The administration of exemestane significantly reduces the incidence of invasive breast cancer in postmenopausal women with moderately increased disease risk, showed the results of a study published in the New England Journal of Medicine.
Estrogens are involved in the normal mammary glands development, but their high circulating levels may increase the likelihood of breast cancer. Currently, the chemoprevention of breast cancer has been focused mainly on the selective estrogen receptor modulator (SERM) tamoxifen and raloxifene, which have anti-estrogenic effects.
Aromatase inhibitors suppress the estrogen levels in postmenopausal women and reduce the development of breast cancer in laboratory conditions. During the early research in this field, the non-steroidal and steroidal aromatase inhibitors reduced the development of contralateral breast cancer to a great extent, when compared to tamoxifen.
For example, after five years’ treatment with tamoxifen, the administration of letrozole reduced the risk by 46%, as compared to placebo. Preclinical models and clinical trials have demonstrated that exemestane is a good candidate for this indication.
The study MAP.3 was an international, randomized, double-blind and placebo-controlled study. It included 4560 postmenopausal women with a mean age of 62.5 years with some of the following risk factors: age> 60 years; five-year risk score on the scale of Gail> 1,66% (1,66% risk of developing invasive breast cancer in the next five years); previous ductal or lobular hyperplasia or lobular carcinoma in situ; ductal carcinoma in situ with mastectomy. Patients were divided into the following groups: exemestane 25 mg plus placebo; exemestane 25 mg plus celecoxib; and placebo plus placebo.
After the three years’ follow-up period it was demonstrated that the administration of exemestane was associated with a significant (65%) breast cancer risk reduction in the tested groups.
Exemestane had reduced the incidence of precancerous lesions as well (ductal carcinoma in situ, lobular carcinoma in situ, atypical ductal hyperplasia, and atypical lobular hyperplasia) which would have most likely lead to a further reduction of the invasive cancer in the long term.
This is the most significant disease risk reduction in the four largest breast cancer prevention studies. In the previous studies, tamoxifen and raloxifen reduced the disease risk respectively 50% and 38% after five years of follow-up. Subsequently, both drugs were approved by the FDA for breast cancer prevention in women with increased disease risk.
Experts hold the opinion that exemestane is a new opportunity for breast cancer prevention in postmenopausal women.
The analysis results show a favorable safety drug profile for this indication. The frequency of osteoporosis, cardiovascular complications and bone fractures were similar in the groups on exemestane and placebo.
For the three-year follow-up period 30% of those surveyed stopped taking the drug because of side effects, which was similar to thе clinical practice observations of aromatase inhibitors as an adjuvant therapy for early breast cancer.
Subgroup analysis showed that even with the intake of calcium and vitamin D, women treated with exemestane had lower bone mineral density (BMD) during the second year of treatment.
Based on the results of MAP.3, exemestane was included in the new practical guidelines of the American Society of Clinical Oncology in 2013 with the following indication: “Exemestane (25 mg per day orally for five years) should be considered as an alternative to tamoxifen or raloxifene for reducing the risk of invasive, positive for the estrogen receptor (ER +) breast tumors in postmenopausal women. The drug should not be administered to reduce the risk of disease in premenopausal women. “