A BRCA1 mutation carrier with three breast primaries and childhood ionizing radiation treatments: A possible gene/environment interaction

Abstract

We report here on a 37-year-old BRCA1 mutation carrier female who has had multiple primary breast cancers and a childhood history of radiation therapy. In 1962, this patient presented at 6 months of age with a palpable abdominal mass which was found to be an infantile hemangio-endothelioma. She received seven radiation treatments for this condition. The radiation field in this six-month-old female was a medial ventral field which extended to just above the lower margin of the rib cage. She had no recurrence of her liver lesion. At the age of 25, she was diagnosed with an infiltrating medullary carcinoma of the right breast. She was treated with lumpectomy and radiation therapy. At age 30, she was diagnosed with an infiltrating ductal carcinoma of the left breast. At age 31, she was diagnosed with her third primary, an infiltrating ductal carcinoma of the right breast. At age 37, she was found to carry a deleterious mutation in the BRCA1 gene (3171 ins5). Although her 57-year-old mother was recently diagnosed with breast cancer, the BRCA1 mutation was found to be paternally inherited. The 3171ins5 mutation has been previously shown to be a disease-causing mutation in other families. Undoubtedly, this patient's history of three primary breast carcinomas is explained by the presence of this deleterious mutation. However, the presentation in this patient is strikingly early and severe. We speculate that this patient's early childhood radiation treatments may have played an environmental role in carcinogenesis in this patient. The orthovoltage machines used at that time may have allowed for substantial radiation scatter in a six-month-old. It is possible that the breast tissue may have received ionizing radiation which produced a “second hit” in the maternally inherited wild-type BRCA1 gene. Individuals with BRCA1 gene mutations are felt to be at moderately increased risk for developing colon cancer. We speculate that this patient may be at substantially increased risk because of the inevitable high radiation doses received by her colon in the early childhood period. We present this as a possible example of gene/environment interaction.