Clinical Impact of Genetic Susceptibility Information

Because the natural history of inherited breast cancer is different from sporadic cases, particularly because of the earlier age of onset and future risk for cancers, recommendations for different management and prevention options may be appropriate. As we learn more about the characteristics of these genetic mutations and the protein products encoded by the genes involved, management issues such as predicted responses to chemotherapy, radiation therapy or surgery may be clarified allowing for a more individualized and targeted approach.

Strategies for cancer prevention in genetically susceptible individuals include enhanced surveillance for early disease detection occurring earlier and more frequently with more intensive methods; prophylactic surgery for removal of the tissue at risk; or chemoprevention with established or novel agents. Mammography is the main stay of breast cancer surveillance. Although not a perfect tool, especially in dense breast tissue, it is the method with which we have the most experience. In a study looking at the efficacy of mammography, it was shown that the predictive value of such screening may be increased 3-fold if a family history is present (24). In the future, other screening methods may be used, such as SPECT imaging or MRI which may improve the efficiency and efficacy of breast cancer detection in high risk women. An alternative option to early detection is prophylactic mastectomy which may reduce the incidence of breast cancer, but not all together, as it would be impossible to remove every breast cell. Eventually, chemoprevention for breast cancer in high risk women may be achieved as we understand more about the genes involved and their protein products.

For early detection of ovarian cancer there are no screening methods identified which are of high yield. Nonetheless, for high risk women it is recommended that they undergo annual serum CA-125 tumor marker measurements and transvaginal ultrasound with color flow Doppler beginning at age 25 until the time of prophylactic oophorectomy (when child-bearing is complete or by age 35 to 40) (25,26). However, even after prophylactic oophorectomy a small risk for ovarian cancer remains. This risk is thought to be due to cancer arising in cells of similar embryonic origin lining the peritoneum. Chemoprevention of ovarian cancer may be achieved with oral contraceptive use, however, these drugs may potentiate the risk for breast cancer (27). Similarly, once menopause is achieved (either naturally or surgically) in a woman with a strong genetic susceptibility for breast cancer, there is considerable controversy regarding the use of hormone replacement therapy.

Unfortunately, data are lacking regarding the efficacy, safety and effectiveness of all of the management and prevention strategies mentioned above. This is why it is of paramount importance that women who undergo genetic risk assessment, testing and counseling consider enrolling in a prospective trial or cancer registry to contribute to data collection that someday will provide answers to these important questions.