Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma

Authors

  • Wendy Y. Chen M.D., M.P.H.,

    Corresponding author
    1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
    2. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts
    • Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115
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    • Fax: (617) 525-2008

  • Susan E. Hankinson,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts
    2. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • Stuart J. Schnitt,

    1. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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  • Bernard A. Rosner,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts
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  • Michelle D. Holmes,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts
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  • Graham A. Colditz

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts
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  • Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31–June 3, 2003.

Abstract

BACKGROUND

Observational studies and randomized trials have demonstrated that hormone replacement therapy (HRT) increases the recipient's risk of developing breast carcinoma. Because it is known that some breast malignancies are hormonally responsive and that others are not, it has been hypothesized that HRT may be associated with the development of estrogen receptor (ER)-positive/progesterone receptor (PR)-positive breast carcinoma more so than with the development of ER-negative/PR-negative breast carcinoma.

METHODS

The Nurses' Health Study is a prospective cohort study that enrolled 121,700 female registered nurses ages 30–55 years in 1976. In the current study, the authors analyzed 2548 malignancies that developed among eligible postmenopausal women in that cohort between 1980 and 2000 and for which data on ER and PR status were available.

RESULTS

Compared with women who had never used HRT, current long-term users of HRT were more likely to develop ER-positive/PR-positive breast carcinoma (multivariate risk ratio [RR], 1.80; 95% confidence interval [CI], 1.52–2.12) but were not any more likely to develop ER-negative/PR-negative disease (multivariate RR, 1.00; 95% CI, 0.72–1.39). This effect grew stronger with increasing duration of current HRT use and was also more pronounced among women with body mass index < 25 kg/m2. Furthermore, the association between HRT use and ER-positive/PR-positive disease was stronger among patients receiving combined HRT (CHRT) regimens, which included estrogen and progesterone, than among users of estrogen alone (ERT). In addition, tumors tended to develop more quickly in current users of CHRT than in ERT users.

CONCLUSIONS

The finding that current users of HRT were more likely to develop ER-positive/PR-positive tumors than they were to develop ER-negative/PR-negative ones suggests that both endogenous and exogenous hormonal factors may influence breast tumor characteristics. In analyses of the effects of hormonal factors on breast tumor development, ER-positive/PR-positive tumors and ER-negative/PR-negative tumors should be considered separately from each other Cancer 2004. © 2004 American Cancer Society.

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