Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Feb:67:116-123.
doi: 10.1016/j.breast.2023.01.005. Epub 2023 Jan 12.

How I treat HER2-low advanced breast cancer

Ilana Schlam  1 , Sara M Tolaney  2 , Paolo Tarantino  3
Affiliations
Review

How I treat HER2-low advanced breast cancer

Ilana Schlam et al. Breast. 2023 Feb.

Abstract

Introduction: Targeting low levels of human receptor epidermal growth factor 2 (HER2) expression has reshaped the treatment paradigm for half of the patients with advanced breast cancer. HER2-low is currently defined as a HER2 immunohistochemical expression of 1+ or 2+ without amplification by in-situ hybridization. Until recently, HER2-targeted agents were ineffective in treating patients with HER2-low disease.

Areas covered: In this narrative review, we summarize the current management of HER2-low breast cancer. We highlight the findings of the DESTINY-Breast 04 phase 3 trial, which confirmed the efficacy of trastuzumab-deruxtecan (T-DXd) for the treatment of patients with advanced, pretreated HER2-low breast cancer. We also discuss how to implement this new treatment option in treatment algorithms of hormone receptor (HR)-positive and triple-negative tumors, as well as how to optimally manage selected toxicities of T-DXd.

Expert opinion: T-DXd is currently the standard of care for patients with advanced, pretreated, HER2-low breast cancer. Based on the design of the DESTINY-Breast04 trial, the current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer. Up to 10-15% of the patients receiving T-DXd are expected to develop interstitial lung disease, which in 1-2% of the cases can be fatal. Adequate monitoring and prompt management are required to minimize the impact of ILD and to safely implement T-DXd in clinical practice.

Keywords: Breast cancer; HER2; HER2-Low; Trastuzumab-deruxtecan.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Summary of selected studies conducted to determine the prognostic significance of HER2-low disease [[21], [22]]. Abbreviations: HER2: human epidermal growth factor receptor 2, HR+: hormone receptor-positive, n= sample size, TNBC: triple-negative breast cancerThe studies that showed no difference in overall survival are marked in green , and those that showed a statistically significant difference in overall survival in purple (White = not evaluated).*Inflammatory breast cancer only
Fig. 2
Fig. 2
Proposed treatment algorithm for hormone receptor-positive (A) and hormone receptor-negative (B) HER2-low breast cancer. Abbreviations: CDK: cyclin dependent kinase, gBRCA 1/2: germline BRCA 1 or 2 pathogenic variant, HER2: human epidermal growth factor receptor 2, HR: hormone receptor, PARP: poly-ADP ribose polymerase, PDL1: program cell death ligand 1, T-DXd: trastuzumab deruxtecan
See this image and copyright information in PMC

References

    1. Lei S., Zheng R., Zhang S., et al. Global patterns of breast cancer incidence and mortality: a population-based cancer registry data analysis from 2000 to 2020. Cancer Commun. 2021;41(11):1183–1194. Nov. - PMC - PubMed
    1. DeSantis C.E., Ma J., Gaudet M.M., et al. Breast cancer statistics, 2019. CA A Cancer J Clin. 2019;69(6):438–451. - PubMed
    1. Swain S.M., Baselga J., Kim S.B., et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–734. Feb 19. - PMC - PubMed
    1. Loibl S.J.J., Sonnenblock A., Parlier D., Winer E., et al. VP6-2022: adjuvant pertuzumab and trastuzumab in patients with early HER-2 positive breast cancer in APHINITY: 8.4 years' follow-up. Ann Oncol. 2022:2022. July 15.
    1. Wolff A.C., Hammond M.E.H., Allison K.H., et al. Human epidermal growth factor receptor 2 testing in breast cancer: American society of clinical oncology/college of American pathologists clinical practice guideline focused update. J Clin Oncol. 2018;36(20):2105–2122. Jul 10. - PubMed