© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 13, 971-980,
July 2, 2003
© 2003 Oxford University Press
ARTICLE |
Roles of Radiation Dose, Chemotherapy, and Hormonal Factors in Breast Cancer Following Hodgkin’s Disease
Affiliations of authors: F. E. van Leeuwen, W. J. Klokman, E. C. Dahler (Department of Epidemiology), B. M. P. Aleman, N. S. Russell (Department of Radiotherapy), A. Broeks (Department of Experimental Therapy), Netherlands Cancer Institute, Amsterdam, The Netherlands; M. Stovall, Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX; M. B. van’t Veer, Department of Hematology, Erasmus Medical Center/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands; E. M. Noordijk, Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands; M. A. Crommelin, Catharina Hospital, Eindhoven, The Netherlands; M. Gospodarowicz, the Princess Margaret Hospital, University of Toronto, Ontario, Canada; L. B. Travis, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Correspondence to: Flora E. van Leeuwen, Ph.D., Department of Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (e-mail: f.v.leeuwen{at}nki.nl).
Background: Female survivors of Hodgkin’s disease (HD) have a strongly elevated risk of breast cancer, but factors responsible for the increased risk are not well known. Methods: We investigated the effects of radiation dose, chemotherapy (CT), and reproductive factors on breast cancer risk in a nested case–control study in The Netherlands in a cohort of 770 female patients who had been diagnosed with HD before age 41. Detailed treatment information and data on reproductive factors were collected for 48 case patients who developed breast cancer 5 or more years after diagnosis of HD and 175 matched control subjects. The radiation dose was estimated to the area of the breast where the case patient’s tumor had developed and to a comparable location in matched control subjects. Relative risks (RRs) of breast cancer were calculated by conditional logistic regression. Statistical tests were two-sided. Results: The risk of breast cancer increased statistically significantly with radiation dose (Ptrend = .01); patients who received 38.5 Gy or more had an RR of 4.5 (95% confidence interval [CI] = 1.3 to 16) times that of patients who received less than 4 Gy. Patients who received both CT and radiotherapy (RT) had a statistically significantly lower risk than those treated with RT alone (RR = 0.45, 95% CI = 0.22 to 0.91). Breast cancer risk increased with increasing radiation dose among patients who received RT only (RR = 12.7, 95% CI = 1.8 to 86, for patients receiving 
38.5 Gy) but not among patients treated with CT and RT. Sixty-nine percent of control subjects treated with RT and more than six cycles of CT, but only 9% of those who received RT alone, reached menopause before age 41. Reaching menopause before age 36 was associated with a strongly reduced risk of breast cancer (RR = 0.06, 95% CI = 0.01 to 0.45). Conclusion: Breast cancer risk increases with increasing radiation dose up to at least 40 Gy. The substantial risk reduction associated with CT may reflect its effect on menopausal age, suggesting that ovarian hormones promote tumorigenesis after radiation has produced an initiating event.
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Correspondence about this Article
- Re: Roles of Radiation Dose, Chemotherapy, and Hormonal Factors in Breast Cancer Following Hodgkin’s Disease
- Steven Narod and Jan Lubinski
J Natl Cancer Inst 2003 95: 1552.[Extract] [Full Text] [PDF]
- Re: Radiation Therapy in the Treatment of Hodgkin’s Disease—Do You See What I See?
- Berthe M. P. Aleman, Nicola S. Russell, Harry Bartelink, and Flora E. van Leeuwen
J Natl Cancer Inst 2004 96: 235-236.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Radiation Therapy in the Treatment of Hodgkin’s Disease—Do You See What I See?
- Dan L. Longo
J Natl Cancer Inst 2004 96: 236-237.[Extract] [Full Text] [PDF]
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