The use of trastuzumab-based chemotherapy has dramatically improved outcome for patients with early stage HER2-positive breast cancer. Given the excellent outcomes seen to date and the toxicities associated with therapy, it is critical to establish whether additional therapies can further improve outcome, and conversely if there are patients who would have a favorable outcome with less therapy.
The addition of pertuzumab to trastuzumab-based chemotherapy results in improved survival for patients with metastatic HER2-positive breast cancer and higher response rates in the pre-operative setting. Although results of the AFFINITY trial demonstrated improved outcome for adding pertuzumab to trastuzumab-based chemotherapy, the benefit was largely restricted to patients with node-positive breast cancer. Additionally, it is unclear if patients treated pre-operatively require the continued addition of pertuzumab to trastuzumab. Neratinib, a pan-HER tyrosine kinase inhibitor, reduces recurrence rate when used following adjuvant trastuzumab, but the benefit appears restricted to hormone receptor-positive breast cancers and diarrhea is a significant issue with this agent. In contrast, de-escalating treatment for patients with stage 1 HER2-positive breast cancer with the use of paclitaxel and trastuzumab is associated with extremely favorable outcomes.
To date, the treatment of HER2-positive early stage breast cancer has not taken hormone receptor status into account when selecting HER2-directed therapies. Breast cancers that express both hormone receptors and HER2 are heterogeneous and a significant proportion have a luminal A phenotype, suggesting the possibility that combined estrogen receptor and HER2 inhibition may be especially important, given the crosstalk between these pathways. Further evaluation of non-chemotherapeutic approaches in triple positive breast cancers is justified.
Citation Format: O'Regan RM. Adjuvant therapy for HER2-positive breast cancers: is less more? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES4-2.