Download Talk_HusseinAlHusban

Assessing the utility of lymphovascular invasion as a
prognostic factor in operable invasive breast cancer
DR HUSSEIN AL-HUSBAN, JBS, BREAST SURGEON, KING HUSSEIN BREAST UNIT
Overview
Breast cancers are neoplasms derived from epithelial cells that are found in the
terminal duct lobular unit.
An invasive breast cancer is one in which there is dissemination lobules into the
adjacent normal tissue.
Invasive cancers have characteristics by which it can be classified.
Classification of invasive breast cancer
TNM classification of breast tumors
Correlation of UICC and TNM classification of
tumors
Breast Cancer Survival by Stage
Adapted from midland cancer registry
Prognostic Factors
Prognostic factors are of value for three main reasons:
1. To predict outcome for an individual patient.
2. To allow comparisons of treatment between groups of patients at similar risk of
recurrence and death.
3. To improve our understanding of breast cancer and develop new therapeutic
approaches.
Breast cancer prognostic factors include:
Tumor size.
Histologic grade.
Axillary status.
Histologic type.
Metastatic disease.
Hormonal status.
Age.
Lymphovascular invasion.
Gender.
Perineural invasion.
Aim of the study
To evaluate the association between LVI and different clinico-pathologic
features of breast cancer.
Lymphovascular invasion
What is lymphovascular invasion or angiolymphatic invasion?
If cancer cells are seen in small blood (or lymph) vessels under microscope. When
cancer is growing in these vessels, there is an increased risk that it has spread
outside the breast.
Why the term lymphovascular invasion is used?
In the breast. It may not be possible to distinguish lymphatic channels from blood
vessels on routine hematoxylin and eosin-stained sections .
Assessment of lymphovascular invasion
Must be diagnosed outside the borders of the invasive carcinoma (peritumoral
tissue).
The most common area to find LVI within 0.1 cm of the edge of carcinoma.
At least three different tumor sections should be examined from each specimen.
Positive LVI is carcinoma cells present within definite endothelial lined space
(lymphatic and/or blood vessel).
Some immunohistochemical (IHC) using lymphovascular endothelial specific
marker D2-40 and CD34 are special tests that the pathologist may use to help
identify the invasion, but these tests are not necessary in every case.
Breast cancer cells present in vascular space
Introduction
Lymphovascular involvement (LVI) is an essential step for breast cancer
progression and metastasis. It has been suggested as a prognostic marker for
long term survival in lymph node negative tumors. In an interesting paper
Rakha, et al., reported the role of LVI as a prognostic marker for breast cancer.
LVI has been found to predict worse outcome and higher metastatic potential .
This was consistent among different subgroup analyses based on established
clinico-pathologic features of breast cancer. In a follow-up multi-institutional
study, Rakha et al. reported the role of LVI as an outcome predictor among
metaplastic breast cancer patients.
Despite this suggested role as a prognostic marker, Ejlertsen, et al., reported a
low potential of LVI as a high-risk predictor. In their study, patients were
classified as low risk vs. high-risk group and the potential of LVI to predict high
risk was investigated. LVI was found to be associated with overall survival in the
high-risk group only. Additionally, most of the data on the prognostic value was
derived from lymph node negative patients. Furthermore, most of the studies
focused on the role of LVI in predicting disease survival and metastatic
potential. The association between LVI and different clinicopathologic features
has been rarely investigated.
Pathobiology, 2015. 82(3-4): 113-23.
J Am Coll Surg, 2005. 200(6): 912-21.
Cancer, 2012. 118(15): 3670-80.
Rev Bras Ginecol Obstet, 2015. 37(7): 308-13.
Br J Cancer, 2015. 112(2): 283-9.
Methods
Two hundred and ninety eight patients with a diagnosis of invasive breast
cancer who undergone surgery in King Hussein Medical City (KHMC) between
2007 and 2014 were included in this study. The study was approved by the
local ethics committee of the Royal Medical Service. All patients had full
clinicopathologic evaluation at the pathology department in KHMC.
LVI positive patients had larger tumor
size
LVI positive patients had higher number
of involved lymph nodes
LVI occurrence did not differ with age
LVI varied by tumor grade
Lymphovascular invasion represents an
initiating event for perineural invasion
LVI occurrence did not vary with ER
status
LVI positive tumors were more common
in PR negative tumors
LVI was more common among patients
with Her2 positive tumors
Discussion
In this paper in attempt to characterized the association between LVI and other clincopathological characteristic of
breast cancer it will also provide better understanding of biology and molecular control of LVI in breast cancer .
LVI was associated with :
large tumor
high grade tumor
more lymphnode involvement
◦ ( Ugras et la reported low incidence of lymph node involvement in patent with negative LVI)
◦ ( Rakha et la reported that about 80% of patent with lymph node negative breast cancer had negative LVI) .
◦ similarly our data on the association between tumor size and grade are completely confirmed with previous report .
additionally was associated with both PR negative and HER2 positive
◦ Interestingly, the association between LVI and these markers has not been investigated thoroughly.
◦ (Marinho et al., reported a negative association between ER, PR status and LVI ). our study support Marinho report on negative
association between ER and LVI, but don't agree Marinho reports about PR and our findings are indicating a critical role of PR in
controlling LVI .
◦ (Rakha et al., reported the occurrence of LVI was similar in patients with Her2 positive and negative tumors. In contrast, our data
indicates a higher occurrence of LVI in Her2 positive patients.)
BMC Cancer, 2008. 8: 64.
A unique aspect of this paper is the characterization between hormonal status and LVI. In order for LVI to occur
tumor cells should release a variety of factors such as matrix metalloproteinase's and angiogenic mediators to
disrupt the integrity of the endothelial barrier.
These factors will facilitate invasion through vascular wall. Both estrogen and progestin has been involved in
angiogenesis. Estrogen and progestin have been shown to play a role in angiogenesis . Estrogen is has a
proangiogenic effect whereas progestin has a tissue dependent proangiogenic effect Interestingly, the levels of
ER did not vary with presence or absence of LVI. This finding suggests that either ER is not involved in LVI or the
levels of estrogen rather that the number of its receptors is involved in LVI.
Moreover, tumors with negative PR had more LVI suggesting that progestin has an antiangiogenic effect in breast
cancer.
Alternatively, this can be attributed to a vessel stabilizing effect of progestin. Such an effect would make the
peritumoral vasculature more resistant to tumor invasion. Better understanding and characterization of this
finding might allow for the development of new targets to inhibit tumor metastasis.
Conclusion
Lymphovascular invasion is associated with larger tumors .
Lymphovascular invasion can predict the extent of lymph node involvement.
 Lymphovascular invasion is associated with high grade tumor .
Can be used to predict the hormonal status of breast cancer.
Lymphovascular invasion should be incorporated in tumor classification and
treatment modality selection.
THANK YOU