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

Cancer Chemother Pharmacol. 2018 Feb;81(2):269-275. doi: 10.1007/s00280-017-3491-6. Epub 2017 Dec 1.

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.

Keywords: Adjuvant therapy; Bone metabolism; Endocrine therapy; Lipid metabolism; Postmenopausal.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism*
  • Breast Neoplasms / drug therapy*
  • Chemotherapy, Adjuvant
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Collagen Type I / blood
  • Female
  • Humans
  • Letrozole / adverse effects*
  • Letrozole / therapeutic use
  • Lipids / blood*
  • Middle Aged
  • Postmenopause
  • Prospective Studies
  • Toremifene / adverse effects*
  • Toremifene / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • Cholesterol, LDL
  • Collagen Type I
  • Lipids
  • Letrozole
  • Toremifene
  • Cholesterol
  • Alkaline Phosphatase