Dr Werutsky on the Effects of HER2-Low Breast Cancer Subtype on Treatment Outcomes

“The intrinsic subtypes of HER2 low are prognostic, and they [result in] different outcomes in 5 years.”

Gustavo Werutsky, MD, PhD, medical oncologist, Breast Cancer Program, Hospital Moinhos de Vento; investigator, Oncology Research Centre, Hospital São Lucas PUCRS University, discusses findings from an exploratory analysis of the phase 3 EORTC10041/BIG 03-04 MINDACT trial (NCT00433589) that characterized HER2-low early breast cancer by molecular subtype and outlined associations between HER2-low subtype and clinical outcomes with chemotherapy and endocrine therapy.

This analysis included 2320 patients with HER2-low tumors, defined as tumors that were HER2 1+ or 2+ nonamplified by immunohistochemistry. Patients were classified into 4 HER2 subtypes: luminal A, luminal B, HER2 enriched, and basal. Genomic risk was assessed using the MammaPrint 70-gene signature.

The MammaPrint test classified 68.4% of tumors as low risk and 31.5% of tumors as high risk (P < .0001). Among HER2 1+ tumors (n = 1505), 74.8% and 25.2% were low and high risk, respectively. Among HER2 2+ tumors (n = 815), these respective rates were 56.9% and 43.1% (P < .0001). Among patients with HER2 1+ disease, 74.2% had luminal A disease, 18.1% had luminal B disease, 74.8% had MammaPrint low-risk disease, and 25.2% had MammaPrint high-risk disease. These respective rates among patients with HER2 2+ disease were 56.2%, 34.6%, 56.9%, and 43.1%.

Investigators also explored the prognostic capabilities of MammaPrint. Patients in this analysis with MammaPrint low-risk disease had a 5-year distant metastasis-free survival (DMFS) rate of 96.5% (95% CI, 95.6%-97.4%) vs 92.5% (95% CI, 90.5%-94.4%) among those with MammaPrint high-risk disease (HR, 1.9; 95% CI, 1.4-2.5; P < .0001). The 5-year DMFS rates among patients with luminal A and luminal B disease, respectively, were 96.5% (95% CI, 95.5%-97.4%) and 92.8% (95% CI, 90.7%-95.1%). These findings showed that clinical outcomes in HER2-low early breast cancer are associated with MammaPrint genomic risk, Werutsky concludes.