Addressing Racial Disparities in HER2-Positive Breast Cancer Outcomes

In this interview, Zunairah Shah, MD, from Roswell Park Comprehensive Cancer Center, discusses her research on racial disparities in outcomes for patients with HER2-positive metastatic breast cancer treated with antibody-drug conjugates (ADCs) such as T-DM1 and T-DXd. Dr Shah highlights significant differences in survival rates among racial groups, explores the underlying biological, social, and systemic factors driving these disparities, and outlines actionable steps that oncologists and health systems can take to promote equity in cancer care.

Dr Zunairah Shah: My name is Zunairah Shah. I'm a third-year oncology fellow at Roswell Park Comprehensive Cancer Center. I'm interested in breast oncology, especially in clinical trials and real-world data.

How do you interpret the observed survival disparities among racial groups treated with HER2-directed antibody-drug conjugates (ADCs), and what actionable steps can be taken within clinical pathways to mitigate these inequities?

Dr Shah: First, looking briefly at the disparities we observed in HER2 metastatic breast cancer (mBC), we found that among those treated with ado-trastuzumab emtansine (T-DM1) and/or trastuzumab deruxtecan (T-DXd), their 5-year survival probabilities varied. For example, non-Hispanic White patients had an 83% survival probability, Black patients had 80%, Hispanic patients had 87%, and Asian patients had around 89%. Clearly, Black patients were doing worse than other ethnic groups.

We adjusted for different factors such as body mass index (BMI), age, lines of treatment, lung diseases, and other comorbidities, but the hazard ratio remained at 1.28. This means that even after accounting for those variables, Black patients were still doing worse. The exact reason is hard to pinpoint, as we did not delve into granular data. We're currently conducting a retrospective institutional-level study to examine factors such as insurance and other socioeconomic factors.

Some actionable steps within clinical pathways include promoting inclusive trial designs and expanding access to ADCs in underserved communities. For example, the EMILIA trial that led to T-DM1’s approval had only 6% Black patients in the T-DM1 arm. We advocate for more inclusive trial designs, enhanced real-time tracking of racial outcomes in institutional quality dashboards, and embedding social determinants of health into electronic health record (EHR) workflows to enable earlier intervention.

Given that T-DM1 and T-DXd showed significant survival differences at 3 years, how should oncologists approach treatment sequencing in the context of heavily pretreated patients with HER2+ mBC?

Dr Shah: The cohort we looked at included patients from as early as 2013, and at that time, T-DXd was not approved for second-line use. So, the patients who received T-DXd were more heavily pre-treated and received it as a third-line therapy. However, since the DESTINY-Breast03 trial, T-DXd has been approved for second-line treatment.

Now patients get it earlier, but we still have limited prospective data on the sequencing of T-DM1 and T-DXd. It’s not entirely clear or settled which patients should receive which agent first, who will respond best, and what resistance may occur when transitioning from one ADC to another. This remains an area of active debate and uncertainty.

With the survival rate exceeding 80% at 5 years across all patients, how should ADCs influence long-term management strategies, including surveillance and quality of life considerations?

Dr Shah: As patients are living longer, we need to incorporate patient-reported outcomes and quality-of-life metrics into follow-up care. We must offer more integrative care that considers quality-of-life assessments and includes continuous monitoring for adverse effects during ADC therapy. Ensuring equitable access to supportive care services, especially for racially marginalized groups, is also essential.

The study used propensity score matching to account for age and comorbidities—how confident are you in using real-world evidence like this to inform pathway updates compared to randomized controlled trials?

Dr Shah: When we submitted the abstract, we had used propensity score matching. But by the time the study was presented at the American Society of Clinical Oncology (ASCO) conference on May 30th, we had performed a multivariable analysis, which is much more robust than propensity matching. Even after using the Cox model and adjusting for age, BMI, lines of treatment, and lung diseases, the hazard ratio for Black vs White patients remained 1.28 and was statistically significant.

So, even with covariate adjustments, disparities persisted. While randomized controlled trials (RCTs) remain the gold standard, real-world evidence plays an indispensable role, particularly in examining underrepresented populations in trials. It provides valuable insights into disparities in access, adherence, and response—factors not captured in tightly controlled RCTs—and helps inform interim updates to clinical pathways while awaiting more mature RCT data and assessing the treatment effectiveness across broader clinical scenarios.

What mechanisms—biological, social, or systemic—do you believe are driving the poorer outcomes among Black patients in this cohort, and how can clinical pathways be adapted to ensure more equitable care delivery?

Dr Shah: These disparities are likely multifactorial. There could be biological differences in tumor biology, pharmacogenomics, or comorbidity burden. Social factors may include barriers to timely access, financial toxicity, or health literacy. Systemic issues such as gaps in follow-up also play a role.

To improve equity, clinical pathways can be adapted to include expanding patient navigation services and financial counseling programs. Outcomes should be routinely stratified by race to identify and close gaps in care delivery.