title: Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database.
abstract: OBJECTIVE
  To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype.
  
  
  METHODS
  Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2-, low/intermediate grade), luminal B (ER/PR+, HER2-, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER-, PR-, HER2-). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT.
  
  
  RESULTS
  With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively.
  
  
  CONCLUSIONS
  TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.
authors.affiliation: Department of Radiation Oncology, University of Washington, Seattle, Washington. Electronic address: ydt2@uw.edu.
authors.forename: Yolanda D
authors.initials: YD
authors.lastname: Tseng
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Hajime
authors.initials: H
authors.lastname: Uno
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Hughes
authors.affiliation: Department of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Niland
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Wong
authors.affiliation: Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Richard
authors.initials: R
authors.lastname: Theriault
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Blitzblau
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Northwestern Lake Forest Hospital, Lake Forest, Illinois.
authors.forename: Tara
authors.initials: T
authors.lastname: Breslin
authors.affiliation: Baptist Cancer Center, Memphis, Tennessee; Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Edge
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hassett
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Rinaa S
authors.initials: RS
authors.lastname: Punglia
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000532:radiotherapy*; D057216:Propensity Score; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018570:Risk Assessment; D013997:Time Factors; D000068878:Trastuzumab / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab