Breast Cancer in Childhood Cancer Survivors

Children who receive cancer diagnoses often require radiation as part of multimodal therapy. However, long-term childhood cancer survivors who undergo radiation therapy are at risk for a number of medical conditions, including second malignancies, heart disease, and developmental problems. For example, young women who received 40 Gy chest irradiation for Hodgkin lymphoma by age 25 were estimated to have cumulative risk for breast cancer as high as 29% by age 55 (J Natl Cancer Inst 2005; 97:1428). In addition, other studies have identified an inverse relation between age of exposure to chest irradiation and subsequent risk for breast cancer (J Clin Oncol 2003; 21:4386).

To examine the association between irradiation for childhood cancer and risk for breast cancer later in life, investigators performed a case-control study involving 6647 women survivors of childhood cancer who received radiation treatment from 1970 through 1986. Initial cancers were Hodgkin lymphoma (65.0% of patients), sarcomas (20.0%), leukemia (5.8%), non-Hodgkin lymphoma (3.3%), brain cancer (2.5%), kidney cancer (2.5%), and neuroblastoma (0.8%). A total of 120 patients with subsequent breast cancer were identified; each was matched to four controls based on age at initial cancer diagnosis and time since initial diagnosis. Review of medical records allowed calculation of radiation doses to the chest and ovaries.

Median age at diagnosis of initial cancer was 16.0 years, and median age at diagnosis of subsequent breast cancer was 35.9 (range, 20.9–49.6). The median interval from initial cancer to breast cancer was 19.4 years (range, 6.7–29.6 years). Risk for developing breast cancer rose linearly with radiation dose, to an extreme of an 11-fold higher risk for women who received local doses of approximately 40 Gy compared with those who received no radiation (P for trend, <0.0001). src="http://oncology-hematology.jwatch.org/math/ge.gif" alt="≥" border="0">5 Gy irradiation to the ovaries in conjunction with treatments for initial cancers (excess odds ratio, 0.36; P=0.002). Chemotherapy for initial cancers was not significantly associated with breast cancer risk when analyses were adjusted for radiation dose to the chest and ovaries.

Comment: These data support previous findings that indicate excess risk for breast cancer in patients who received chest irradiation during treatment for childhood cancer. Notably, this risk was reduced in patients who also received radiation therapy to the ovaries, presumably from ablation of ovarian function and the resultant suppression of hormonal stimulation of breast tissue. Although these findings highlight the need to remain vigilant for second primary tumors in childhood cancer survivors, current treatments for young patients with the most common cancers involve either no radiation therapy or reduced radiation doses and smaller port sizes, which we hope will result in fewer cases of breast cancer among childhood cancer survivors.