title: Intermittent Letrozole Administration as Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone Receptor-Positive Early Breast Cancer: A Biologic Study.
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.
  
  
  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).
  
  
  CONCLUSIONS
  Intermittent letrozole significantly affects estradiol levels.
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy. Electronic address: alessandra.balduzzi@ieo.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balduzzi
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.affiliation: Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sandri
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dellapasqua
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cardillo
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Montagna
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cancello
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Iorfida
authors.affiliation: Department of Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ghisini
authors.affiliation: Division of Pathology, European Institute of Oncology, Milan, Italy; School of Medicine, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Division of Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Intra
authors.affiliation: Division of Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.affiliation: Department of Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage*; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077289:Letrozole
keywords: Adjuvant endocrine treatment; Estradiol serum level; Estrogen receptor; Intermittent administration; Progesterone receptor