Breast Cancer Research: Dr. Feldman Explains New Study on Exemestane

by Columbia Surgery on September 26, 2011

As reported in the New York Times June 5, 2011, the drug exemestane (Aromasin) was found to significantly reduce the occurrence of breast cancer in post-menopausal women at high risk of developing breast cancer. Not only was the risk of breast cancer reduced by 65% in the study, but the drug was found safe and more tolerable than other drugs in its class.

The ensuing media attention has generated a flurry of questions among patients with breast cancer, many of whom are asking whether they can take exemestane instead of tamoxifen, with the hope of avoiding the side effects associated with the latter medication.

To clear up some common misconceptions and put this study in perspective, Sheldon Feldman, MD, Chief of the Breast Surgery Section at NewYork-Presbyterian/Columbia, talked with the Columbia Surgery blog.

Q: What did this study find?

Dr. Feldman: The study included about 4500 postmenopausal women at moderately high risk of developing breast cancer. Half the participants took exemestane and half took a placebo for three years. At that point, 11 of the women taking exemestane had developed breast cancer, and 32 taking the placebo had developed breast cancer. That translates to a 65% reduction in risk associated with this medication.

The drug also reduced the incidence of precancerous lesions including ductal carcinoma in situ, lobular carcinoma in situ, atypical ductal hyperplasia, and atypical lobular hyperplasia.

Q: What kind of drug is exemestane?

Dr. Feldman: Exemestane is an aromatase inhibitor, which are agents that suppress estrogen production and inhibit the development of breast cancer after menopause.

After menopause, a woman’s body makes very little estrogen. The little that is made is produced by the adrenal glands, which make testosterone, and then the aromatase enzyme converts the testosterone into estrogen. Aromatase inhibitors block this conversion, thereby shutting of the main source of estrogen production in postmenopausal women.

Before menopause, the body is flooded with estrogen because the ovaries are still working. So if aromatase inhibitors like exemestane are given to premenopausal women, the drug won’t stop the estrogen production from the ovaries.

Q: What does this study suggest for women interested in preventing breast cancer?

Dr. Feldman: This is the question that needs to be carefully looked at, because there are some common misconceptions arising in the wake of this study.

First, women need to understand that exemestane is only effective after menopause. If women take it before menopause, they will not receive the estrogen-suppressing benefit.

Second, this study investigated using exemestane for preventing breast cancer from occurring in the first place — not treating it after it has been diagnosed. Exemestane has previously been shown to be effective to treat women with breast cancer, and like tamoxifen, exemestane is commonly used for treatment. The importance of this study is that it provides clear evidence about its value in preventing breast cancer as well.

Third, the patients in the exemestane study were at higher risk of developing breast cancer than the general population, based on a risk assessment model called Gail, but the study did not include women who have BRCA1 or BRCA2 gene mutations, who are at the highest risk.

Q: Is exemestane effective in preventing all forms of breast cancer?

Dr. Feldman: In short, no. There are many different types of breast cancer. This study found exemestane was only effective in preventing estrogen receptor or progesterone receptor positive breast cancers, which are easier to treat and less dangerous than other types of breast cancer. The drug had no significant effect in preventing other types of breast cancer.

Clearly it is an important thing to prevent any type of breast cancer, but in the long term no survival benefit has been demonstrated with the use of exemestane.

If we could find ways to prevent the more aggressive forms of breast cancer with the worst prognosis, such as HER2 or triple-negative breast cancer, then we would be better able to improve survival rates associated with breast cancer. The ‘home run’ in breast cancer research will be to develop an agent to prevent estrogen receptive negative breast cancer and to be able to offer that prevention to younger women with many years of potential future risk.

Q: How does exemestane compare to tamoxifen and raloxifene?

Dr. Feldman: Historically, tamoxifen was found to be effective in preventing breast cancer because women who took it for treatment of cancer in one breast were found to have a significantly reduced risk of developing cancer in the opposite breast. We know that taking tamoxifen before menopause, earlier in life, has a long-term protective effect, and that tamoxifen and raloxifene are effective in preventing breast cancer in both pre- and post-menopausal women. Exemestane, on the other hand, is effective only after menopause. It can’t be used to protect women during the important years before menopause, but only in their later years.

The research so far indicates that exemestane appears to be safer than tamoxifen and raloxifene, which are associated with a higher risk of endometrial cancer and blood clots, as well as effects such as fatigue and depression. Because of these risks and effects, many women are reluctant to take tamoxifen and raloxifene. Although bone loss has been a concern with other aromatase inhibitors, exemestane did not produce any measurable changes in bone health. Its main side effects included aches, hot flashes, joint pain, and fatigue – but overall these effects were less problematic than those associated with tamoxifen. So overall, exemestane’s safety profile appears to be very reassuring.

Q: How do you counsel women about preventing breast cancer?

Dr. Feldman: Reducing risk for breast cancer may involve many options. Lifestyle choices, especially diet and weight management, are extremely important. I counsel women to maintain a healthy weight, because fat cells have estrogen receptors in them, and more fat cells promote breast cancer. Good nutrition and good quality food are both very important.

When we are considering methods of prevention, medications have to be nontoxic and have acceptable side effects, or women will not take them. If there were a completely nontoxic pill to prevent breast cancer, people would take it – but there isn’t, so the better option is to exercise and eat well.

Beyond lifestyle measures, we can offer many options, both medical and surgical. Exemestane is one more tool we now have available, which may be a good choice for post-menopausal women at high risk based on their family history. Women at very high risk, such as those with BRCA1 or BRCA2 gene mutations, may choose surgical prevention; at the Breast Surgery Section we have great surgical techniques including excellent reconstructive methods, and the rate of risk-reducing mastectomies has been increasing.

In short, anyone concerned about risk of breast cancer should come to NYP/Columbia for an evaluation and to learn about the options for prevention.

Full text of the study on exemestane is available at the New England Journal of Medicine: Exemestane for Breast-Cancer Prevention in Postmenopausal Women.

{ 2 comments… read them below or add one }

Elizabeth F. August 19, 2013 at 6:03 pm

After almost 4 years on exemestane I am overwhelmingly fatigued with a feeling of weakness & sometimes experience heart palpitations. My oncologist has told me to take two weeks without this med. & hopefully I will regain strength. At what point is living with these symptoms unacceptable? I spend days resting in bed for the most part. can’t wait for the five years to be over !

Columbia Surgery September 3, 2013 at 9:41 am

Hi Elizabeth,

I have forwarded your question to Dr. Feldman and have received the following response:

Hopefully your symptoms will be improved off exemestane. An alternative to discontinuing the medication is to discuss with your oncologist of switching to a different aromatase inhibitor or tamoxifen which may be more tolerable.

For more information about Dr. Feldman, please visit his physician profile at: You may also reach him at, 212-305-9676. Best regards.

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