title: Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer.
abstract: BACKGROUND
  Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer.
  
  
  METHODS
  Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years).
  
  
  RESULTS
  PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy.
  
  
  CONCLUSIONS
  Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy. Electronic address: giuseppe.viale@ieo.it.
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.affiliation: International Breast Cancer Study Group, Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.affiliation: Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, University of Glasgow, Glasgow, UK.
authors.forename: B A
authors.initials: BA
authors.lastname: Gusterson
authors.affiliation: Department of Pathological Anatomy, University of Bari, Bari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Maiorano
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Mastropasqua
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sonzogni
authors.affiliation: Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, University of Glasgow, Glasgow, UK.
authors.forename: E
authors.initials: E
authors.lastname: Mallon
authors.affiliation: Department of Medicine, Research Unit in Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
authors.affiliation: International Breast Cancer Study Group Coordinating Center, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.affiliation: International Breast Cancer Study Group, Statistical Center, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Regan
authors.affiliation: International Breast Cancer Study Group, Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Price
authors.affiliation: Melbourne Pathology, Collingwood, Victoria, Australia.
authors.forename: R W
authors.initials: RW
authors.lastname: Brown
authors.affiliation: Department of Pathology, Institute of Oncology, Ljubljana, Slovenia.
authors.forename: R
authors.initials: R
authors.lastname: Golouh
authors.affiliation: Department of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Crivellari
authors.affiliation: Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Karlsson
authors.affiliation: Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Öhlschlegel
authors.affiliation: International Breast Cancer Study Group, Statistical Center, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Boston, MA, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.affiliation: European Institute of Oncology, Milan, Italy; Department of Medicine, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Scientific Committee, International Breast Cancer Study Group, Bern, Switzerland; School of Public Health, University of Sydney, Sydney, Australia.
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003520:Cyclophosphamide / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008593:Menopause / Q000502:physiology; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate