Prosigna Scores, Ovarian Suppression, and Chemotherapy Omission: Iain MacPherson, PhD

In this interview with the American Journal of Managed Care^® (AJMC^®), Iain MacPherson, professor of breast oncology at Glasgow University, explained the significance of the results from the OPTIMA trial (NCT07106632) and what they might mean for patients and clinicians in practice. Watch part 1 of the interview here.

Mandating ovarian function suppression (OFS) for all premenopausal participants was a critical study design decision, MacPherson said, and may explain why the study succeeded where prior trials fell short, and why its findings apply equally across premenopausal and postmenopausal women. Previous trials evaluating gene expression tests in premenopausal patients with high-risk, hormone receptor–positive breast cancer produced inconsistent results, and current guidelines have generally discouraged the use of such tests in this population. A key reason may be that those earlier studies were confounded by an overlooked variable: chemotherapy itself induces temporary ovarian suppression in most premenopausal women who receive it.

As a result, prior trials that omitted OFS were effectively comparing tamoxifen alone against tamoxifen plus chemotherapy plus chemotherapy-induced ovarian suppression, making it impossible to isolate chemotherapy's true contribution to outcomes. OPTIMA addressed this directly by requiring all premenopausal enrollees to receive OFS alongside oral endocrine therapy, eliminating that confounding factor and enabling a cleaner comparison. Notably, OFS has since become the standard of care for this patient population, further validating the trial's design.

The trial results showed that nearly 70% of patients who would otherwise have received chemotherapy had a low Prosigna risk-of-recurrence score and were able to forgo treatment. At 5 years, invasive breast cancer–free survival (a composite end point encompassing local and distant recurrences, new primary breast cancers, and death from any cause) was approximately 94% regardless of whether chemotherapy was administered. The trial's noninferiority analysis confirmed that the test-directed approach fell well within the prespecified 3% margin, with results compatible with excluding any difference greater than 2%, and equally compatible with chemotherapy providing no benefit at all in the low-score population.

The implications for patients are profound. Adjuvant chemotherapy typically spans 3 to 6 months of intravenous treatment and carries a broad burden of acute and lasting toxicities, including hair loss, nausea, fatigue, neuropathy, and risk of serious infection. Many patients are unable to work during treatment, and recovery can be prolonged with ripple effects extending to families, caregivers, and broader society. OPTIMA is actively capturing these broader economic impacts, with a comprehensive health economic analysis expected later this year