It is widely known that the female hormones called estrogens play an active role in normal breast development but not many know that they can also promote breast cancer in women with high circulating plasma estrogen levels.
Chemoprevention of breast cancer has focused on tamoxifen and raloxifene, which are the selective estrogen-receptor modulators (SERMs) that exert antiestrogenic effects on breast besides exerting agonist or antagonist effects on other organs. However, these medications are known to have several side effects.
AdvertisementThe NCIC Clinical Trials Group Mammary Prevention.3 trial (NCIC CTG MAP.3) is a randomized, double-blind, placebo-controlled study carried out between February 11, 2004, and March 23, 2010, on 4560 women from Canada, the USA, France and Spain.
The trial tried to evaluate the positive role of the drug exemestane in reducing breast cancer risk in postmenopausal women.
Eligible candidates had the following characteristics -
• Postmenopausal women 60 years of age or older
• Women 35 years of age or older were eligible if they were postmenopausal
• Gail 5-year risk score greater than 1.66% (chances, in 100, of invasive breast cancer developing within 5 years)
• Prior atypical ductal or lobular hyperplasia / lobular carcinoma in situ
• Ductal carcinoma in situ, with mastectomy.
Women were considered ineligible for the study if they -
• Were premenopausal
• Had prior invasive breast cancer
• Prior ductal carcinoma in situ treated with lumpectomy
• Were known carriers of the BRCA1 or BRCA2 gene
• Had a history of other malignancies
• Had uncontrolled hypothyroidism or hyperthyroidism
• Had chronic liver disease.
The subjects were randomly assigned to any one of the following three treatment groups using a dynamic minimization algorithm.
They include -
• 25 mg of exemestane plus placebo,
• 25 mg of exemestane plus celecoxib,
• Placebo plus placebo pills
These were administered every day after a morning meal.
The exemestane and placebo groups were well balanced in all aspects such as race, body-mass index, and breast cancer risk factors.
The trial was event-determined. Duration of therapy lasted for a maximum of 5 years or until the initiation of a breast event, cancer, or a heart-related event or in the case of development of unacceptable toxicity.
Exemestane was found to significantly reduce invasive breast cancers in postmenopausal women (with moderate increased risk) for breast cancer. It reduced the relative incidence of invasive breast cancers by 65%, from 0.55% to 0.19%.
During follow up, exemestane was not associated with any serious toxic effects and brought about only minimal changes in health-related quality of life in those women with an increased risk of breast cancer.
"Exemestane for Breast-Cancer Prevention in Postmenopausal Women";Paul E. Goss, M.D., Ph.D., James N. Ingle, M.D., José E. Alés-Martínez, M.D., Ph.D etal ;N Engl J Med 2011; 364:2381-2391 June 23, 2011