High-Risk Ovarian Screening Management
There are two major options for managing women at increased risk: screening or risk-reducing surgery.[24–34] Currently, ovarian cancer screening tools are less than ideal and there are no data to support the efficacy of ovarian cancer screening in the general population.[25,26] Recommendations and practice guidelines published by the National Comprehensive Cancer Network (NCCN) are used to manage ovarian cancer risks in patients with family characteristics suggestive of hereditary breast and ovarian cancer syndrome, or HBOC (Table 4). For high-risk women followed at MDACC with ovaries intact, ovarian cancer screening includes a transvaginal ultrasound, CA-125 blood test, and pelvic exam every 6 months. Clinicians measure CA-125 levels at each patient visit to the high-risk clinic and monitor for changes in CA-125 over time. The transvaginal ultrasound is used to detect any abnormalities in the ovaries, such as hemorrhagic cysts, complex cysts, and free fluid in the pelvis. For patients with Lynch syndrome, screening for endometrial and ovarian cancer includes annual endometrial biopsy, transvaginal ultrasound, and a CA-125 blood test.
NCCN Practice Guidelines in Oncology for Hereditary Breast and/or Ovarian Cancer
At a woman’s appointment in the high-risk screening clinic, results of the transvaginal ultrasound and CA-125 are reviewed with the patient. Each patient is educated and counseled about the management of her ovarian and/or endometrial cancer risk, as well as screening and/or prophylactic surgical recommendations. Our clinicians emphasize that ovarian cancer is difficult to detect and current screening tools for ovarian and endometrial cancer are limited.[25,26]
Multiple studies have illustrated that premenopausal women with a BRCA1/BRCA2 mutation substantially reduce their risk of ovarian cancer by 85% to 95% by undergoing a prophylactic bilateral salpingo-oophorectomy (BSO). In addition, prophylactic salpingo-oophorectomy in a premenopausal woman decreases her risk of breast cancer by 50% to 60%.[27–33] Women with a BRCA1/BRCA2 mutation are counseled to undergo risk-reducing surgery at age 35 to 40 years, or after childbearing is complete. One study demonstrated risk-reducing surgery was associated with a lower risk of ovarian cancer, breast cancer, and cancer-specific mortality.[30]
Women with a BRCA1/BRAC2 mutation who have undergone a salpingo-oophorectomy still have a low residual risk of primary peritoneal carcinoma (PPC). The lifetime risk of PPC after a BSO is estimated to be 1.1% in BRCA1/BRAC2 mutation carriers.[30] While there are no data to support screening after a prophylactic BSO, our clinicians recommend annual CA-125 screening after surgery.
When discussing risk-reducing surgery, timing of the surgery is an important consideration. A 40-year-old woman with a BRCA1 mutation has a 2.3% risk of developing ovarian cancer, and a 0.1% risk if she has a BRCA2 mutation.[18,34] The risk of ovarian cancer begins to increase dramatically in women after 40 years of age, so the urgency of risk-reducing surgery is lower in women younger than age 40. Our clinicians encourage high-risk women to complete childbearing prior to prophylactic surgery, if they want to start a family or have more children. They also consider the ages at ovarian cancer diagnosis in affected family members, using this information to guide the timing of prophylactic surgery. These factors are discussed with the patient at length and are used to determine the appropriate age at which a high-risk woman should undergo surgery.
The decision to undergo a prophylactic BSO is not an easy one for premenopausal women at high-risk of developing ovarian cancer. Women often have to balance the quality of life changes that can occur after BSO—menopausal symptoms including hot flashes, night sweats, vaginal dryness, mood swings, and osteoporosis—against the benefit of surgery in substantially reducing their risk of developing ovarian cancer.[35–37] We at MDACC provide patients with a decision-making resource, “Ovarian Cancer Risk-Reducing Surgery,” offered by the Family Risk Assessment Program at Fox Chase Cancer Center in Philadelphia. This pamphlet is easy to read and comprehend, and it is used frequently by our patients.
In our experience, patients have a variety of questions and concerns about the timing of surgery, whether their uterus should also be removed along with their ovaries, use of hormone replacement therapy (HRT) for menopausal symptoms, and possible sexual dysfunction after surgery. Total hysterectomy and BSO is recommended in patients with Lynch syndrome because it is an effective strategy for prevention of endometrial and ovarian cancer.[38] For patients with a BRCA1/BRCA2 mutation, the question of removal of the uterus is not as clear because they are not at high-risk to develop endometrial cancer as a result of their mutation. If the patient has a history of abnormal Pap smears or is taking tamoxifen(Drug information on tamoxifen), however, a total hysterectomy may be considered.[39]
HRT is a topic of discussion requiring patient education communicated by our high-risk physicians. Replacing estrogen and progesterone(Drug information on progesterone) may relieve vasomotor symptoms, but it can also increase the risks for breast cancer. HRT is not usually prescribed to women with a personal history of breast cancer.[40] Venlafaxine (Effexor), an antidepressant, is often given to women who are unable to take synthetic hormones to relieve menopausal symptoms.[41–43] In addition, low-dose vaginal estrogen may be considered for vaginal dryness even if a patient has a history of breast cancer, as there is a low systemic absorption of estrogen when it is used in this manner. At MDACC, a sexual counselor on staff is available to meet with patients to discuss the effect that a BSO may have on sexual functioning, and how to cope with and manage these issues after surgery.
HBOC Case Study
Family history of cancer.
The patient, “KF,” presented to MDACC with a recent diagnosis of high-grade serous ovarian cancer diagnosed at age 45. Her family history was significant for a sister, 55 years old, who was diagnosed with breast cancer at the age of 49. KF underwent comprehensive BRCA1 and BRCA2 genetic testing and was identified as having a BRCA1 mutation. Her sister then tested positive for the BRCA1 mutation and proceeded with a prophylactic BSO. (See Figure 1.) Pathological review of the sister’s surgical specimen revealed an occult fallopian tube cancer. High-risk ovarian screening and risk-reduction surgery in KF’s sister benefited her by preventing a late-stage fallopian tube cancer.
Lynch Case Study
Family history of cancer.
The patient, “MP,” presented for a genetics consultation because her sister had been diagnosed with colon cancer at 39 years of age and her brother was diagnosed with bladder cancer at age 36 and colon cancer at age 50. MP’s brother was found to have an MSH2 mutation consistent with Lynch syndrome. MP and her sister subsequently underwent single-site MSH2 genetic testing for the familial mutation and were also found to have inherited the mutation. (See Figure 2.) She and her sister both had intact ovaries and uteri, therefore they needed increased surveillance because of their known increased risk of ovarian and endometrial cancer. Prior to their brother’s genetic evaluation, the family had not known about the cancer risks associated with Lynch syndrome and the benefits of increased cancer surveillance. Now, MP and her sister are able to be monitored for their ovarian and endometrial cancer risks associated with Lynch syndrome and can consider whether to undergo risk-reducing surgery.
Educating and Supporting At-Risk Patients
Patient education and counseling are essential in women at increased risk for ovarian and endometrial cancer. Women must be educated regarding the signs, symptoms, and risks associated with these cancers. These high-risk women should seek out medical professionals who can evaluate their risk for cancer and recommend high-risk screening and/or risk-reducing surgery if appropriate. Prophylactic surgery is a life-changing decision, so at-risk women considering surgery must be provided with as much information as possible.
There are multiple advantages of a high-risk cancer screening clinic: it offers up-to-date information about cancer screening and prevention while providing the patient with emotional and psychosocial support. Women are able to openly discuss their questions, fears, and concerns with their doctors and nurses and in so doing are empowered to make educated decisions about a variety of potentially life-changing risk-reduction options. Educational and advocacy resources can be provided to assist patients, such as information from “FORCE” (Facing Our Risks of Cancer Empowered; www.facingourrisk.org) and “Be Bright Pink” (www.bebrightpink.org), national nonprofit organizations devoted specifically to educating and supporting individuals with BRCA1/BRCA2 mutations. Novels written by patients who have a BRCA mutation, including “Pretty Is What Changes” and “Previvors,” are discussed with women at MDACC who have been identified as being at high risk for breast/ovarian cancer and who express interest in reading more about this condition from a patient’s perspective. In addition to receiving a variety of educational and informative materials, at-risk women are managed and followed closely in a screening clinic by a high-risk specialist, to prevent them from being lost to follow-up.
With adequate education, counseling, and resources, high-risk women are supported physically, mentally, and emotionally in living with a higher risk for developing a gynecologic cancer.
Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
