Who wouldnâ€™t be drawn in by this headline: Breast Cancer Risk Slashed by Hormone-Blocking Pill, Study Shows. But as is so often the case, the headline doesnâ€™t tell the whole story.
As youâ€™ve probably seen, the media have been reporting findings from the MAP.3 (mammary prevention-3) trial that were presented this week at the American Society of Clinical Oncology meeting in Chicago and simultaneously published in the New England Journal of Medicine.
The trial followed more than 4,500 women over a five-year period. To enroll in the study, a woman had to be 35 years of age or older, post-menopausal, and at increased risk of developing breast cancer because of her age (60 or over) or Gail risk score or because she had previously been diagnosed with atypical hyperplasia, or lobular carcinoma in situ (LCIS), or ductal carcinoma in situ (DCIS) that was treated with a mastectomy. The trial was not open to women who were known to have a BRCA1 or BRCA2 mutation.
Half of the women were randomized to the group that received the aromatase inhibitor exemestane (brand name Aromasin). The other half received a placebo. At a median follow-up of three years, the researchers found that the group of women receiving exemestane had a 65 percent reduction in invasive cancers.
That sounds impressive, but this is what it means in real numbers: There were 11 invasive cancers that developed in the 2285 women who were given exemestane, compared to 32 in the 2275 women who took the placebo. This means the drug prevented 21 cancers. In addition, fewer cases of DCIS, LCIS, and atypical hyperplasia were found in the group receiving exemestane: there were 9 diagnoses of DCIS in the exemestane group compared to 14 in the placebo group, and there were 4 cases of atypical hyperplasia and LCIS in the exemestane group compared with 11 in the placebo group.
MAP.3 is the first randomized trial to report on the use of an aromatase inhibitor for breast cancer risk reduction. While I applaud the focus on prevention, I am not sure exemestane is the answer we have been looking for. First of all, this drug can only be used in postmenopausal women. (Only postmenopausal women can use an aromatase inhibitor. That’s because postmenopausal women get most of their estrogen from the conversion of androgens into estrogen by the aromatase enzyme, while premenopausal women get most of their estrogen directly from their ovaries.)
Furthermore, most of the cancers prevented were the so-called “good” onesâ€“invasive and noninvasive (DCIS) that are estrogen receptor (ER)-positive, HER2-negative, and node negative. These tend to be more common in postmenopausal women and have a good prognosis.
In addition, the discussion about side effectsâ€”in the article, and by the mediaâ€”are a bit misleading. It is true that exemestane does not have the same side effects as tamoxifen which has a different mechanism of action. But because aromatase inhibitors like exemestane blocks estrogen production throughout the body, they have their own side effects, such as arthritis and joint pain, hot flashes, sexual problems, fatigue, and insomnia. These were dismissed as not serious, but it should be noted that one-third of the women on exemestane stopped taking it during the three years of the study. There was some bone loss as well but no increase in fractures. This is not surprising, since the median time women were studied was three years, and the median age of the participants was 62, which is before the major risk for fracture develops.
It also is not known how long women would need to take exemestane to benefit. There is some suggestion from the cancer data that the protective effect might persist after the drug has been stopped, but I wonder if doctors and patients will be willing to test that hypothesis.
Currently, two drugs are FDA-approved for breast cancer prevention in high-risk women, tamoxifen and raloxifene. (Tamoxifen has been used as a breast cancer treatment for decades. Raloxifene is not used to treat breast cancer.) Studies have shown that these drugs also reduce breast cancer risk, but with no change in the mortality of the disease. This will most likely be true for exemestane as well. Also, as the studyâ€™s authorâ€™s note, many high-risk women have chosen not to take tamoxifen or raloxifene, because they believe the risks from the side effects do not outweigh the benefits. Currently, only about 4 percent of women who are at increased risk for breast cancer have chosen to take either of these drugs.
We desperately need ways to prevent breast cancer but so far all our approaches have been aimed at postmenopausal women with relatively good prognosis lesions. We need to focus on finding a way to prevent the more aggressive cancers that are killing premenopausal women around the worldâ€”a much more difficult goal. We need to find the cause of the disease, and stop it once and for all. Women can help this effort by joining the Love/Avon Army of Women. By taking part in the research, we can be the generation that stops all breast cancer once and for all.