In Reply We appreciate the concern voiced by Lønning regarding the menopausal status of study participants in our trial, and the reliability of the commercial liquid chromatography and tandem mass spectrometry (LC/MS) assay as compared with the radioimmunoassay performed in a research laboratory. Although all patients met strict entry criteria for a postmenopausal state, we were surprised to find estradiol levels above the postmenopausal range in 28 of 76 (37%) of baseline samples. In addition to confirming oophorectomy and prior chemotherapy, we tested baseline follicle-stimulating hormone levels in 63 patients with baseline estradiol measured by both LC/MS and radioimmunoassay. As documented in eTable 2 in the Supplement, 6 patients with baseline estradiol elevation had undergone oophorectomy and in 2 of these patients, estradiol was elevated by both assays. As reported in our article, follicle-stimulating hormone was in the postmenopausal range for 21 of 24 (88%) of patients with baseline estradiol above the postmenopausal range by LC/MS. The remaining 3 patients were receiving ovarian suppression treatment plus an aromatase inhibitor (AI), where follicle-stimulating hormone does not accurately reflect ovarian function even when estradiol is adequately suppressed. We acknowledge that it is difficult to guarantee patient adherence to AI therapy. In addition to the data of Kunovac Kallak et al,1 the HOBOE study identified some postmenopausal patients whose estradiol levels were elevated at baseline, and a subset whose estradiol was not suppressed 6 to 12 months after letrozole exposure.2
Melisko ME, Hwang J, Rugo HS. Concerns About Methodology of a Trial Investigating Vaginal Health During Aromatase Inhibitor Therapy for Breast Cancer—Reply. JAMA Oncol. 2017;3(8):1142. doi:10.1001/jamaoncol.2017.2077
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