High incidence of germline BRCA mutation in patients with ER low-positive/PR low-positive/HER-2 neu negative tumors.

BACKGROUND: The 2015 National Comprehensive Cancer Network guidelines recommend that genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple-negative breast cancer (TNBC). As a result of the 2010 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast cancer, patients with breast cancers that are estrogen receptor (ER) or progesterone receptor (PR) low-positive (1%-9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low-positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in undertesting for BRCA mutations. METHODS: A prospectively maintained research database of breast cancer patients evaluated at The University of Texas MD Anderson Cancer Center between 2004 and 2014 was reviewed; 314 patients were identified with HER2/neu-negative breast cancers expressing ER and PR <10% with known BRCA mutation status. RESULTS: Three hundred fourteen patients had breast cancers expressing ER and PR <10%; 238 (75.8%) had HR-negative cancers (<1% ER and PR), and 76 (24.2%) had HR-low-positive cancers (1%-9% ER and/or PR). Among patients with HR-negative tumors, 86 of 238 (36.1%) had a BRCA1/2 mutation, whereas in the HR-low-positive group, 30 of 76 (39.5%) had a BRCA1/2 mutation. In multivariate analysis, HR status (<1% vs 1%-9%) was not significantly associated with BRCA1/2 mutations. CONCLUSIONS: The incidence of BRCA1/2 mutations is similar in patients with HR-low-positive breast cancer and patients with HR-negative breast cancer. Genetic counseling and BRCA testing should be offered to patients under age 60 who have HR-low-positive breast cancers. Cancer 2015;121:3435-43. © 2015 American Cancer Society.

Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer.

PURPOSE: Cancer-related fatigue (CRF) is the most common symptom in patients with advanced cancer. The primary objective of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF. PATIENTS AND METHODS: Patients with advanced cancer with ≥ three CRF-related symptoms (ie, fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days. The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale from baseline to day 15. Secondary outcomes included anorexia, anxiety, depression, and symptom distress scores. RESULTS: A total of 84 patients were evaluable (dexamethasone, 43; placebo, 41). Mean (± standard deviation) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group (9 [± 10.3] v 3.1 [± 9.59]; P = .008). The improvement in FACIT-F total quality-of-life scores was also significantly better for the dexamethasone group at day 15 (P = .03). The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group (P = .013, respectively). No differences were observed for ESAS overall symptom distress (P = .22) or psychological distress score (P = .76). Frequency of adverse effects was not significantly different between groups (41 of 62 v 44 of 58; P = .14). CONCLUSION: Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.

Exemestane in the prevention setting.

Aromatase inhibitors are well-established therapies in the neoadjuvant, adjuvant and metastatic settings for breast cancer. In adjuvant trials, this class of drugs has shown preventative properties by decreasing the rate of contralateral breast cancer. Recently, the National Cancer Institute of Canada Clinical Trials Group MAP.3 study evaluated exemestane as a breast cancer prevention agent for women with specified higher risks of developing breast cancer. We review the history of exemestane and evaluate the available evidence of its use for breast cancer prevention.

Aromatase inhibitors and breast cancer prevention.

INTRODUCTION: Endocrine therapy with selective estrogen receptor modulators (SERMs) has been the mainstay of breast cancer prevention trials to date. The aromatase inhibitors, which inhibit the final chemical conversion of androgens to estrogens, have shown increased disease-free survival benefit over tamoxifen in patients with primary hormone receptor-positive breast cancer, as well as reducing the risk of developing contralateral breast cancers. The aromatase inhibitors are being actively evaluated as prevention agents for women with a history of ductal carcinoma in situ as well as for women who are considered to be at high risk for developing primary invasive breast cancer. AREAS COVERED: This review evaluates the available prevention data, as evidenced by the decrease in contralateral breast cancers, when aromatase inhibitors are used in the adjuvant setting, as well as the emerging data of the aromatase inhibitors specifically tested in the prevention setting for women at high risk. EXPERT OPINION: Exemestane is a viable option for breast cancer prevention. We continue to await further follow-up on exemestane as well as other aromatase inhibitors in the prevention setting for women at high risk of developing breast cancer or with a history of ductal carcinoma in situ.

Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience.

PURPOSE: To compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. PATIENTS AND METHODS: A total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. RESULTS: Fifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P < .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] = 3.16; 95% CI, 1.55 to 6.42; P = .002), estrogen receptor (ER) negativity (OR = 1.96; 95% CI:1.05 to 3.65; P = .03) and concurrent trastuzumab use (OR = 4.18; 95% CI, 2.04 to 8.57; P < .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P = .001) and OS (P = .01) rates than patients who did not. CONCLUSION: BRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers.