Annals of Oncology Advance Access published online on July 24, 2009
Annals of Oncology, doi:10.1093/annonc/mdp317
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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
1 Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy
2 International Breast Cancer Study Group, Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA
3 Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, University of Glasgow, Glasgow, UK
4 Department of Pathological Anatomy, University of Bari, Bari, Italy
5 Department of Medicine, Research Unit in Medical Senology, European Institute of Oncology, Milan, Italy
6 International Breast Cancer Study Group Coordinating Center, Bern, Switzerland
7 International Breast Cancer Study Group, Statistical Center, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, USA
8 International Breast Cancer Study Group, Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA
9 Melbourne Pathology, Collingwood, Victoria, Australia
10 Department of Pathology, Institute of Oncology, Ljubljana, Slovenia
11 Department of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy
12 Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
13 Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
14 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
15 European Institute of Oncology, Milan, Italy
16 Department of Medicine, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
17 Scientific Committee, International Breast Cancer Study Group, Bern, Switzerland
18 School of Public Health, University of Sydney, Sydney, Australia
* Correspondence to: Prof. G. Viale, Department of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; Tel: +39 (02) 5748 9419; Fax: +39 (02) 5748 9417; E-mail: giuseppe.viale{at}ieo.it
Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer.
Patients and 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.
Conclusion: 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.
adjuvant therapy, breast cancer, endocrine responsiveness, metastasis, prognosis, vascular invasion
Received for publication March 20, 2009. Revision received May 4, 2009. Accepted for publication May 13, 2009.