Among premenopausal patients with hormone receptor–positive, early-stage breast cancer enrolled in the SOFT trial, those with a high score on the Breast Cancer Index genomic assay had an increased risk of distant recurrence—and those with a low score on the Breast Cancer Index may have benefited more from the addition of ovarian suppression therapy to endocrine therapy after 12 years of follow-up, according to novel findings presented by O’Regan et al at the San Antonio Breast Cancer Symposium (SABCS) 2022 (Abstract GS1-06).

Background

“The SOFT trial showed that adding ovarian function suppression to endocrine therapy benefited a subset of premenopausal [patients] with [hormone receptor]–positive, early-stage breast cancer. However, [ovarian function suppression] increases short- and long-term toxicity and is not tolerated by all patients,” said study author Ruth O’Regan, MD, Professor and Chair of the Department of Medicine and the Charles A. Dewey Professor at the University of Rochester, as well as Physician-in-Chief of Strong Memorial Hospital. “Therefore, determining which patients truly need [ovarian function suppression] is crucial to avoid added toxicities in patients who are unlikely to benefit.”

Incorporating the molecular grade index and the expression ratio of the HOX13 gene to the IL17BR gene (H/I ratio), the Breast Cancer Index may assess the risk of late distant recurrence of hormone receptor–positive, early-stage breast cancer. The H/I ratio is capable of determining which patients may benefit from extended durations of endocrine therapy.

Study Methods and Findings

In a subset of 1,687 premenopausal patients with hormone receptor–positive, early-stage breast cancer who received endocrine therapy with or without chemotherapy—and were enrolled in the SOFT trial—Dr. O’Regan and her colleagues evaluated whether the Breast Cancer Index was capable of predicting prognoses and benefits from ovarian function suppression. The analysis showed that, after 12 years of follow-up, the Breast Cancer Index was prognostic of distant recurrence. Among patients without lymph node involvement, those with a high Breast Cancer Index had a 98% increased risk of distant recurrence compared with recurrence in those with a low Breast Cancer Index. A similar increase was observed in patients whose cancer had spread to one to three lymph nodes.

Furthermore, among patients with a low H/I ratio, adding ovarian function suppression to exemestane or tamoxifen resulted in a reduced risk of recurrence after 12 years compared with treatment with tamoxifen alone (11.6% and 7.3%, respectively).

The predictive benefit of the H/I ratio was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Conclusions

“Previously, high H/I ratio has been shown to predict which patients benefit from longer durations of endocrine therapy, which could indicate sensitivity to such therapy. However, benefiting from [ovarian function suppression] may not be related to endocrine sensitivity,” highlighted Dr. O’Regan. “It is possible that patients with endocrine-resistant cancers may benefit more from [ovarian function suppression], which could explain our findings.”

“If validated, the H/I ratio may be useful to determine which premenopausal patients require [ovarian function suppression], thereby avoiding additional toxicity in those who are unlikely to benefit,” Dr. O’Regan concluded.

Disclosure: The research in this study was funded by Biotheranostics.