Abstract
Whether patients with breast cancer who carry a BRCA1/2 variant can safely undergo breast-conserving therapy (BCT) remains controversial. To compare survival rates after BCT vs mastectomy in BRCA1/2 variant carriers and noncarriers in a large series of unselected patients with breast cancer. In this cohort study, a large consecutive series of 8396 unselected patients with primary breast cancer underwent either BCT, mastectomy with radiotherapy, or mastectomy alone from October 1, 2003, to May 31, 2015, at the Breast Center of Peking University Cancer Hospital in China. All patients were assessed for BRCA1/2 germline variant status. Statistical analysis was performed from May 1 to September 30, 2020. The primary outcomes were breast cancer-specific survival (BCSS) and overall survival (OS); secondary outcomes included recurrence-free survival, distant recurrence-free survival, and ipsilateral breast tumor recurrence. Of these 8396 Chinese patients (8378 women [99.8% women]; mean [SD] age, 50.8 [11.4] years; 187 BRCA1 carriers, 304 BRCA2 carriers, and 7905 noncarriers), 3135 (37.3%) received BCT, 1511 (18.0%) received mastectomy with radiotherapy, and 3750 (44.7%) received mastectomy alone. After a median follow-up of 7.5 years (range, 0.3-16.6 years), both BRCA1 and BRCA2 variant carriers treated with BCT had similar rates of survival compared with those treated with mastectomy with radiotherapy (BCSS: hazard ratio [HR] for BRCA1, 0.58 [95% CI, 0.16-2.10]; P = .41; HR for BRCA2, 0.46 [95% CI, 0.15-1.41]; P = .17; OS: HR for BRCA1, 0.61 [95% CI, 0.18-2.12]; P = .44; HR for BRCA2, 0.72 [95% CI, 0.26-1.96]; P = .52) or mastectomy alone (BCSS: HR for BRCA1, 0.70 [95% CI, 0.22-2.20]; P = .54; HR for BRCA2, 0.59 [95% CI, 0.18-1.93]; P = .39; OS: HR for BRCA1, 0.77 [95% CI, 0.27-2.21]; P = .63; HR for BRCA2, 0.62 [95% CI, 0.22-1.73]; P = .37) after adjusting for clinicopathologic factors and adjuvant therapy. For noncarriers, patients receiving BCT had significantly better survival than those receiving mastectomy with radiotherapy (BCSS: HR, 0.45 [95% CI, 0.36-0.57]; P < .001; OS: HR, 0.46 [95% CI, 0.37-0.58]; P < .001) or mastectomy alone (BCSS: HR, 0.71 [95% CI, 0.57-0.89]; P = .003; OS: HR, 0.71 [95% CI, 0.58-0.87]; P < .001) in multivariable analyses. This study suggests that BRCA1/2 variant carriers treated with BCT have survival rates at least comparable to those treated with mastectomy with radiotherapy or mastectomy alone and that BCT could be an option for BRCA1/2 variant carriers when the tumor is clinically appropriate for BCT.
Highlights
Randomized clinical trials have demonstrated that breast-conserving therapy (BCT) with radiotherapy is equivalent to mastectomy in overall survival (OS) and breast cancer–specific survival (BCSS) among patients with early-stage breast cancer.[1,2,3,4,5] Since BCT has been widely used for patients with early-stage breast cancer worldwide for more than 2 decades
This study suggests that BRCA1/2 variant carriers treated with BCT have survival rates at least comparable to those treated with mastectomy with radiotherapy or mastectomy alone and that BCT could be an option for BRCA1/2 variant carriers when the tumor is clinically appropriate for BCT
Multivariable analyses showed that BRCA1 variant carriers treated with BCT had similar survival compared with those treated with mastectomy with radiotherapy (BCSS: hazard ratio [HR], 0.58 [95% CI, 0.16-2.10]; P = .41; OS: HR, 0.61 [95% CI, 0.18-2.12]; P = .44) or mastectomy alone (BCSS: HR, 0.70 [95% CI, 0.22-2.20]; P = .54; OS: HR, 0.77 [95% CI, 0.27-2.21]; P = .63) after adjusting for age at diagnosis, family history of breast and ovarian cancer, year of diagnosis, tumor size, tumor grade, lymph node, estrogen receptor, progesterone receptor, ERBB2, and adjuvant therapy (Table 2)
Summary
Randomized clinical trials have demonstrated that breast-conserving therapy (BCT) with radiotherapy is equivalent to mastectomy in overall survival (OS) and breast cancer–specific survival (BCSS) among patients with early-stage breast cancer.[1,2,3,4,5] Since BCT has been widely used for patients with early-stage breast cancer worldwide for more than 2 decades. Recent analyses based on population or registry studies involving many patients showed that BCT is associated with even better OS than mastectomy among patients with early-stage breast cancer.[6,7,8,9,10,11,12,13,14,15] By contrast, it is still debated whether BCT could be safely used for BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) variant carriers with breast cancer. It is well documented that women carrying a germline variant in BRCA1/2 genes have a high risk of breast cancer but are at increased risk of developing a second primary breast cancer, in the contralateral breast.[16,17,18,19,20,21,22,23,24,25,26] the results are not fully in concordance, many studies showed that BRCA1/2 variant carriers receiving BCT experienced a higher rate of ipsilateral breast cancer recurrence (especially second primary tumor) than did noncarriers.[17,18,23,25,26] the potential high risk of local recurrence after BCT and other unique features in BRCA1/2 variant carriers with breast cancer raised concerns about whether BCT is associated with survival compared with mastectomy
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