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May 20, 2021

Anthracycline Use in ERBB2-Positive Breast Cancer: It Is Time to Re-TRAIN

Author Affiliations
  • 1Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles
JAMA Oncol. 2021;7(7):975-977. doi:10.1001/jamaoncol.2021.1314

It made perfect sense to use an anthracycline in the original adjuvant trastuzumab trials. At the time these large, randomized studies were being planned, almost a quarter century ago, anthracycline-taxane combinations were the accepted standard for treating high-risk breast cancer.1 In fact, treatment with an anthracycline for the ERBB2-positive subtype drew even further support from a number of studies, including a large meta-analysis, comparing anthracycline-based to nonanthracycline-based chemotherapy that strongly suggested that the benefit of anthracyclines is greatest in ERBB2-positive breast cancers.2 These data led some to view ERBB2 as a biomarker for sensitivity to anthracyclines. While the association between ERBB2 status and anthracycline benefit was fairly consistent, in an effort to avoid the post hoc ergo propter hoc fallacy, scientists set out to test whether ERBB2 was actually causing anthracycline sensitivity. Interestingly, results of ERBB2 transfection experiments demonstrated that ERBB2 amplification itself does not render cancer cells more responsive to anthracyclines,3,4 prompting a search for the causative gene.

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