Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population.

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction.

Multidisciplinary treatment for locally advanced breast cancer with internal mammary lymph node metastasis in an elderly patient.

Internal mammary lymph node (IMLN) metastasis is one of the important prognostic indicators in breast cancer. However, the management for IMLN metastasis is not established. The dissection for IMLN metastasis is not recommended in the National Comprehensive Cancer Network guidelines version3. 2015. Furthermore, radiotherapy including IMLN region and biopsy have attendant risks and hence should be performed with caution. Here, we describe our experience of multidisciplinary treatment for locally advanced breast cancer with IMLN metastasis in an elderly patient. Core-needle biopsy of the breast tumor histologically diagnosed the tumor as estrogen receptor positive, progesterone receptor positive, human epidermal growth factor receptor-2 negative, and high Ki-67 labeling index. IMLN swelling was detected by ultrasonography and breast cancer metastasis was diagnosed by fine-needle aspiration cytology. The patient underwent mastectomy and axillary lymph node dissection, followed by postmastectomy radiation therapy. Systemic therapy using tegafur plus uracil (UFT®; Taiho Pharmaceutical Co., Ltd, Tokyo, Japan) and letrozole was beneficial treatment for disease control.