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Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients

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Abstract

Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients. Clinical information for age at diagnosis, stage, pathology, treatment and outcome was assembled for the study cohort; the median follow-up was 12.4 years. PR status was determined by immunohistochemistry using a rabbit monoclonal antibody on tissue microarrays built from breast tumor surgical excisions. Survival analyses, Kaplan–Meier functions and Cox proportional hazards regression models were applied to assess the associations between PR and breast cancer specific survival. Progesterone receptor was positive in 51% of all cases and 67% of estrogen receptor positive (ER+) cases. Survival analyses for both the whole cohort and ER+ cases given tamoxifen therapy showed that patients with PR+ tumors had 24% higher relative probability for breast cancer specific survival as compared to PR− patients, adjusted for ER, HER2, age at diagnosis, grade, tumor size, lymph node status and lymphovascular invasion covariates. Higher PR expression showed stronger association with patient survival. Log-likelihood ratio tests of multivariate Cox proportional hazards regression models demonstrated that PR was an independent statistically significant factor for breast cancer specific survival in both the whole cohort and among ER+ cases treated with tamoxifen. PR adds significant prognostic value in breast cancer beyond that obtained with estrogen receptor alone.

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Acknowledgments

This research was supported by a Canadian Breast Cancer Research Alliance Translation Acceleration Grant and the National Cancer Institute Strategic Partnering to Evaluate Cancer Signatures program (UO1-CA114722). Torsten O. Nielsen is a Michael Smith Foundation for Health Research Senior Scholar. The Genetic Pathology Evaluation Centre is supported by an unrestricted educational grant from sanofi-aventis. We thank Blake Gilks, Allen Gown, and David Huntsman for assistance during assay development (staining and scoring).

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Authors and Affiliations

  1. Genetic Pathology Evaluation Centre at Vancouver General Hospital, Prostate Center, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada

    Shuzhen Liu, Erika Mehl, Samuel Leung, Ashish Rajput, Maggie C. U. Cheang & Torsten O. Nielsen

  2. Breast Cancer Outcomes Unit and Population and Preventive Oncology Programs at BC Cancer Agency, Vancouver, BC, Canada

    Stephen K. Chia

  3. Anatomical Pathology, Room JP1401, 855 West 12th Avenue, Vancouver, BC, V5Z 1M9, Canada

    Torsten O. Nielsen

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  1. Shuzhen Liu
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Correspondence to Torsten O. Nielsen.

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Liu, S., Chia, S.K., Mehl, E. et al. Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients. Breast Cancer Res Treat 119, 53–61 (2010). https://doi.org/10.1007/s10549-009-0318-0

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  • DOI: https://doi.org/10.1007/s10549-009-0318-0

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