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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Thursday, April 13, 2023
Of women diagnosed with hormone receptor–positive, HER2-negative early breast cancer, those who are very young and premenopausal tend to have higher rates of recurrence and death than those who are older and either premenopausal or postmenopausal, and genomic characteristics may be at least partly to blame, according to Sherene Loi, MD, PhD, of Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues. Their research employed next-generation sequencing and tumor samples of what is probably the largest available cohort of young, premenopausal women with hormone receptor–positive, HER2-negative early breast cancer, all participants in the Suppression of Ovarian Function Trial (SOFT).
Some key genomic features “are particularly enriched with younger age rather than menopausal status per se…[providing] rationale for genomic subgrouping,” the authors noted in Annals of Oncology. “Prospective trials in young women with hormone receptor–positive, HER2-negative early breast cancer addressing these specific [priority] molecular pathways [may] be pivotal to improving their clinical outcomes.”
Specifically, younger women (< 40 years; n = 359) compared with older women (≥ 40 years; n = 917) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number amplifications (47% vs. 26%) but significantly lower frequencies of mutations in PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%). Further, younger women had significantly higher frequencies of features suggestive of homologous recombination deficiency (27% vs. 21%) and a higher proportion of PIK3CA mutations with concurrent copy number amplifications (23% vs. 11%). Genomic features suggestive of homologous recombination deficiency, PIK3CA mutations with copy number amplifications, and copy number amplifications were associated with significantly worse distant recurrence–free interval and overall survival, according to the investigators.
Poor prognostic features (n = 584; 46%) versus none (n = 692; 54%) were associated with an 8-year distant recurrence–free interval of 84% versus 94%, respectively, and overall survival of 88% versus 96%. Women up to age 40 who had poor prognostic features seemed to have the poorest outcomes, with an 8-year distant recurrence–free interval of 74% (vs. 85%) and overall survival of 80% (vs. 93%).
Disclosure: The study authors’ disclosure information can be found at annalsofoncology.org.
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