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- W4362561497 abstract "<div>Abstract<p>Intratumor heterogeneity is postulated to cause therapeutic resistance. To prospectively assess the impact of HER2 (<i>ERBB2</i>) heterogeneity on response to HER2-targeted therapy, we treated 164 patients with centrally confirmed HER2-positive early-stage breast cancer with neoadjuvant trastuzumab emtansine plus pertuzumab. HER2 heterogeneity was assessed on pretreatment biopsies from two locations of each tumor. HER2 heterogeneity, defined as an area with <i>ERBB2</i> amplification in >5% but <50% of tumor cells, or a HER2-negative area by FISH, was detected in 10% (16/157) of evaluable cases. The pathologic complete response rate was 55% in the nonheterogeneous subgroup and 0% in the heterogeneous group (<i>P</i> < 0.0001, adjusted for hormone receptor status). Single-cell <i>ERBB2</i> FISH analysis of cellular heterogeneity identified the fraction of <i>ERBB2</i> nonamplified cells as a driver of therapeutic resistance. These data suggest HER2 heterogeneity is associated with resistance to HER2-targeted therapy and should be considered in efforts to optimize treatment strategies.</p>Significance:<p>HER2-targeted therapies improve cure rates in HER2-positive breast cancer, suggesting chemotherapy can be avoided in a subset of patients. We show that HER2 heterogeneity, particularly the fraction of <i>ERBB2</i> nonamplified cancer cells, is a strong predictor of resistance to HER2 therapies and could potentially be used to optimize treatment selection.</p><p><i>See related commentary by Okines and Turner, p. 2369</i>.</p><p><i>This article is highlighted in the In This Issue feature, p. 2355</i></p></div>" @default.
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- W4362561497 date "2023-04-03" @default.
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- W4362561497 title "Data from Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab" @default.
- W4362561497 doi "https://doi.org/10.1158/2159-8290.c.6548945" @default.
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