Effects of Exemestane on Bone Strength

The NCIC CTG was conducting an international breast cancer prevention trial (MAP.3) examining the effects of a new therapy (exemestane) for breast cancer prevention in postmenopausal women at increased risk of developing this disease. Results showed that after a median follow up of 35 months, exemestane was superior to placebo in breast cancer prevention. Exemestane blocks estrogen production, which may be beneficial for preventing breast cancer, but may have negative effects on bone. As postmenopausal women are at risk for developing osteoporosis, determining whether exemestane causes bones to weaken is crucial for women considering it for long-term use. Dr. Cheung's team followed the bone health of 354 women in MAP.3 in detail over 2 years and found that volumetric bone mineral density (by high resolution peripheral quantitative computer tomography (HR-pQCT) at the radius and tibia as well as areal bone mineral density by dual energy x-ray absorptiometry (DXA) at the hip and spine decreased significantly with the use of exemestane. The long term effects of exemestane on bone will be examined up to 5 years of therapy and then 2 years post therapy to delineate the effects of exemestane on bone strength. This research will inform us on the safety of exemestane for breast cancer prevention.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

Women participating in the MAP.3 clinical trial at centres with access to HR-pQCT

Exclusion Criteria:

1. Women with osteoporosis;
2. Women with T-score of -2.0 or below at the lumbar spine (L1-L4), total hip or femoral neck;
3. Women with a fragility fracture after age 40;
4. Women who have been on any bone drug, such as hormone replacement therapy, selective estrogen receptor modulators, bisphosphonates, teriparatide, parathyroid hormone, sodium fluoride, strontium, calcitonin and high dose vitamin D (more than 2000iu of vitamin D3 daily),in the past 3 months;
5. Women who have ever been on a bisphosphonate for more than 6 months;
6. Women who have ever been on strontium for more than 1 month;
7. Women who are on chronic oral steroids (the equivalent of 5mg of prednisone a day or higher for more than 2 weeks within the past 6 months and will likely require ongoing therapy);
8. Women with Paget's disease, Cushing's disease, hyperparathyroidism, uncontrolled hyperthyroidism or other metabolic bone diseases;
9. Women with decompensated diseases of the liver, bowel, kidney, pancreas, lung, or heart.

• BACKGROUNDGoss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, McTiernan A, Robbins J, Johnson KC, Martin LW, Winquist E, Sarto GE, Garber JE, Fabian CJ, Pujol P, Maunsell E, Farmer P, Gelmon KA, Tu D, Richardson H; NCIC CTG MAP.3 Study Investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011 Jun 23;364(25):2381-91. doi: 10.1056/NEJMoa1103507. Epub 2011 Jun 4. PMID 21639806
• RESULTCheung AM, Tile L, Cardew S, Pruthi S, Robbins J, Tomlinson G, Kapral MK, Khosla S, Majumdar S, Erlandson M, Scher J, Hu H, Demaras A, Lickley L, Bordeleau L, Elser C, Ingle J, Richardson H, Goss PE. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):275-84. doi: 10.1016/S1470-2045(11)70389-8. Epub 2012 Feb 7. PMID 22318095