Intermittent Letrozole Administration as Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone Receptor-Positive Early Breast Cancer: A Biologic Study

Clin Breast Cancer. 2015 Oct;15(5):e257-62. doi: 10.1016/j.clbc.2015.03.007. Epub 2015 Apr 30.

Abstract

Background: Letrozole withdrawal for 3 months might permit estrogenic stimulation in residual resistant breast cancer disease susceptible to letrozole reintroduction. We investigated the impact of a 3-month letrozole-free interval on serum estradiol levels in patients with early stage breast cancer.

Patients and methods: Postmenopausal women with estrogen receptor- and/or progesterone receptor-positive (> 10% of immunoreactive cells), node-negative early breast cancer were eligible. Patients received letrozole for 5 years with a 3-month treatment-free interval after the first year of therapy. The primary end point was to evaluate the increase in serum estradiol levels after a 3-month treatment-free interval. The secondary end points were the evaluations of other biologic markers (eg, follicle-stimulating hormone, luteinizing hormone, cholesterol, high-density lipoprotein, triglycerides, osteocalcin).

Results: From November 2007 to February 2012, 130 evaluable patients were enrolled. The median age was 61 years. Mean values of estradiol levels at time of discontinuation were 5.6 pg/mL (standard deviation 1.7). Estradiol levels increased after a 3-month treatment-free interval by a mean of 3.3 pg/mL (66%; P < .0001). Follicle-stimulating hormone and luteinizing hormone levels decreased from baseline by a mean of 7.5 mU/mL (P < .0001), and 1.4 mU/mL (P = .0062), respectively. Triglycerides decreased from baseline by a mean of 8.6 mg/dL (P = .036), and osteocalcin increased by a mean of 2.8 ng/mL (P = .013).

Conclusion: Intermittent letrozole significantly affects estradiol levels.

Keywords: Adjuvant endocrine treatment; Estradiol serum level; Estrogen receptor; Intermittent administration; Progesterone receptor.

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Chemotherapy, Adjuvant / methods
  • Female
  • Humans
  • Letrozole
  • Middle Aged
  • Nitriles / administration & dosage*
  • Postmenopause*
  • Receptors, Estrogen / metabolism
  • Triazoles / administration & dosage*

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Nitriles
  • Receptors, Estrogen
  • Triazoles
  • Letrozole