Journal of the National Cancer Institute Advance Access originally published online on December 25, 2007
JNCI Journal of the National Cancer Institute 2008 100(1):32-40; doi:10.1093/jnci/djm267
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© The Author 2007. Published by Oxford University Press.
ARTICLES |
Effect of Systemic Adjuvant Treatment on Risk for Contralateral Breast Cancer in the Women's Environment, Cancer and Radiation Epidemiology Study
Affiliations of authors: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (L. Bertelsen, JHO, LM, JC); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (L. Bernstein, RWH, BL, DCT); Department of Epidemiology, University of Iowa, Iowa City, IA (CFL); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (KEM); Department of Epidemiology, School of Medicine, University of California, Irvine, CA (HAC); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York (CBB, MC, JLB); Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (BE); Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX (MS); International Epidemiology Institute, Rockville, MD (JDB); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (JDB); New York University School of Medicine, New York (RES)
Correspondence to: Lisbeth Bertelsen, MD, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark (e-mail: lisbethb{at}cancer.dk).
Background: Results from randomized trials indicate that treatment with tamoxifen or chemotherapy for primary breast cancer reduces the risk for contralateral breast cancer. However, less is known about how long the risk is reduced and the impact of factors such as age and menopausal status.
Methods: The study included 634 women with contralateral breast cancer (case patients) and 1158 women with unilateral breast cancer (control subjects) from the Women's Environment, Cancer and Radiation Epidemiology Study. The women were younger than age 55 when they were first diagnosed with breast cancer during 1985–1999. Rate ratios (RRs) and 95% confidence intervals (CIs) for contralateral breast cancer after treatment with chemotherapy or tamoxifen were assessed by multivariable adjusted conditional logistic regression analyses.
Results: Chemotherapy was associated with a lower risk for contralateral breast cancer (RR = 0.57, 95% CI = 0.42 to 0.75) than no chemotherapy. A statistically significant association between chemotherapy and reduced risk for contralateral breast cancer persisted up to 10 years after the first breast cancer diagnosis and was stronger among women who became postmenopausal within 1 year of the first breast cancer diagnosis (RR = 0.28, 95% CI = 0.11 to 0.76). Tamoxifen use was also associated with reduced risk for contralateral breast cancer (RR = 0.66, 95% CI = 0.50 to 0.88) compared with no use, and the association was statistically significant for 5 years after the first diagnosis.
Conclusion: The associations between chemotherapy and tamoxifen treatment and reduced risk for contralateral breast cancer appear to continue for 10 and 5 years, respectively, after the initial breast cancer is diagnosed. Ovarian suppression may have a role in the association between chemotherapy and reduced risk for contralateral breast cancer.
| CONTEXT AND CAVEATS Prior knowledge Breast cancer patients who are treated with tamoxifen or chemotherapy have a reduced risk for contralateral breast cancer. Study design Case–control study of women 54 years of age and younger with contralateral or unilateral nonmetastatic invasive breast cancer who were treated with tamoxifen, chemotherapy, radiotherapy, or surgery alone. Contributions Chemotherapy was associated with a reduced risk for contralateral breast cancer that continued 10 years after diagnosis. The association was stronger among women who became postmenopausal within 1 year of their first breast cancer diagnosis. Tamoxifen treatment was associated with a reduced risk for contralateral breast cancer that continued for 5 years after diagnosis. Implications Ovarian suppression may be involved in the association between reduced risk for contralateral breast cancer and chemotherapy. Limitations Although the study was restricted to nonmetastatic breast cancer, it is possible that metastases were classified as new primary breast cancers. Findings were based solely on breast cancer survivors; thus, the potential for survivor bias exists and the findings may not apply to all breast cancer patients. No adjustments for oophorectomy or ovarian radiation were performed.
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Manuscript received June 19, 2007; revised October 16, 2007; accepted November 8, 2007.
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J Natl Cancer Inst 2008 100: 1.
J Natl Cancer Inst 2008 100: 1.