Women treated for Hodgkin’s lymphoma by the age of 16 may have a subsequent risk, which is as high as 35%, of
developing breast cancer by the age of 40.[17,18] One study suggests that
higher doses of radiation (median dose, 40 Gy in breast cancer cases) and
treatment received between the ages of 10 and 16 years correspond with higher risk. Unlike the risk for secondary leukemia, the risk of
treatment-related breast cancer did not abate with duration of follow-up, i.e., increased risk persisted more than 25 years after treatment.[17,19,20]
In these studies, the great majority (85%–100%) of patients who developed
breast cancer did so either within the field of radiation or at the
margin.[17,18,19] A Dutch study examined 48 women who developed breast cancer at least 5 years after treatment for Hodgkin’s disease and compared them with 175 matched female Hodgkin’s disease patients who did not develop breast cancer. Patients treated with chemotherapy and mantle radiation were less likely to develop breast cancer than those treated with mantle radiation alone, possibly because of chemotherapy-induced ovarian suppression (RR = 0.06; 95% CI, 0.01–0.45). Another study of 105 radiation-associated breast cancer patients and 266 age-matched and radiation-matched controls showed a similar protective effect for ovarian radiation. These studies suggest that ovarian hormones promote the proliferation of breast tissue with radiation-induced mutations.
The question arises whether breast cancer patients treated with lumpectomy and radiation therapy
(L-RT) are at increased risk for second breast malignancies or other malignancies
compared with those treated by mastectomy. Outcomes of 1,029 L-RT patients
were compared with 1,387 patients who underwent mastectomies.
After a median follow-up of 15 years, there was no difference in the risk of
second malignancies. Further evidence from three randomized controlled trials is also reassuring. One report of 1,851 women randomly assigned to undergo total mastectomy, lumpectomy alone, or L-RT showed rates of contralateral breast cancer to be 8.5%, 8.8%, and 9.4%, respectively. Another study of 701 women randomly assigned to undergo radical mastectomy or breast-conserving surgery followed by radiation therapy demonstrated the rate of contralateral breast carcinomas/100 woman-years to be 10.2 versus 8.7, respectively. The third study compared 25-year outcomes of 1,665 women randomly assigned to undergo radical mastectomy, total mastectomy, or total mastectomy with radiation. There was no significant difference in the rate of contralateral breast cancer according to treatment group, and the overall rate was 6%.
Obesity is associated with increased breast cancer risk, especially among postmenopausal women who do not use HRT/HT. The Women’s Health Initiative Observational Study observed 85,917 women, aged 50 to 79 years, and collected information on weight history as well as known risk factors for breast cancer. Height, weight, and waist and hip circumferences were measured. With a median follow-up of 34.8 months, 1,030 of the women developed invasive breast cancer. Among the women who never used HRT/HT, increased breast cancer risk was associated with weight at entry, body mass index (BMI) at entry, BMI at age 50, maximum BMI, adult and postmenopausal weight change, and waist and hip circumference. Weight was the strongest predictor, with a RR of 2.85 (95% CI, 1.81–4.49) for women weighing more than 82.2 kg, compared with those weighing less than 58.7 kg.