Breast cancer is the most common cancer globally and the second most common cause of cancer deaths among women in the United States (US), with an estimated 317,000 new cases and 42,000 breast cancer-related deaths projected for the US in 2025 (1–4). The prognosis and selection of therapy for breast cancer is guided by clinical presentation, including patient age, tumor stage, and pathological features such as tumor subtype defined according to human epidermal growth factor receptor 2 (HER2) and estrogen and progesterone receptor (ER and PR) status. Approximately 70% of tumors are hormone receptor-positive (HR+) and HER2-negative, while triple-negative breast cancer (TNBC), defined as testing negative for all three receptors (ER, PR, and HER2), accounts for approximately 10% to 15% of all breast cancers and is more common among African American women and those with a BRCA1 mutation (3–5).

The presence of a pathogenic or likely pathogenic variant in the BRCA1 and/or BRCA2 gene markedly increases the risk of breast cancer occurrence and its recurrence after standard therapy (6, 7). For patients with early-stage breast cancer, identification of a BRCA mutation (BRCAm) is an important consideration in therapeutic decision-making, both regarding surgical approach as well as choice of systemic therapy (8–11). The presence of a germline BRCAm is predictive of clinical response to specific therapies, particularly to poly(ADP-ribose) polymerase (PARP) inhibitors, such as olaparib (12, 13). Adjuvant olaparib received regulatory approval in the US in March 2022, based on results of the phase 3 OlympiA clinical trial (NCT02032823) demonstrating significant overall survival (OS) benefit of olaparib vs placebo, for treating adult patients with germline BRCA-mutated early-stage, high-risk HER2-negative breast cancer who had received definitive local therapy and neoadjuvant or adjuvant chemotherapy and who were selected for therapy based on an approved companion diagnostic test (14–16); and sustained benefit of the 1-year olaparib regimen was demonstrated at median 6-year follow-up (17). This followed the approval in January of 2018 of olaparib for patients with metastatic germline BRCA-mutated HER2-negative breast cancer who had received prior chemotherapy in the neoadjuvant, adjuvant, or metastatic setting (18).

Current US consensus guidelines for BRCAm testing differ somewhat in details, but all recommend genetic testing that includes both BRCA1 and BRCA2 for all patients with TNBC and male breast cancer and for patients with a personal history of breast cancer, with a pertinent family history, or with high-risk, HER2-negative breast cancer (to aid in adjuvant treatment decisions with olaparib) (19–21). Consensus guidelines of the American Society of Breast Cancer Surgeons have recommended genetic testing for all patients with breast cancer since 2019, to include at least BRCA1, BRCA2, and PALB2 (19), while more recent joint guidelines from the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO) recommend BRCAm testing for all patients ≤65 years with newly diagnosed stage I-III breast cancer and those >65 years old with TNBC or high-risk early-stage disease (20).

Reported BRCAm testing rates in the US for patients with breast cancer have been slowly increasing in the last decade (22–24). However, testing rates were only 34% among women and 61% among men with breast cancer diagnosis in 2019 and followed to March 2021 (24). Information about current real-world BRCA genetic testing patterns, BRCAm prevalence, and therapy selection for HER2-negative early-stage breast cancer in the US would aid in identifying areas of unmet need for this patient population. Our objectives were to describe BRCAm testing patterns and results for patients with HER2-negative early-stage breast cancer treated in US community settings and, for patients tested for BRCAm, to describe their characteristics and therapy, including adjuvant olaparib use.

We followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline in reporting this retrospective cohort study (25). The study protocol was approved by the Advarra Institutional Review Board, with a waiver of informed consent for the secondary analysis of existing data (26).

In this retrospective study of patients with HER2-negative early-stage breast cancer, we found that just over half of 3741 patients treated in US community settings were tested for BRCAm in 2022 and 2023 (51% and 56%, respectively), with greater frequency overall among patients with TNBC (70%) than with HR+/HER2-negative breast cancer (50%). Moreover, 79% of patients ≤50 years old were tested, as compared with 39% of those >65 years old. The percentages of patients BRCAm tested were in the 50% to 59% range for White, Black/African American, and Asian individuals, the three largest racial groups, as well as for Hispanic/Latino and non-Hispanic/non-Latino individuals. Over 99% of the 1969 patients with a known genomic source were tested for gBRCAm, with a small minority (n=7) tested for somatic BRCAm. Positive test results for BRCAm were recorded for 3% of patients with HR+/HER2-negative disease and for 13% with TNBC. Of the patients with BRCA-mutated breast cancer, the majority (93 of 96) underwent definitive surgery and received neoadjuvant or adjuvant therapy, or both, including 14 (15%) who received adjuvant olaparib.

Our findings suggest that BRCAm testing rates continue to slowly increase in the US. In another study of adult women of all ages (≥20 years old) using data from the Surveillance, Epidemiology, and End Results (SEER) registries in California and Georgia, testing rates rose from 22% to 34% for women with breast cancer diagnosis in 2013 to 2019 and followed through the first quarter of 2021 (24) (vs. 51%–56% in 2022–2023 in our study). An earlier study using the same SEER registries for women with breast cancer diagnosed in 2013–2014 found that genetic testing rates were greater for women with TNBC (40%) than for those with HR+/HER2-negative subtype (23%) (29), a similar pattern to our more recent findings (70% vs. 50%, respectively). In a prior study of 28,655 older women, ages ≥66 years, with diagnosis in 2010–2017 of HER2-negative early-stage breast cancer, and who underwent primary surgery, 7578 (26%) were BRCAm tested (30); this percentage was 39% among women >65 years old in our study.

Different from the SEER registry study, which reported lower testing rates among Asian, Black, and Hispanic patients compared with White patients (24), we found that the percentages of patients tested were relatively similar across racial groups, although with the caveat that there are potential differences in patient characteristics and insurance coverage between our largely Midwestern, community-based patient population and the SEER registries in California and Georgia. We observed, as expected, that tumor characteristics at diagnosis indicated more high-risk disease among patients with TNBC than those with HR+ tumors, with greater percentages of TNBC at stage III, with nodal involvement, with grade 3 disease, and with BRCAm. Moreover, as generally accepted (3–5), Black/African American patients were proportionately over-represented in the TNBC cohort (comprising 33% of all 289 Black/African American patients) as compared with White patients (15% of all 1546 White patients).

The March 2022 approval of adjuvant olaparib for high-risk early-stage BRCA-mutated breast cancer provided the first available adjuvant targeted therapy for the patients in this study (with initial diagnosis from January 1, 2022, to January 22, 2024) and theoretically could have provided motivation for increased BRCAm testing. Nonetheless, 30% of patients with TNBC did not have a BRCAm test, despite practice guideline recommendations (19). Of the 96 patients with BRCAm in this study, 39% were >50 years old and 15% were >65 years old, highlighting the importance of BRCAm testing for patients of all ages with stages I-III HER2-negative breast cancer. Moreover, we observed that approximately one-fifth of patients (21%) had BRCAm testing after definitive surgery, which meant that BRCAm test results were available too late to factor into surgical decision-making and possibly too late to influence adjuvant therapy decisions. Prior research has suggested that patients are more likely to agree to receive BRCAm testing based on a recommendation by their health care provider and as an opportunity to be fully informed about their breast cancer (31). Providers are more likely to recommend BRCAm testing for patients with a family history, at younger ages, and with TNBC; patient refusal and insurance issues were reported as barriers to BRCAm testing (32). In their recent review of genetic testing for BRCAm breast cancer, Arun and coworkers propose several strategies to improve testing rates, including population-based screening of individuals at high risk of BRCAm, free genetic counseling, and provision of training and education for health care providers, together with increasing awareness for patients (33). Additional studies around factors to facilitate BRCAm testing may be helpful to increase testing rates, to identify patients with BRCA-mutated breast cancer who could benefit from targeted treatments, and to better inform surgical decisions.

A total of 18 patients with HER2-negative early-stage breast cancer in this study received adjuvant olaparib, and all 18 patients had received a BRCAm test, as recommended. Similarly, a recent US retrospective study found that, of 134 olaparib users with HER2-negative early-stage breast cancer, all had received at least one BRCAm test (germline and/or somatic) (34). Further study of a more contemporary cohort will extend our understanding of BRCAm genetic testing patterns and olaparib use in this patient population.

This study used a large database with follow-up until early 2025 to study BRCAm testing among almost 3800 patients with HER2-negative early-stage breast cancer treated at US community practices. The database included detailed clinical information, with minimal missing data regarding tumor characteristics at diagnosis, menopausal status, and insurance status, although ECOG performance status was not documented for approximately half of patients. However, the fact that we required documented HER2 and HR status may have resulted in selection bias favoring patients who were more likely to have comprehensive diagnostic testing, including BRCAm tests, and those with complete documentation in their medical records. Moreover, the generalizability of our findings may be limited beyond the included health systems, most in the Midwest, or for patients treated at academic centers. In addition, as for all database studies, we cannot rule out the limitation of possible errors in data recording. Finally, this descriptive study enrolled patients with early-stage breast cancer, for whom lengthy follow-up is needed to evaluate recurrence and survival outcomes. Future long-term studies are needed to evaluate the outcomes of different surgical approaches and neoadjuvant and adjuvant therapy selection for patients with HER2-negative early-stage breast cancer according to BRCAm status and by HR status.

Testing rates for BRCAm in the US remain suboptimal relative to practice guideline recommendations and the availability of adjuvant targeted therapy. Particular areas of unmet need include BRCAm testing for more patients with HER2-negative early-stage breast cancer, particularly those with HR+ disease and including patients >50 years of age. Moreover, improvements are needed in testing timelines by implementing genetic testing before surgery to guide surgical and systemic therapy decision-making. Future work will investigate use of olaparib for HER2-negative early-stage breast cancer in the US in subsequent years.