Pelvic radiotherapy,sex hormones,and breast cancer

Radiotherapy for malignant and benign gynecologic disease in middle age has been found to be associated inversely with the risk of breast cancer in several published studies. The ovaries received substantial doses of radiation from such treatments, in the tens of Gray (Gy) from radiotherapy for cervical cancer and one to 10 Gy from radiotherapy for benign gynecologic disease (BGD). The relative risk of breast cancer incidence or mortality decreased with increasing radiation dose to the ovaries between zero to six Gy but varied little with further increases in dose. Evidence of a protective effect even among women irradiated past the age of 50 suggests a mechanism other than that associated with induction of an early menopause. An inverse association with radiotherapy among women over age 50 was seen only for women with ovarian doses exceeding about four to five Gy, namely, those treated for cervical cancer or with external beam X-rays for BGD. Ovarian doses of two to three Gy from intrauterine radium (²²⁶Ra) treatments for BGD were not associated with an appreciably reduced risk of breast cancer, even though the treatments has the intended effect of inducing menopause in women in their mid-40s. The relevant target cells in the ovaries for radiologic menopause likely are those involved in estrogen production. Although the postmenopausal ovary has largely stopped producing estrogens, it continues to secrete androgens. Serum hormone measurements on a small sample of cervical cancer patients indicate that high-dose pelvic radiotherapy eliminates or greatly reduces this residual androgen-producing activity in ovaries of postmenopausal women. Taken together, these observations point to possible differential sensitivity to radiation inactivation of cells in the ovary that produces estrogens and androgens, respectively, and to the possible importance of continued androgen production by the postmenopausal ovary in the etiology or progression of breast cancer.