Women treated with radiation therapy for Hodgkin’s disease are at a strongly increased risk of breast cancer. Now, a new study suggests that this risk for breast cancer increases with increasing radiation dose. However, adding chemotherapy to radiation is associated with a reduction in this risk, possibly by inducing premature menopause. The findings appear in the July 2 issue of the Journal of the National Cancer Institute.
Flora E. van Leeuwen, Ph.D., of the Netherlands Cancer Institute, and her colleagues examined radiation dose, chemotherapy with alkylating agents, and reproductive factors in women diagnosed with Hodgkin’s disease before age 41. They compared these factors in 48 women who had developed breast cancer 5 or more years after their Hodgkin’s disease diagnosis and 175 matched control women who did not develop breast cancer.
Among patients treated with radiation alone, the risk of breast cancer increased with increasing radiation dose. Patients who received 38.5 Gy or more of radiation had 4.5 times the risk of breast cancer than patients who received less than 4 Gy. This dose-dependent increase in breast cancer risk was not seen in patients who received both radiation and chemotherapy. Patients who were treated with both chemotherapy and radiation therapy had a 61% lower risk of breast cancer than patients treated with radiation therapy alone.
The authors suggest that the decrease in risk of breast cancer in patients treated with radiation therapy and chemotherapy may be associated with chemotherapy-induced premature menopause. They found that 69% of patients treated with chemotherapy plus radiation reached menopause before the age of 41, compared with only 9% of patients treated with radiation alone. Reaching menopause before age 36 was associated with a 94% reduction in risk of breast cancer, compared with reaching menopause after age 45.
These findings suggest that ovarian hormones play a role in promoting tumor growth after radiation has initiated the process, potentially explaining why women who are exposed to radiation at a young age experience a much greater increase in breast cancer risk than women who are exposed in their 30s or 40s.
The authors acknowledge that their study involved only a small number of breast cancer patients and did not have the power to examine the role of other breast cancer risk factors, such as use of hormone replacement therapy and pregnancies before and after treatment for Hodgkin’s disease. More insight may come from a large, ongoing study coordinated by the National Cancer Institute, the authors say.
In an accompanying editorial, Dan L. Longo, M.D., of the National Institute on Aging in Baltimore, Md., says that although the current study is small, the findings are robust. “These data make a strong argument for radiation therapy as the initiator and physiologic sex hormones as promoters of secondary breast cancer,” he says.
However, he cautions that the findings are based on older chemotherapy regimens and that newer, less toxic forms of chemotherapy have virtually no effect on the onset of menopause and therefore may not be associated with a decrease in risk of breast cancer.
Longo adds that even low doses of radiation substantially increase the risk of breast cancer and points out that 80% to 85% of patients with Hodgkin’s disease can be cured without radiation treatment. He argues that radiation therapy should be reserved for patients with large masses or those who do not respond completely to chemotherapy.
Contact: Netherlands Cancer Institute
Department of Communications
Van Leeuwen FE, Klokman WJ, Stovall M, Dahler EC, van’t Veer MB, Noordijk EM, et al. Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin’s disease. J Natl Cancer Inst 2003;95:971–80.
Editorial: Longo D. Radiation therapy in the treatment of Hodgkin’s disease–Do you see what I see? J Natl Cancer Inst 2003;95:928–9.
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.