Discoveries in Breast Cancer

Discoveries in Breast Cancer

Disclosures: Bao reports being employed by Pfizer. Please see study for all other authors’ relevant financial disclosures.
July 16, 2021
1 min read

HER2–low expression linked to inferior PFS after treatment with CDK4/6 inhibitors

Disclosures: Bao reports being employed by Pfizer. Please see study for all other authors’ relevant financial disclosures.
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HER2–low expression was linked to inferior progression-free survival among breast cancer patients with estrogen receptor-positive, HER2-negative metastatic disease treated with CDK4/6 inhibitors, according to research presented at ASCO 2021.

“Markers for the efficacy of CDK 4/6 inhibitors in [ER-positive], HER2-negative advanced breast cancer are currently limited,” Kelvin K. H. Bao, MBBChir, MA, FRCR, from the department of clinical oncology at Queen Elizabeth Hospital, Hong Kong, said during a presentation. “Studies have identified bidirectional cross-talks that exist between ER and HER2 pathways. And they contribute to endocrine resistance.

“The breast cancer subgroup with the newly proposed name of HER2 low, defined as tumors with an HER2 IHC score of 1+ or 2+ with negative ISH, could be a potential marker candidate,” she continued.

Bao and colleagues evaluated the impact of low HER2 expression on outcomes in patients with breast cancer who had ER-positive, HER2-negative metastatic disease.

Using their institution’s cancer registry, they identified 106 patients with metastatic breast cancer who received CDK4/6 inhibitors in addition to letrozole or fulvestrant from March 2017 through June 2020.

Among patients included in the study, 84% received palbociclib while the others received ribociclib. Approximately half (50.9%) of patients received CDK4/6 inhibitors as first-line treatment, and 77.3% of patients were considered to have HER2–low expressing disease.

After adjusting for line of treatment, progesterone receptor status and extent of disease, Bao and colleagues determined that HER2–low expression was associated with significantly lower progression free survival compared with those who had HER2-IHC 0 disease (8.9 months vs. 18.8 months; P = .041).

“We observed that in patients with ER-positive, HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitor, HER2-low expression was associated with an inferior PFS and may be a potential marker candidate for CDK 4/6 inhibitor performance,” Bao said. “In fact, our results complement the findings of a recent study by Prat et al. on the intrinsic subtypes genomic analysis of the MONALEESA trials, where the HER2-enriched subtype was shown to have a higher risk of disease progression comparing to the luminal A subtype.”