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.
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
The trial tried
to evaluate the positive role of the
in reducing breast cancer risk in postmenopausal women.
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.
considered ineligible for the study if they -
• 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
uncontrolled hypothyroidism or hyperthyroidism
• Had chronic
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
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
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%.
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