A reduction of gynaecological adverse events has been reported in trials comparing aromatase inhibitors with tamoxifen as adjuvant treatment in postmenopausal women with early breast cancer, but there is a paucity of randomised studies specifically investigating their effects on the uterus. We report here the results of a prospective phase III trial comparing the effects of tamoxifen and exemestane by transvaginal ultrasound (TVUS).
Patients and methods
Postmenopausal patients with ER+ early breast cancer were randomised to receive tamoxifen 20 mg once daily or exemestane 25 mg once daily as adjuvant hormone therapy. TVUS was performed at baseline and at 6 and 12 months to measure endometrial thickness (ET) and uterine volume (UV).
Results
A total of 123 women were randomised to tamoxifen (n = 61) or exemestane (n = 62). A significantly higher proportion of patients in the tamoxifen group had increased ET at 6 and 12 months from randomisation compared with the exemestane group (66.1% and 64.3% versus12.1% and 6.8%, respectively; P <0.0001). Mean ET and UV also significantly increased with tamoxifen compared to exemestane at both time points (P <0.01 for all comparisons).
Conclusion
Tamoxifen is associated with endometrial thickening and increased uterine volume in a significant proportion of postmenopausal women with early breast cancer. Our study confirms the lack of endometrial effects of exemestane, which may be of interest to patients and clinicians when choosing among adjuvant endocrine options for breast cancer.
EllménJ., HakulinenP., PartanenA., HayesD.F.: Estrogenic effects of toremifene and tamoxifen in postmenopausal breast cancer patients.Breast Cancer Res Treat, 82: 103–111, 2003.
2.
MachadoF., RodriguezJ.R., LeonJ.P., RodriguezJ.R., ParrillaJ.J., AbadL.: Tamoxifen and endometrial cancer. Is screening necessary? A review of the literature.Eur J Gynaecol Oncol, 26: 257–265, 2005.
American College of Obstetricians and Gynecologists Committee on Gynecologic Practice.ACOG committee opinion. No. 336: Tamoxifen and uterine cancer.Obstet Gynecol, 107: 1475–1478, 2006.
NevenP., VergoteI.: Should tamoxifen users be screened for endometrial lesions?Lancet, 351: 155–157, 1998.
7.
KarlssonB., GranbergS., WiklandM., YlostaloP., TorvidK., MarsalK., ValentinL.: Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding— a Nordic multicenter study.Am J Obstet Gynecol, 172: 1488–1494, 1995.
8.
SalazarE.L., ParedesA., CalzadaL.: Endometrial thickness of postmenopausal breast cancer patients treated with tamoxifen.Gynecol Endocrinol, 21: 312–316, 2005.
9.
GardnerF.J., KonjeJ.C., BrownL., KhannaS., BellS.C., TaylorD.J., al-AzzawiF.: Uterine surveillance of asymptomatic postmenopausal women taking tamoxifen.Climacteric, 1: 180–187, 1998.
10.
LoveC.D., MuirB.B., ScrimgeourJ.B., LeonardR.C., DillonP., DixonJ.M.: Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening.J Clin Oncol, 17: 2050–2054, 1999.
11.
MouritsM.J., Van der ZeeA.G., WillemseP.H., Ten HoorK.A., HollemaH., De VriesE.G.: Discrepancy between ultrasonography and hysteroscopy and histology of endometrium in postmenopausal breast cancer patients using tamoxifen.Gynecol Oncol, 73: 21–26, 1999.
12.
TesoroM.R., BorgidaA.F., MacLaurinN.A., AsuncionC.M.: Transvaginal endometrial sonography in postmenopausal women taking tamoxifen.Obstet Gynecol, 93: 363–366, 1999.
13.
BertelliG., VenturiniM., Del MastroL., GarroneO., CossoM., GustavinoC., CusimanoE., GuidoT., NicolòG., RossoR.: Tamoxifen and the endometrium: findings of pelvic ultrasound examination and endometrial biopsy in asymptomatic breast cancer patients.Breast Cancer Res Treat, 47: 41–46, 1998.
14.
CohenI., RosenD.J., ShapiraJ., CordobaM., GilboaS., AltarasM.M., YigaelD., BeythY.: Endometrial changes with tamoxifen: comparison between tamoxifen-treated and nontreated asymptomatic, postmenopausal breast cancer patients.Gynecol Oncol, 52: 185–190, 1994.
15.
LahtiE., BlancoG., KauppilaA., Apaja-SarkkinenM., TaskinenP.J., LaatikainenT.: Endometrial changes in post-menopausal breast cancer patients receiving tamoxifen.Obstet Gynecol, 81: 660–664, 1993.
16.
SantenR.J., BrodieH., SimpsonE.R., SiiteriP.K., BrodieA.: History of aromatase: saga of an important biological mediator and therapeutic target.Endocr Rev, 30: 343–375, 2009.
17.
CoombesR.C., KilburnL.S., SnowdonC.F., ParidaensR., ColemanR.E., JonesS.E., JassemJ., Van de VeldeC.J., DelozierT., AlvarezI., Del MastroL., OrtmannO., DiedrichK., CoatesA.S., BajettaE., HolmbergS.B., DodwellD., MickiewiczE., AndersenJ., LonningP.E., CocconiG., ForbesJ., CastiglioneM., StuartN., StewartA., FallowfieldL.J., BertelliG., HallE., BogleR.G., CarpentieriM., ColajoriE., SubarM., IrelandE., BlissJ.M.: Survival and safety of exemestane versus tamoxifen after 2–3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.Lancet, 369: 559–570, 2007.
18.
CuzickJ., SestakI., BaumM., BuzdarA., HowellA., DowsettM., ForbesJ.F.: ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial.Lancet Oncol, 11: 1135–1141, 2010.
19.
ReganM.M., NevenP., Giobbie-HurderA., GoldhirschA., EjlertsenB., MauriacL., ForbesJ.F., SmithI., LángI., WardleyA., RabaglioM., PriceK.N., GelberR.D., CoatesA.S., ThürlimannB.: BIG 1–98 Collaborative Group; International Breast Cancer Study Group (IBCSG): Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1–98 randomised clinical trial at 8.1 years median follow-up.Lancet Oncol, 12: 1101–1108, 2011.
20.
KungF.T., ChangS.Y.: The relationship between ultrasonic volume and actual weight of pathologic uterus.Gynecol Obstet Invest, 42: 35–38, 1996.
21.
DijkhuizenFPHLJ, BrölmannH.A.M., OdderB.J.J., RoumenR.M.H., CoeberghJ.W.W., HeintzA.P.M.: Transvaginal ultrasonography and endometrial changes in postmenopausal breast cancer patients receiving tamoxifen.Maturitas, 25: 45–50, 1996.
22.
MarchesoniD., DriulL., FabianiG., Di LoretoC., CataldiP., MozzanegaB.: Endometrial histologic changes in post-menopausal breast cancer patients using tamoxifen.Int J Gynaecol Obstet, 75: 257–263, 2001.
23.
McGonigleK.F., ShawS.L., VasilevS.A., Odom-MaryonT., RoyS., SimpsonJ.F.: Abnormalities detected on transvaginal ultrasonography in tamoxifen-treated postmenopausal breast cancer patients may represent endometrial cystic atrophy.Am J Obstet Gynecol, 178: 1145–1150, 1998.
24.
KiebackD.G., HarbeckN., BauerW., HadjiP., WeyerG., MenschikT., HasenburgA.: Endometrial effects of exemestane compared to tamoxifen within the Tamoxifen Exemestane Adjuvant Multicenter (TEAM) trial: results of a prospective gynecological ultrasound substudy.Gynecol Oncol, 119: 500–505, 2010.
25.
BertelliG., HallE., IrelandE., SnowdonC.F., JassemJ., DrosikK., Karnicka-MlodkowskaH., CoombesR.C., BlissJ.M.: Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)—a randomised controlled trial of exemestane versus continued tamoxifen after 2–3 years tamoxifen.Ann Oncol, 21: 498–505, 2010.
