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
. 2025 Jun;211(2):351-362.
doi: 10.1007/s10549-025-07649-y. Epub 2025 Mar 25.

Treatment patterns and outcomes in HER2-low metastatic breast cancer patients previously treated with chemotherapy: a US real-world cohort study

Shanu Modi  1 , Suyuan Zhang  2 , Danalyn Byng  3 , Shannon Hunter  2 , Alessandria Strübing  3 , Yan Xiong  2 , Kyle Dunton  4 , Zacharie Mbanya  5 , William Jacot  6
Affiliations

Treatment patterns and outcomes in HER2-low metastatic breast cancer patients previously treated with chemotherapy: a US real-world cohort study

Shanu Modi et al. Breast Cancer Res Treat. 2025 Jun.

Abstract

Purpose: Real-world outcomes are poorly understood for patients with human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1+ or 2+ with negative in situ hybridization) metastatic breast cancer (mBC).

Methods: Using for the first time a nationwide electronic health record-derived de-identified database, we assessed demographics, treatment patterns, and outcomes of patients with HER2-low mBC who previously received one line of chemotherapy in the metastatic setting. The post-chemotherapy line was termed the index line of therapy (LOT).

Results: 3765 patients [hormone receptor (HR)-positive: 78.8%, HR-negative: 21.0%] met the inclusion criteria (1 January 2011-30 April 2023). 61.7% of HR-positive patients received endocrine therapy prior to the index LOT. The largest patient percentage received single-agent chemotherapy at the index and subsequent two LOTs. For the overall cohort, the median real-world time to treatment discontinuation/death was 4.1 months (95% CI: 3.9-4.2) and the median real-world time to next treatment/death was 5.1 months (95% CI: 4.8-5.3) from the index LOT. Median real-world overall survival (all patients) was 15.8 months (95% confidence interval: 15.2-16.5, median follow-up = 54.5 months) from the index LOT.

Conclusion: These data highlight the unmet clinical needs of patients with HER2-low mBC by characterizing the treatment patterns and poor outcomes in this population on the current standard of care.

Keywords: Cohort study; HER2-low; Metastatic breast cancer; Real-world evidence; T-DXd.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: SM: Grants or contracts (to institution): AstraZeneca, Daiichi Sankyo, Duality Bio, Genentech, Nuvation, Seagen; consulting fees: AstraZeneca, Daiichi Sankyo, Duality Bio, Eli Lilly, Genentech, Gilead, GSK, Macrogenics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Daiichi Sankyo, Seagen; support for attending meetings and/or travel: AstraZeneca, Daiichi Sankyo, Seagen. SZ, YX, SH: Employees of Daiichi Sankyo, Inc. DB, AS: Employees of Daiichi Sankyo Europe GmbH. KD: Employee of Daiichi Sankyo UK Ltd. ZM: Employee of AstraZeneca. WJ: Grants or contracts: AstraZeneca, Daiichi Sankyo; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, BMS, Daiichi Sankyo, Eisai, Lilly (France), MSD, Novartis, Pfizer, Roche, Seagen; support for attending meetings and/or travel: AstraZeneca, Chugai, Eisai, GSK, Lilly (France), Novartis, Pfizer, Pierre Fabre, Roche, Sanofi Aventis; participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, BMS, Daiichi Sankyo, Eisai, Gilead, Lilly (France), MSD, Novartis, Pfizer, Roche, Seagen. Ethical approval: All the results presented in this article are in aggregate form, and no personally identifiable information was used for this study. The data were de-identified and subject to obligations to prevent re-identification and protect patient confidentiality.

Figures

Fig. 1
Fig. 1
Cohort attrition diagram. The data source for this study was the Flatiron Health mBC database, encompassing approximately 800 sites of care in the US. The study cohort consisted of adult patients with HER2-low (IHC 1+ or 2+ with negative ISH) mBC who initiated a subsequent LOT following 1 qualifying line of chemotherapy in the metastatic setting. The subsequent LOT was referred to as the index LOT, and the start date of the index LOT was referred to as the index LOT date. HER2, human epidermal growth factor 2; HR; hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; LOT, line of therapy; mBC, metastatic breast cancer; T-DXd, trastuzumab-deruxtecan
Fig. 2
Fig. 2
Treatment patterns before and after index treatment in the HR-positive and HR-negative cohorts. Sankey diagram showing treatments in > 1% of patients for the pre-index LOT, index LOT, and 2 subsequent LOTs (if any) in A HR-positive patients (n = 2966) and B HR-negative patients (n = 792). All patients (100%) received chemotherapy in the index LOT −1 per study inclusion criteria. Chemo + ET not given together as combination therapy. Treating with chemotherapy is known to re-sensitize tumors to ET, thus this may reflect situations where patients are on ET, then a few cycles of chemotherapy are given to reduce tumor load and then continue treatment with ET. IO was given alone or in combination with other therapies. Percentage shown inside the bars wherein the denominator for each regimen includes the number of people who received the previous line, including death and censored events. CDK4/6i cyclin dependent 4/6 kinase inhibitor, ET endocrine therapy, HR hormone receptor, IO immunotherapy, LOT line of therapy
Fig. 3
Fig. 3
Real world outcomes from the index LOT date in the HR-positive and HR-negative cohorts. Survival and discontinuation outcomes by HR status: A rwTTD/D, rwTTNT/D, and rwOS in the HR-positive cohort over a median follow-up time of 57.0 months (95% CI: 52.4–62.1) from the initial treatment date by reverse Kaplan–Meier method; B rwTTD/D, rwTTNT/D, and rwOS in the HR-negative cohort over a median follow-up of 42.6 months (36.4–49.1) from the initial treatment date by reverse Kaplan–Meier method. CI confidence interval, HR hormone receptor, rwOS real-world overall survival, rwTTD/D real-world time to treatment discontinuation or death, rwTTNT/D real-world time to next treatment or death
See this image and copyright information in PMC

References

    1. Tarantino P et al (2020) HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol 38:1951–1962. 10.1200/jco.19.02488 - PubMed
    1. Viale G et al (2023) Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer. ESMO Open 8:101615. 10.1016/j.esmoop.2023.101615 - PMC - PubMed
    1. Schettini F et al (2021) Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer 7:1. 10.1038/s41523-020-00208-2 - PMC - PubMed
    1. Hamilton EP et al (2024) Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): updated survival results of DESTINY-Breast03. J Clin Oncol 42:1025–1025. 10.1200/JCO.2024.42.16_suppl.1025
    1. Mosele F et al (2023) Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nat Med 29:2110–2120. 10.1038/s41591-023-02478-2 - PMC - PubMed