title: Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis.
abstract: OBJECTIVE
  Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear.
  
  
  OBJECTIVE
  To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer.
  
  
  METHODS
  Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015.
  
  
  METHODS
  Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n = 20). Two authors independently analyzed the studies for inclusion.
  
  
  METHODS
  Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model.
  
  
  RESULTS
  The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P = .85; n = 378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P = .12; n = 378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P = .07; n = 334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P < .001; n = 1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P < .001; n = 1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P < .001; n = 918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P = .03; n = 355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P = .11; n = 537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%).
  
  
  CONCLUSIONS
  Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Spring
authors.affiliation: Department of Medicine, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Arjun
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Reynolds
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Gadd
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
authors.forename: Leif W
authors.initials: LW
authors.lastname: Ellisen
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Isakoff
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bardia
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen