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Racial disparities in overall survival after the introduction of cyclin-dependent kinase 4/6 inhibitors for patients with hormone receptor-positive, HER2-negative metastatic breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have improved HR + /HER2− metastatic breast cancer (MBC) outcomes. However, it is still unclear whether the response to CDK4/6i is similar for all races. Therefore, we aimed to assess overall survival (OS) trends stratified by race in patients with HR + /HER2− MBC after the approval of CDK4/6i, as part of the standard of care, in 2015.

Methods

We performed a population-based study using the SEER database. Patients with HR + /HER2− MBC were divided into two time-based cohorts: 1) pre-CDK4/6i era (diagnosed in 2011–2013) and 2) post-CDK4/6i era (diagnosed in 2015–2017). We used propensity score matching and identified 2,684 patients in each cohort that matched in several characteristics. Kaplan–Meier methods were used to estimate 2-year OS. Association between cohort and OS was evaluated using marginal Cox proportional hazards models with robust sandwich variance estimator. We conducted competing risk analysis to estimate the risk of breast cancer death in both cohorts.

Results

The 2-year OS rate was 65% for the post-CDK4/6i era and 62% for the pre-CDK4/6i era (stratified log-rank p = 0.025). The 2-year OS for non-Hispanic White (NHW) patients improved in the post-CDK4/6i era compared to the pre-CDK4/6i era (67% vs. 63%, p = 0.033). However, OS did not improve for non-Hispanic Black (NHB) (54% vs. 54%, p = 0.876) or Hispanic (67% vs. 65%, p = 0.617) groups. The risk of breast cancer death decreased in the post-CDK4/6i era as compared to the pre-CDK4/6i era (2-year risk of breast cancer death: 33% vs. 30%, p = 0.015); however, this effect was observed only in NHW (sHR 0.84, p = 0.005) women, but not in NHB (sHR 0.94, p = 0.630) or Hispanic (sHR 0.91, p = 0.550) women.

Conclusions

Our study confirms that outcomes for HR + /HER2− MBC have improved after CDK4/6i were introduced in 2015. However, this effect is primarily driven by the improved OS in NHW patients, without significant improvement in OS in NHB or Hispanics.

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Data availability

This study was conducted using matrices obtained from SEER*Stat 8.4.0.1. We used the SEER database research plus the 2021 submission to collect the data. The spreadsheet created for the data analysis is available for the public after a request for the SEER software from the NCI is granted. The selection criteria necessary to obtain the matrix we used for this study are specified in the methods section of the manuscript.

Abbreviations

OS:

Overall survival

MBC:

Metastatic breast cancer

HR:

Hormone receptor

CDK4/6i:

Cyclin-dependent kinase 4/6 inhibitors

SEER:

Surveillance, epidemiology and end results

NHW:

Non-Hispanic White

NHB:

Non-Hispanic Black

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Acknowledgements

The manuscript development is supported by The Einstein Paul Calabresi Career Development Program (NIH 5K12CA132783-08) and NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA (Grant Number UL1TR001073).

Funding

The authors declare that no funds or grants were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Medicine, Hematology/Oncology, Carole and Ray Neag Comprehensive Cancer Center, UCONN Health, Farmington, CT, USA

    Alvaro Alvarez

  2. Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Rd, Bronx, NY, 10461, USA

    Ana M. Bernal & Jesus Anampa

Authors
  1. Alvaro Alvarez
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  2. Ana M. Bernal
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  3. Jesus Anampa
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Contributions

All authors contributed to this study’s conception and design. JA performed data collection and statistical analysis; AMB contributed to material preparation. AA wrote the first draft of the manuscript and JA and AMB contributed to the following versions. All authors reviewed and approved the final draft.

Corresponding author

Correspondence to Jesus Anampa.

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Competing interests

Alvaro Alvarez, Ana M. Bernal, and Jesus Anampa declare no conflict of interest during the preparation of this manuscript.

Ethical approval

This study was approved by the Institutional Board Review (IRB) of Albert Einstein College of Medicine. Due to the retrospective nature of this study, no informed consent was required.

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Alvarez, A., Bernal, A.M. & Anampa, J. Racial disparities in overall survival after the introduction of cyclin-dependent kinase 4/6 inhibitors for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Breast Cancer Res Treat 198, 75–88 (2023). https://doi.org/10.1007/s10549-022-06847-2

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