Serum lipid and bone metabolism effects of Toremifene vs. Letrozole as adjuvant therapy for postmenopausal early breast cancer patients: results of a multicenter open randomized study

Tadahiko Shien,Yasuhiro Yanagita,Muneaki Sano,Chizuko Kanbayashi,Nobuaki Sato,Kansei Komaki,Hiromitsu Jinno,Shoshu Mitsuyama,Tomomi Fujisawa,Morihiko Kimura,Hiroyoshi Doihara,Keisei Anan,Mikihiro Kusama,Keisuke Miyauchi,Tadashi Ikeda

doi:10.1007/s00280-017-3491-6

Abstract

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1–2, node metastases (n = 0–3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.

Highlights

Patients and methodsSelective estrogen receptor modulators (SERMs) and aromatase inhibitors (AI) are standard adjuvant hormone therapies for estrogen receptor (ER) positive breast cancer patients
We examined the differences between TOR and LET in terms of their influences on lipid profiles and bone metabolism, by conducting a prospective randomized phase II study
We have previously shown that TOR is superior to TAM in terms of the serum lipid profile [5] and that TOR provides better effects than ANA in terms of lipid profiles and bone metabolism in postmenopausal females with early breast cancer [6]

Summary

Introduction

Selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AI) are standard adjuvant hormone therapies for estrogen receptor (ER) positive breast cancer patients. Selecting the most appropriate drug for an individual patient is difficult due to lack of data, especially regarding adverse effects. The influences on lipid and bone metabolism are among the most important adverse effects of hormone therapy. These side effects must be taken into consideration when prescribing SERMs and AI. Toremifene (TOR), a SERM, has prognostic effects and a safety profile similar to those of tamoxifen (TAM) [1, 2]. Harvey et al reported that the risks of stroke, pulmonary embolism, and cataract may be lower with TOR than with TAM and that the risks of pulmonary embolism and deep vein thrombosis are lower than with raloxifene [3]

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