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William J. Gradishar, MD, FACP, FASCO


Secondary SOFT Analysis of Intrinsic Subtypes of Breast Cancer and Risk of Recurrence

By: Victoria Kuhr, BA
Posted: Thursday, July 27, 2023

The SOFT trial showed the benefit of adding ovarian function suppression to adjuvant endocrine therapy in reducing the risk of recurrence compared with endocrint therapy alone in premenopausal women with hormone receptor–positive, HER2-negative breast cancer. Now, according to a secondary analysis of this landmark study, Lauren Claire Brown, MD, PhD, of Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues observed that these women younger than age 40 tended to have an aggressive disease biology, with fewer luminal A and more luminal B and nonluminal tumors than women older than age 40. These findings were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 504).

The study included premenopausal women with hormone receptor–positive, HER2-negative breast cancer. Gene-expression analyses were performed via the NanoString Breast Cancer 360 assay on RNA isolated from formalin-fixed paraffin-embedded tumor samples from the SOFT trial that were hormone receptor–positive, HER2-negative (n = 1,245 of 3,047). The primary endpoint was distant recurrence-free interval, and secondary endpoints were breast cancer–free interval and disease-free survival.

Tumor samples from 1,084 of the 1,245 patients underwent PAM50 testing. The researchers reported the characteristics in this cohort were similar to those of the entire SOFT trial population. The median follow-up was 12 years.

However, the subtype distribution significantly differed between very young (< age 40) and young (≥ age 40) premenopausal women (P < .001). Very young women had fewer luminal A tumors (53%) compared with young women (75%). Additionally, very young women had more luminal B and basal/HER2-E tumors than young women (38% vs. 22% and 5%/3% vs. 3%/1%, respectively).

In patients with node-negative disease, 36% of very young patients had risk of recurrence (ROR)-high scores compared with 14% of young women (P < .001). Prognostic and predictive analyses of both intrinsic subtypes and ROR score are ongoing.

Disclosure: Dr. Brown reported no conflicts of interest. For full disclosures of the other study authors, visit

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