 211 (52.1%) cases that matched the criteria of the U.K. and Netherlands trials, of which 62 (29.4%) were upgraded to IDC. A total of 113 (27.9%) cases met the criteria for clinical trials in Japan and the U.S., 25 (22.1%) of which were upgraded to IDC and 47 (34.6%) which matched when considering biopsy methods. The number of cases upgraded to IDC decreased to four (8.5%). CONCLUSIONS: This study demonstrated that there were a certain number of mixed IDC. We will pay attention to the results of ongoing clinical trials regarding how the presence of this mixed IDC affects the prognosis in non-surgery cases. Careful follow-up is recommended for non-surgical treatment.

Optimal Breast Density Characterization Using a Three-Dimensional Automated Breast Densitometry System.

Dense breasts are a risk factor for breast cancer. Assessment of breast density is important and radiologist-dependent. We objectively measured mammographic density using the three-dimensional automatic mammographic density measurement device Volpara™ and examined the criteria for combined use of ultrasonography (US). Of 1227 patients who underwent primary breast cancer surgery between January 2019 and April 2021 at our hospital, 441 were included. A case series study was conducted based on patient age, diagnostic accuracy, effects of mammography (MMG) combined with US, size of invasion, and calcifications. The mean density of both breasts according to the Volpara Density Grade (VDG) was 0-3.4% in 2 patients, 3.5-7.4% in 55 patients, 7.5-15.4% in 173 patients, and ≥15.5% in 211 patients. Breast density tended to be higher in younger patients. Diagnostic accuracy of MMG tended to decrease with increasing breast density. US detection rates were not associated with VDG on MMG and were favorable at all densities. The risk of a non-detected result was high in patients without malignant suspicious calcifications. Supplementary use of US for patients without suspicious calcifications on MMG and high breast density, particularly ≥25.5%, could improve the breast cancer detection rate.

Magnetically Guided Localization Using a Guiding-Marker System® and a Handheld Magnetic Probe for Nonpalpable Breast Lesions: A Multicenter Feasibility Study in Japan.

Accurate pre-operative localization of nonpalpable lesions plays a pivotal role in guiding breast-conserving surgery (BCS). In this multicenter feasibility study, nonpalpable breast lesions were localized using a handheld magnetic probe (TAKUMI) and a magnetic marker (Guiding-Marker System®). The magnetic marker was preoperatively placed within the target lesion under ultrasound or stereo-guidance. Additionally, a dye was injected subcutaneously to indicate the extent of the tumor excision. Surgeons checked for the marker within the lesion using a magnetic probe. The magnetic probe could detect the guiding marker and accurately localize the target lesion intraoperatively. All patients with breast cancer underwent wide excision with a safety margin of ≥5 mm. The presence of the guiding-marker within the resected specimen was the primary outcome and the pathological margin status and re-excision rate were the secondary outcomes. Eighty-seven patients with nonpalpable lesions who underwent BCS, from January to March of 2019 and from January to July of 2020, were recruited. The magnetic marker was detected in all resected specimens. The surgical margin was positive only in 5/82 (6.1%) patients; these patients underwent re-excision. This feasibility study demonstrated that the magnetic guiding localization system is useful for the detection and excision of nonpalpable breast lesions.

A Retrospective Analysis of the Relationship Between the Result of BRCA1/2 Genetic Testing and Surgical Method Selection in Japan.

BACKGROUND: We studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear. PATIENTS AND METHODS: The study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium. RESULTS: Our study included 318 female patients. Among these patients, 23.7% of patients with BRCA1/2 mutations and 61.8% of patients without these variants underwent breast-conserving surgery (P < .01). Among the patients with BRCA1/2 mutations, those who chose breast-conserving surgery tended not to undergo risk-reducing salpingo-oophorectomy (P < .05). Among the patients with BRCA1/2 mutations who underwent mastectomy for the affected side, 31.8% received contralateral risk-reducing mastectomy. Patients diagnosed with breast cancer under the age of 50 years were more likely to have contralateral risk-reducing mastectomy than patients over the age 50 years (P < .05). CONCLUSIONS: Patients with BRCA1/2 mutations tend to choose mastectomy. However, it is speculated that the final surgical method selection is made in consideration of not only the test results but also with careful consideration of the patient, taking into account other factors including individual values for risk-reducing surgeries and the age of breast cancer onset.

How pregnancy and childbirth affect the working conditions and careers of women surgeons in Japan: findings of a nationwide survey conducted by the Japan Surgical Society.

PURPOSE: To identify the conflicts between a career as a surgeon and pregnancy and childbirth for women in Japan. METHODS: The Japan Surgical Society conducted a nationwide survey on pregnancy and childbirth among its members who are women. The questionnaire included items regarding demography, working styles, and pregnancy and childbirth, including adverse events and harassment. RESULTS: The response rate was 29.9% (1068 responses, median age, 37 years). Among the responders, 61% were married and 47% had children (average number of children, 1.7). Half of the respondents reported having experienced sexual harassment and 62% reported having received unwelcome comments about pregnancy. About 20% had undergone fertility treatment. In total, 51% had pregnancies, with miscarriages in 33% of these. The top answer for the best timing for pregnancy and childbirth was after becoming board-certified. Nearly one-third of first-time mothers experienced adverse events during pregnancy and delivery, and 28% quit or changed their job because of their pregnancy and the birth of their first child. CONCLUSIONS: Japanese women who choose a career as a surgeon face obstacles during pregnancy and childbirth. It is vital to share the findings of this study and understand the issues associated with pregnancy and childbirth regardless of gender. Interventions are essential to ensure that every pregnant surgeon has a safe working environment to allow unobstructed development of her career.

BRCAness as a prognostic indicator in patients with early breast cancer.

BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P < 0.001), nuclear grade III (76.1% vs. 48.4%, P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P < 0.001). Five-year disease free survival (DFS) (54.0% vs. 88.0%, P < 0.001) and overall survival (OS) (76.3% vs. 93.1%, P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184-7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618-11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.

Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome.

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.

BRCAness as an Important Prognostic Marker in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy: A Multicenter Retrospective Study.

Triple-negative breast cancer (TNBC) has several subtypes. The identification of markers associated with recurrence and poor prognosis in patients with TNBC is urgently needed. BRCAness is a set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation, or deletion, results in DNA repair deficiency. In the current study, we evaluated the clinical significance and prognosis of BRCAness in a multicenter retrospective study. Ninety-four patients with TNBC treated with neoadjuvant chemotherapy were enrolled from three university hospitals for this retrospective study. BRCAness was evaluated in 94 core needle biopsy (CNB) specimens prior to neoadjuvant chemotherapy and 49 surgical specimens without pathological complete response (pCR). The samples were assessed using multiplex ligation-dependent probe amplification, and the amplicons were scored. Of the 94 patients, 51 had BRCAness in CNB specimens. There were no significant differences in pCR rates or recurrence between the BRCAness and non-BRCAness groups. Among surgical specimens, the BRCAness group had a significantly shorter recurrence-free survival and overall survival compared with the non-BRCAness group. The BRCAness of surgical specimens was found to be an important marker to predict prognosis in patients with TNBC after neoadjuvant chemotherapy. A clinical trial to assess the clinical impact of carboplatin with BRCAness is planned.

Current conditions and issues of physicians and working conditions at institutions accredited by the Japanese Breast Cancer Society.

BACKGROUND: In Japan, with the rapid increase of breast cancer patients, there has been increasing demand for breast cancer treatment. As the main workforce for breast cancer treatment, women physicians are thought to be in key positions, since the number of women physicians has recently been increasing. METHODS: To clarify the current statuses and issues of physicians and work conditions at the accredited breast cancer care facilities, a survey was conducted by the Japanese Breast Cancer Society (JBCS). RESULTS: The main workforces engaged in breast cancer care are surgeons, and the number of breast surgeons of all institutions in this survey was 1338 (full time 1124, part time 214). The percentages of women among surgeons, breast specialists accredited by the JBCS, and residents are 22%, 25%, and 38%, respectively. Among breast specialists, more women tended to work at university hospitals and cancer hospitals. Twenty-eight percent of women were married and among those, 76% had at least one child. Many hospitals allow short working hours or exemption from in-house call for women surgeons during pregnancy and child-rearing. In contrast, half of the facilities apply a "single doctor-in-charge system", where the patient's primary physician has to be on-call every day. Many institutions convene conferences for breast cancer treatment planning before or after the scheduled working hours. CONCLUSIONS: Current systems for treatment of breast cancer should be improved so that all surgeons specializing in the breast can develop their career while maintaining their personal life.

Developing the structure of Japan's cancer survivorship guidelines using an expert panel and modified Delphi method.

PURPOSE: To develop consensus-based components used in the first evidence-based cancer survivorship guidelines in Japan. METHODS: Purposive sampling was used to recruit a panel of experts in oncology clinical practice, nursing, health science, epidemiology, and patient advocacy. The panel engaged in a modified Delphi process to (1) generate consensus related to the definition of survivorship, (2) determine the aim and target users of the guideline, and (3) identify clinical issues for inclusion. A Web-based survey and panel meeting were conducted to obtain the panelists' feedback on the initial draft proposed by the secretariat. Multiple online votes were then completed until all elements of the proposed guidelines reached an approval rate of 80% or higher. Following each round, iterative refinements were made based on all panelists' feedback. RESULTS: Twenty-two experts were enrolled in the panel and participated in four rounds of online voting and two face-to-face meetings. Ultimately, the panel reached consensus on the definition of survivorship, the aim of the guidelines, and target users. Moreover, 11 of the original 17 clinical issues were retained. Finally, the panel selected two priority areas to implement immediately. CONCLUSION: The panel's consensus on the definition of survivorship, aim and target users of the guideline, and 11 clinical issues will serve as a compass for the development of comprehensive cancer survivorship guidelines in Japan. IMPLICATIONS FOR CANCER SURVIVORS: A culturally sensitive consensus approach was developed to improve the long term health and well- being of cancer survivors in Japan.

BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.

BACKGROUND: Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations. METHODS: A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR). RESULTS: (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p = 1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p = 0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39 years, compared with 46 years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX ≥ 2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p = 0.022), age at diagnosis ≤35 years (OR 0.149, 95% CI 0.023-0.954, p = 0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p = 0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p = 0.459 and p = 0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p = 0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p = 0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR. CONCLUSION: DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35 years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.

Genetic variations in triple-negative breast cancers undergoing neo-adjuvant chemotherapy.

Aim: Triple negative breast cancer (TNBC) is known as aggressive subtype and have no identified targeted therapies. We examined the relationship of neoadjuvant chemotherapy response to genetic variations of TNBC. Methods: The tumors used in this study were collected from Showa University Hospital, Japan. Thirteen formalin-fixed paraffin-embedded tumors from Japanese TNBC patients who underwent neoadjuvant chemotherapy were used for analysis. Of these, eight surgically resected tumors showed progressive disease and/or recurrence after treatment (PD/REC), and biopsy tissues from five patients showing pathological complete response (pCR) were analyzed. DNA extracted from tissue sample were analyzed. The Miseq system and Trusight Tumor Sequence panel kit were used to sequence 174 amplicons over 82 exons of 26 cancer-related genes to identify genetic mutations. Results: Seven somatic non-synonymous variants were detected in three genes (FOXL2, PIK3CA, and TP53) in all five pCR patients, and six somatic non-synonymous variants in two genes (PTEN and TP53) were detected in six of eight PD/REC patients. Eight of 13 TNBC tumors were found to have TP53 pathogenic variants, in both pCR and PD/REC cases. Conclusion: Although TP53 variation was detected in both pCR and PD/REC cases, each location and type of the variant were different. We could not identify genetic mutations associated with chemotherapy response and recurrence.

QOL Evaluation of Nab-Paclitaxel and Docetaxel for Early Breast Cancer.

OBJECTIVE: A previous randomized phase II study showed that neoadjuvant nab-paclitaxel (nab-PTX) 100 mg/m2) was effective and well-tolerated in patients with HER2-negative early-stage breast cancer, compared with docetaxel (DTX). We evaluated patient outcomes in terms of the Functional Assessment of Cancer Therapy-Breast (FACT-B), as a measure of health-related quality of life (HRQoL). MATERIALS AND METHODS: Stage I-III HER2-negative breast cancer patients from the previous study were included. They received either four cycles of nab-PTX (100 mg/m2 days 1/8/15) every 4 weeks, or DTX (75 mg/m2 day 1) every 3 weeks, both followed by four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC). Patients completed a health-related quality-of-life questionnaire at baseline, after one and four cycles of taxanes, before administration of FEC, and after administration of one and four cycles of FEC. RESULTS: Thirty-six eligible patients were enrolled. The baseline characteristics of the two groups were well balanced. FACT-B scores at baseline and after four cycles of taxanes were 115/108 (DTX/nab-PTX) and 99/92, respectively. There were no significant differences between DTX and nab-PTX for FACT-B, FACT-B-Trial Outcome Index (FACT-B-TOI) and FACT-General. FACT-B and FACT-B TOI scores tended to decrease after one cycle and after four cycles of chemotherapy which did not recover to the baseline scores through the end of chemotherapy in each group. CONCLUSION: There were no significant safety differences between nab-PTX and DTX. HRQoL tended to decrease during taxane-based anticancer treatment, with no significant differences between the treatments. We suggest that the HRQoL questionnaire has limited ability to evaluate different chemotherapy schedules. Trial registration UMIN000009855. Nov 20, 2012 registered.

A genome-wide association study identifies three novel genetic markers for response to tamoxifen: A prospective multicenter study.

PURPOSE: Although association studies of genetic variations with the clinical outcomes of breast cancer patients treated with tamoxifen have been reported, genetic factors which could determine individual response to tamoxifen are not fully clarified. We performed a genome-wide association study (GWAS) to identify novel genetic markers for response to tamoxifen. EXPERIMENTAL DESIGN: We prospectively collected 347 blood samples from patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. We used Ki-67 response in breast cancer tissues after preoperative short-term tamoxifen therapy as a surrogate marker for response to tamoxifen. We performed GWAS and genotype imputation using 275 patients, and an independent set of 72 patients was used for replication study. RESULTS: The combined result of GWAS and the replication study, and subsequent imputation analysis indicated possible association of three loci with Ki-67 response after tamoxifen therapy (rs17198973 on chromosome 4q34.3, rs4577773 on 6q12, and rs7087428 on 10p13, Pcombined = 5.69 x 10-6, 1.64 x 10-5, and 9.77 x 10-6, respectively). When patients were classified into three groups by the scoring system based on the genotypes of the three SNPs, patients with higher scores showed significantly higher after/before ratio of Ki-67 compared to those with lower scores (P = 1.8 x 10-12), suggesting the cumulative effect of the three SNPs. CONCLUSION: We identified three novel loci, which could be associated with clinical response to tamoxifen. These findings provide new insights into personalized hormonal therapy for the patients with breast cancer.

Diagnostic accuracy of contrast-enhanced spectral mammography in comparison to conventional full-field digital mammography in a population of women with dense breasts.

BACKGROUND: Contrast-enhanced spectral mammography to compare clinical efficacy of contrast-enhanced spectral mammography (CESM) and conventional digital mammography (MMG) with histopathology as gold standard in dense breasts. PATIENTS AND METHODS: A total of 143 breasts of 72 women who underwent CESM and MMG between 2011 and 2014 at Showa University Hospital were analyzed. RESULTS: 129 (90.2 %) of 143 breasts revealed dense breasts on MMG. 58 (40.6 %) of 143 breasts were diagnosed with breast cancer at histopathology. The remaining 85 breasts were diagnosed with benign findings after image assessments and/or core needle biopsy. CESM revealed 8 false-negative cases among 58 breast cancer cases (sensitivity 86.2 %) and 5 false-positive cases (specificity 94.1 %). Accuracy was 90.9 %. Conventional MMG was assessed true positive in 31 of 58 breast cancer cases (sensitivity 53.4 %) and false positive in 12 cases (specificity 85.9 %). Accuracy was 72.7 %. Sensitivity (p < 0.001), specificity (p = 0.016) and accuracy (p < 0.001) were significantly higher on CESM compared to MMG. MMG missed malignancy in 27 breasts. Of these, 25 were dense breasts. Of these 25, 20 (80.0 %) breasts were positive on CESM. CONCLUSION: These findings suggest that CESM offers superior clinical performance compared to MMG. Use of CESM may decrease false negatives especially for women with dense breasts.

Significant Effect of Polymorphisms in CYP2D6 on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study.

Purpose: CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen, "endoxifen." There are still controversial reports questioning the association between CYP2D6 genotype and tamoxifen efficacy. Hence, we performed a prospective multicenter study to evaluate the clinical effect of CYP2D6 genotype on tamoxifen therapy.Experimental Design: We enrolled 279 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. Ki-67 response in breast cancer tissues after tamoxifen therapy was used as a surrogate marker for response to tamoxifen. We prospectively investigated the effects of allelic variants of CYP2D6 on Ki-67 response, pathological response, and hot flushes.Results: Ki-67 labeling index in breast cancer tissues significantly decreased after preoperative tamoxifen monotherapy (P = 0.0000000000000013). Moreover, proportion and Allred scores of estrogen receptor-positive cells in breast cancer tissues were significantly associated with Ki-67 response (P = 0.0076 and 0.0023, respectively). Although CYP2D6 variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (P = 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele).Conclusions: This is the first prospective study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy. Our results suggest that genetic variation in CYP2D6 is a key predictor for the response to tamoxifen in patients with breast cancer. Clin Cancer Res; 23(8); 2019-26. ©2016 AACR.

Mentorship as Experienced by Women Surgeons in Japan.

BACKGROUND: Women have accounted for over 30% of new medical students since 1995 in Japan. Establishing support systems for women surgeons to continue their work is a major issue in Japan. Mentorship can be one of the most effective means to help women surgeons to continue their work. The purpose of this study was to clarify the current status of mentorship among Japanese women surgeons and to discuss the role of mentors for women surgeons. METHODS: Invitation letters were sent to all female members of the Japan Association of Women Surgeons in April 2011. An 84-item questionnaire survey was sent to those who agreed to participate in this study via the internet. RESULTS: Fifty-five surgeons participated in this study, a response rate of 48.7%. Sixty-seven percent of respondents found it difficult to continue in their job; 85% thought mentorship was necessary for women surgeons to progress in their careers; and 84% reported that they already had a mentor. Respondents thought that a mentor helped them to advance their clinical career, to stay in their job, and to provide moral support. However, mentors appeared to be less useful in helping them to advance their research career, to network, to increase their status, and to achieve a work-life balance. CONCLUSIONS: This study revealed areas where mentors appeared to be less helpful to women surgeons. The survey gave an indication of how to help improve and develop the career and personal life of women surgeons in Japan.