Differences in Treatment Outcomes Between Patients with HER2-Low versus HER2-Zero, Hormone Receptor-Positive Advanced-Stage Breast Cancer Treated with Ribociclib

Abstract

Background

Metastatic breast cancers (MBC) with no expression of human epidermal growth factor receptor-2 (HER2) are recently classified into two groups; HER2-zero [HER2-immunohistochemistry (IHC) score of 0 (IHC-0)] and HER2-low, defined as those with IHC score of 1+ or 2+ with negative in situ hybridization (ISH) assay. We investigate differences in treatment outcomes between both groups treated with endocrine therapy (ET) and the CDK4/6 inhibitor ribociclib.

Methods

Data were retrospectively collected for patients with HR-positive+/HER2−negative MBC who received ribociclib with an aromatase inhibitor (AI) or fulvestrant and were divided into two groups: HER2-zero and HER2-low.

Results

A total of 257 patients, median age 48 (22–87) years, all with MBC who were treated with ET and ribociclib were enrolled. One hundred and thirty-seven (53.3%) patients had de novo MBC, and majority (n = 162, 63.0%) received ribociclib as a first-line therapy. In total, 114 (44.4%) patients had HER2-zero (IHC-0), while 143 (55.6%) others had HER2-low disease. The overall response rate (ORR) was 52.0% for the HER2-zero group compared to 39.4% for the HER2-low group, p = 0.005. The median PFS was 22.2 (95% confidence interval [CI], 19.4-NR) months for HER2-zero versus 17.3 (95% CI, 14.1–20.6) months for HER2-low, P = 0.0039. In multivariable analysis, HER2-low expression remained significant determinant of inferior PFS after adjusting for other factors, including the site of metastasis, prior chemotherapy, and the line of treatment.

Conclusion

In patients with MBC treated with ET and ribociclib, level of HER2 negativity may affect treatment outcomes; patients with HER2-zero had better response rate and PFS compared to those with HER2-low disease. These findings, if confirmed in larger studies, may help oncologists select patients with HER2-low for better treatment options.

Keywords:

• breast cancer
• CDK4/6 inhibitors
• endocrine therapy
• HER2-low
• HER2-zero

Data Sharing Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Declarations

The study was approved by the Institutional Review Board (IRB) (Approval Number: 20 KHCC 136) at King Hussein Cancer Center, and all procedures were performed based on the regulations of Helsinki. Given the retrospective nature of the study and lack of patients’ identifiers, consent to participate was waived the IRB.

Consent for Publication

Data submitted are entirely unidentifiable, and there are no details on individuals reported within the manuscript.

Acknowledgment

The abstract of this paper was presented at the 2022 San Antonio Breast Cancer Symposium (SABCS), San Antonio, TX, USA (06-10 December 2022) as a poster presentation with interim findings. The poster’s abstract was published as a conference proceeding: Cancer Research; 2023; 83 (5_Supplement): P4-07-33. Available at: https://aacrjournals.org/cancerres/article/83/5_Supplement/P4-07-33/717994/Abstract-P4-07-33-Differences-in-Treatment

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declared that they have no conflicting interest.

Additional information

Funding

This research was not funded.