Breast cancer

ESMO 2021: Instability in HER2 expression over disease progression opens up treatment options


HER2-low expression is highly unstable during breast cancer evolution suggesting that biopsies of locoregional relapses or distant metastases might reveal potentially new therapeutic opportunities for some patients, research suggests.

Presenting at ESMO Breast Cancer 2021, Dr Federica Miglietta said access to anti-HER2 agents is currently restricted to patients with HER2-positive patients as defined by IHC score 3+ and/or HER2 gene amplification by ISH.

Yet about half of patients traditionally classified as HER2-negative demonstrate HER2-low expression defined as IHC score 1+ of 2+ and ISH not amplified.

A study of 547 patients comparing matched samples of primary breast cancer (PBC) and locoregional relapse/distant metastases found HER2-low represented 45% of the overall HER2-negative PBC cohort and 49% of the HER2-negative relapse cohort.

The study also found the overall rate of HER2 discordance between the primary breast cancer and relapse samples was 39%.

Most of the discordance was driven by HER2-0 at PBC switching to HER2-low at relapse (15% conversion) and HER2-low switching to HER2 at relapse (14% conversion).

“As expected, HER2-positive breast cancer was the most stable with 10% of the total cases showing either a gain or loss of HER2 positivity.”

Dr Miglietta, from the University of Padova in Italy, said HER2 expression tended to be more unstable in HR+/HER2-negative patients than triple negative patients (discordance rate 45% v 37% respectively).

She said novel HER2-targeted agents have recently showed promising activity in heavily pre-treated advanced breast patients exhibiting HER2-low expression.

These included antibody-drug conjugates such as trastuzumab deruxtecan and trastuzumab duocarmazine.

“Our findings stress the importance of retesting HER2 at relapse since it may open new therapeutic opportunities in a not negligible proportion of HER2-negative breast cancer patients and better assist clinicians in the selection of patients suitable for novel HER2-targeted strategies in the context of clinical trials.”

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