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Ovarian Cancer Chemoprevention

    Basics

Overview

Chemoprevention is the use of medication to reduce risk or prevent diseases such as cancer in healthy people. Some chemoprevention medications may reduce the risk for ovarian cancer. Just how well these drugs perform in high-risk women depends on each woman’s individual level of risk. Because some chemoprevention research may not apply to every person with hereditary cancer risk, when considering your best risk management options, it is important to have a clear a sense of your own risk, as well as the potential benefits and side effects of these medications. A health care team with expertise in managing high-risk patients can help you get a clearer idea of your risk for cancer so you can choose a risk management option that is right for you.

Oral contraceptives

Oral contraceptives are medications used by women for birth control; these medications have other important benefits and downsides. 

Impact on risk for ovarian cancer

Studies of women in the general population show that using birth control pills lowers the risk for ovarian cancer, but whether the medications provide the same protection for BRCA mutation carriers is unclear. A 2004 study involving 451 BRCA carriers who took oral contraceptives found that compared to women who did not use contraceptives, ovarian cancer risk decreased depending on the length of time the contraceptives were used:

  • Women who used oral contraceptives for at least 1 year had about a 15% reduced risk. 
  • Women who used oral contraceptives for 6 or more years had a 38% reduced risk. 

Other studies have had varied results, likely because findings may differ depending upon on the participants enrolled or the research design, studies on the same topic do not always have the same result.

Recent analyses of published data from multiple studies found that oral contraceptive use was associated with a reduced risk of ovarian cancer in both of BRCA1 and BRCA2 mutation carriers.1,2 

Impact on risk for breast cancer

Using oral contraceptives greatly reduces the risk of pregnancy and may also decrease the chance of developing ovarian cancer, but also comes with a downside. All women who use these medications, whether or not they have BRCA mutations, may be at increased risk for breast cancer. A recent study of more than 2,000 women showed that among women with BRCA1 mutations:3

those who began using oral contraceptives before age 20 had a 45% increased risk of breast cancer compared to BRCA1 carriers who never used oral contraceptives. 

those who took oral contraceptives between ages 20 and 25 were at slightly increased risk for developing breast cancer before age 40. The risk was greater for women who used birth control pills for longer periods of time. 

These data support an earlier study that showed women with BRCA1 mutations who first used oral contraceptives before 1975, before age 30, or who used them for 5 or more years had an increased risk of early-onset breast cancer compared to BRCA1 carriers who never used the medications. (This study found no increased risk for breast cancer in women who carried a BRCA2 mutation.) A different study found no increased risk for breast cancer with use of more modern low-dose oral contraceptives. 

What does this mean for BRCA mutation carriers?

Because these studies were strictly observational, the findings were limited.

The study authors’ conclusions are noteworthy, but do not prove that taking oral contraceptives actually decreases ovarian cancer risk or increases breast cancer risk. More research is needed to understand contraceptive use and cancer risk in BRCA carriers.

Members of our advisory board agree that BRCA mutation carriers under the age of 25 must balance the risk of breast cancer with the risk of unintended pregnancy.  

Oral contraceptives may not be appropriate for all women with BRCA mutations who want to reduce their risk for ovarian cancer. Birth control pills can have side effects, including a slightly increased risk for blood clots. Anyone considering the use of oral contraceptives to lower their cancer risk should discuss the benefits, risks and limitations with their health care team and with experts in managing high-risk women.

1Moorman, P.G., Myers, E.R., et al. “Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: A systematic review and meta-analysis.” Journal of Clinical Oncology (2013), Volume 31, Number 33: p. 4188-98.

2Friebel, T.M., Domchek, S.M., Rebbeck, T.R., “Modifiers of Cancer Risk in BRCA1 and BRCA2 Mutation Carriers:  Systematic Review and Meta-Analysis,Journal of the National Cancer Institute, (2014), Volume 106, Number 6: p. dju091.

3Kotsopoulos, J., Narod, S.A., et al. “Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers.” Breast Cancer Research and Treatment (2014), Volume 143, Number 3: p. 579-86.

Analgesics

Analgesics are medications used for pain relief. They include many common over-the-counter painkillers called Non-steroidal Anti-inflammatories (NSAIDs), such as aspirin and ibuprofen (Advil, Motrin) and acetaminophen (Tylenol). Research to determine whether these medications decrease ovarian cancer risk produced conflicting results. One study showed a 25% reduction in ovarian cancer risk in women who took aspirin on a regular basis and a 50% ovarian cancer risk reduction in women who took acetaminophen on a regular basis compared to women who did not take either drug. A more recent study showed a similar risk reduction for ovarian cancer in women who took acetaminophen on a regular basis but not women who took aspirin. A third study showed no reduction in ovarian cancer risk in women who took acetaminophen. The Nurses Health Study, a large research effort following 76,821 nurses, found a risk reduction associated with NSAIDs in general but not with aspirin use. None of these studies specifically reviewed ovarian cancer risk in women with BRCA mutations. Because these studies were only observational, they do not prove taking analgesics actually lowered cancer risk.

Certain analgesics in the NSAID category may increase the risk for death from heart disease. A recent clinical trial studying whether Celebrex might reduce the risk for colon polyps was discontinued due to an increase in heart disease and heart-disease related deaths in people who took the medication compared to people who took a placebo. The risk was still low for death by heart disease: about 3% for people who were on the highest dose, and 2% risk for people on the lower dose. However, in that particular study, the benefits of Celebrex were not believed to outweigh the risks.

Clearly more research is needed in order to better understand analgesic use and the risk for ovarian cancer, particularly in BRCA carriers. Anyone considering analgesics to decrease their risk for cancer should discuss the benefits, risks and limitations with their health care team and experts in managing high-risk women.

Fenretinide

Fenretinide is a medication related to Vitamin A. Research studies suggest Fenretinide might reduce the risk of several types of cancers. One small study looked at ovarian cancer risk in breast cancer survivors who took this medication to prevent recurrence of their breast cancer. The study found Fenretinide reduced ovarian cancer risk during the 5 years women took it, compared to women who did not take it. The risk-lowering effect did not continue when the medication was stopped. The study also suggested this protective effect against ovarian cancer may be stronger in women with BRCA mutations than women with sporadic breast cancer.

More research is needed. Current clinical trials are studying whether Fenretinide can lower ovarian cancer risk in high-risk women with BRCA mutations. Results from this research will not be available for several years.

Clinical Trials

ClinicalTrials.gov
This site, produced by the U.S. National Library of Medicine (NLM), provides patients, family members, and members of the public easy and free access to information on clinical studies for a wide range of diseases and conditions.

Phase II Randomized Study of Levonorgestrel in Patients at High Risk for Ovarian Cancer

Fenretinide Followed by Surgery Compared With Surgery Alone in Preventing Ovarian Cancer in Patients at Increased Risk


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