Oral contraceptives cut inherited cancer risk

Good news: the protective effects of oral contraceptives (OCs) against ovarian cancer extend not only to healthy women, but to those who carry an inherited risk as well.

While only 10% of all ovarian cancers can be attributed to a genetic mutation in the BRCA1 or BRCA2 genes, women who carry mutations of either gene have a high lifetime risk for the disease, says Steven Narod, MD, PRCPC, chair of breast cancer research at the Women’s College Hospital, University of Toronto (Ontario). Narod is a molecular epidemiologist who, along with others, mapped the gene for hereditary breast-ovarian cancer syndrome.

He served as lead investigator for the multinational study that shows the pill’s effect in reducing ovarian cancer risk in women with the mutated genes.1 The study shows that birth control pills appear to cut the risk of ovarian cancer in half among women with the genetic mutations.

Researchers in Canada, Sweden, Norway, Italy, England, and the United States compared OC use in 207 women with the inherited form of the disease with 161 of their sisters, some of whom also had the genetic mutations.

Women who had used OCs any time in the past had an overall 50% lower risk of ovarian cancer, the researchers discovered. If the use had extended for more than six years, the risk was decreased by 60%.

While many family planners may not regularly see women who have identified BRCA1 or BRCA2 mutations, it is important to recognize the noncontraceptive benefits offered by OCs, say reproductive health experts.

"I think the clinical message here is another confirmation that the powerful protection of oral contraceptives not only applies to women in general, but to women who have elevated risk and, therefore, particular concerns about this often fatal gynecologic malignancy," says Andrew Kaunitz, MD, professor and assistant chair of the department of OB/GYN at the University of Florida Health Sciences Center in Jacksonville.

For Stephen Rubin, MD, professor and chief of the division of gynecologic oncology at the University of Pennsylvania Medical Center, the study is consistent with what is now known about OCs and the risk of ovarian cancer in the general population. While Rubin, who wrote a commentary on the new study,2 finds it "interesting and provocative," he does not believe it offers a complete answer to the effects of OCs in women with the inherited risk. "I think we will have to wait for further results before we can say definitely what the effects of OCs are in this patient population," he says.

OCs and breast cancer risk

The same genetic defects that lead to ovarian cancer also cause breast cancer. Use of combined oral contraceptives must be weighed in treatment of such women, says Narod. Breast cancer tumors appear to be sensitive to estrogen, he notes. For women with documented BRCA1 mutations, exposure to estrogen may increase their already-heightened risk for the disease, a premise his research team is studying.

"We are hoping to look at 500 women with breast cancer with BRCA1 mutations, 500 women with the same mutations who didn’t get breast cancer, and compare their OC use," the researcher explains. "I think that should be finished within a year."

Clinicians need to remember that a large re-analysis3,4 of 54 studies representing 90% of the world’s data on breast cancer showed that women are not at increased risk for the disease after more than 10 years after stopping the Pill, Kaunitz notes.

"When collaborative investigators did their re-analysis and looked at OC use in women with a positive family history of breast cancer again, there was no different association than women in general," he says. "Long-term OC use had no impact on the risk of breast cancer being diagnosed later in life."

Clinicians should understand that women with a family history of breast cancer are at high risk compared with other women, Kaunitz says. It is just that the pill does not alter that risk, he explains.

OCs and oophorectomies

Women with identified BRCA mutations traditionally have had oophorectomies (removal of the ovaries) to minimize their risk of devel oping ovarian cancer. With data now in hand, providers may want to begin OC use in this population during the reproductive years and follow it closely with oophorectomies, Narod suggests.

"I think the combination of OCs and preventive surgery should be very close to complete prevention," he observes. "Unfortunately, I don’t see the third arm of that, which is ovarian cancer screening, so I think the mainstay should be OCs and prophylactic oophorectomy." (The 1994 National Institutes of Health Consensus Development Conference on Ovarian Cancer concluded that there was no evidence to support routine ovarian cancer screening for all women.)

Rubin agrees with Narod’s position and says, "From a clinician’s point of view, I think it would be perfectly reasonable for these women who go on OCs to have their breasts followed carefully, and when they are through childbearing, have their ovaries removed."

References

1. Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk of hereditary ovarian cancer. N Engl J Med 1998; 339:424-428.

2. Rubin SC. Chemoprevention of hereditary ovarian cancer. N Engl J Med 1998; 339:469-471.

3. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347:1,713-1,727.

4. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: Further results. Contraception 1996; 54(suppl):1S-106S.