Impact that Timing of Genetic Mutation Diagnosis has on Surgical Decision Making and Outcome for BRCA1/BRCA2 Mutation Carriers with Breast Cancer

Abstract

Background Deleterious BRCA mutation carriers with breast cancer are at increased risk for additional breast cancer events. This study evaluated the impact that timing of identification of BRCA+ status has on surgical decision and outcome. Methods The authors reviewed all BRCA carriers at their institution whose breast cancer was diagnosed between January 1996 and June 2015. Patient surveys, medical records, and institutional databases were used to collect data. Differences in surgical choice were analyzed using the chi-square test, and rates of subsequent breast cancer events were estimated using the Kaplan–Meier method. Results The study investigated 173 BRCA carriers with breast cancer (100 BRCA1, 73 BRCA2). Of the women with known BRCA mutation before surgery and unilateral stages 0 to 3 breast cancer (n = 63), 12.7 % underwent lumpectomy, 4.8 % underwent unilateral mastectomy (UM), and 82.5 % underwent bilateral mastectomy (BM). These surgical choices differed significantly (p < 0.0001) from those of patients unaware of their mutation at the time of surgery (n = 93) (51.6 % had lumpectomy, 19.4 % had UM, 29 % had BM). Of the patients with BRCA mutation identified after surgery who underwent lumpectomy or UM, 36 (59 %) of 66 underwent delayed BM. The patients with BRCA+ known before diagnosis presented with significantly lower-stage disease (p = 0.02) at diagnosis (69 % stage 0 or 1) than those whose BRCA mutation was identified after cancer diagnosis (40 % stage 0 or 1). Conclusions The study findings showed that BRCA mutation status influences surgical decision. The rates of BM were higher for the patients with BRCA mutation known before surgery. Identification of BRCA mutation after surgery frequently leads to subsequent breast surgery. Genetic testing before surgery is important for patients at elevated risk for BRCA mutation.

Clinical Decision-Making in Patients with Variant of Uncertain Significance in BRCA1 or BRCA2 Genes

“…When evaluating BRCA known pathogenic mutation carriers with newly diagnosed unilateral stage 0–III breast cancer ( n = 63), BRCA pathogenic mutation carriers had expectedly high rates of TM + CPM of (83%) compared with lumpectomy (13%) or TM alone (5%). 4 In comparison, in the average risk breast cancer population at Mayo Clinic Rochester (excluding patients with BRCA VUS or BRCA deleterious mutation), 25% chose TM + CPM compared with 51% lumpectomy and 24% TM. 5 Comparison of these two groups to our BRCA VUS carriers who had known VUS status before surgery demonstrates similar rates of prophylactic mastectomy between those with a VUS and those with no known pathogenic mutation (22 vs. 25%, respectively; Fig.…”

“…Surgical choices of patients with breast cancer diagnosed with a BRCA1 or BRCA2 variant of uncertain significance compared with breast cancer patients at Mayo Clinic Rochester with known BRCA1 or BRCA2 deleterious mutations and breast cancer patients with no known mutation or variant 4,5 …”

Patients’ Views of Treatment‐Focused Genetic Testing (TFGT): Some Lessons for the Mainstreaming of BRCA1 and BRCA2 Testing

“…It is possible that the lack of recognition regarding the treatment potential of TFGT among participants was due, in part, to the ways in which this technology is mobilized in the clinic. In the case of breast cancer, the treatment or curative response is commonly combined with preventive measures in the form of bilateral mastectomy (Chiba et al 2016 ). Thus, it is not surprising that patients might conflate treatment and prevention in their accounts.…”

Hereditary Cancer Syndromes—A Primer on Diagnosis and Management

“…For example, in women presenting with primary breast cancer, bilateral mastectomy is often selected for BRCA carriers because the risk of ipsilateral or contralateral breast cancer remains high. 59 Although in vitro studies found that BRCA-mutated cell lines were exquisitely sensitive to platinum agents, clinical studies preferentially selecting platinum agents in BRCA-mutated breast cancers are inconclusive. 60 Additional Cancer Risk and Surveillance Germline pathogenic mutations in the BRCA genes are also associated with an increased risk of prostate cancer, uveal melanoma, pancreaticobiliary cancer (Table 1).…”