Assessment of Therapeutic Response by Intrinsic Subtype for HER2-Positive Breast Tumors

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In an analysis of outcomes in the North Central Cancer Treatment Group/Alliance N9831 trial reported in the Journal of the National Cancer Institute, Edith A. Perez, MD, of the Mayo Clinic Cancer Center, and colleagues found that patients with tumors scored as HER2-enriched or luminal subtype derived a recurrence-free survival benefit from the addition of adjuvant trastuzumab (Herceptin) to chemotherapy.

In the study, the Prosigna algorithm on the NanoString platform was used to define the intrinsic subtype, risk of recurrence scores, and risk categories for 1,392 patients with HER2-positive tumors, including 484 who received adjuvant chemotherapy and 908 who received chemotherapy plus trastuzumab.

Subtypes and Outcomes

Overall, 72% of patient tumors were scored as HER2-enriched, 21% were scored as luminal type, and 7% were scored as basal-like. Recurrence-free survival was significantly improved with trastuzumab treatment among patients with HER2-enriched tumors (hazard ratio [HR] = 0.68, P = .005) and in all those with luminal-type tumors (HR = 0.52, P = .01) but not in those with basal-like tumors (HR = 1.06, P = .87). The benefit of trastuzumab did not reach significance in patients with luminal A profiles (HR = 0.62, P = .20) but was significant among those with luminal B profiles (HR = 0.45, P = .02).

The investigators concluded: “The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype.”

The study was supported by grants from the National Cancer Institute (NCI), the Breast Cancer Research Foundation, the 26.2 with Donna Foundation, the NCI Breast SPORE, the Mayo Clinic Comprehensive Cancer Center, and the Mayo Foundation.

Perez EA, et al: J Natl Cancer Inst 109:djw207, 2016.




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