BackgroundThe impact of timing of genetic testing on surgical decision making in women with breast cancer and BRCA mutation is not well known.MethodsWomen who were found to carry a deleterious BRCA mutation and had been diagnosed with breast cancer were identified from a database at Beaumont Health. Women who had received BRCA positive results at least a day prior to their index surgery were considered to be aware of their mutation status prior to surgery. Baseline characteristics and surgical choices were compared between women who were aware of their mutation status prior to surgery and those who were not. Fischer’s exact test was used for categorical variables and Mann–Whitney U-Test was used for continuous variables.ResultsA total of 220 patients were included in the final analysis, 208 (94.5%) with unilateral breast cancer and 12 (5.5%) with bilateral breast cancer. Out of the 208 patients with unilateral breast cancer, 106 (51.0%) patients were aware of their mutation status prior to index surgery while 102 (49%) were not. A significantly (p < 0.05) higher proportion of women underwent contralateral prophylactic mastectomy in the group that was aware of their mutation status prior to index surgery compared to the group that was not (76.4% vs 14.7%).ConclusionsOur study demonstrates that knowledge of BRCA mutation status impacts surgical decision making in favor of bilateral mastectomy in patients who are aware of their results prior to index surgery. This finding supports the practice of preoperative genetic testing in patients with newly diagnosed breast cancer.

The utility and benefit of integrating germ-line genetic testing into the management of newly diagnosed breast cancer is not fully understood. This study evaluates the impact of preoperative genetic testing on surgical decision making in patients with newly diagnosed breast cancer. Women with newly diagnosed breast cancer were classified into preoperative or postoperative genetic testing group, depending on whether they received their genetic testing results prior to or after their first surgery. Demographics, tumor characteristics, surgical treatment, and results of genetic testing were retrospectively collected. A total of 997 patients were evaluated, 531 (53.3%) in the preoperative genetic testing group and 466 (46.7%) in the postoperative group. Majority (87.2%) of BRCA-positive women in the preoperative group underwent bilateral mastectomy as first surgery. Majority (70.6%) of BRCA-positive women in postoperative group underwent partial mastectomy as first surgery prior to receiving their genetic testing result. Nearly half (41.2%) of these women in the postoperative group with partial mastectomy underwent bilateral mastectomy after receiving their BRCA-positive result. Time from diagnosis to first surgery was longer in the preoperative genetic testing group. Younger age, bilateral cancer, BRCA1/2-positive results, and preoperative genetic testing were significant predictors of bilateral mastectomy at first surgery. Preoperative genetic testing impacts initial surgical treatment in BRCA1/2-positive patients and reduces the need for additional surgeries.

The utility of multigene panels in retesting patients who previously tested negative for a pathogenic mutation by BRCA1/2 testing is not well established. Patients who previously tested negative for a pathogenic BRCA1/2 mutation by standard sequencing, and who were seen in cancer genetics center between November 1, 2012 and June 30, 2015 for additional testing utilizing multigene panels, were identified using our genetic testing registry. Data on demographics, personal and family history of cancer, results of panel testing and the impact on patient management was collected retrospectively. A total of 122 patients underwent retesting during the study period. Thirteen (11%) pathogenic mutations were identified in the following genes: CHEK2(4), PALB2(3), ATM(2), CDH1, APC, BARD1 and MRE11A. Eleven out of these thirteen mutations were deemed actionable based on published guidelines. Of these eleven, seven patients had an actual change in clinical management as a result of retesting. Furthermore, retesting also led to a change in clinical management in the two patients with mutations in genes (BARD1 and MRE11A) which do not have clear guidelines for management. There were no significant differences in demographics and personal and family history of cancer between patients who tested positive and those who tested negative on retesting. This study demonstrates the clinical utility of multigene panels in a group of high risk individuals who previously tested negative for a BRCA1/2 mutation. This retesting approach revealed a pathogenic mutation in 11% of cases. Retesting led to significant change in clinical management in a majority of patients with actionable mutations (7 out of 11), as well as in those with mutations in genes which do not have specific management guidelines.