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.
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.
Viale
G
G
Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy. Electronic address: giuseppe.viale@ieo.it.
Giobbie-Hurder
A
A
International Breast Cancer Study Group, Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA.
Gusterson
B A
BA
Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, University of Glasgow, Glasgow, UK.
Maiorano
E
E
Department of Pathological Anatomy, University of Bari, Bari, Italy.
Mastropasqua
M G
MG
Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy.
Sonzogni
A
A
Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy.
Mallon
E
E
Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, University of Glasgow, Glasgow, UK.
Colleoni
M
M
Department of Medicine, Research Unit in Medical Senology, European Institute of Oncology, Milan, Italy.
Castiglione-Gertsch
M
M
International Breast Cancer Study Group Coordinating Center, Bern, Switzerland.
Regan
M M
MM
International Breast Cancer Study Group, Statistical Center, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, USA.
Price
K N
KN
International Breast Cancer Study Group, Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA.
Brown
R W
RW
Melbourne Pathology, Collingwood, Victoria, Australia.
Golouh
R
R
Department of Pathology, Institute of Oncology, Ljubljana, Slovenia.
Crivellari
D
D
Department of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy.
Karlsson
P
P
Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Öhlschlegel
C
C
Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.
Gelber
R D
RD
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.
Goldhirsch
A
A
European Institute of Oncology, Milan, Italy; Department of Medicine, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Coates
A S
AS
Scientific Committee, International Breast Cancer Study Group, Bern, Switzerland; School of Public Health, University of Sydney, Sydney, Australia.
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
D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate