Preconception planning for diabetic women, growing data on the value of prophylactic oophorectomies and a possible alternative to the Pap test are featured in this issue’s Health Update.
When to Consider Prophylactic Oophorectomy
When assessing a patient’s risk of gynecologic malignancy, Teresa Diaz-Montes, M.D., gynecologic oncologist at Mercy Medical Center, who also sees patients at Anne Arundel Medical Center, recommends starting with a detailed family history. “I think that it’s important to take a comprehensive family history of first-degree relatives for ovarian, uterine, breast and colon cancer,” she says. “For example, families that carried a genetic predisposition for colon cancer are at higher risk of uterine cancer. When I explore the family history, I ask about all of these.”
Family Colon Cancer History Increases Risk
As many as one million Americans may have Lynch syndrome, an under-diagnosed hereditary disorder in which a mutation in a mismatch repair gene (MMR) can cause colon cancer in up to 85% of those affected. Lynch Syndrome is also the cause of other cancers, including uterine, ovarian and breast cancer, though at lower rates. These patients are also at risk for getting malignancies at a younger age.
Dr. Diaz-Montes states, “I ask patients about their family history every time I see them to determine if there’s any change in family history since I last saw them. A family history of male breast cancer is very suggestive of BRCA2, and these patients should be referred to a specialist. One of my patients had multiple family members diagnosed with colon cancer, including a father and brother both dying from the disease. She was also diagnosed with colon cancer at a young age.When she came to me, she was already diagnosed with uterine cancer. This is indicative of the type of patient who should receive genetic counseling and testing, and who may be a candidate for a prophylactic hysterectomy and oophorectomy.”
A Canadian study of more than 5,000 women published in early 2014 in the Journal of Clinical Oncology found that prophylactic oophorectomy reduced all-cause mortality by 77% among women who carry a BRCA1 or BRCA2 genetic mutation. Mortality was cut chiefly by reducing the risk of ovarian, tubal or peritoneal cancers, but also by reducing the risk of breast cancer.
Tailor Treatment to the Individual
While the investigators in this study recommended that women undergo oophorectomy by age 35, Dr. Diaz-Montes prefers to tailor treatment to the individual’s situation. “I don’t believe in pushing all women to hysterectomy by a specific age,” she says. “You have to individualize your recommendations depending on the patient’s needs. If a 35-year-old woman wants to have children, you need to take that into account when considering the risks and benefits of a procedure.”
Dr. Diaz-Montes further points out that the age at which a young woman is at risk depends at least in part on the affected family member’s age at diagnosis. If a mother had ovarian cancer early, such as at age 41, her daughter is at increased risk for that cancer a decade sooner (e.g., age 31).
A common blood test for ovarian cancer is useful, but results must be interpreted with caution. Dr. Diaz-Montes says, “Elevated levels of CA 125 are not diagnostic of cancer, but are good indicators of response to therapy. This protein can be elevated due to a number of other factors, such as pregnancy or a menstrual cycle. I see elevated CA 125 in my office every day and reassure younger women that it usually isn’t cancer. However, in post menopausal women, it’s often diagnostic.”
According to Dr. Diaz-Montes, prophylactic oophorectomy can be performed using minimally invasive approaches, including laparoscopic or robotic surgery. “We now have solid evidence that this procedure significantly decreases the risk of ovarian cancer and also decreases the risk of breast cancer in women with BRCA1 and BRCA2 genetic mutations,” she concludes.
Pre-Gestational Diabetics Should Plan Ahead
Diabetes affects about 6-7% of pregnancies, with 10% of those caused by pre-gestational diabetes. Alice Cootauco, M.D., perinatologist at the Perinatal Center at the University of Maryland St. Joseph Medical Center, is hoping to reduce the incidence of birth defects and pregnancy complications by getting diabetic women to improve their glycemic control before they get pregnant.
“We like to have their hemoglobin A1c levels at less than 6% before they conceive,” she says. “Women with pre-gestational diabetes below these rates have similar rates of congenital anomalies to the general population, at about 2-3%. But if their A1c levels are near 10%, they have a 20-25% risk of birth defects. Most of that risk occurs in the first eight weeks of gestation. We would love to have them see their primary care physician, then come in for a consult with a perinatologist before getting pregnant.“
Dr. Cootauco adds, “When a pre-gestational diabetic woman presents, she should be tested for underlying vascular complications, including retinopathy, nephropathy and cardiovascular disease, as these women have a higher risk of pregnancy complications. They need an ophthalmologic screening, a 24-hour urine collection to evaluate total protein and creatinine clearance, and a baseline EKG and thyroid function test, since they are also at higher risk for thyroid disease. They should be started on folic acid, at least 400 micrograms per day, and they ideally also would consult with a nutritionist.”
Diabetic patients also have a higher risk of preeclampsia, hydramnios (an increase in amniotic fluid that can lead to pre-term delivery) and fetal growth abnormalities, including growth restriction and macrosomia (large baby), which increases the likelihood of a cesarean section. Other risks to the fetus include hypoglycemia, hypocalcemia, cardiac hypertrophy and hyperbilirubinemia.
When to Screen
“Patients with a body mass index (BMI) above 30, a family history of diabetes or a personal history of gestational diabetes should be screened in their first trimester,” Dr. Cootauco advises. “Those expecting multiples or those at advanced maternal age are at higher risk of becoming diabetic, but don’t need to be screened early.They can be screened at the routine time; 24-28 weeks gestational age.”
“The treatment hasn’t changed much in the past few years,” notes Dr. Cootauco. “Diet modifications and exercise are always the first line of defense. The most commonly used oral hypoglycemic agents are glyburide and metformin. While not FDA-approved specifically for pregnancy, studies have shown that they don’t cross the placenta, so they can be prescribed for most women.” Type I diabetics and women who cannot achieve control with an oral agent require insulin therapy with a combination of short- and long-acting insulins. Women on insulin pumps can continue their pumps.
Many hypertensive medications, such as ACE-inhibitors and ARBs, are contraindicated during pregnancy. Those with a history of being safe for pregnant women include nifedipine, labetalol and methyldopa. Dr. Cootauco stresses, “Most diabetic women can have a successful pregnancy if they have optimal glucose control before they become pregnant.”
Will DNA Test Replace the Pap Test?
In early March 2014, a federal advisory panel unanimously approved Roche’s Cobas HPV DNA test as a primary screening tool for women ages 25 and older. Presently, the DNA test is chiefly used in conjunction with the Pap test. Current U.S. guidelines recommend that women ages 30-65 undergo either co-testing with both HPV and Pap every five years, or Pap testing alone every three years. Women ages 21-30 are recommended to have Pap testing every three years.
The DNA test has been found to have greater sensitivity in detecting pre-cancerous lesions than the Pap test. It is also considered to be more objective, as it does not rely on interpretation of slides under microscopic examination.
Teresa Diaz-Montes, M.D., gynecologic oncologist, Mercy Medical Center and Anne Arundel Medical Center
Alice Cootauco, M.D., perinatologist at the Perinatal Center at the University of Maryland St. Joseph Medical Center