title: Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial.
abstract: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown.
  
  
  
  This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS.
  
  
  
  One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29).
  
  
  
  Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials.
authors.affiliation: Hematology/Oncology Department, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gingras
authors.affiliation: Frontier Science (Scotland) Ltd., Kincraig, UK.
authors.forename: Eileen
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Breast Data Center, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Evandro
authors.initials: E
authors.lastname: De Azambuja
authors.affiliation: Radiation Oncology Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: David H A
authors.initials: DH
authors.lastname: Nguyen
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Miguel
authors.initials: M
authors.lastname: Izquierdo
authors.affiliation: National Cancer Institute, Bethesda, MD, USA.
authors.forename: Jo
authors.initials: J
authors.lastname: Anne Zujewski
authors.affiliation: Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Inbar
authors.affiliation: Department of Oncology, Division of Cancer, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Naume
authors.affiliation: Medical Oncology Unit, Azienda Istituti Ospitalieri, Cremona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
authors.affiliation: Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gralow
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Harris
authors.affiliation: Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.affiliation: Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Moreno-Aspitia
authors.affiliation: Breast Data Center, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart
authors.affiliation: Breast Data Center, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Azim
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001365:Axilla; D001940:Breast; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D008198:Lymph Nodes / Q000473:pathology*; D015182:Lymphatic Irradiation / Q000706:statistics & numerical data; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D011799:Quinazolines / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies; D015996:Survival Rate; D000068878:Trastuzumab / Q000627:therapeutic use; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human