Breast Cancer: Targets and Therapy (Jul 2023)

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

  • Sharaf B,
  • Abu-Fares H,
  • Tamimi F,
  • Al-Sawajneh S,
  • Salama O,
  • Daoud R,
  • Alhajahjeh A,
  • Al-Lababidi S,
  • Abdel-Razeq H

Journal volume & issue
Vol. Volume 15
pp. 541 – 548

Abstract

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Baha’ Sharaf, Hala Abu-Fares, Faris Tamimi, Suhaib Al-Sawajneh, Osama Salama, Rand Daoud, Abdulrahman Alhajahjeh, Sawsan Al-Lababidi, Hikmat Abdel-Razeq Department of Internal Medicine, King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman, 11941, Jordan, Tel +962-6 5300460, Ext: 1000, Email [email protected]: 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

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