Saving Lives Through Genetic Testing and Prophylactic Surgery

Posted by The Evidence Blog on May 15, 2013

By Diane Allingham-Hawkins, PhD, FCCMG, FACMG, Senior Director, Genetic Test Evaluation Program and Technical Editing

In an op-ed piece published in the New York Times on May 14, 2013, actress and director Angelina Jolie bravely revealed that she is a carrier of a variant in the BRCA1 gene, one of the genes associated with familial breast and ovarian cancer. Furthermore, Jolie revealed that she had recently undergone a bilateral prophylactic mastectomy and reconstructive surgery to reduce her risk of breast cancer. Jolie discovered that she is a BRCA1 carrier after her mother, Marcheline Bertrand, died of ovarian cancer in 2007 at the age of 56.

Jolie’s revelations provide a good opportunity to reflect on testing for variants in the two major genes associated with familial breast and ovarian cancer, BRCA1 and BRCA2, and the impact such testing can have on patient outcomes. Variants in these two genes are estimated to occur in 3% to 5% of breast cancer cases and up to 10% of ovarian cancer cases. Currently, most professional guidelines recommend that BRCA1 and BRCA2 testing be considered in patients with breast cancer who are at high risk for a hereditary form of breast cancer. These include men with breast cancer, women with breast cancer diagnosed before the age of 45 years, women with epithelial ovarian cancer, fallopian tube cancer or primary peritoneum cancer, patients with multiple primary tumors (i.e., bilateral breast cancer or both breast and ovarian cancer), patients with triple-negative breast cancer, and those with a family history that suggests a familial form of breast or ovarian cancer. Female carriers of variants in BRCA1 or BRCA2 have an increased risk of breast cancer (up to 85% by age 70 years) and ovarian cancer (up to 68% by age 70 years), while male carriers have an approximately 7% lifetime risk of breast cancer. Furthermore, carriers are at increased risk for other malignancies, including pancreatic and prostate cancer.
While the risk numbers for BRCA1 and BRCA2 carriers are sobering, there is good news. As Jolie points out, the prophylactic mastectomy she underwent reduced her risk of breast cancer to 90% and also reduces the risk of breast cancer by up to 64% in those who have not undergone mastectomy. Research shows that up to 55% of BRCA1 and BRCA2 carriers elect to undergo prophylactic oophorectomy, while up to 44% elect to undergo prophylactic mastectomy. Among those who choose not to undergo risk-reducing surgery, the majority have increased cancer screening by mammography (81%), breast MRI (46%), CA-125 testing (52%) and/or transvaginal ultrasound (42%). Although screening modalities will not prevent cancer, they increase the chance that a cancer will be detected earlier, which offers a better chance of successful treatment.

Among the largely unregulated and unproven landscape of genetic testing, the example of BRCA1 and BRCA2 testing offers a clear example of the potential of genetic testing to save lives. We applaud Ms. Jolie for her courage in not only making an informed medical decision that was right for her and her family but also for sharing her journey with the hope that other women facing similar situations may be inspired to seek out the medical advice they need to make their own informed decisions.

Topics: Hayes Blog, Genetic Testing