Abstract 177P
Background
Up to 50% of pts with breast cancer and germline pathogenic/likely pathogenic BRCA variants are missed by current testing guidelines. Timely determination of germline BRCA mutation (gBRCAm) status is integral to facilitating an effective treatment strategy. Prior studies suggest that gBRCAm-associated HR+ HER2-negative eBC has a higher ODX RS vs gBRCA wild type (gBRCAwt). However, data from large cohorts are limited.
Methods
We conducted a retrospective cohort study using the US Electronic Health Record-derived de-identified Flatiron Health database. We selected pts ≥18 years with HR+ HER2-negative eBC, diagnosed from March 2007–October 2022 with a confirmed ODX RS. gBRCA testing rates were calculated by year of eBC diagnosis. Prevalence of gBRCAm was described by ODX RS category (low <11, intermediate 11–25, high >25).
Results
A total of 3672 pts with a confirmed ODX RS (category: low n=961; intermediate n=2172; high n=539) were included. Median age was 62 years (IQR 53, 69), 75.6% were white and 83.4% received treatment at community oncology clinics. Of 1163 pts (31.7%) tested, 37 (3.2%) had gBRCAm. Prevalence of gBRCAm was highest in the high ODX RS category (n=14, 7.5%) vs intermediate (n=19, 2.8%) and low (n=4, 1.4%). gBRCA testing increased over time from 2011–2014 (13.7%) to 2019–2022 (32.4%) for eBC pts. The testing rates were similar across ODX RS categories. Table: 177P
Rates of gBRCA testing in pts with HR+ HER2-negative eBC with a confirmed ODX RS*
| Rate of gBRCA testing within 6 months of eBC diagnosis | 2011–2014 | 2015–2018 | 2019–2022 |
| Overall | 13.7% | 22.4% | 32.4% |
| ODX RS High | 12.1% | 26.3% | 30.8% |
| ODX RS Intermediate | 14.5% | 21.5% | 32.9% |
| ODX RS Low | 12.4% | 22.2% | 32.1% |
*Between 2007 and 2010 only 8 ODX RS tests were performed, and so data are not shown. ODX RS, Oncotype DX Recurrence Score.
Conclusions
In this modern retrospective cohort, ODX RS appeared higher in gBRCAm-associated HR+ HER2-negative eBC vs sporadic/untested pt tumors. Despite an increasing trend in gBRCA testing, around two-thirds of HR+ HER2-negative eBC pts in this cohort did not undergo genetic testing, including 351 pts with high ODX RS who may benefit from newer risk-reducing strategies. Based on the recently demonstrated improved survival from adjuvant olaparib in gBRCAm pts, wider implementation of genetic testing may be warranted in this population.
Editorial acknowledgement
Writing and editorial assistance was provided by Sara Shaw PhD CMPP of BOLDSCIENCE Inc., funded by AstraZeneca and MSD.
Legal entity responsible for the study
AstraZeneca.
Funding
This study was supported by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who are codeveloping olaparib (MSD).
Disclosure
F. Lynce: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Merck, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Eisai, CytomX, Incyte. R.A. Khan: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. L. Berrocal-Almanza: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Miranda: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. L. Luo: Financial Interests, Personal, Full or part-time Employment, I am a full time employee at AstraZeneca AstraZeneca; Financial Interests, Personal, Stocks/Shares, I have AstraZeneca stocks/shares: AstraZeneca. X. Xu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. All other authors have declared no conflicts of interest.