PAM50 HER2-E Subtype Predicts Response Following Dual HER2 Blockade

PAM50 HER2-enriched subtype predicts pathologic complete response following neoadjuvant lapatinib and trastuzumab with or without endocrine therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer, particularly those with HER2+, hormone receptor (HR)-positive disease, according to findings that will be presented at the 2016 San Antonio Breast Cancer Symposium.¹

Previous studies have demonstrated that 6% to 36% of patients with HER2+ breast cancer achieve pathologic complete response with neoadjuvant dual HER2 blockade without chemotherapy. It is unclear, however, which subpopulations derive the maximum benefit from dual anti-HER2 therapies without chemotherapy.

Researchers therefore prospectively evaluated the ability of the PAM50 HER2-enriched intrinsic subtype to predict pathologic complete response in the breast following 18 weeks of neoadjuvant dual HER2 blockade.

For the multicenter, open-label, phase 2, translational research PAMELA study (ClinicalTrials.gov Identifier: NCT01973660), investigators enrolled 151 patients with HER2+ breast cancer to receive 18 weeks of neoadjuvant treatment with lapatinib and trastuzumab. Of those, 60.2% were postmenopausal, 63.5% had negative axillary lymph nodes, and 66.9% had the PAM50 HER2-enriched subtype. Patients with HR-positive disease also received letrozole if postmenopausal or tamoxifen if premenopausal.

Results showed that 30.5% of patients overall, 18.2% with HR-positive disease, and 43.2% with HR-negative disease achieved a pathologic complete response. Researchers found that 40.6% of patients with the HER2-enriched subtype achieved a pathologic complete response compared with 10.0% of those with non-HER2-enriched subtypes (P < .0001).

Among patients with HR-positive disease, 31.6% of patients with the HER2-enriched subtype had a pathologic complete response, vs 5.3% of those with non-HER2-enriched subtypes (P = .006). Among patients with HR-negative disease, 46.0% and 27.3% of those with and without the HER2-enriched subtype achieved a pathologic complete response, respectively (P = .331).

The study demonstrated that the HER2-enriched subtype was predictive of pathologic complete response regardless of HR status in women with HER2-positive breast cancer undergoing adjuvant lapatinib and trastuzumab with or without endocrine therapy.

Reference

1. Prat Aparicio A, Cortes Castan J, Pare L, et al. PAM50 intrinsic subtype as a predictor of pathological complete response following neoadjuvant dual HER2 blockade without chemotherapy in HER2-positive breast cancer: First results of the PAMELA clinical trial. Paper presented at: 2016 San Antonio Breast Cancer Symposium (SABCS); December 6-10, 2016; San Antonio, TX.