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Original Investigation
February 6, 2020

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

Author Affiliations
  • 1Department of Medicine, Stanford University, Stanford, California
  • 2Department of Epidemiology and Population Health, Stanford University, Stanford, California
  • 3Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
  • 4Department of Medicine, University of Michigan School of Public Health, Ann Arbor
  • 5Department of Health Management & Policy, University of Michigan School of Public Health, Ann Arbor
  • 6Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
  • 7Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
  • 8Department of Radiation Oncology, University of Michigan, Ann Arbor
JAMA Oncol. Published online February 6, 2020. doi:10.1001/jamaoncol.2019.6400
Key Points

Question  Is the increasing use of germline genetic testing associated with the treatment of women diagnosed with breast cancer?

Findings  In this population-based cohort study of 20 568 women who were diagnosed with stages 0 to III breast cancer from 2014 to 2016 and received germline genetic testing, women with pathogenic variants in BRCA1, BRCA2, and other breast cancer–associated genes were more likely to receive bilateral mastectomy, less likely to receive radiotherapy after lumpectomy, and more likely to receive chemotherapy for early-stage hormone receptor-positive disease.

Meaning  Women with germline pathogenic variants in breast cancer susceptibility genes have been found to have different patterns of breast cancer treatment, which may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.


Importance  The 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 ≥70 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 Relevance  Women 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.

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