MAP.3: Exemestane reduced risk for breast cancer by 65%

Issue: July 10, 2011

2011 ASCO Annual Meeting

CHICAGO – Phase-3 results from the MAP.3 trial showed that the aromatase inhibitor exemestane reduced the risk for developing breast cancer by 65% in women at high-risk.

Additionally, researchers observed a 60% reduction in invasive breast cancer plus pre-invasive ductal carcinoma in situ, and fewer cases of cancer precursor lesions such as atypical ductal hyperplasia and atypical lobular hyperplasia in the exemestane group.

“Exemestane can be considered a new option for breast cancer prevention in post menopausal women. Women meeting the inclusion criteria of the MAP.3 trial, which would include all women over 60, and their doctors should be made aware of these important results,” Paul E. Goss, MD, PhD, professor of medicine at Harvard Medical School and Massachusetts General Hospital, said. Goss discussed the findings during a Saturday press conference at the 2011 ASCO Annual Meeting. “For women outside the criteria, further data is clearly needed. Because of the significant reduction of breast cancer and the excellent safety profile, exemestane has more potential for wider scale implementation than the selective estrogen receptor modulators.”

From 2004 to 2010, 4,569 postmenopausal women with one or more risk factors – Gail score >1.66%, prior atypical ductal hyperplasia, atypical locular hyperplasia, lobular carcinoma in situ or DCIS with mastectomy or age over 60 – were randomly assigned to exemestane (Aromasin, Pharmacia and Upjohn) or placebo (n=2,248).

At a median follow-up of 35 months, the annual incidence of invasive breast cancer was 0.19% for patients assigned to exemestane (n=2,240) vs. 0.55% for patients assigned to placebo (HR=0.35, 95% CI 0.18-0.70). There were 10 diagnoses of DCIS in the experimental group vs. 27 in the placebo group, and one diagnosis of LCIS in the experimental group vs. five cases in the placebo group.

Patients assigned to exemestane had superior outcomes when assessed by Gail score, age, BMI, prior LCIS and prior DCIS. The annual incidence rate of invasive breast cancer or DCIS was 0.35% with exemestane and 0.77% with placebo (HR=0.47; 95% CI 0.27-0.79). There were 20 diagnoses of invasive breast cancer or DCIS in the exemestane group vs. 44 in the placebo group.

We looked for serious toxicities and we did not find any,” Goss said. “When we unblended the results, we found that that incidence of osteoporosis, cardiovascular disease and clinical fractures were identical in the two arms.”

Incidence of hypercholesterolemia was also equal in both arms. Toxicities such as hot flashes, fatigue, sweating, insomnia and arthralgia were slightly more common in the exemestane arm, but Goss said the clinical difference was only 3% and did not appear to affect self-reports of overall health-related quality of life. – by Jason Harris

For more information:

Goss PE. #LBA504. Presented at: the 2011 ASCO Annual Meeting.

Disclosure: Dr. Goss reported receiving honoraria from GlaxoSmithKline, Novartis and Pfizer.

Exemestane gives us another option to improve chemoprevention for women who are at high-risk for breast cancer. At this point, we can utilize tamoxifen or prophylactic surgery and each option has positive and negative aspects. This is another medical therapy we can add into our armamentarium to help reduce the risk for women who are at high risk. This study, while the first of its kind, is very intriguing and should be discussed with women who are at high-risk for breast cancer as an agent to prevent this disease. We have ways to reduce the risk for this disease and we need to discuss them with patients. Raloxifene, tamoxifen – if you think about all the women who could benefit from these drugs? They’re underutilized. Breast cancer is the one cancer where we have chemopreventive agents and we really need to discuss them with our patients.

- Jennifer C. Obel, MD
Medical Oncologist, NorthShore University Health System, Chicago

Disclosure: Dr. Obel reported no relevant financial disclosures.

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