Genomic Testing Gaps, Chemotherapy Decisions in Young Women With HR+ Breast Cancer: Mitali Shah, MD

Young women with hormone receptor (HR)–positive breast cancer occupy an underexamined space in genomic risk stratification.

In a conversation with The American Journal of Managed Care^® (AJMC^®), Mitali Shah, MD, an internal medicine resident at The Ohio State University, discusses findings from a new analysis of chemotherapy use among women younger than 50 with low Oncotype DX recurrence scores and what those findings mean for health systems, payers, and the patients most likely to fall through the gaps.

This interview has been lightly edited.

AJMC: Your analysis focused on chemotherapy use among women younger than 50 with HR–positive breast cancer and low Oncotype DX recurrence scores. What were the headline findings?

Shah: So, for a little bit of background, the Oncotype DX recurrence score is basically a 21-gene assay. It analyzes a tumor sample to quantify the likelihood of disease recurrence and predict chemotherapy benefit in patients with HR-positive, HER2-negative, early-stage breast cancer. A higher score equals a higher risk of recurrence and a greater likelihood of benefit from chemotherapy. This is very effective in postmenopausal women, but younger, premenopausal women with intermediate scores, anywhere between 16 and 25, may still benefit from chemotherapy.

There was actually a trial called the RxPONDER trial, which demonstrated a benefit of chemotherapy in this population of patients with 1 to 3 positive lymph nodes, regardless of their recurrence score. So, our major study findings were that among women less than 50 years old with low recurrence scores, chemotherapy receipt was strongly associated with specific factors like higher tumor stage, poorly differentiated grade, and regional node involvement. Basically, despite a low recurrence score, young age and node positivity were associated with adjuvant chemotherapy recommendations.

AJMC: Why does this patient population warrant its own focused analysis, separate from what we already know about postmenopausal breast cancer?

Shah: There's a lot of data that looks at the postmenopausal population and what we do for breast cancer in that specific age group, but there's a lack of prospective data that evaluates the predictive ability of this recurrence score in this specific population, which is why it's important to study.

What these findings indicate is that recommending chemotherapy in a population that we may not have previously expected to benefit may actually positively impact patients' long-term outcomes.

AJMC: Unnecessary chemotherapy harms patients and adds cost to the system. From a managed care standpoint, what levers are most likely to close the gap between what guidelines recommend and what patients actually receive?

Shah: As an internal medicine resident, I myself have not made the decision of starting a patient on chemotherapy or not, but I've seen oncologists do it, and that decision is certainly a multifaceted one. Testing, such as the Oncotype recurrence score, is one of the tools that can help root these decisions in evidence and standardize care, especially for this very specific patient population.

AJMC: Genomic testing isn't equally available to all patients. What disparities have emerged in who gets tested?

Shah: Being able to practice at an institution like Ohio State means we have access to a lot of resources that sometimes we don't even really recognize. But there have been observational studies that show racial and ethnic disparities and that testing rates are generally lower in patients with no insurance, Medicaid coverage, lower neighborhood income, and higher social deprivation indices.

From a larger geographic and practice-level standpoint, testing is more common, as you can imagine, in bigger academic centers like ours and National Cancer Institute-designated cancer centers compared with more rural settings, safety net hospitals, or smaller community practices. Unfortunately, this translates to differences in outcomes for patients and represents a gap in care that I think we need to be more aware of.

AJMC: What is the single most actionable takeaway from your analysis for health system leaders and payers trying to improve care quality and reduce unnecessary treatment in this population?

Shah: I think from our study specifically, one thing that I've personally taken away is that standardizing reflex genomic testing, like the Oncotype DX score. Moving towards a more pathway-based treatment decision for every eligible patient would help in that sense.