Table 2.

MAP.3 Exemestane Prevention Trial: strengths and weaknesses

StrengthsWeaknesses
Three-fourths of breast cancers ER positive and account for most breast cancer deathsNot including bone measurements (DXA scan) as predetermined endpoints, instead relying on self-report
Strong rationale based on contralateral breast cancer reduction in adjuvant trials
Placebo-controlled designLack of active comparator (e.g., raloxifene) to determine best hormonal strategy: no estrogen at all vs. best balance between agonistic and antagonistic effects
Eligibility used a pragmatic and clinically relevant algorithm:
  • 1. age ≥60 y

  • 2. Gail model

  • 3. history of IEN

Loose definition of “high risk,” especially including all women ≥60 years of age, even those with Gail model risk ≤1.66%
Fast recruitmentStudy immaturity: powered for 38 invasive cancers for final analysis with 3-year recruitment +1.2-y follow-up. Although technically acceptable, probably not clinically meaningful. Follow-up too short for safety and risk:benefit assessment
Main findings: predictable high activity and excellent safety/tolerability profileCrossover to exemestane is being offered to women on placebo. Resulting contamination diminishes the value of follow-up, making MAP.3 a large proof-of-principle trial (activity vs. efficacy).