The Headline: Genomic-guided chemotherapy omission is expanding in clinically high-risk ER+/HER2− breast cancer.
The Study: The phase 3 OPTIMA trial randomized 4,429 women 40 and older recommended to receive chemotherapy based on clinical factors to standard chemotherapy followed by endocrine therapy or to a Prosigna-directed chemotherapy decision. Prosigna (PAM50)-directed strategy spared chemotherapy in the two-thirds (68%) of women with low-risk genomics (score ≤60) without compromising 5-year invasive breast cancer–free survival (94% vs 95% in the all-chemo arm), meeting prespecified noninferiority criteria. Notably, outcomes were consistent across menopausal and nodal subgroups, including women with N2 disease (19%) and premenopausal women receiving ovarian function suppression (e.g. GNRH agonist, 37%). That last point is important, as it has long been hypothesized that a significant component of chemo benefit for premenopausal women with ER+/HER2- breast cancer is ovarian suppression alone. A burning question remains: Who the heck orders Prosigna in practice? Practically speaking, this may be most useful as a validated avenue to spare chemo for women with N2 disease.
TBL: These findings support broader use of genomic profiling to safely de-escalate chemotherapy in biologically low-risk but clinically high-risk ER+/HER2- breast cancer. | Stein, ASCO 2026
The Study: The phase 3 OPTIMA trial randomized 4,429 women 40 and older recommended to receive chemotherapy based on clinical factors to standard chemotherapy followed by endocrine therapy or to a Prosigna-directed chemotherapy decision. Prosigna (PAM50)-directed strategy spared chemotherapy in the two-thirds (68%) of women with low-risk genomics (score ≤60) without compromising 5-year invasive breast cancer–free survival (94% vs 95% in the all-chemo arm), meeting prespecified noninferiority criteria. Notably, outcomes were consistent across menopausal and nodal subgroups, including women with N2 disease (19%) and premenopausal women receiving ovarian function suppression (e.g. GNRH agonist, 37%). That last point is important, as it has long been hypothesized that a significant component of chemo benefit for premenopausal women with ER+/HER2- breast cancer is ovarian suppression alone. A burning question remains: Who the heck orders Prosigna in practice? Practically speaking, this may be most useful as a validated avenue to spare chemo for women with N2 disease.
TBL: These findings support broader use of genomic profiling to safely de-escalate chemotherapy in biologically low-risk but clinically high-risk ER+/HER2- breast cancer. | Stein, ASCO 2026