Calculated risk of breast cancer following mantle irradiation determined by measured dose.

Tumor registry data indicate a two- to fourfold increased incidence of breast cancer following mantle irradiation, but cumulative risk is unknown. Radiation exposure to the breasts underlying the mantle block ranges from 4 to 40 Gy and is dependent on relative positions of the breasts and mantle block. Unshielded outer breast quadrants near axillary nodal regions receive 36 to 40 Gy, while central breast quadrants under the lung blocks receive approximately 4 Gy as determined by dose volume histogram analysis. Relative dose risk analysis for breast cancer following mantle irradiation was performed and indicated an overall excess risk of 1.5 for the upper outer quadrant (total dose 40 Gy), 1.3 for the upper and lower inner, and central quadrants (total dose 15 to 20 Gy), and 1.2 for the lower outer quadrant (total dose 4 Gy). Linear and cell-kill carcinogenesis models demonstrated similar relative risk assessments in the low-dose regions, defined as < 15 Gy. Predicted risk for breast cancer in the high-dose regions (> or = 15 Gy) varied considerably according to the model evaluated. The linear model predicted a three to ten times greater risk above baseline breast cancer incidence for the high-dose regions. In contrast, the cell-kill model predicted no excess cases of breast cancer, assuming cell death at these higher dose levels. The greatest relative predicted risk is observed in women < 20 years of age at the time of irradiation; however, women older than 20 years continue to have a 50% higher than baseline risk for subsequent breast cancer development. All women treated for Hodgkin's lymphoma should undergo dose volume histogram evaluation. Prospective clinical and mammographic evaluations should be performed in all female patients following mantle irradiation to better define the risk for secondary breast carcinogenesis.