Abstract P2-09-05: Germline <i>BRCA1/2</i> mutation testing in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC): A real-world study in the Syapse Learning Health Network (LHN)
Authors: Alexander Niyazov, Monika Izano, Colden Johanson, Sheetal Walters, Anna Berry, Bhakti Arondekar, A. Douglas Laird, Lillian Shahied Arruda, Henry Kaplan
Journal: Cancer Research (2022)

Abstract Background: Germline (g)BRCA1/2 mutations represent approximately 5% of metastatic breast cancer. Poly ADP-ribose polymerase inhibitors (PARPi) have shown improved clinical outcomes, a manageable toxicity profile, and favorable patient (pt)-reported outcomes versus chemotherapy in pts with gBRCA1/2 mutated HER2- locally advanced or metastatic breast cancer. With the advent of PARPi, clinical guidelines have broadened eligibility criteria for gBRCA1/2 testing. However, limited information is available on the impact of the COVID-19 pandemic on gBRCA1/2 testing rates. We assessed trends and factors associated with gBRCA1/2 testing in pts with HER2- ABC before and during the COVID-19 pandemic. Methods: This retrospective study included pts from the Syapse LHN, a longitudinal database of pts with cancer cared for in community-based, integrated care delivery networks in 25 states in the United States. Pts were eligible for gBRCA1/2 testing from initial ABC diagnosis until death or date of last contact with the participating health system. Information on gBRCA1/2 testing was obtained from scaled sources and further curated by Certified Tumor Registrars. Logistic regression evaluated the associations between age at diagnosis, family history of relevant cancer, race/ethnicity, median household income, health system, and diagnosis year with gBRCA1/2 testing among HER2- ABCs; models included hormone receptor status. Results: The study population included 1769 pts with HER2- ABC, including 577 pts with triple negative ABC initially diagnosed from 2010: 96% were women, 69% were non-Hispanic White, and 94% had an estimated median household income &amp;gt;$30,000 USD; median age at initial diagnosis was 61 years. The percentage of pts ever gBRCA1/2-tested among those eligible increased over time: 26%, 28%, and 31% by end of 2018, 2019, and 2020, respectively. Similarly, the percentages of new testing among eligible but not previously tested pts increased from 2018-March 2020, decreased from April-September 2020, and trended upwards thereafter (Table 1). In logistic regression models combining data from pre- and post-COVID-19 periods, family history of relevant cancer (odds ratio [OR]=1.9; 95% CI, 1.5-2.4), younger age at diagnosis (&amp;gt;65 reference; &amp;lt;45: OR=12.8, 95% CI, 8.9-18.3; 45-54: OR=6.7, 95% CI, 4.9-9.3; 55-64: OR=2.0, 95% CI, 1.5-2.8), and diagnosis year of 2013 or later (OR=1.9, 95% CI, 1.4-2.6) were significantly associated with increased odds of gBRCA1/2 testing. Positive hormone receptor status (OR=0.5; 95% CI, 0.4-0.6) and Hispanic ethnicity (OR=0.5; 95% CI, 0.3-0.9) were significantly associated with reduced odds; associations with non-Hispanic Black ethnicity did not reach statistical significance (OR=0.8; 95% CI, 0.6-1.1). Conclusion: Following the expanded eligibility criteria for gBRCA1/2 testing, testing rates increased from 2018 to 2019 and decreased only slightly during the national COVID-19 lockdown. Age at diagnosis, family history, diagnosis year, ethnicity, and hormone receptor status impacted the odds of testing. Given that gBRCA1/2 mutations are actionable, focused efforts should be developed to resume the pre-pandemic trajectory of gBRCA1/2 mutation testing. Funding: Pfizer Inc Table 1.Percentages of Newly gBRCA1/2-Tested Pts with HER2- ABC Who Were Eligible for Testing Anytime During the Time Period and Not Previously TestedTime Period2018, % (n/N)2019, % (n/N)2020, % (n/NJanuary-March2.3 (10/427)2.7 (14/512)4.3 (23/537)April-June2.9 (13/447)3.4 (18/536)2.8 (14/495)July-September4.3 (20/468)4.7 (27/569)2.5 (13/517)October-December1.9 (9/478)3.1 (17/548)3.5 (16/456)Total8.4 (52/622)10.0 (76/757)8.8 (66/747)A pt diagnosed in February and tested in April of 2018 would be included in the denominator (N) for January-March and April-June of 2018 and in the numerator (n) for April-June of 2018. Citation Format: Alexander Niyazov, Monika Izano, Colden Johanson, Sheetal Walters, Anna Berry, Bhakti Arondekar, A. Douglas Laird, Lillian Shahied Arruda, Henry Kaplan. Germline BRCA1/2 mutation testing in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC): A real-world study in the Syapse Learning Health Network (LHN) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-05.