Chapter 9

Chemoprevention

IF YOU’RE CONSIDERING OPTIONS to reduce your cancer risk, you have two choices: chemoprevention, as described in this chapter, and surgery (chapters 10 and 12). Taking chemoprevention medications doesn’t guarantee you’ll never develop cancer, but it can decrease your risk. If you still have your breasts and ovaries, you’ll need to maintain surveillance to find any early cancers. Some women take chemoprevention drugs and then later further reduce their risk with surgery.

Chemoprevention isn’t for everyone. You may welcome its noninvasive risk-reducing potential or may decide the possible side effects outweigh the benefits, depending on your overall health and tolerance for risk. Some studies of these medications haven’t specifically focused on high-risk women; fewer have focused specifically on BRCA mutation carriers. A healthcare team with expertise in managing high-risk patients can give you a clear sense of how various chemoprevention drugs might affect your risk.

Risk-Reducing Medications for Breast Cancer

Tamoxifen

Researchers have studied the benefit of tamoxifen in different populations of women, with different results for each group. In a study of women with BRCA-related cancer in one breast, those who took tamoxifen demonstrated a significantly reduced risk in the other breast.¹ The medication appeared to work for both BRCA1 and BRCA2 mutation carriers. The research on tamoxifen for previvors shows different results. A large U.S. study showed that tamoxifen substantially reduced the chance for breast cancer in high-risk women.² Most participants didn’t have BRCA mutations. Among the nineteen women with BRCA mutations, only those with a mutation in BRCA2 benefited. The medication didn’t seem to help women who had BRCA1 mutations. A second study in the United Kingdom reviewed a similar group of high-risk women who took tamoxifen for eight years and were then followed for twenty years.³ Participants weren’t tested to determine whether any of them had BRCA mutations. This study showed a reduced risk for ER+ breast cancers, but not for ER– breast cancers.

Based on this limited research, most experts believe tamoxifen effectively decreases risk for breast cancer in survivors and previvors, especially those who have BRCA2 mutations. Not all experts agree that it is equally effective for BRCA1 mutation carriers, who tend to develop ER– cancers. If you’re considering tamoxifen for chemoprevention, discuss the benefits and limitations with your oncologist.

Tamoxifen and raloxifene are reliable and effective multitasking medications. Aside from potentially preventing breast cancer, they improve bone density. Both, however, have side effects. Taking either medication may cause hot flashes, vaginal dryness, mood changes, and other menopause-like symptoms, which may be mild and well tolerated by some women; others need medication to address their symptoms. SERMs can also cause vaginal bleeding or discharge, headaches, nausea, leg cramps, rashes, and other serious side effects.

Tamoxifen slightly increases a woman’s risk for endometrial cancer—the risk is still relatively low, about two chances in 1,000 per year.⁴ Raloxifene has less risk of uterine cancer. Unlike tamoxifen, it doesn’t have an estrogen-like effect on the uterus. These medications also increase the chance of stroke and blood clots, particularly in those who smoke or have clotting disorders. Neither drug is appropriate for women with a Factor V Leiden mutation, those who have (or have had) blood clots, or those taking estrogen replacement or certain cholesterol-reducing drugs, including Locholest and Questran.

Comparing tamoxifen and raloxifene

Aromatase Inhibitors

AIs aren’t FDA approved to prevent breast cancer. They could be prescribed as a preventive measure in the future if research shows they effectively reduce risk. AIs haven’t been studied as much as SERMs, so experts don’t yet know about their long-term effects or risks. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial found Arimidex reduced the risk of a new cancer in the opposite breast of survivors by 58 percent.⁵ The study didn’t specifically include women with BRCA mutations, so its preventive benefits in mutation carriers remains uncertain. Clinical studies are under way to determine whether AIs reduce postmenopausal breast cancer in high-risk women, including BRCA carriers. You can track the status of these trials at clinicaltrials.gov.

Alternatives under Study

In the Women’s Health Initiative, a national fifteen-year study of cardiovascular disease, cancer, and osteoporosis in postmenopausal women, individuals over age 50 who used aspirin regularly had a 21 percent decreased chance of developing breast cancer.⁶ Regular use of ibuprofen was associated with a 49 percent reduction in breast cancer risk, even in women who had first-degree female relatives (mother, sister, or daughter) with breast cancer. The study was observational only: women who regularly took NSAIDs were less likely to develop breast cancer, but researchers can’t be certain if the NSAIDs or some other factor produced the benefit. Nor did the study specifically focus on high-risk women. The Nurses’ Health Study, a large, long-term research effort following 76,821 nurses, showed that aspirin or other NSAIDs taken at least twice weekly don’t reduce premenopausal breast cancer risk.⁷

Certain NSAIDs increase the potential for death from heart disease. A clinical trial studying whether Celebrex could lessen the risk for colon polyps was discontinued when participants who took the medication suffered more heart disease and related deaths compared to participants who took a placebo. Even though the risk of heart disease-related death was low—about 3 percent of people taking the highest dose and 2 percent risk in those who were taking a lower dose—in this particular study, the risks of Celebrex outweighed the benefits.⁸ Other clinical trials are exploring whether nonsteroidal anti-inflammatory agents decrease breast cancer in high-risk women, including some studies of BRCA mutation carriers. Some medications in this category, including Celebrex and others, increase the risk of heart attack and stroke and shouldn’t be used by anyone at high risk for those conditions.

Fenretinide

Research suggests that fenretinide, a medication related to vitamin A, might prevent new breast tumors in premenopausal women who have been previously diagnosed. Over fifteen years, 1,739 patients previously diagnosed with DCIS or stage 1 breast cancer who weren’t treated with chemotherapy took fenretinide and had 17 percent lower incidence of a second breast cancer diagnosis than women who didn’t take the medication. Fenretinide was effective primarily in premenopausal women; the younger the woman, the more fenretinide reduced risk: 35 percent less in women under age 50, and 50 percent less in women under age 40.⁹ The drug’s protective benefit continued even after women stopped taking it. Impressive results, yet the medication actually increased risk for a second breast cancer in women age 55 and older. The study didn’t include previvors, so researchers can’t conclude that fenretinide prevents breast cancer in these women.

Statins

Millions of people around the world take statins to reduce cholesterol and lower their risk of heart attack. One observational, retrospective study found that women who took statins regularly were 51 percent less likely to develop breast cancer.¹⁰ Researchers can’t be certain statins get the credit—in other studies involving women of average risk, these drugs haven’t shown a protective effect. Studies are under way to determine whether statins reduce risk for high-risk women.

Deslorelin

Removing the ovaries lowers breast cancer risk, particularly in women with BRCA mutations. Deslorelin acetate prevents ovaries from producing estrogen, fueling speculation that it may also protect against breast cancer. Unlike surgical removal of the ovaries, deslorelin’s effect is reversible: once a woman stops taking it, her ovaries begin making estrogen again. One preliminary study of deslorelin in premenopausal women with BRCA mutations showed it decreased breast density, which is linked to lower breast cancer risk and improved detection of early stage tumors by mammography. This research is encouraging; more study is needed to determine whether deslorelin lowers breast cancer risk.

Bisphosphonates

Data from the Women’s Health Initiative show that women who took oral bisphosphonates, bone-building medications used to treat osteoporosis, were 30 to 40 percent less likely to develop invasive hormone receptor-positive breast cancer than women who didn’t take the medication.¹¹ Surprisingly, women who used either Fosamax, Actonel, or Boniva were 58 percent more likely to develop DCIS. Researchers aren’t sure why or how this occurs. They theorize that the medication somehow delays DCIS from evolving into invasive cancer. That would explain why there were fewer invasive cancers and more DCIS during the eight years of the study. An Israeli study found similar results, showing that women who took bisphosphonates for at least one year were 39 percent less likely to develop breast cancer than women who never took the drugs.¹² Whether these drugs can be used proactively remains to be seen and requires clinical trials. Bisphosphonates are associated with an increased risk of femur (thigh bone) fractures and esophageal cancer; the FDA now requires this information to be included in the safety labels of these medications.

Metformin

The most common medication used to treat type 2 diabetes may also inhibit breast cancer cell growth. Increasingly, evidence is mounting that metformin not only reduces blood sugar and insulin levels, it may improve breast cancer outcomes or even decrease risk for new breast tumors. In one study of 22,621 European women with type 2 diabetes, those who took metformin for five years or more had about 60 percent less chance of developing breast cancer compared to those who used other medications.¹³ Metformin may act on both ER+ and triple-negative breast cancers, raising the possibility that it could be equally effective for BRCA1 and BRCA2 mutation carriers.

Related posts:

Dealing with Menopause and Quality-of-Life Issues Managing Lifestyle Choices A Peek Inside: Your Genes at Work Sharing Information with Friends, Family, and Coworkers Mastectomy for Risk Reduction and Treatment Reconstruction: New Breasts after Mastectomy

Stay updated, free articles. Join our Telegram channel

Join