Development of a nomogram to predict recurrence scores obtained using Oncotype DX in Japanese patients with breast cancer.

BACKGROUND: Chemotherapy is crucial for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and its survival benefits may outweigh adverse events. Oncotype DX (ODX) assesses this balance; however, it is expensive. Using nomograms to identify cases requiring ODX may be economically beneficial. We aimed to identify clinicopathological variables that correlated with the recurrence score (RS) and develop a nomogram that predicted the RS. METHODS: We included 457 patients with estrogen receptor-positive, HER2-negative breast cancer with metastases in fewer than four axillary lymph nodes who underwent surgery and ODX at our hospital between 2007 and 2023. We developed nomograms and internally validated them in 310 patients who underwent surgery between 2007 and 2021 and validated the model's performance in 147 patients who underwent surgery between 2022 and 2023. RESULTS: Logistic regression analysis revealed that progesterone receptor (PgR) level, histological grade (HG), and Ki67 index independently predicted the RS. A nomogram was developed using these variables to predict the RS (area under the curve [AUC], 0.870; 95% confidence interval [CI], 0.82-0.92). The nomogram was applied to the model validation group (AUC, 0.877; 95% CI, 0.80-0.95). When the sensitivity of the nomogram was 90%, the model was able to identify 52.3% low-RS and 41.2% high-RS cases not requiring ODX. CONCLUSIONS: This was the first nomogram model developed based on data from a cohort of Japanese women. It may help determine the indications for ODX and the use of nomogram to identify cases requiring ODX may be economically beneficial.

Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306.

BACKGROUND: In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. METHODS: We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. RESULTS: ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175-0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073-0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. CONCLUSIONS: RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes. METHODS: In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses. RESULTS: We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort. CONCLUSION: We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .

Reliability and validity of the Japanese version of the Chemotherapy-induced Alopecia Distress Scale.

BACKGROUND: The Chemotherapy-induced Alopecia Distress Scale (CADS) is a patient-reported outcome measure for assessing distress associated with Chemotherapy-induced alopecia (CIA). This study aimed to confirm the psychometric validity of the Japanese version of the CADS (CADS-J). METHODS: A total of 132 patients with breast cancer who developed CIA were asked to complete the CADS-J twice at 2 week intervals to confirm test-retest reliability. The body image domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) breast cancer-specific module, the self-esteem scale from the Rosenberg Self-Esteem Scale, and the emotional domain of the EORTC QLQ Core 30 were used to confirm the convergent validity of the CADS-J. The overall quality of life and physical domains of the EORTC QLQ Core 30 were used to confirm the discriminant validity of the CADS-J. RESULTS: In total, 125 participants provided valid responses. The mean age was 52.2 years. The overall Cronbach's alpha for the CADS-J was 0.903. The intraclass correlation coefficients of the first and second responses were r = 0.874, r = 0.952, r = 0.911, and r = 0.959 for the physical domain, emotional domain, activity domain, and relationship domain, respectively. In terms of convergent validity, the total CADS-J score was moderately correlated with body image (r = - 0.63), self-esteem (r = - 0.48), and the emotional domain (r = - 0.61). Regarding discriminant validity, the total CADS-J score was weakly correlated with the overall quality of life (r = - 0.34) and physical domain (r = - 0.24). CONCLUSIONS: The CADS-J is psychometrically reliable and valid for evaluating the distress caused by CIA. It is expected to be used in daily practice and as an endpoint in various studies.

High-accuracy prediction of axillary lymph node metastasis in invasive lobular carcinoma using focal cortical thickening on magnetic resonance imaging.

BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC. METHOD: This retrospective analysis included 120 female patients (mean ± standard deviation age, 57.2 ± 11.2 years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH). RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively. CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.

Effectiveness of PET/CT and VATS for detecting and treating internal mammary lymph node metastasis: a case series.

OBJECTIVE: We occasionally observed internal mammary lymph node metastases of breast cancer in a clinical setting. However, unlike a standard treatment in axillary metastasis, surgical resection for internal mammary lymph node metastasis is not prevalent because of unclear safety and benefits. Thus, we aimed to evaluate the diagnostic ability and clinical outcomes of positron emission tomography/computed tomography and video-assisted thoracoscopic surgery. METHODS: We retrospectively investigated 34 patients with breast cancer with abnormal 18F-fluorodeoxyglucose uptake in internal mammary lymph nodes, at a single centre, between January 2015 and June 2022 and identified 11 female patients (mean age ± SD, 51.5 ± 12.9 years) who underwent video-assisted thoracoscopic surgery resection. Positron emission tomography/computed tomography was used to determine the clinical stage. We reviewed the surgical pathology of eleven and two patients who underwent direct-view internal mammary lymph node resection to calculate the positive predictive value of positron emission tomography/computed tomography. RESULTS: Ipsilateral fluorodeoxyglucose accumulation was observed, with an average maximum standardized uptake value of 8.9 (range, 3.1-24.0). No perioperative complications occurred, and all patients who underwent video-assisted thoracoscopic surgery alone were discharged from the hospital on post-operative day 2 or 3. The estimated positive predictive value was 80%. All patients were alive, and seven of nine patients with metastasis were relapse-free, at a mean follow-up period of 17.9 months (range, 1-51). However, two patients had recurrence at 16 and 14 months after surgery for internal mammary lymph node relapse. CONCLUSIONS: Radiotherapy is the standard treatment for suspected internal mammary lymph node metastasis detected using positron emission tomography/computed tomography; however, we could safely perform minimally invasive video-assisted thoracoscopic surgery resection, leading to a definite pathological diagnosis.

Current Status and Issues of the Japan Oncofertility Registry.

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan.

Solitary fibrous tumor of male breast: A case report and literature review.

BACKGROUND: Solitary fibrous tumors (SFT) are uncommon mesenchymal neoplasms which can arise in any anatomical location. Pleural SFTs have been most frequently documented; however, breast SFT is an exceedingly rare entity and seldom present in male breast, with only 8 previously reported cases. Recently, STAT6 immunostaining was considered to be a definitive marker of SFT, however, no case of the male breast SFT showing STAT6 positivity preoperatively has been reported. METHODS AND RESULTS: We describe a case of breast SFT in a 73-year-old male patient with a 12-month history of a palpable breast mass. The only associated clinical symptom was bilateral gynecomastia. An ultrasound scan examination revealed an oval, well-circumscribed and hypoechoic mass with hypervascularity. A core-needle biopsy was performed, and microscopic examination with immunohistochemistry confirmed the diagnosis of SFT. He underwent a complete surgical resection with clear margins, and there were no signs of high cellularity, remarkable mitotic activity, pleomorphism, hemorrhage or necrosis. CONCLUSION: A perioperative immunohistochemical evaluation for diffuse and intense nuclear expression of STAT6 was helpful to distinguish SFT from myofibroblastoma. We, herein, describe the first case of SFT in a male breast, confirmed by STAT6 immunostaining positivity. We also conducted a literature review of all previous cases of breast SFTs.

Clinical prediction model based on 18F-FDG PET/CT plus contrast-enhanced MRI for axillary lymph node macrometastasis.

Purpose: Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are useful for detecting axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC); however, there is limited clinical evidence to demonstrate the effectiveness of the combination of PET/CT plus MRI. Further axillary surgery is not recommended against ALN micrometastasis (lesion ≤2 mm) seen in sentinel lymph nodes, especially for patients who received proper adjuvant therapy. We aimed to evaluate the efficacy of a prediction model based on PET/CT plus MRI for ALN macrometastasis (lesion >2 mm) and explore the possibility of risk stratification of patients using the preoperative PET/CT plus MRI and biopsy findings. Materials and methods: We retrospectively investigated 361 female patients (370 axillae; mean age, 56 years ± 12 [standard deviation]) who underwent surgery for primary IDC at a single center between April 2017 and March 2020. We constructed a prediction model with logistic regression. Patients were divided into low-risk and high-risk groups using a simple integer risk score, and the false negative rate for ALN macrometastasis was calculated to assess the validity. Internal validation was also achieved using a 5-fold cross-validation. Results: The PET/CT plus MRI model included five predictor variables: maximum standardized uptake value of primary tumor and ALN, primary tumor size, ALN cortical thickness, and histological grade. In the derivation (296 axillae) and validation (74 axillae) cohorts, 54% and 61% of patients, respectively, were classified as low-risk, with a false-negative rate of 11%. Five-fold cross-validation yielded an accuracy of 0.875. Conclusions: Our findings demonstrate the validity of the PET/CT plus MRI prediction model for ALN macrometastases. This model may aid the preoperative identification of low-risk patients for ALN macrometastasis and provide helpful information for PET/MRI interpretation.

Characteristics, treatment trends, and long-term outcomes of Japanese patients with pregnancy-associated breast cancer (PABC).

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.

Does breast-conserving surgery with radiotherapy in BRCA-mutation carriers significantly increase ipsilateral breast tumor recurrence? A systematic review and meta-analysis.

BACKGROUND: Breast-conserving surgery (BCS) is often preferred for localized, small breast cancers, but its safety and efficacy in BRCA-mutation carriers is still controversial. This meta-analysis aimed to determine whether there was any significant difference in the incidence of ipsilateral breast tumor recurrence (IBTR) between BRCA-mutation carriers who underwent BCS and controls with sporadic breast cancer. METHODS: A PubMed search was conducted through March 2020 to identify studies examining the risk of IBTR after BCS in BRCA-mutation carriers versus controls. The Cochrane risk-of-bias tool was used to assess the risk of bias. The pooled risk ratio (RR) was calculated using the random-effects model. RESULTS: Thirteen studies involving 701 BRCA-mutation carriers and 4788 controls in total were eventually analyzed. In the meta-analysis, IBTR after BCS was significantly higher in BRCA-mutation carriers (RR: 1.589; 95% confidence interval (CI) 1.247-2.024; P < 0.001). Subgroup analysis of the follow-up time found that the RR for IBTR increased as the observation period lengthened (median follow-up: ≧ 7 years [RR: 1.505; 95% CI 1.184-1.913] and ≧ 10 years [RR: 1.601; 95% CI 1.201-2.132], respectively). However, a qualitative meta-analysis of overall survival in three cohort studies found no evidence to suggest a deterioration in overall survival in patients with BCS. CONCLUSIONS: The present study demonstrated that BRCA-mutation carriers with BCS have a higher risk of IBTR, which tended to persist for a long period and become more apparent with longer observation.

The Role of Cardio-Ankle Vascular Index as a Predictor of Mortality in Patients on Maintenance Hemodialysis.

AIM: Mortality rate of maintenance hemodialysis patients is known to be high. Cardio-ankle vascular index (CAVI) is an index reflecting the proper stiffness of the arterial tree from the origin of the aorta to the ankle. We aimed to clarify the utility of CAVI as a predictor of mortality in hemodialysis patients. The roles of age and nutritional conditions on survival were also examined. METHODS: We followed 242 patients undergoing hemodialysis for 6 consecutive years. Data from 209 patients (mean age was 60 ± 11 years) excluding those with ankle-brachial index <0.90 were then analyzed. CAVI and heart to ankle pulse wave velocity (haPWV) were measured using Vasera 1500. RESULTS: Thirty-eight hemodialysis patients who died during the 6-year period had higher age, cardiothoracic ratio (CTR), CAVI, and haPWV, and lower diastolic blood pressure, albumin, phosphate, and calcium phosphate product. The Kaplan-Meier curves for cumulative survival among the tertile groups showed that the mortality rate was higher in the highest tertile (T3) compared to T1/T2 for both CAVI and haPWV. Receiver operating characteristic (ROC) analysis revealed that CAVI had better discriminatory power for all-cause mortality compared to haPWV. In the Cox-proportional hazards analyses, 1 SD increase in both parameters contributed independently to all-cause mortality [CAVI: HR 1.595 (95% CI 1.108-2.297), haPWV: HR 1.695 (95% CI 1.185-2.425)], as well as age and CTR. Both parameters above the cut-offs estimated in the ROC analysis (CAVI ≥ 9.2, haPWV ≥ 8.9) also had independent contributions to mortality. CONCLUSION: Through the 6 consecutive years of follow-up in 209 HD patients, increased CAVI might represent a major modifiable risk factor for all-cause mortality. Further research is needed to examine whether CAVI-lowering interventions contribute to improved prognosis.

Physician's knowledge, attitudes and practice pattern for breast cancer diagnosed during pregnancy: a survey among breast care specialists in Japan.

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.

Taxane-induced sensory peripheral neuropathy is associated with an SCN9A single nucleotide polymorphism in Japanese patients.

BACKGROUND: Sodium channels located in the dorsal root ganglion, particularly Nav1.7 and Nav1.8, encoded by SCN9A and SCN10A, respectively, act as molecular gatekeepers for pain detection. Our aim was to determine the association between TIPN and SCN9A and SCN10A polymorphisms. METHODS: Three single nucleotide polymorphisms (SNPs) in SCN9A and two in SCN10A were investigated using whole-genome genotyping data from 186 Japanese breast or ovarian cancer patients classified into two groups as follows: cases that developed taxane-induced grade 2-3 neuropathy (N = 108) and controls (N = 78) with grade 0-1 neuropathy. Multiple logistic regression analyses were conducted to evaluate associations between TIPN and SNP genotypes. RESULTS: SCN9A-rs13017637 was a significant predictor of grade 2 or higher TIPN (odds ratio (OR) = 3.463; P = 0.0050) after correction for multiple comparisons, and precision was improved when only breast cancer patients were included (OR 5.053, P = 0.0029). Moreover, rs13017637 was a significant predictor of grade 2 or higher TIPN 1 year after treatment (OR 3.906, P = 0.037), indicating its contribution to TIPN duration. CONCLUSION: SCN9A rs13017637 was associated with the severity and duration of TIPN. These findings are highly exploratory and require replication and validation prior to any consideration of clinical use.

Atypical femoral fracture in patients with bone metastasis receiving denosumab therapy: a retrospective study and systematic review.

BACKGROUND: While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF). While AFF has been reported in patients with osteoporosis receiving denosumab, data are scarce in the context of AFF occurring in patients with bone metastasis receiving monthly denosumab therapy. METHODS: To analyze the incidence of AFF in patients with bone metastasis, we reviewed the medical records of patients who had received monthly denosumab (120 mg) treatment from May 2012 to June 2017 at any of the three participant institutions. RESULTS: The study population consisted of 277 patients who had received a median of 10 doses (range, 1-79) of denosumab. Five patients were diagnosed as having AFF or symptomatic atypical femoral stress reaction (AFSR) needing surgical intervention, representing an incidence rate of 1.8% (95% confidence interval, 0.77-4.2). These patients had received 15, 45, 45, 46 or 47 doses of denosumab, respectively. Four of the patients had received prior zoledronic acid treatment. The results of our analysis suggested that long-term use of denosumab, especially for more than 3.5 years, and prior use of zoledronic acid were risk factors for the development of AFF. CONCLUSIONS: We found the AFF events in 5 patients (1.8%) among 277 cancer patients who had received monthly denosumab (120 mg) treatment. Long-term denosumab treatment and prior zoledronic acid treatment were identified as risk factors for the development of AFF.

Impact on disease-free survival of the duration of ovarian function suppression, as postoperative adjuvant therapy, in premenopausal women with hormone receptor-positive breast cancer: a retrospective single-institution study.

INTRODUCTION: Although tamoxifen (TAM) plus ovarian function suppression (OFS) is considered as a standard adjuvant treatment for premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not yet been established. This retrospective study was designed to assess the duration of OFS and the impact of the duration of OFS on the DFS in these patients. METHODS: We retrospectively reviewed the data of premenopausal patients with breast cancer who received TAM + OFS (goserelin or leuprorelin) as adjuvant therapy between February 2004 and June 2015. The primary analysis was a comparison of the disease-free survival (DFS) between patients who received OFS for 3 years or less (OFS ≤ 3 years group) and those who received OFS for longer than 3 years (OFS > 3 years group). RESULTS: We analyzed the data of 215 premenopausal patients diagnosed as having hormone receptor-positive breast cancer. A propensity score-matched model showed the absence of any significant difference in the DFS between the OFS ≤ 3 years group and OFS > 3 years group (6-year DFS rate, 93.2 vs. 94.0%; log-rank test p = 0.767). CONCLUSIONS: Our data showed that among premenopausal women with hormone receptor-positive breast cancer who received TAM + OFS as adjuvant endocrine therapy, there was no significant difference in the DFS between the OFS ≤ 3-year group and OFS > 3-year group. A randomized trial is needed to establish the optimal duration of OFS for these patients.

Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese.

PURPOSE: Whether age and inter-individual variability of pharmacogenetics are risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive. This study was conducted to evaluate the influence of previously investigated single nucleotide polymorphisms (SNPs) and age, using genotype data from a prospective study of paclitaxel-related toxicity in Japanese patients with breast cancer. METHODS: Peripheral blood mononuclear cells from 127 Japanese women with breast cancer who received weekly adjuvant paclitaxel were used to genotypes SLCO1B3 T334G (rs4149117), CYP2C8 A1196G (rs10509681), ABCB1 C1236T (rs1128503), ABCB1 G2677T/A (rs2032582), and ABCB1 C3435T (rs1045642). Genotypic and clinical factors were investigated for associations with PIPN. RESULTS: Of the five SNPs evaluated, no SNPs were significantly associated with grade 2 or higher PIPN. However, ABCB1 1236 TT showed a trend to associate with grade 2 or higher PIPN compared to ABCB1 CT/CC (odds ratio 2.1, 95% CI 0.991-4.548, p = 0.051). In subgroup analysis, patients ≥60 years old with an ABCB1 1236 TT had a higher incidence of ≥grade 2 PIPN compared to patients with CT or CC genotype (p = 0.027). On multivariable analysis, age ≥60 years and the ABCB1 1236 TT showed a significant association with ≥grade 2 PIPN (p = 0.005 and p = 0.034, respectively). CONCLUSIONS: ABCB1 1236 TT genotype and older age might be a predictor of PIPN, which diminishes quality of life of cancer survivors.

Clinicopathological predictive factors for ipsilateral and contralateral events following initial surgery to treat ductal carcinoma in situ.

BACKGROUND: Ipsilateral breast tumor recurrence (IBTR) after partial breast resection and contralateral breast tumor recurrence (CBTR) have been shown to occur relatively frequently in patients with ductal carcinoma in situ (DCIS). However, there is only limited data from Japanese institutes to support this. METHODS: Of 301 consecutive DCIS patients, 179 patients underwent a mastectomy, and the other 122 underwent partial resection in the National Cancer Center Hospital, Tokyo, with a median follow-up period of 2,106 days. We reviewed clinicopathological parameters including age, menopausal status, body mass index, family history (FH) of breast cancer, tumor size, histological subtype, nuclear grade (NG), hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, treatment, and the surgical margin status of partially resected specimens. The risk associated with each of these parameters for IBTR in 122 patients who underwent partial resections, and for CBTR in a total of 301 patients were calculated using Cox proportional hazard general linear models. RESULTS: Of the 122 patients who underwent partial breast resection, IBTR occurred in 7 (5.7%). The risk of IBTR was higher or tended to be higher in younger patients or those with lower NG tumors, but did not change significantly with respect to margin status or irradiation. Amongst the entire cohort of 301 patients, CBTR occurred in 18 cases (6.0%). CBTR occurred significantly more frequently in patients with a FH of breast cancer and with HR+/HER2- subtype tumors by univariate analyses, and tumor subtype was an independent risk factor for CBTR by multivariate analysis. CONCLUSIONS: The local recurrence rate was low following partial resection of DCIS. Younger age was a risk factor for IBTR, whereas the HR+/HER2- tumor subtype and a FH of breast cancer were risk factors for CBTR.

[Moving forward to overcome infertility after breast cancer treatment].

An increase in the number of young women with breast cancer together with improved outcomes after breast cancer treatments have lead healthcare providers and society in general to become more aware of fertility preservation. The potential for infertility caused by cancer treatment is one of the most important quality-of-life issues for young women with cancer, and guidelines and decision-aids to support those who wish to have children after cancer treatment have been developed. To move forward, a prospective database needs to be developed in order to overcome safety concerns, and to allow network building among breast oncologists and reproductive specialists. A multidisciplinary team is also urgently needed to address psychosocial and ethical issues.

Perception and needs of reproductive specialists with regard to fertility preservation of young breast cancer patients.

BACKGROUND: Treatment-related infertility is one of the important quality-of-life issues in young breast cancer (YBC) patients. Although existing guidelines recommend supporting fertility preservation (FP) of YBC, the perceptions of reproductive specialists (RS) has not been evaluated. We investigated the perceptions and needs of RS with regard to FP of YBC patients. METHODS: A cross-sectional survey was sent to 423 certified RS registered to the Japan Society for Reproductive Medicine to self-evaluate their perceptions and needs regarding FP in YBC patients. RESULTS: Two hundred RS (47 %) responded to the survey. 99 % responded that RS should be engaged in FP of YBC patients. 88 % responded that they would like to treat YBC patients, while 46 % responded that cancer treatment is more important than childbirth, even when the patient is recurrence-free 5 years after primary treatment. Respondents affiliated to private clinics were more likely to accept both fertilized and unfertilized egg preservation than those affiliated with academic or general hospitals. 70 % responded that they were anxious about treating breast cancer patients: concerns regarding a greater or unknown risk of recurrence (66 %), insufficient knowledge about breast cancer (47 %), and lack of a patient's spouse/partner (24 %) were identified as major barriers in supporting FP for YBC patients. CONCLUSIONS: RS recognize the need for FP in YBC patients and are willing to participate in their care. Affiliation of RS was related to a positive attitude to egg preservation. Various concerns regarding FP among RS indicate the need for evidence that supports the safety of FP, inter-disciplinary communication, and practice guidelines.