In a study reported in Journal of Clinical Oncology, Tomasz Huzarski, MD, PhD, of Pomeranian Medical University, Szczecin, Poland, and colleagues from the Polish Hereditary Breast Cancer Consortium assessed survival among women with early-onset breast cancer with and without BRCA1 mutation and identified prognostic factors among those with BRCA1-positive disease. They found that 10-year overall survival was similar in BRCA1-positive and BRCA1-negative disease. Positive lymph node status was a predictor of increased mortality and oophorectomy a predictor of reduced mortality in women with BRCA1-positive disease.
Study Details
In the study, 3,345 women aged ≤ 50 years with stage I to III invasive breast cancer from 17 affiliated centers in Poland were tested for three founder mutations in BRCA1 (5382insC, C61G, and 4153delA). Dates of diagnosis were between 1996 and 2006. Diagnosis had to be pathologically confirmed by core or fine-needle aspiration biopsy. Patients with a previous diagnosis of contralateral breast cancer or another cancer were excluded from the analysis. Information on tumor characteristics and treatments received was retrieved from medical records, and dates of death were obtained from the vital statistics registry.
Survival analysis was conducted using a Cox proportional hazards model, with covariates including BRCA1 status, tumor size (four categories), nodal status (negative vs positive), estrogen receptor (ER) status (positive vs negative), progesterone receptor (PR) status (positive vs negative or missing), HER2 status (positive vs negative or missing), tamoxifen use (yes vs no), and chemotherapy. Oophorectomy (yes vs no) was a time-dependent covariate.
Mutation carriers were diagnosed at an earlier age (42 vs 44 years, P < .001) and were less likely to have ER-positive (16% vs 62%, P < .001), PR-positive (20% vs 70%, P < .001), and HER2-positive (6.5% vs 21%, P < .001) disease, more likely to have triple-negative disease (69% vs 13%, P < .001), and more likely to have had oopherectomy (50% vs 14%), with most (108 of 115 mutation carriers) having the procedure after breast cancer diagnosis.
Survival Analysis
Mean follow-up was 7.4 years. The 10-year overall survival rate was 80.9% for mutation carriers vs 82.2% for noncarriers (hazard ratio [HR] on univariate analysis = 1.14, P = .42). After adjustment for other prognostic features, the hazard ratio for mutation carriers became significant (1.81, P = .002). Among the subgroup of 485 women with triple-negative cancer, overall survival for mutation carriers was not inferior to that of noncarriers.
Ten-year overall survival was 84.1% among BRCA1 carriers with small (> 2 cm) tumors, 89.9% for node-negative patients, and 68.6% for node-positive patients. Among carriers with tumors ≤ 1 cm, 27.5% were node-positive, and 10-year overall survival was 81.8% in these patients. Patients with cancers that were either node-positive or > 5 cm constituted a high-risk group; 44% of the mutation carriers were in this group and had 10-year overall survival of 68.2%.
Predictive Factors
Among all patients, factors significantly predictive of survival on multivariate analysis in addition to BRCA1-positive status were PR-positive status (HR = 0.63, P < .001), HER2-positive status (HR = 1.68, P < .001), tumor size ≥ 5 cm (HR = 2.28, P < .001), node-positive disease (HR = 3.04, P < .001), and oopherectomy (HR = 0.58, P = .03).
Among mutation carriers, multivariate analysis showed that positive lymph node status was a predictor of poorer survival (HR = 4.1, P < .001) and oopherectomy was a predictor of improved survival (HR = 0.30, P = .01). Oophorectomy was associated with a smaller, nonsignificant benefit in noncarriers (HR = 0.83, P = .52). The hazard ratio associated with oophorectomy among mutation carriers was similar when patients with oophorectomy before diagnosis were excluded from analysis.
Factors not significantly associated with overall survival for mutation carriers on multivariate analysis included year of birth, age at diagnosis, ER, PR, and HER2 status, tumor size, and receipt of chemotherapy.
Effect of Chemotherapy
The hazard ratio for survival with use of chemotherapy in mutation carriers was 0.79 (P = .66) on univariate analysis and 0.42 (P = .18) on multivariate analysis. Only 18 women who were carriers of a BRCA1 mutation received no chemotherapy. Among noncarriers, the hazard ratio associated with chemotherapy use was 1.56 (95% confidence interval [CI] = 0.88–2.78).
The interaction between chemotherapy use and survival by mutation status was significant (P = .01). Among mutation carriers treated with adjuvant chemotherapy, the hazard ratio associated with CMF (cyclophosphamide, methotrexate, and fluorouracil) vs an anthracycline-based regimen was 0.67 (95% CI = 0.31–1.45) on univariate analysis and 0.81 (P = .62) on multivariate analysis.
The investigators concluded, “The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.” ■
Disclosure: The study authors reported no potential conflicts of interest.
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