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Women who carry BRCA1 and BRCA2 mutations have elevated lifetime prevalence of breast and ovarian malignancies. In an analysis conducted at one large U.S. cancer center, 303 women from 106 families with deleterious BRCA mutations in two or more generations were identified. All women had breast or ovarian cancer; age at diagnosis was compared between generations.
Median age at diagnosis of breast or ovarian cancer was 48 years (range, 23–70) in the older generation and 42 years (range, 20–86) in the younger generation.
Litton JK et al. Earlier age of onset of BRCA mutation-related cancers in subsequent generations. Cancer 2011 Sep 12; [e-pub ahead of print]. (http://dx.doi.org/10.1002/cncr.26284)
Comment
As a possible explanation of these results, the authors point to the phenomenon of genetic anticipation (in which a hereditary disease occurs at younger ages in subsequent generations because of DNA instability). However, they also note that earlier initiation of screening as well as use of more-effective screening (e.g., breast magnetic resonance imaging) might help explain the earlier diagnoses in the second generation. Although the authors did not provide information on the age at which BRCA carrier status was determined or tumor stage at diagnosis, I suspect that in the older generation, carrier status was usually confirmed after cancer was diagnosed, but in the younger generation, carriers were aware of their mutation status before the diagnosis of breast or ovarian malignancy. If so, the diagnosis of malignancies at younger ages might simply reflect progress in our understanding of hereditary breast and ovarian cancer syndrome leading to earlier identification of carriers and earlier, more effective deployment of screening strategies. Regardless of underlying explanation, these intriguing results underscore the importance of early screening in women who harbor deleterious BRCA mutations.