Breast Cancer Coverage from Every Angle

Treatment Implications of Breast Tumors’ Switch to HER2-Low Status in Recurrence

By: Vanessa A. Carter, BS
Posted: Tuesday, June 22, 2021

Federica Miglietta, MD, of the University of Padova, Italy, and colleagues presented findings from reportedly the first study to determine how breast cancers evolve from HER2-negative primaries to HER2-low recurrent tumors during the European Society for Medical Oncology (ESMO) Breast Cancer Virtual Congress 2021 (Abstract 4MO_PR). Specifically, approximately 29% of patients converted to, or from, HER2-low status, and the researchers noted that this expression is unstable during the evolution of breast cancer.

“The results provide a whole new insight on how HER2-low tumors might evolve as a subgroup, possibly challenging the current dichotomy between HER2-positive and HER2-negative breast cancer,” stated Dr. Miglietta in an ESMO press release. “Our findings stress the importance of re-testing HER2 expression on tumor relapse since it might provide the option of new therapeutic opportunities, currently in a trial, and hopefully in the near future, in the clinic.”

The investigators focused on samples from 575 patients with matched primary and relapsed breast cancers. Primary tumor types included HER2-negative/hormone receptor (HR)-positive (luminal-like, 59%), HER2-positive (25%), and triple-negative (16%). Cases that were HER2-negative were classified as HER2-low or HER2-0.

The rates of HER2-low cases in primary and relapsed tumors were 34% and 38%, respectively. HER2-low status in primary and relapsed samples was more common in HER2-negative/HR-positive (47% and 54%) and triple-negative (41% and 40%) tumors (P = .006). With HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%), the overall rate of HER2 discordance was 38%.

About 9% of cases acquired or lost HER2 positivity. Patients who had a HER2-negative tumor that was luminal-like had a HER2 discordance rate of 45%, whereas those with triple-negative disease had a rate of 35% (P = .080); this was notably due to cases switching from HER2-0 to HER2-low in 40% of HER2-negative/HR-positive and 24% of triple-negative cases (P = .088).

Disclosure: For full disclosures of the study authors, visit

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