Journal of the National Cancer Institute Advance Access originally published online on May 12, 2009
JNCI Journal of the National Cancer Institute 2009 101(10):729-735; doi:10.1093/jnci/djp090
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© The Author 2009. Published by Oxford University Press.
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Population-Based Study of Peritumoral Lymphovascular Invasion and Outcome Among Patients With Operable Breast Cancer
Affiliations of authors: Department of Oncology (BE), Department of Pathology (FR), Department of Breast Surgery (NK), and DBCG Data Center (M-BJ, HTM), Rigshospitalet; Department of Pathology, Herlev Hospital (BBR); and Department of Oncology and Haematology, Roskilde Hospital (DBT), Copenhagen University Hospital, Copenhagen, Denmark; Unit of Breast Surgery (PC) and Department of Oncology (MO), Aarhus Sygehus, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark (MEK)
Correspondence to: Bent Ejlertsen, MD, PhD, Department of Oncology, Bldg 4262 Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark (e-mail: ejlertsen{at}rh.dk).
Background: Lymphovascular invasion has been associated with poor prognosis in women with breast cancer, but it is unclear whether the presence of lymphovascular invasion should be considered sufficient to reclassify breast cancer patients who are at a low risk of recurrence into a high-risk category.
Methods: Of the 16 172 patients with operable breast cancer who were entered into the Danish Breast Cancer Cooperative Group Registry from January 1, 1996, to December 31, 2002, lymphovascular invasion was classified at primary diagnosis in 16 121 patients as present (n = 2453, 15%) or as absent (n = 13 206, 82%). Patients with at least one of the risk criteria (positive lymph nodes, tumor size > 2 cm, high grade, hormone receptor–negative tumor, or younger than 35 years) were assigned to the high-risk group; the other patients were assigned to the low-risk group. All procedures, including report forms, central review, and querying, were specified in advance. Kaplan–Meier analyses were used to estimate disease-free intervals and overall survival rates among patients with and without lymphovascular invasion, and multivariable analysis was used to adjust for differences in baseline characteristics and therapy. All statistical tests were two-sided.
Results: Complete follow-up was achieved for 15 659 patients. The median estimated potential follow-up was 6.4 years for invasive disease–free interval and 7.7 years for overall survival. Invasive disease–free interval and overall survival were statistically significantly associated with lymphovascular invasion within the high-risk group (hazard ratio [HR] for invasive disease = 2.29, 95% confidence interval [CI] = 2.14 to 2.45, P < .001; and HR for death = 2.42, 95% CI = 2.25 to 2.61, P < .001) but not within the low-risk group. At 5 years after surgery, 65.4% (95% CI = 63.5% to 67.3%) and 85.2% (95% CI = 84.5% to 85.9%) of those in the high-risk group with and without lymphovascular invasion were alive; 98.1% (95% CI = 87.6% to 99.7%) and 94.1% (95% CI = 93.2% to 94.8%) of those in the low-risk group with and without lymphovascular invasion were alive. These differences persisted in a multivariable analysis, and for overall survival, a statistically significant interaction (P = .03) was observed between lymphovascular invasion and risk group.
Conclusions: In this prospective population-based study, lymphovascular invasion was not an independent high-risk criterion. Lymphovascular invasion should not by itself be considered sufficient to move patients from a low-risk group to a high-risk group.
| CONTEXT AND CAVEATS Prior knowledge Although lymphovascular invasion of breast cancer has been associated with poor outcome, it is unclear whether it is an independent risk factor for recurrence. Study design The outcomes of survival and invasive disease among breast cancer patients in Denmark were evaluated based on the presence or absence of lymphovascular invasion. Contribution Lymphovascular invasion was associated with reduced survival rate and shorter time to invasive disease for patients who were at high risk of recurrence based on previously defined criteria; no association was observed for patients at low risk of recurrence. Implications Lymphovascular invasion was not an independent risk factor for disease recurrence in this population. Limitations In most of the samples, tumor invasion was detected using a general tissue staining procedure rather than a cell type–specific procedure that could have improved the accuracy. The extent of invasion, which has previously been found to be related to prognosis, was not evaluated. From the Editors
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Manuscript received October 10, 2008; revised February 6, 2009; accepted March 13, 2009.
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  M. Chivukula, A. Brufsky, and N. E. Davidson Small Beginnings: Do They Matter? The Importance of Lymphovascular Invasion in Early Breast Cancer J Natl Cancer Inst, May 20, 2009; 101(10): 698 - 699. [Full Text] [PDF]
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