Comparing survival outcomes between breast-conserving surgery and mastectomy among BRCA carriers and non-carriers

Abstract

Background/Objective: Breast cancer is the most common cancer and third leading cause of cancer deaths among females in Hong Kong. Hereditary cancers account for 5-10% of breast cancers, of which, 80% of hereditary breast cancer is due to BRCA1 and BRCA 2 mutations. The aims of management of breast cancer in BRCA mutation carriers are threefold - curative, risk reduction, and good cosmesis. Currently, controversy exists between breast-conserving surgery (BCS) and mastectomy for BRCA mutation carriers with some studies suggesting a higher ipsilateral breast cancer recurrence rate for BCS. Survival data is limited. This study aims to evaluate the survival outcomes between BCS and mastectomy among BRCA and non-BRCA mutation carriers in breast cancer patients. Methods: This is a retrospective study analyzing prospectively maintained data for BRCA carriers and non-carriers diagnosed with breast cancer who underwent genetic testing between January 1st, 2007 to December 31st, 2018 and received either a breast-conserving surgery (BCS) or mastectomy. Patients who were tested positive for BRCA 1 or 2 were included; those that were tested positive for other pathogenic mutations such as PTEN, TP53 were excluded. Stage IV disease and bilateral breast cancer patients were also excluded. Local recurrence, overall survival, cancer-specific survival, and disease-free survival were analyzed by Log-rank test. Subgroup analyses of survival between different disease stages, BRCA status, surgical option and triple-negative tumors were conducted by Log-rank test with p-values adjusted by Benjamini and Hochberg (BH) method. A Cox proportional hazards model was used to investigate the associated risk factors. Results: A total of 3080 patients were included in the analysis, with 142 BRCA mutation carriers and 2938 non-carriers. The BCS and mastectomy rates in the BRCA mutation group were 42.3% and 57.7% respectively compared to 33.8% and 66.2% in the non-carrier group (p=0.048). There was no statistical significance between the different surgical groups and BRCA carrier status regarding local recurrence rate. Log-rank test showed that a poorer disease staging showed significantly worse overall survival, cancer-specific survival, and disease-free survival (p<0.0001). In a subgroup analysis, BRCA mutation carriers with Stage I disease who received BCS or mastectomy had a worse overall survival compared to non-carrier groups (p=0.0097). This finding was similar for cancer specific survival (p=0.0031). There was no difference in survival for other disease stages, disease-free survival, or triple-negative breast cancer patients. A Cox proportional hazards model revealed that BRCA mutation status (p=0.71) and type of surgery (p=0.30) were not independent risk factors for poorer survival. Conclusions: BCS is not associated with adverse long-term survival outcomes in BRCA mutation carriers and has no survival benefits over mastectomy. The consideration for BCS should be based on surgical eligibility irrespective of genetic status. With appropriate preoperative counseling, BCS should be offered as an option to BRCA mutation carriers.