Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved.

Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved.

Endocr Relat Cancer. 2013 Apr 26;

Authors: Lonning P, Eikesdal HP

Abstract
Following their successfull implementation for the treatment of metastatic breast cancer, the 'third-generation' aromatase inhibitors (anastrozole, letrozole and exemestane) now has become standard adjuvant endocrine treatment for postmenopausal estrogen receptor positive breast cancers. These drugs are all characterized by potent aromatase inhibition, causing >98% inhibition of estrogen synthesis in vivo. A recent meta-analysis found no difference in anti-tumour efficacy between these three compounds. As of today, aromatase inhibitor monotherapy or sequential treatment using tamoxifen followed by an aromatase inhibitor for a total of 5 years are considered equipotent treatment options. Yet currently trials are addressing the potential benefit of extending treatment duration beyond 5 years. Regarding side effects, aromatase inhibitors are not found associated with enhanced risk of cardiovascular disease, and enhanced bone loss is prevented by adding bisphosphonates in concert for those at danger of developing osteoporosis. However, arthralgia and carpal tunnel syndrome preclude drug administration among a few patients. While recent findings have questioned the use of aromatase inhibitors among overweigth and, in particular, obese patients, this problem seems to focus on premenopausal patients treated with an aromatase inhibitor and an LH-RH analogue in concert, questioning the efficacy of LH-RH analogues rather than aromatase inhibitors among overweigth patients. Finally, recent findings revealing a benefit from adding the mTOR inhibitor everolimus to treatment endocrine treatment indicates targeted therapy against defined growth factor pathways to be a way forward reversing acquired resistance to endocrine therapy.

PMID: 23625614 [PubMed - as supplied by publisher]

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