Allison W Kurian1,2, Kevin C Ward3, Paul Abrahamse4,5, Ann S Hamilton6, Dennis Deapen6, Monica Morrow7, Reshma Jagsi8, Steven J Katz4,5. 1. Department of Medicine, Stanford University, Stanford, California. 2. Department of Epidemiology and Population Health, Stanford University, Stanford, California. 3. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. 4. Department of Medicine, University of Michigan School of Public Health, Ann Arbor. 5. Department of Health Management & Policy, University of Michigan School of Public Health, Ann Arbor. 6. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. 7. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. 8. Department of Radiation Oncology, University of Michigan, Ann Arbor.
Abstract
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.
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.
Authors: Pat W Whitworth; Peter D Beitsch; Rakesh Patel; Barry Rosen; Gia Compagnoni; Paul L Baron; Rache Simmons; Eric A Brown; Linsey Gold; Dennis Holmes; Linda Ann Smith; Michael Kinney; Ian Grady; Patricia Clark; Karen Barbosa; Samuel Lyons; Lee Riley; Cynara Coomer; Lisa Curcio; Antonio Ruiz; Sadia Khan; Heather MacDonald; Kevin Hughes; Mary Kay Hardwick; Brandie Heald; Sandra B Munro; Sarah M Nielsen; Edward D Esplin Journal: JAMA Netw Open Date: 2022-09-01
Authors: Bhavana V Chapman; Diane Liu; Yu Shen; Oluwafikayo O Olamigoke; David S Lakomy; Angelica M Gutierrez Barrera; Shane R Stecklein; Gabriel O Sawakuchi; Scott J Bright; Isabelle Bedrosian; Jennifer K Litton; Benjamin D Smith; Wendy A Woodward; George H Perkins; Karen E Hoffman; Michael C Stauder; Eric A Strom; Banu K Arun; Simona F Shaitelman Journal: Int J Radiat Oncol Biol Phys Date: 2021-10-03 Impact factor: 8.013
Authors: Bhavana V Chapman; Diane Liu; Yu Shen; Oluwafikayo O Olamigoke; David S Lakomy; Angelica M Gutierrez Barrera; Shane R Stecklein; Gabriel O Sawakuchi; Scott J Bright; Isabelle Bedrosian; Jennifer K Litton; Benjamin D Smith; Wendy A Woodward; George H Perkins; Karen E Hoffman; Michael C Stauder; Eric A Strom; Banu K Arun; Simona F Shaitelman Journal: Int J Radiat Oncol Biol Phys Date: 2021-09-25 Impact factor: 7.038
Authors: Allison W Kurian; Kevin C Ward; Paul Abrahamse; Irina Bondarenko; Ann S Hamilton; Dennis Deapen; Monica Morrow; Jonathan S Berek; Timothy P Hofer; Steven J Katz Journal: J Clin Oncol Date: 2021-02-09 Impact factor: 44.544