Abstract
Purpose
We have limited capability to predict survival among patients treated for metastatic HER2-positive breast cancer. Further research is warranted to identify significant prognostic and predictive factors.
Methods
We identified all HER2-positive metastatic breast cancer patients receiving trastuzumab at the Sunnybrook Odette Cancer Centre (SOCC) from 1999 to 2013 through the Cancer Care Ontario (CCO) Registry (n = 256) and selected patients with available pathology reports (n = 154). A retrospective review was completed documenting clinical, pathologic, and laboratory characteristics at the time of first trastuzumab therapy and survival outcomes. Cox proportional hazards regression models were used to identify prognostic factors for overall survival (OS) (primary endpoint) and failure-free survival (FFS), adjusted for the known prognostic factors of the presence of CNS metastases and the presence of ≥ 2 distant metastatic sites.
Results
A multivariable model identified older age [hazard ratio (HR) 1.18/decade, 95% confidence interval (CI) 1.02–1.37)], increased platelet-to-lymphocyte ratio (PLR) (HR 1.75/log-unit, 95% CI 1.25–2.46), increased serum alkaline phosphatase (ALP) (HR 1.87/log-unit, 95% CI 1.41–2.49), and ER positivity (HR 0.63, 95% CI 0.42–0.96) as significant prognostic factors for OS after adjusting for the presence of CNS metastasis (HR 3.19, 95% CI 1.59–6.38) and the presence of ≥ 2 distant metastatic sites (HR 2.10, 95% CI 1.19–3.70). PLR (HR 1.54/log-unit, 95% CI 1.12–2.12) was the only prognostic factor associated with FFS after adjusting for CNS and ≥ 2 distant metastatic sites.
Conclusion
Older age, increased PLR, and ALP were identified as poor prognostic factors and ER positivity as a favorable prognostic factor for OS after adjusting for the presence of CNS metastasis and the presence of number of ≥ 2 distant metastatic sites. Increased PLR was a poor prognostic factor for both OS and FFS, and warrants further investigation into its prognostic ability amongst patients with HER2-positive metastatic breast cancer.
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Acknowledgements
We would like to acknowledge our funding for this project by the Canadian Institutes of Health Research (CIHR), Canadian Cancer Society (grant # 319406) and Sunnybrook Research Institute Innovation Fund and The University of Toronto. We would also like to thank CCO and the health care professionals and breast cancer patients at SOCC for their help with this project.
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KI. Pritchard has consulted for Pfizer, Roche, Amgen, Novartis, Eisai and Genomic Health. JMS. Bartlett has consulted for Insight Genetics, BioNTech, Due North, Biotheranostics and Oncology Education. The other authors have no conflicts of interest to declare.
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Blanchette, P.S., Desautels, D.N., Pond, G.R. et al. Factors influencing survival among patients with HER2-positive metastatic breast cancer treated with trastuzumab. Breast Cancer Res Treat 170, 169–177 (2018). https://doi.org/10.1007/s10549-018-4734-x
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DOI: https://doi.org/10.1007/s10549-018-4734-x