Effects of Vaginal Estrogens on Serum Estradiol Levels in Postmenopausal Breast Cancer Survivors Taking an Aromatase Inhibitor or a Selective Estrogen Receptor Modulator.
Authors: Wills S. , Ravipati A. , Venuturumilli P. , Kresge C. , Folkerd E. , Dowsett M. , Hayes D. , Decker D. 
Published: December 2010

Abstract
Introduction: Intravaginal estradiol (E2) has been proposed as a safe alternative to systemic estrogen therapy. We report serum E2 levels in breast cancer survivors using either vaginal E2 ring (Estring®) or beta E2 tablet (Vagifem®) while also taking an aromatase inhibitor (AI) or selective estrogen receptor modulator (SERM). These patients are compared to a group of breast cancer survivors using an AI but not taking a VE. Patients and Methods: Postmenopausal women with estrogen receptor positive breast cancer (n=24) using an AI or SERM and vaginal estrogens (VE) to control atrophic vaginitis (ring inserted every 90 days; n=10 or 1 tablet inserted 2 x per week; n=14) and 24 control survivors using an AI without VE were enrolled after informed consent. Serum samples were drawn from ring patients pre-insertion and 30 and 60 days post insertion, from tablet patients the morning prior to insertion and 12 hours post insertion, and from controls taking an AI &gt;14 d. Serum samples were assayed for E2 concentrations by highly sensitive radio-immunoassay (Cancer Res 1987;47:1957). Statistical analyses were carried out using SAS® System, v. 9.2. Results: Patient data are provided in tables 1 and 2 (control data not shown). Circulating E2 levels pre-insertion in tablet patients were not significantly different than those in control patients (mean difference=4.7 pmol/l SD:3.2; CI: 2.9-4.9, p=0.48). E2 levels pre-insertion in patients using the ring were significantly greater than controls (mean difference=14.2 pmol/l; SD:7.2;CI, 11-19:p=0.0001). In tablet patients, E2 levels at 12 hours post insertion were 76 pmol/l higher than at pre-insertion baseline (SD:97; CI, 14-89, p&lt;0.0001), and E2 levels at 12 weeks post insertion in ring patients were 30 pmol/l higher than at pre-insertion baseline(SD:50; CI: 10-20, p=0.001). Discussion: Our data did not show a significant difference in pre-insertion E2 levels for the tablet compared to controls, but we did observe a significant difference in pre-insertion E2 levels for the ring compared to controls. Importantly, we also observed a significant elevation in E2 levels in most patients using VEs post insertion, regardless of the type of device (tablet or ring). The clinical significance of vaginal E2 absorption is unknown, although elevated E2 levels are diametrically opposite of the desired effect for breast cancer patients taking an AI. Vaginal estrogen in patients receiving an adjuvant AI must be advised with caution.ID#SERM/AIPRE-INSERTION PMOL/LPOST-INSERTION PMOL/LMONTHS ON TABLETV4T4.61424V10T35.449V13TIS193V14T1330813V2L4.91912V9L&lt;3.01938V11L&lt;3.01318V5E105773V1A&lt;3.01912V3A&lt;3.0&lt;3.014V6A&lt;3.08918V7A&lt;3.03348V8A5.322936V12A&lt;3.06113IS=Insufficient sample; A=anastrozole; L=letrozole; E=exemestane; T=tamoxifen; R=raloxifeneTable 2. Cases on VE E2 Ring and AI or SERMID #SERM/AIPRE-INSERTION PMOL/L30 DAYS PMOL/L60 DAYS PMOL/LMONTHS ON RINGE6T25222015E9T11169.815E10T15201712E8R18151412E4L19161512E5L&lt;3.0&lt;3.0&lt;3.09E7L&lt;3.0&lt;3.0&lt;3.054E1A121071693E2A1511116E3A2131356
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 806.