A new analysis of breast cancer clinical trials has exposed a striking racial and ethnic imbalance in the evidence base behind poly (ADP-ribose) polymerase, or PARP, inhibitors—targeted drugs increasingly used for patients whose tumors carry harmful BRCA1 or BRCA2 mutations. The study, published in Cancer Causes & Control, found that Black and Hispanic patients were enrolled at dramatically lower rates than White patients in phase II and phase III trials conducted between 2016 and 2023. The researchers warn that the imbalance threatens both the fairness of cancer research and the reliability with which trial results can be applied to communities already facing unequal breast cancer outcomes.
PARP inhibitors work by exploiting a weakness in cancer cells’ DNA-repair systems. PARP proteins help repair certain forms of single-strand DNA damage. When PARP is blocked, damaged DNA can accumulate and eventually produce double-strand breaks. Tumor cells with defective BRCA1 or BRCA2 genes are already impaired in repairing double-strand breaks through a pathway known as homologous recombination. Blocking PARP therefore creates a form of “synthetic lethality”: the combined defects can selectively destroy cancer cells while leaving many normal cells more viable. Olaparib and talazoparib have demonstrated clinical benefits in BRCA-mutated, HER2-negative breast cancer, including triple-negative breast cancer, a particularly aggressive subtype.
Despite the biological promise of these drugs, relatively little has been known about who is represented in the trials used to establish their effectiveness. To investigate the issue, Parnian Kheirkhah Rahimabad, Simran Sekhon and Elizabeth John conducted a systematic review of PARP inhibitor studies involving breast cancers with BRCA1 or BRCA2 mutations. They searched PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and the Cochrane Library. After screening the available literature, nine phase II or phase III trials met the criteria for analysis. The studies included trials of olaparib, talazoparib, niraparib and veliparib across advanced, metastatic, early-stage and neoadjuvant treatment settings.
Together, the nine trials enrolled 2,845 White patients, 136 Black patients, 83 Hispanic patients, 662 Asian patients and 247 patients classified in an “Other” category. Because the racial composition of the Other group was not specified, the investigators excluded it from their principal comparisons. The raw numbers reveal the scale of the disparity: White participants outnumbered Black participants by more than 20 to 1 and Hispanic participants by more than 34 to 1. These differences cannot be interpreted simply as reflecting the racial distribution of the general population, because the study also compared trial participation with the number of incident breast cancer cases recorded in population-based data.
The researchers calculated an enrollment fraction, or EF, by dividing the number of patients from each racial group enrolled in the trials by the number of incident breast cancer cases in that group. Among patients with breast cancer of any type, the EF was highest for Asian patients at 0.85 percent, followed by White patients at 0.47 percent. The fraction fell to 0.12 percent for Black patients and just 0.06 percent for Hispanic patients. In practical terms, the analysis suggests that Black patients were enrolled at roughly one-quarter the odds of White patients, while Hispanic patients were enrolled at approximately one-eighth the odds. The reported enrollment odds ratios were 0.26 for Black patients and 0.12 for Hispanic patients compared with White patients, with the overall racial comparison reaching statistical significance at p < .001.
Asian enrollment initially appeared unusually high, with an odds ratio of 1.80 compared with White participants. However, the authors emphasize that this figure should not be interpreted as evidence that Asian Americans were overrepresented in U.S. trials. Many Asian participants were recruited from clinical sites in Asian countries, rather than from the Asian American population in the United States. When the investigators repeated the analysis after excluding the Asian group, the lower enrollment odds for Black and Hispanic patients remained essentially unchanged and statistically significant. This sensitivity analysis strengthens the central finding: the disparity affecting Black and Hispanic patients was not an artifact created by international Asian enrollment.
The consequences extend beyond questions of demographic fairness. Clinical trials are designed to estimate how well a treatment works, how safe it is and which patients are most likely to benefit. If participants do not reflect the populations who will receive the treatment, researchers may have less statistical power to detect differences in drug response, toxicity or quality-of-life outcomes across groups. Genetic ancestry, tumor biology, access to genetic testing, coexisting conditions, previous treatments and social determinants of health can all influence outcomes. A trial with very few Black or Hispanic participants may therefore provide limited insight into how PARP inhibitors perform for those patients in routine clinical practice.
The problem may be especially important in breast cancer because racial and ethnic disparities are already documented across diagnosis, treatment and survival. Black women are more likely to develop triple-negative breast cancer and often experience poorer outcomes, while Hispanic patients can face barriers involving insurance, transportation, language access, specialist care and participation in genetic testing. BRCA mutations are clinically important because they can determine eligibility for PARP inhibitor therapy, yet unequal access to testing and hereditary cancer services may prevent some patients from ever reaching the treatment pathway. Under-enrollment in therapeutic trials adds another layer to this problem, potentially leaving the populations most affected by aggressive disease with the least direct representation in the evidence supporting new therapies.
The authors describe their findings as a warning about the generalizability of PARP inhibitor trial results in the United States. Their analysis is based on publicly available data from the Surveillance, Epidemiology, and End Results program and previously published medical literature, and it cannot identify every reason patients were or were not enrolled. The included trials may also have differed in geographic distribution, eligibility requirements, recruitment practices and the way race and ethnicity were recorded. Race and ethnicity are social classifications rather than precise biological categories, and broad labels can conceal substantial differences among communities. Even with these limitations, the consistency of the enrollment gap across the reviewed studies points to a systemic issue rather than an isolated failure of one trial.
Closing that gap will require more than simply reporting participant demographics after a study ends. Trial sponsors and investigators may need to plan recruitment targets using disease burden and eligible-patient populations, open sites in communities historically excluded from research, provide transportation and language support, simplify referral pathways and build durable partnerships with local clinicians and patient organizations. Broader access to BRCA testing and genetic counseling could also help identify patients who may qualify for PARP inhibitor studies. More complete reporting of race, ethnicity, country of recruitment and ancestry would make future analyses more meaningful. As PARP inhibitors continue to move into earlier stages of breast cancer treatment, equitable enrollment will be essential to ensure that advances in DNA-repair medicine benefit—and are demonstrably safe and effective for—the full population living with breast cancer.
Subject of Research: Racial and ethnic representation in breast cancer clinical trials involving PARP inhibitors and BRCA1/2 mutations
Article Title: Racial and ethnic disparities in enrollment for clinical trials of poly (ADP-ribose) polymerase (PARP) inhibitors in breast cancer treatment
Article References: Kheirkhah Rahimabad P, Sekhon S, John E. Cancer Causes & Control. 2026;37:150. Additional studies referenced include the OlympiA, OlympiA-related olaparib, EMBRACA, BRAVO, BROCADE3 and S1416 trials.
Image Credits: AI Generated
DOI: 10.1007/s10552-026-02236-y
Keywords: Breast cancer; triple-negative breast cancer; PARP inhibitors; BRCA1; BRCA2; clinical trials; racial disparities; ethnic disparities; health equity; enrollment bias; genetic testing; synthetic lethality
