Breast cancer as a second primary in patients with prostate cancer--estrogen treatment or association with family history of cancer?
In a large population based study we reported an increased risk of male breast cancer after prostate cancer. In the current study we performed a comprehensive investigation of whether treatment for prostate cancer and/or family history is responsible for the excess risk. This study had 2 parts. 1) We performed a nested case-control study in 41 men who had previously been identified with first prostate cancer, followed by male breast cancer and in 81 matched controls with prostate cancer only. The medical records of these men were retrieved and clinical data such as stage, grade and treatment were extracted. 2) We also performed a family study including relatives of men with a diagnosis of prostate as well as breast cancer, irrespective of which was first. The 878 relatives were identified through parish offices and linked to the Swedish Cancer Registry to evaluate the occurrence of breast, prostate and other cancers and calculate if there were any excess risks for different cancers. Cases with prostate plus breast cancer received estrogen treatment more often than controls with prostate cancer only (p = 0.03). The period of estrogen treatment was longer in the cases, although it was not statistically significant. Mean time from prostate cancer diagnosis to breast cancer diagnosis was 47.6 months. Cases and controls did not differ in grade or stage. In the family study an increased risk of prostate cancer was found in relatives (SIR 2.14, 95% CI 1.09 to 3.18). For other cancers no significantly increased risks were found. In 2 families pedigree analysis using the BRCAPRO program (http://www3.utsouthwestern.edu/cancergene/) revealed an estimated 100% and 49% probability in families 1 and 2, respectively, that the proband was a BRCA2 carrier. Our data suggest that most of the increased risk of breast cancer following prostate cancer can be explained by estrogen treatment. However, in a small number of men with prostate as well as breast cancer pedigree analysis suggests that BRCA2 mutation might be the underlying cause.