Experts Discuss Role of AIs in Pre/Postmenopausal Patients

CHICAGO--Aromatase inhibitors(AIs) have an unquestioned role to playin the treatment of postmenopausalwomen with breast cancer, but there isno single best approach for their use inall patients, Eric Winer, MD, said at the8th Annual Lynn Sage Breast Cancer symposium. In a separate meeting presentation,Nancy Davidson, MD, cautionedphysicians about the use of AIs in premenopausalwomen with hormone-receptor-positive breast cancer andchemotherapy-induced amenorrhea.

It's not possible to provide a "simpleanswer" to the question of the best approachfor use of AIs in women with heterogeneous breast tumors, said Dr.Winer, director of the Breast OncologyCenter and associate professor of medicine,Harvard Medical School.

The optimal strategy for incorporatingAIs into the adjuvant treatment ofpostmenopausal women with breast cancerhas not been defined, Dr. Winer said.When given as initial therapy, AIs haveimproved disease-free survival but notoverall survival. When given as part of acrossover clinical trial design, the drugshave increased both disease-free and overallsurvival. However, follow-up of patientstreated with AIs has been limited.Although therapy in excess of 10 yearsmay provide the most benefit, long-termsafety and efficacy data are lacking, hecommented.

Based on available data, Dr. Winer saidhe believes that AIs should be used in thetreatment of postmenopausal womenwith breast cancer, but given the heterogeneousnature of breast tumors and thetypes of patients in this population, hesuspects that there will not be a singleoverall governing strategy for administeringthe drugs.

Safety in Premenopausal Women
In her presentation on ovarian suppression/ablation in premenopausalbreast cancer patients, Dr. Davidsonstressed that tamoxifen is the standard ofcare for these women, that ovarian suppression/ablation by surgery or LHRHagonists might be used in addition and isbeing studied, and that AIs are investigationalin these women.

Dr. Davidson, professor of oncologyand director of the Breast Cancer ResearchProgram, The Sidney KimmelComprehensive Cancer Center, JohnsHopkins University, pointed out that theamenorrhea caused by cytotoxic therapyis "not the same as menopause, and cliniciansshould think hard about the safetyof AIs for such patients."

She presented findings from a "sobering"case report involving the use of AIsin 45 women with chemotherapy-inducedamenorrhea (J Clin Oncol 24:2444-2447, 2006). The patients had a medianage of 47 years and varied experience withAIs: 16 women received an AI as initialtherapy, 20 were later switched to an AI,and 9 had extended AI therapy.

While on AIs, 12 (27%) of the womenrecovered ovarian function over a medianperiod of 12 months. Menses returnedin 10 women, a pregnancy occurredwithout a return to menses in onewoman, and a biochemical assay determinedrestoration of ovarian function inthe remaining patient. The authors concludedthat AIs may promote recovery ofovarian function in some women withchemotherapy-induced amenorrhea andshould be used with caution.

"Lots of questions remain about adjuvantendocrine therapy for premenopausalwomen," Dr. Davidson said,including determining if additionalbenefits beyond those of tamoxifen maybe achieved, how long ovarian suppressionshould last, and whether ovariansuppression should continue after chemotherapy.

The role of endocrine therapy in combinationwith ovarian suppression andthe use of AIs need to be elucidated, Dr.Davidson said. Three ongoing clinical trialsby the International Breast CancerStudy Group (IBCSG) may provide insight,she said (see box below).