Association of Germline Genetic Testing Results With Locoregional and Systemic Therapy in Patients With Breast Cancer

Abstract

IMPORTANCEThe increasing use of germline genetic testing may have unintended consequences on treatment. Little is known about how women with pathogenic variants in cancer susceptibility genes are treated for breast cancer.OBJECTIVE To determine the association of germline genetic testing results with locoregional and systemic therapy use in women diagnosed with breast cancer.DESIGN, SETTING, AND PARTICIPANTS For this population-based cohort study, data from women aged 20 years or older who were diagnosed with stages 0 to III breast cancer between 2014 and 2016 were accrued from the Surveillance, Epidemiology and End Results (SEER) registries of Georgia and California. The women underwent genetic testing within 3 months after diagnosis and were reported to the Georgia and California SEER registries by December 1, 2017.EXPOSURES Pathogenic variant status based on linked results of clinical germline genetic testing by 4 laboratories that did most such testing in the studied regions.MAIN OUTCOMES AND MEASURES Potential deviation of treatment from practice guidelines was assessed in the following clinical scenarios: (1) surgery: receipt of bilateral mastectomy by women eligible for less extensive unilateral surgery (unilateral breast tumor);(2) radiotherapy: omission in women indicated for postlumpectomy radiotherapy (all lumpectomy recipients except age Ն70 with stage I, estrogen and/or progesterone receptor [ER/PR] positive, ERBB2 [formerly HER2]-negative disease); and (3) chemotherapy: receipt by women eligible to consider chemotherapy omission (stages I-II, ER/PR-positive, ERBB2-negative, and 21-gene recurrence score of 0-30, which was the upper limit of the intermediate risk range during the study years). The adjusted percentage treated and adjusted odds ratio (OR) are reported based on multivariable modeling for each treatment-eligible group.RESULTS A total of 20 568 women (17.3%) of 119 198 were eligible (mean [SD] age, 51.4 [12.2]). Compared with women whose test results were negative, those with BRCA1/2 pathogenic variants were more likely to receive bilateral mastectomy for a unilateral tumor (61.7% vs 24.3%; OR, 5.52, 95% CI, 4.73-6.44), less likely to receive postlumpectomy radiotherapy (50.2% vs 81.5%; OR, 0.22, 95% CI, 0.15-0.32), and more likely to receive chemotherapy for early-stage, ER/PR-positive disease (38.0% vs 30.3%; OR, 1.76, 95% CI, 1.31-2.34). Similar patterns were seen with pathogenic variants in other breast cancer-associated genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53) but not with variants of uncertain significance. CONCLUSIONS AND RELEVANCEWomen with pathogenic variants in BRCA1/2 and other breast cancer-associated genes were found to have distinct patterns of breast cancer treatment; these may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.

CHEK2 Pathogenic Variants in Greek Breast Cancer Patients: Evidence for Strong Associations with Estrogen Receptor Positivity, Overuse of Risk-Reducing Procedures and Population Founder Effects

“…Therefore, the exact reasons for the uptake of these procedures have not been elucidated. These findings indicate the overuse of prophylactic mastectomy, based on the calculated cumulative breast cancer risks for females with CHEK2 pathogenic variants, in line with other studies [ 31 , 32 ].…”

Strategies to enhance identification of hereditary breast cancer gene carriers

“…These studies include data to suggest high rates of bilateral mastectomy reported among breast cancer patients with a BRCA1/2 variant of uncertain significance [33], as well as those with non-BRCA1/2 moderate penetrance genes [34,35], suggesting potential overtreatment. Additionally, a recently published cancer registry-based study suggested that those with P/LP BRCA1/2 and other breast cancer-associated genes may have patterns of breast cancer treatment which are less concordant with practice guidelines; including being more likely to receive bilateral mastectomy for a unilateral tumor, less likely to receive post-lumpectomy radiotherapy, and more likely to receive chemotherapy for early-stage, ER/PR-positive disease [34]. Similarly, studies from us and others have reported on risk-reducing oophorectomies conducted among those with BRCA1/2 carriers have reported lower rates among Black women compared to non-Hispanic whites [36].…”

IMProving care After inherited Cancer Testing (IMPACT) study: protocol of a randomized trial evaluating the efficacy of two interventions designed to improve cancer risk management and family communication of genetic test results

“…Using inherited breast cancer as an example, follow-up strategies to manage elevated breast cancer risks may include either enhanced breast cancer screening or bilateral mastectomy for high penetrance genes, such as BRCA1/2 and PALB2 [28]. In contrast, only heightened screening is recommended for those with P/ LP variants in moderate penetrance genes, such as ATM and CHEK2; yet, prior research by us and others suggests that some women have bilateral mastectomies even though it may not be medically justified [29,30]. Furthermore, while risk-reducing oophorectomy is recommended for BRCA1/2 carriers around the age of 35-45, there is insufficient evidence to recommend this procedure for all women with ATM, CHEK2, or PALB2 P/LP variants [28]; however, our prior study suggested that some of these women still have oophorectomies [29].…”