title: The impact of tumor progesterone receptor status on optimal adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer: a decision analysis.
abstract: BACKGROUND
  Emerging data suggest that treatment outcomes with aromatase inhibitors (AIs) and/or tamoxifen may differ for tumors that express both the estrogen receptor (ER) and the progesterone receptor (PR) (ER+/PR+) compared with those that lack PR expression (ER+/PR-). However, the optimal sequencing of AIs and tamoxifen as adjuvant therapy is not known and may differ for biologic subsets of cancers.
  
  
  METHODS
  Markov models were used to simulate disease-free survival (DFS) separately among postmenopausal women with ER+/PR+ cancers and women with ER+/PR- cancers. By using risk estimates reported from randomized clinical trials, treatment with 5 years of an AI alone with sequential treatment consisting of tamoxifen with crossover to an AI at 2 years was compared.
  
  
  RESULTS
  For women with ER+/PR+ cancers, sequential therapy with tamoxifen followed by crossover to an AI at 2 years yielded modest improvements in 10-year DFS estimates compared with planned AI monotherapy (84.3% vs. 82.2% and 68.8% vs. 64.8% for lymph node-negative and lymph node-positive patients, respectively). However, for women with ER+/PR- cancers, upfront treatment with an AI yielded improved outcomes with 10-year DFS rates of 90.5% and 80.1% for the lymph node-negative and node-positive groups, respectively, compared with 88.2% and 76.1%, respectively, for sequential treatment with tamoxifen followed by an AI.
  
  
  CONCLUSIONS
  Modeling estimates suggested that the optimal endocrine treatment strategy may differ based on the biologic features of breast cancer tumors. Patients with ER+/PR+ tumors achieved optimal 10-year DFS estimates with tamoxifen followed by a crossover to AI therapy, whereas patients with ER+/PR- tumors fared best when they initiated treatment with AI.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Rinaa S
authors.initials: RS
authors.lastname: Punglia
authors.forename: Karen M
authors.initials: KM
authors.lastname: Kuntz
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Jane C
authors.initials: JC
authors.lastname: Weeks
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018592:Cross-Over Studies; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008390:Markov Chains; D008875:Middle Aged; D015233:Models, Statistical; D008962:Models, Theoretical; D009367:Neoplasm Staging; D016017:Odds Ratio; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D011980:Receptors, Progesterone / Q000032:analysis*; D013629:Tamoxifen / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D011980:Receptors, Progesterone; D013629:Tamoxifen