Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer

OBJECTIVES:

Primary

Previously: To determine if exemestane reduces the incidence of invasive breast cancer
compared with placebo.

Currently: To determine the frequency of serious adverse events for post-menopausal women at
high-risk of developing breast cancer who choose to receive 5 years of exemestane as
preventative therapy.

Secondary

Previously: (same as is currently listed in PDQ) Currently: To address the Trial Committee
and Sponsor's commitment to allow women who are randomized to the MAP.3 trial to receive 5
years of exemestane therapy.

OUTLINE: This study was a randomized, double-blind, placebo-controlled, multicentre study.
Protocol-specified analyses were performed in April 2011. The results of these analyses are
posted in the Results section. Following the amendment of May 2011, the study is now
open-label and all eligible patients are receiving exemestane from participating sites for a
total of 5 years. After exemestane is stopped, there is no further follow-up.

PROJECTED ACCRUAL:There were 4560 women from the United States, Canada, Spain and France who
took part in this study.

- At increased risk of developing breast cancer, due to at least one of the following
risk factors:

- Gail score ≥ 1.66

- Age ≥ 60 years

- Prior atypical ductal hyperplasia, lobular hyperplasia, or lobular carcinoma in
situ on breast biopsy

- Prior ductal carcinoma in situ (DCIS) treated with total mastectomy with or
without tamoxifen (tamoxifen must have been completed ≥ 3 months prior to
randomization)

- No prior DCIS treated with lumpectomy with or without radiation

- No prior invasive breast cancer

- Not BRCA1 or BRCA2 carriers

PATIENT CHARACTERISTICS:

Previous:

- 35 and over

- Female

- Postmenopausal, defined as one of the following:

- over 50 years of age with no spontaneous menses for at least 12 months before
study entry

- 50 years of age or under with no menses (spontaneous or secondary to
hysterectomy) for at least 12 months before study entry AND with
follicle-stimulating hormone level within postmenopausal range

- Underwent prior bilateral oophorectomy

- No other malignancies within the past 5 years except adequately treated nonmelanoma
skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively
treated solid tumors with no evidence of disease for ≥ 5 years

- No uncontrolled hypothyroidism or hyperthyroidism

- No major medical or psychiatric illness (including substance and alcohol abuse within
the past 2 years) that would preclude study participation or compliance

- Must be accessible for treatment and follow-up

- Willing to complete quality of life questionnaires in either English or French

Current: MAP.3 participants who were randomized to the exemestane arm, are currently
receiving exemestane as part of the MAP.3 study and who have not completed 5 years of
exemestane.

OR MAP.3 study participants who were randomized to the placebo arm and who have either
completed 5 years of study drug or who are still receiving placebo. Note: this applies only
to centres that choose to allow placebo "cross-over".

PRIOR CONCURRENT THERAPY:

Previous:

- More than 3 months since prior and no concurrent hormone replacement therapies

- More than 3 months since systemic estrogenic, androgenic, or progestational agents

- More than 3 months since prior and no concurrent hormonal therapies, including, but
not limited to the following:

- Luteinizing-hormone releasing-hormone analogs (e.g., goserelin or leuprolide)

- Progestogens (e.g., megestrol)

- Prolactin inhibitors (e.g., bromocriptine)

- Antiandrogens (e.g., cyproterone acetate)

- Selective estrogen-receptor modulators (e.g., tamoxifen, toremifene, or
raloxifene)

- No investigational drug within 30 days or 5 half lives prior to randomization

- No concurrent endocrine therapy

- No concurrent estrogens, androgens, or progesterones

- Concurrent low dose (≤ 100 mg/day) prophylactic aspirin allowed

- Concurrent bisphosphonates for prevention or treatment of osteoporosis allowed

- No other concurrent medications that may have an effect on study endpoints

Current: There are no prior concurrent therapy restrictions for the amended MAP.3 study.