Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts.

PURPOSE: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. EXPERIMENTAL DESIGN: The study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. RESULTS: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSIONS: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649-57. ©2016 AACR.

Impact of neoadjuvant chemotherapy on axillary nodal involvement in patients with clinically node negative triple negative breast cancer.

BACKGROUND: We evaluated the impact of Neoadjuvant Chemotherapy (NAC) versus primary surgery (PS) on axillary disease burden/surgery in clinically node negative Triple Negative Breast Cancer (TNBC). METHODS: Two hundred forty-three Stage I-III TNBC patients have enrolled on an IRB approved multisite prospective registry. Clinical and treatment information was collected. RESULTS: One hundred fifty-five patients with clinically node negative TNBC were identified. 47%, 49%, and 4% of patients had T1, T2, and T3 disease, respectively. Patients underwent PS (103/155, 66%) or NAC (52/155, 34%) at the discretion of treating physicians. 17% of PS and 0% of NAC patients were node positive at surgery (P=0.006). For T2 disease, 32% of PS and 0% of NAC patients were node positive at surgery (P=0.001). NAC patients had a lower chance of positive SLNB (0% vs. 12%, P=0.004) and undergoing ALND (2% vs. 22%, P=0.001) than PS patients. CONCLUSION: In this clinically node negative TNBC cohort, all NAC-treated patients were node negative at surgery, whereas 17% of PS patients had involved axillary nodes. NAC should be considered for clinically node negative TNBC to reduce the extent of axillary surgery even if breast conservation is not planned.

Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing.

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged ≤60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I-IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African-American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (≤50 years), 11.4 % (51-60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p = .0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC.

Commentary on the Canadian National Breast Screening study.

In the setting of the 25-year follow-up of the Canadian National Breast Screening Study, the Society of Surgical Oncology continues to endorse mammographic screening for women beginning at 40 years of age, while acknowledging that mammography has both risks and benefits. Further investigation is warranted to develop better screening methods and to determine optimal screening schedules for women based on their risk of future breast cancer and their imaging characteristics.

A comparison of prognostic tumor markers obtained on image-guided breast biopsies and final surgical specimens.

BACKGROUND: This study was initiated to determine whether tumor markers obtained on image-guided breast biopsy specimens provide accurate prognostic information for women with invasive breast cancer. METHODS: Prognostic tumor markers on preoperative image-guided biopsy and final surgical specimens were compared in 44 patients with invasive breast cancer. RESULTS: Progesterone receptor (PR) discordance was 18%. In 87% of PR discordant cases, the image-guided biopsy was positive and the final specimen was negative (P = 0.03). Tumor grade was discordant in 36% of patients Discordance for estrogen receptor (ER) = 2%; MIB-1 = 18%; Her2/neu = 9%; EGFR = 10%; p53 = 9%; and bcl-2 = 0%. The discordance for these markers was random and did not reach statistical significance. CONCLUSION: Image-guided core needle biopsies provide reliable information for the majority of prognostic tumor makers. A positive progesterone receptor is significantly more likely to be determined by core biopsy rather than the final surgical specimen. Tumor grade should be based upon the final surgical specimen whenever possible.