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The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer

  • Epidemiology
  • Published:
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Abstract

Purpose

Combinations of endocrine therapy (ET) and targeted therapy (CDK4/6 or mTOR inhibitors) are standard of care for HR+/HER2− metastatic breast cancer (MBC). When ET is not effective, chemotherapy is commonly used. However, clinical outcomes of chemotherapy in the endocrine-resistant setting are limited. The purpose of this study was to identify predictive factors and the compare efficacies of chemotherapy agents in endocrine-resistant MBC.

Methods

We conducted a retrospective study of patients with HR+/HER2− MBC who received chemotherapy after progression on ET with or without targeted therapy at MD Anderson Cancer Center from 1999 to 2017. We collected baseline clinicopathological and all treatment data. Primary endpoint was time to treatment failure (TTF) of first-line chemotherapy for MBC.

Results

For the 1258 patients analyzed, mean age was 55.3 years (range 21–91). Previous treatment with targeted therapy was recorded for 390 patients (31%): 264 with CDK4/6 inhibitor, 205 with mTOR inhibitor, and 79 treated with both. The most frequent chemotherapy agents were capecitabine (48.9%) and taxanes (28.6%). After adjustment for all factors in a multivariate model, previous treatment with a CDK4/6 inhibitor had the strongest negative effect on TTF regardless of ET duration (hazard ratio [HR] 1.84; 95%CI 1.49–2.27; p < 0.001). Conversely, capecitabine had significantly longer median TTF than taxanes regardless of whether patients had prior exposure to taxanes in primary setting (6.1 vs 4.9 months; HR 0.64; 95%CI 0.55–0.75; p < 0.001).

Conclusions

Previous exposure to CDK4/6 inhibitor had a negative predictive effect for the efficacy of chemotherapy. Capecitabine had the best efficacy against endocrine-resistant breast cancer.

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Abbreviations

ET:

Endocrine therapy

HR+:

Hormone receptor-positive

HER2−:

Human epidermal growth factor receptor 2-negative

CDK4/6:

Cyclin-dependent kinase 4 and 6

mTOR:

Mammalian target of rapamycin

ER:

Estrogen receptor

PR:

Progesterone receptor

IBC:

Inflammatory breast cancer

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Acknowledgements

We would like to thank Sunita Patterson (Scientific Publications, Research Medical Library, MD Anderson Cancer Center) for her help in editing this article and Limin Hsu, Modesto Patangan, and Akshara Raghavendra, our data management team, for help with our database.

Funding

This research was supported by the Morgan Welch Inflammatory Breast Cancer Research Program, a State of Texas Rare and Aggressive Breast Cancer Research Program Grant, and National Institutes of Health/National Cancer Institute grant P30 CA016672 (Cancer Center Support Grant; used the Biostatistics Resource Group and the Clinical and Translational Research Center).

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Authors and Affiliations

  1. Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sudpreeda Chainitikun, Ruben Rodriguez-Bautista, Toshiaki Iwase, Debu Tripathy, Takeo Fujii & Naoto T. Ueno

  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    James P. Long

  3. Department of Personalize Medicine Laboratory, National Cancer Institute, Mexico City, Mexico

    Ruben Rodriguez-Bautista

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  1. Sudpreeda Chainitikun
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  2. James P. Long
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Correspondence to Naoto T. Ueno.

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The authors declare that they have no conflicts of interest.

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This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of The University of Texas MD Anderson Cancer Center (PA18-1135) approved this study.

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Chainitikun, S., Long, J.P., Rodriguez-Bautista, R. et al. The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer. Breast Cancer Res Treat 183, 729–739 (2020). https://doi.org/10.1007/s10549-020-05837-6

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