Angelina Jolie’s mother and maternal grandmother died of ovarian cancer; her mother’s sister died of breast cancer. After testing positive for a clinically significant BRCA mutation, Ms. Jolie became a “previvor,” a woman who is currently healthy but at very high risk for developing a life-threatening breast or ovarian malignancy. Advances in genetic testing will result in many more women being identified as BRCA previvors. These women face many daunting decisions concerning options for risk-reducing breast and pelvic surgery. We gynecologists need to be prepared to help shepherd them through this process.
Which of our patients should be tested for BRCA mutations?
Experts have provided complex guidance on who should be tested for a BRCA mutation.1 These recommendations include testing women with a personal history of:
• epithelial ovarian cancer
• fallopian tube cancer, or
• primary peritoneal cancer.
Women with a personal history of breast cancer at an early age also should consider being tested. If women with breast or ovarian cancer, or both, test positive for BRCA1 or BRCA2, then living family members can be offered testing.
Healthy women with a family history of breast and/or ovarian cancer also may benefit from genetic testing. My clinical experience is that, unless the family history is as dramatic as that of Ms. Jolie, it requires considerable time and expertise to assemble a valid extended-family history and provide an estimate of risk. This task may be best completed by a genetic counselor. A simple, Web-based BRCA risk-assessment tool is provided by Myriad Genetics.2
A clinically significant BRCA mutation is detected. What is your patient’s risk?
Unfortunately, women with BRCA mutations are at very high risk for breast and ovarian cancer.
BRCA1. For patients with a BRCA1 mutation, the mean cumulative cancer risk to age 70 years is approximately 57% for breast cancer (95% confidence interval [CI], 47% to 66%) and 40% for ovarian cancer (95% CI, 35% to 46%).3
BRCA2. For patients with a BRCA2 mutation, the mean cumulative cancer risk to age 70 years is 49% for breast cancer (95% CI, 40% to 57%) and 18% for ovarian cancer (95% CI,13% to 23%). Tables 1 and 2 provide an approximation of the risk of developing breast or ovarian cancer for BRCA1 previvors aged 30, 40, and 50. The breast and ovarian cancer risk for BRCA2 previvors (not shown) is less than that for BRCA1 previvors.
Options for risk-reducing surgery
Risk-reducing breast and pelvic surgery markedly lessens the risk of developing cancer in the breast and ovary, decreasing the risk of mortality not only from breast cancer and ovarian cancer but from all causes.4
How many women choose risk-reducing surgery, and why? In a cohort of 306 healthy BRCA mutation carriers in the Netherlands, 10 years of follow-up revealed that 75% underwent risk-reducing pelvic surgery, and 50% underwent risk-reducing mastectomy.5 The age of the woman and her desire to preserve child-bearing strongly influenced the decision to undergo prophylactic surgery and the timing of the surgery.
Following risk-reducing surgery, most women are satisfied with their choice. In one follow-up study, the authors reported that women who had difficulty arriving at a decision were less satisfied with their choice to have risk-reducing surgery than women who arrived at their decision with confidence.6
Risk-reducing breast surgery: What’s involved?
As can be seen in Tables 1 and 2, the risk of your 30-year-old patient with a BRCA1 mutation developing breast cancer throughout her 30s is much greater than her risk of developing ovarian cancer. For this patient, bilateral total mastectomy is the standard risk-reducing procedure because subcutaneous mastectomy may leave islands of glandular tissue that may serve as a nidus for cancer development. However, both nipple-sparing and skin-sparing mastectomy have been reported to be successful in most cases, and may be favored by many women.8,9 Following risk-reducing breast surgery, most women can immediately begin multistage breast reconstruction.
Ms. Jolie underwent a “nipple delay” surgery 2 weeks before her mastectomy. This procedure involves lifting a portion of the nipple skin off the underlying breast to stimulate the nipple to start drawing its blood flow from the surrounding skin rather than the underlying tissue. In addition, during the nipple delay procedure a biopsy of the tissue from beneath the nipple is performed to ensure that no cancer is present.
Risk-reducing pelvic surgery: Essential steps
The standard operation to reduce the risk of ovarian cancer in BRCA mutation carriers is a bilateral salpingo-oophorectomy (BSO). Additional steps should be performed to assess for distant disease, including:
• careful assessment of all peritoneal surfaces
• pelvic washing for cytology
• omental biopsy
• cytologic smear of the diaphragm.
The fallopian tube should be resected in its entirety, but cornual resection is not necessary. Care should be taken to remove the entire ovary and avoid leaving small remnants of the ovary on the proximal vascular pedicles. Consideration should be given to performing a hysterectomy at the time of risk-reducing BSO. If the uterus is removed, estrogen-only hormone therapy (HT) can be prescribed. Estrogen-only HT causes fewer adverse events than combination estrogen-progestin therapy.