Risk of Subsequent Breast Cancer in Women with Early Stage HER2-Positive Breast Cancer in a Large Community Health Plan

Abstract

Purpose

Clinical outcomes have improved for women with early stage, HER2-positive breast cancer following the FDA approval of adjuvant trastuzumab use in 2006. However, only limited information exists on such patients’ outcomes in real-world settings outside of clinical trials. We examined the risk of subsequent breast cancer in women with HER-2 positive disease, and the impact of trastuzumab use, in a large California community-based health plan.

Patients and Methods

A cohort of 3550 women with HER2-positive breast cancer (stages I–III) from 2009–2017 were followed through December 2018. We calculated subsequent breast cancer (SBC) rates overall and by trastuzumab use. Multivariable Cox proportional hazards modeling was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for SBC by trastuzumab use.

Results

Within the cohort diagnosed with HER2-positive disease, 81% received adjuvant trastuzumab. After 4.1 mean years follow-up (maximum 10 years), the risk of SBC was 22% lower with adjuvant trastuzumab use (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.66–0.92) compared with non-use. The cumulative incidence of SBC precipitously rose two years after diagnosis and by the 10th year, the cumulative incidence was 31% among those who had trastuzumab therapy versus 34% without this therapy.

Conclusion

In community practice settings, the cumulative incidence of SBC in patients with early stage HER2-positive BC was 31% at 10 years in a cohort treated with adjuvant trastuzumab. Trastuzumab use was associated with a 22% reduced risk of developing SBC. This residual disease burden suggests breast cancer outcomes may be improved with further treatment given the advent of next-generation HER2-targeted therapies.

Keywords:

• breast cancer
• survival
• mortality
• HER2 positive
• recurrence
• relapse
• cohort study
• real world

Data Sharing Statement

This dataset includes identifiers; thus investigators cannot share the dataset at this time. However, de-identified dataset may be made available to requestors following data use agreements and KPSC IRB approval. Please contact corresponding author.

Ethics Approval and Informed Consent

The KPSC Institutional Review Board reviewed and approved this study; as the study was based on electronic health records (EHR), written or verbal patient consent was waived.

Acknowledgments

The authors thank the patients of Kaiser Permanente for helping to improve care with information collected through the electronic health record systems.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Dr Reina Haque reports Kaiser Permanente Southern California received research support from AstraZeneca for a study outside submitted work. Dr Nina Oestreicher is a former employee of Puma Biotechnology. Dr Deepa Lalla is affiliated with PUMA Biotechnology. Dr Rowan T Chlebowski reports personal fees from Up-to-Date, Novartis, and AstraZeneca, during the conduct of the study. The authors report no other conflicts of interest in this work.

Additional information

Funding

Kaiser Permanente Southern California received research support from PUMA Biotechnology.