title: Pilot trial of preoperative (neoadjuvant) letrozole in combination with bevacizumab in postmenopausal women with newly diagnosed estrogen receptor- or progesterone receptor-positive breast cancer.
abstract: BACKGROUND
  Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of antiestrogen adjuvant therapy. We designed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab (anti-VEGF) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor-positive breast cancer.
  
  
  METHODS
  Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer. Patients were followed for toxicity at 3-week intervals, and tumor assessment (a physical examination and ultrasound) was performed at 6-week intervals. Positron emission tomography (PET) scans were performed before therapy and 6 weeks after the initiation of therapy.
  
  
  RESULTS
  Twenty-five evaluable patients were treated. The regimen was well-tolerated, except in 2 patients who were taken off the study for difficulties controlling their hypertension. An objective clinical response occurred in 17 of 25 patients (68%), including 16% complete responses (CRs) and 52% partial responses. The 4 patients with clinical CRs manifested pathologic CRs in their breasts (16%), although 1 patient had residual tumor cells in her axillary nodes. Eight of 25 patients (32%) attained stage 0 or 1 status. The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks (P < .0036).
  
  
  CONCLUSIONS
  Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and resulted in impressive clinical and pathologic responses. The Translational Breast Cancer Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population.
authors: Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA. andres.forero@ccc.uab.edu
authors: Andres
authors: A
authors: Forero-Torres
authors: Mansoor N
authors: MN
authors: Saleh
authors: Janice A
authors: JA
authors: Galleshaw
authors: Cheryl F
authors: CF
authors: Jones
authors: Jatin J
authors: JJ
authors: Shah
authors: Ivor J
authors: IJ
authors: Percent
authors: Lisle M
authors: LM
authors: Nabell
authors: John T
authors: JT
authors: Carpenter
authors: Carla I
authors: CI
authors: Falkson
authors: Helen
authors: H
authors: Krontiras
authors: Marshall M
authors: MM
authors: Urist
authors: Kirby I
authors: KI
authors: Bland
authors: Jennifer F
authors: JF
authors: De Los Santos
authors: Ruby F
authors: RF
authors: Meredith
authors: Valerie
authors: V
authors: Caterinicchia
authors: Wanda K
authors: WK
authors: Bernreuter
authors: Janis P
authors: JP
authors: O'Malley
authors: Yufeng
authors: Y
authors: Li
authors: Albert F
authors: AF
authors: LoBuglio
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D000068258:Bevacizumab; D000077289:Letrozole