Patients with the HER2-enriched subtype of HER2-positive breast cancer are most likely to benefit from dual HER2 blockade therapies, a study published in The Lancet Oncology has shown.1

HER2-positive breast cancer comprises a normal-like subtype and 4 intrinsic molecular subtypes: luminal A, luminal B, HER2-enriched, and basal-like. Because the HER2-enriched subtype has the highest activation of the EGFR-HER2 pathway, researchers sought to evaluate whether patients with this subtype benefit most from dual HER2 blockade.

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The open-label, phase 2 PAMELA trial ( Identifier: NCT01973660) enrolled 151 adult women with previously untreated HER2-positive, stage I to IIIA invasive breast cancer regardless of hormone receptor status. At baseline, 67% of patients had the HER2-enriched subtype, 15% had luminal A, 11% had luminal B, 6% had basal-like, and 2% had normal-like subtypes.

Participants received neoadjuvant lapatinib orally daily and trastuzumab intravenously every 3 weeks for 18 weeks. Patients with hormone receptor-positive disease also received letrozole orally daily if menopausal or tamoxifen orally daily if premenopausal.

At time of surgery, 30% (95% CI, 23-39) of patients had achieved a pathologic complete response in the breast, including 41% (95% CI, 31-51) of the 101 patients with the HER2-enriched subtype and 10% (95% CI, 4-23) of the 50 patients with non-HER2-enriched subtypes.

Results showed that patients with the HER2-enriched subtype, as determined with the PAM50 predictor, were more than 6 times as likely to achieve a pathologic complete response at the time of surgery than those without the HER2-enriched subtype (odds ratio, 6.2; 95% CI, 2.3-16.8; P =.0004).

The findings suggest that harboring the PAM50 HER2-enriched phenotype is predictive of response to dual HER2 blockade in HER2-positive early breast cancer.


1. Llombart-Cussac A, Cortes J, Pare L, et al. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol. 2017 Feb 23. doi: 10.1016/S1470-2045(17)30021-9. [Epub ahead of print]