Clinicopathological and ultrasound characteristics of breast cancer in BRCA1 and BRCA2 mutation carriers.

PURPOSE: BRCA1 and BRCA2 tumors exhibit different characteristics. This study aimed to assess and compare the ultrasound findings and pathologic features of BRCA1 and BRCA2 breast cancers. To our knowledge, this is the first study to examine the mass formation, vascularity, and elasticity in breast cancers of BRCA-positive Japanese women. METHODS: We identified patients with breast cancer harboring BRCA1 or BRCA2 mutations. After excluding patients who underwent chemotherapy or surgery before the ultrasound, we evaluated 89 cancers in BRCA1-positive and 83 in BRCA2-positive patients. The ultrasound images were reviewed by three radiologists in consensus. Imaging features, including vascularity and elasticity, were assessed. Pathological data, including tumor subtypes, were reviewed. RESULTS: Significant differences in tumor morphology, peripheral features, posterior echoes, echogenic foci, and vascularity were observed between BRCA1 and BRCA2 tumors. BRCA1 breast cancers tended to be posteriorly accentuating and hypervascular. In contrast, BRCA2 tumors were less likely to form masses. In cases where a tumor formed a mass, it tended to show posterior attenuation, indistinct margins, and echogenic foci. In pathological comparisons, BRCA1 cancers tended to be triple-negative subtypes. In contrast, BRCA2 cancers tended to be luminal or luminal-human epidermal growth factor receptor 2 subtypes. CONCLUSION: In the surveillance of BRCA mutation carriers, radiologists should be aware that the morphological differences between tumors are quite different between BRCA1 and BRCA2 patients.

Prognostic effect of subsequent childbirth after the diagnosis of breast cancer using propensity score matching analysis.

BACKGROUND: Among younger patients, one of the important concerns is whether they can give birth safely. Although previous studies have investigated this topic, many aspects remain unclear owing to potential biases. We aimed to evaluate the prognostic effect of subsequent childbirth after the diagnosis using propensity score matching. METHODS: A single-center retrospective cohort study was conducted. This study included patients aged ≤ 45 years, diagnosed with breast cancer between 2005 and 2014. Patients with and without subsequent childbirth were assigned to the childbirth and non-childbirth cohorts, respectively. Relapse-free survival (RFS) and overall survival (OS) of the childbirth cohort were compared with those of the non-childbirth cohort. The covariates in the propensity score model included age, tumor size, node status, number of preceding childbirths before the diagnosis, estrogen receptor, and human epidermal growth factor receptor 2 status. RESULTS: 104 patients with childbirth and 2250 without childbirth were assigned to the respective cohorts. At a median follow-up of 82 months, the childbirth cohort showed a significantly longer RFS than the non-childbirth cohort (HR = 0.469 [0.221-0.992]; p = 0.047). There was no significant difference in the OS (HR = 0.208 [0.029-1.494]; p = 0.119). After matching, subsequent childbirth was not significantly associated with RFS (HR = 0.436 [0.163-1.164], p = 0.098) and OS (HR = 0.372 [0.033-4.134], p = 0.402). CONCLUSIONS: Subsequent childbirth was not associated with an increased risk of relapse and mortality. It is important to make younger patients aware of these novel findings and aid them in their decision-making.

Classification of Local Recurrence After Nipple-Sparing Mastectomy Based on Location: The Features of Nipple-Areolar Recurrence Differ from Those of Other Local Recurrences.

BACKGROUND: Little information is available about the clinical and pathologic characteristics of local recurrence (LR) after nipple-sparing mastectomy according to the locations of LR. METHODS: This study classified 99 patients into the following two groups according to the location of LR after nipple-sparing mastectomy: nipple-areolar recurrence (NAR) group and other locations of LR (oLR) group. The study evaluated whether the location of LR was associated with disease-free survival (DFS) after LR resection. RESULTS: For about half of the patients (44.4 %) with NAR, the primary cancer was estrogen receptor (ER)-negative and human epidermal growth factor receptor 2 (HER2)-positive. Conversely, in most of the patients with oLR (79.2 %), the primary cancer was ER-positive and HER2-negative. Among the LR tumors, the frequency of noninvasive carcinoma in the NAR tumors was significantly higher than in the oLR tumors (51.9 % vs 4.2 %, respectively). During a median follow-up period of 46 months, the location of LR was not associated with DFS after LR. In the NAR group, the presence or absence of LR tumor invasiveness was the only factor associated with DFS. In the oLR group, age at primary surgery was the only factor associated with DFS. CONCLUSION: This multi-institutional retrospective study demonstrated that the features of NAR, such as the characteristics of the primary and recurrent tumors and the prognostic factors after LR resection, were quite different from those of oLR.

Relationship Between Breast Density, Breast Cancer Subtypes, and Prognosis.

BACKGROUND: In the United States, Europe, and Asia, a consensus has been reached that there is a higher risk of breast cancer in high density breasts. However, there are some contrary reports that suggest the absence of an association between breast composition and breast cancer subtype; thus, there is conflicting evidence. The purpose of this study was to investigate trends in the incidence of breast cancer subtypes according to breast composition and analyze the survival rates in Japanese women. PATIENTS AND METHODS: Between 2007 and 2008, 1258 Japanese patients with invasive breast cancer who underwent mammography and obtained a pathological diagnosis in our institution were included in the study. We compared cancer subtypes with breast composition types (dense and non-dense breast), and classified them based on initial mammography findings. Information on 5- and 10-year survival rates was collected by chart review for patients with dense and nondense breasts. Statistical analysis was performed using the Pearson's chi-square test for breast composition and cancer subtype. The effect of breast composition on mortality was examined using a multivariate Cox proportional hazards model, and adjusted hazard ratios were calculated. RESULTS: No significant difference was found between breast cancer subtype and breast composition (P = .08). Five-year (log-rank test, P = .09) and 10-year (log-rank test, P = .31) survival rates were not significantly different between breast composition types. CONCLUSION: There was no significant association between breast composition and cancer subtypes. There was also no significant difference in the prognosis between patients with and without dense breasts.

Long-Term Oncologic Safety of Nipple-Sparing Mastectomy With Immediate Reconstruction.

BACKGROUND: We assessed the long-term oncologic safety of nipple-sparing mastectomy (NSM) compared to skin-sparing mastectomy (SSM) for primary breast cancer patients with immediate reconstruction. PATIENTS AND METHODS: Data of stage 0-III primary breast cancer patients undergoing NSM (n = 190) or SSM (n = 729) from June 2006 to December 2012 were retrospectively collected. Nipple-tumor distance (NTD) was measured on pretreatment mammography, magnetic resonance imaging, or ultrasonography findings. NSM patients with NTD < 1 cm were excluded. Locoregional recurrence (LRR) rates were compared between groups. Disease-free survival (DFS) and overall survival (OS) according to surgical procedure were assessed. RESULTS: The median (range) follow-up period for NSM and SSM was 71 (10-131) months and 79 (9-140) months, respectively. LRR developed in 11 patients with invasive ductal carcinoma (5.8%) for NSM and 44 (42 in patients with invasive ductal carcinoma and 2 in patients with ductal carcinoma-in-situ) (6.0%) for SSM. Hormone receptor and HER2 status were not associated with LRR in either group. DFS and OS rates did not differ between groups (DFS: 89.3% for NSM, 89.3% for SSM, P = .87; OS: 98.4% for NSM, 94.5% for SSM, P = .43). CONCLUSION: NSM with immediate reconstruction was as safe as SSM for primary breast cancer with respect to prognosis and local control, regardless of the presence of invasive carcinoma or breast cancer subtype.

Response and Prognosis of Docetaxel and Cyclophosphamide as Neoadjuvant Chemotherapy in ER+ HER2- Breast Cancer: A Prospective Phase II Study.

BACKGROUND: Although a docetaxel and cyclophosphomide (TC) regimen without anthracycline as adjuvant therapy became one of the standard regimens especially for ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer, the efficacy of TC as neoadjuvant chemotherapy (NAC) is not known. We conducted the prospective trial to assess the efficacy of a TC regimen in the neoadjuvant setting for stage II to III ER+/HER2- primary breast cancer. PATIENTS AND METHODS: A TC regimen that included 75 mg/m2 of docetaxel and 600 mg/m2 of cyclophosphamide for 4 cycles every 3 weeks was administered as NAC. Primary endpoints are the rate of clinical response (clinical partial response and clinical complete response) and pathologic complete response; secondary endpoints are the disease-free survival and overall survival rates. RESULTS: Thirty (71.4%) of 42 tumors had clinical response. No patient achieved pathologic complete response. At the median follow-up period of 105.2 months (range, 12.1-119.7 months), the disease-free survival rate was 81.6%, and the distant disease-free survival rate was 86.8%. In terms of survival, only 1 patient died during the study period. The overall survival rate was 97.4% during the study period. Patients who developed distant recurrence had a trend to have progesterone receptor-negative or weakly positive compared with those who did not develop any recurrence (85.7% vs. 45.2%; P = .05). CONCLUSIONS: Our prospective study showed that a TC regimen as NAC achieved a high clinical response rate in stage II to III ER+/HER2- breast cancer. A TC regimen without anthracycline as NAC might be one of the options for patients with ER+/HER2- breast cancer without high-risk factors including progesterone receptor negativity.

A nomogram for predicting locoregional recurrence in primary breast cancer patients who received breast-conserving surgery after neoadjuvant chemotherapy.

BACKGROUND: We sought to develop and validate a predictive model of locoregional recurrence (LRR) in patients who underwent breast-conserving therapy (BCT) after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: The clinicopathological characteristics of 520 consecutive primary breast cancer patients with residual tumor who underwent BCT after NAC between 2001 and 2008 were evaluated. Predictive variables of LRR were determined using a multivariate Cox proportional hazards model. The model was validated for discrimination and calibration by bootstrap re-sampling. RESULTS: At a median follow-up period of 51 months, 64 patients (12%) had developed LRR. Clinical stage T3 or T4, lymphovascular invasion, nuclear grade >3, and ≥4 positive lymph nodes metastasis were positively correlated with LRR. The nomogram for predicting LRR developed by using these four-clinicopathologic variables demonstrated high concordance. Patients with score 0-1 derived by the prediction model had significantly low LRR rate compared with patients with score 2 or higher (P < 0.001). CONCLUSIONS: This nomogram may be useful to predict LRR in primary breast cancer patients who underwent BCT after NAC with high reproducibility. This model is useful to conduct a study-identifying patients who may need an additional treatment to standard adjuvant therapy because of a high probability of LRR.

Sentinel node biopsy after neoadjuvant chemotherapy in cytologically proven node-positive breast cancer.

INTRODUCTION: Several studies have assessed the feasibility of sentinel lymph node biopsy (SLNB) after NAC in patients with breast cancer, but diagnostic accuracy has varied. We prospectively evaluated the diagnostic accuracy of SLNB in detecting axillary lymph node (ALN) metastases after NAC in patients with cytologically proven positive nodes before chemotherapy. PATIENTS AND METHODS: We studied 95 breast cancer patients with cytologically proven positive nodes and a partial or complete clinical response to NAC in the breast lesions confirmed using magnetic resonance imaging. Patients then underwent SLNB followed by ALN dissection. The identification rate of sentinel lymph nodes (SLNs) and the false negative rate of nodal metastases were assessed. Subgroup analysis was conducted according to several clinical factors. RESULTS: SLNs were successfully identified in 81 (85.3%) of the 95 patients. Among these 81 patients, 51 (63.0%) had ALN metastases on final pathologic examination after NAC. Eight of the 51 patients with ALN metastases had negative results on SLNB (false negative rate, 15.7%). Univariate analysis indicated that the false negative rate was significantly lower only in the HER2-negative group (P = .003). CONCLUSION: SLNB after NAC did not correctly predict the presence or absence of axillary node metastases in patients with breast cancer who had cytologically proven positive nodes before NAC. However, the diagnostic accuracy might be different in cancer subtypes, therapeutic effect of chemotherapy, or sentinel lymph node status after chemotherapy. Well-powered studies are needed to confirm diagnostic accuracy of SLNB after NAC according to subgroup in patients with breast cancer.

Current strategy for triple-negative breast cancer: appropriate combination of surgery, radiation, and chemotherapy.

Triple-negative breast cancer (TNBC) often grows rapidly and has poor outcomes, with a high recurrence rate and a short interval between recurrence and death. New molecular-targeted therapies are being developed, but cannot be used at present. Other strategies for the management of TNBC are needed. TNBC is characterized by an expanding growth pattern without extensive intraductal spread and is a good candidate for breast-conserving therapy (BCT) with sufficient margins. The local recurrence rate after BCT is not high as those of other subtypes of breast cancer. In contrast, the regional recurrence rate is higher in TNBC than in other subtypes. Sentinel node biopsy and axillary resection should therefore be performed with the upmost caution. Radiation therapy has been shown to be useful for the management of TNBC. Radiation therapy of the chest wall after mastectomy and the regional area as well as the breast after breast-conserving surgery should be considered. Chemotherapy is the only systemic treatment available for TNBC. In our hospital, a combination of cyclophosphamide, epirubicin, and 5-fluorouracil (FEC) followed by docetaxel (DTX) or DTX followed by FEC has been used to treat tumors more than 2 cm in diameter or node-positive breast cancer. Neoadjuvant chemotherapy with these regimens has produced pathological complete response (pCR) rates higher than 20% in patients with TNBC, regardless of the specific order of agents. Tumors tend to shrink towards their center and can be a good indication for BCT. After 3 years, a pCR is associated with good outcomes, whereas a non-pCR sometimes results in distant recurrence, even when residual tumor is minimal. Patients should be closely observed during neoadjuvant chemotherapy. If there is any evidence of tumor progression, the chemotherapeutic regimen should be modified or surgery performed, without losing the opportunity to administer potentially effective treatment. Several studies indicate that neoadjuvant chemotherapy with platinum-based regimens is effective for TNBC and is thus an important treatment option. We have used regimens combining epirubicin and cyclophosphamide (EC) to treat tumors 1-2 cm in diameter without node metastasis, and 2 of 21 patients presented with distant metastases (disease-free interval, 2 and 5 years). We have not used systemic therapy to treat tumors 1 cm or less in diameter without node metastasis, and all 8 patients are alive without recurrence for more than 4 years. After distant recurrence in patients with TNBC, the same chemotherapeutic agents as those used for other subtypes of breast cancer are recommended, but the response is often disappointing, leading to poor outcomes. TNBC presents with different clinical features from other subtypes. The treatment strategy should be selected according to the characteristics of the specific subtype of breast cancer.