Lymphovascular Invasion In Breast Cancer Research Articles

Can combined tomosynthesis with unenhanced MRI be used as a predictive tool for lymphovascular invasion?

BackgroundThe presence of lymphovascular invasion (LVI) in cases with breast cancer is considered a bad prognostic sign. The purpose of this study is to compare the efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) versus unenhanced magnetic resonance imaging (UE-MRI + DBT) in predicting LVI in women with pathologically confirmed breast cancer.MethodsThis prospective self-controlled study enrolled a total of 70 cases of pathologically proven breast cancer. All the patients underwent tomosynthesis, non-contrast, and post-contrast MRI. Depending on the broken halo sign seen in tomosynthesis, peritumoral edema, dark rim diffusion at diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) values evaluated in MRI.ResultsThe accuracy of LVI detection by tomosynthesis was 58%; unenhanced and enhanced MRI had the same results at 60%. The accuracy of detecting LVI was raised to 64% by combining the tomosynthesis results with unenhanced MRI.ConclusionsTomosynthesis parameters are promising tools in detecting LVI in breast cancer with better diagnostic accuracy in combination with unenhanced MRI.

Radiomics-based analysis of dynamic contrast-enhanced magnetic resonance image: A prediction nomogram for lymphovascular invasion in breast cancer

ObjectiveTo develop and validate a nomogram for quantitively predicting lymphovascular invasion (LVI) of breast cancer (BC) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomics and morphological features. MethodsWe retrospectively divided 238 patients with BC into training and validation cohorts. Radiomic features from DCE-MRI were subdivided into A1 and A2, representing the first and second post-contrast images respectively. We utilized the minimal redundancy maximal relevance filter to extract radiomic features, then we employed the least absolute shrinkage and selection operator regression to screen these features and calculate individualized radiomics score (Rad score). Through the application of multivariate logistic regression, we built a prediction nomogram that integrated DCE-MRI radiomics and MR morphological features (MR-MF). The diagnostic capabilities were evaluated by comparing C-indices and calibration curves. ResultsThe diagnostic efficiency of the A1/A2 radiomics model surpassed that of the A1 and A2 alone. Furthermore, we incorporated the MR-MF (diffusion-weighted imaging rim sign, peritumoral edema) and optimized Radiomics into a hybrid nomogram. The C-indices for the training and validation cohorts were 0.868 (95% CI: 0.839–0.898) and 0.847 (95% CI: 0.787–0.907), respectively, indicating a good level of discrimination. Moreover, the calibration plots demonstrated excellent agreement in the training and validation cohorts, confirming the effectiveness of the calibration. ConclusionThis nomogram combined MR-MF and A1/A2 Radiomics has the potential to preoperatively predict LVI in patients with BC.

Assessment of Lymphovascular Invasion in Breast Cancer Using a Combined MRI Morphological Features, Radiomics, and Deep Learning Approach Based on Dynamic Contrast-Enhanced MRI.

Assessment of lymphovascular invasion (LVI) in breast cancer (BC) primarily relies on preoperative needle biopsy. There is an urgent need to develop a non-invasive assessment method. To develop an effective model to assess the LVI status in patients with BC using magnetic resonance imaging morphological features (MRI-MF), Radiomics, and deep learning (DL) approaches based on dynamic contrast-enhanced MRI (DCE-MRI). Cross-sectional retrospective cohort study. The study included 206 BC patients, with 136 in the training set [97 LVI(-) and 39 LVI(+) cases; median age: 51.5 years] and 70 in the test set [52 LVI(-) and 18 LVI(+) cases; median age: 48 years]. 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, diffusion-weighted imaging (DWI), and DCE-MRI. The MRI-MF model was developed with conventional MR features using logistic analyses. The Radiomic feature extraction process involved collecting data from categorized DCE-MRI datasets, specifically the first and second post-contrast images (A1 and A2). Next, a DL model was implemented to determine LVI. Finally, we established a joint diagnosis model by combining the MRI-MF, Radiomics, and DL approaches. Diagnostic performance was compared using receiver operating characteristic curve analysis, confusion matrix, and decision curve analysis. Rim sign and peritumoral edema features were used to develop the MRI-MF model, while six Radiomics signature from the A1 and A2 images were used for the Radiomics model. The joint model (MRI-MF + Radiomics + DL models) achieved the highest accuracy (area under the curve [AUC] = 0.857), being significantly superior to the MRI-MF (AUC = 0.724), Radiomics (AUC = 0.736), or DL (AUC = 0.740) model. Furthermore, it also outperformed the pairwise combination models: Radiomics + MRI-MF (AUC = 0.796), DL + MRI-MF (AUC = 0.796), or DL + Radiomics (AUC = 0.826). The joint model incorporating MRI-MF, Radiomics, and DL approaches can effectively determine the LVI status in patients with BC before surgery. 4 TECHNICAL EFFICACY: Stage 2.

MRI radiomics for the preoperative evaluation of lymphovascular invasion in breast cancer: A meta-analysis

PurposeTo evaluate the ability of preoperative MRI-based radiomic features in predicting lymphovascular invasion (LVI) in patients with breast cancer. MethodsPubMed, Embase, Web of Science, Cochrane Library databases, and four Chinese databases were searched to identify relevant studies published up until June 15, 2023. Two reviewers screened all papers independently for eligibility. We included diagnostic accuracy studies that used radiomics-MRI for LVI in patients with breast cancer, using histopathology as the reference standard. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score. Overall diagnostic odds ratio (DOR), sensitivity, specificity and area under the curve (AUC) were calculated to assess the prediction efficacy of MRI-based radiomic features in patients with breast cancer. Spearman’s correlation coefficient was calculated and subgroup analysis performed to investigate causes of heterogeneity. ResultsEight studies comprising 1685 female patients were included. The pooled DOR, sensitivity, specificity, and AUC of radiomics in detecting LVI were 23 [confidence interval (CI) 16,32], 0.89(0.86,0.92), 0.82 (0.78,0.86), and 0.83(0.78,0.87), respectively. The meta-analysis showed significant heterogeneity among the included studies. No threshold effect was detected. Subgroup analysis showed that more than 200 participants, radiomics with clinical factors, semiautomatic segmentation method and peritumoral or intra- and peritumoral model [DOR: 28(18,42), 26(19,37), 34(16,70), 40(10,156), respectively] could improve diagnostic performance compared with less than 200 participants, only radiomics, manual segmentation method, and tumor model [DOR: 16(7,37), 21(6,73), 20(12,32), 21(13,32), respectively], but 3.0 T MR and multiple sequences approach [DOR: 27(15,49),17(8,35)] couldn’t improve diagnostic performance compared with 1.5 T and DCE radiomic features [DOR:27(7,99),25(17,37)]. ConclusionOur meta-analysis showed that preoperative MRI-based radiomic features performs well in predicting LVI in patients with breast cancer. This noninvasive and convenient tool may be used to facilitate preoperative identification of LVI in breast cancer.

Updates on Lymphovascular Invasion in Breast Cancer.

Traditionally, lymphovascular invasion (LVI) has represented one of the foremost pathological features of malignancy and has been associated with a worse prognosis in different cancers, including breast carcinoma. According to the most updated reporting protocols, the assessment of LVI is required in the pathology report of breast cancer surgical specimens. Importantly, strict histological criteria should be followed for LVI assessment, which nevertheless is encumbered by inconsistency in interpretation among pathologists, leading to significant interobserver variability and scarce reproducibility. Current guidelines for breast cancer indicate biological factors as the main determinants of oncological and radiation therapy, together with TNM staging and age. In clinical practice, the widespread use of genomic assays as a decision-making tool for hormone receptor-positive, HER2-negative breast cancer and the subsequent availability of a reliable prognostic predictor have likely scaled back interest in LVI's predictive value. However, in selected cases, the presence of LVI impacts adjuvant therapy. This review summarizes current knowledge on LVI in breast cancer with regard to definition, histopathological assessment, its biological understanding, clinicopathological association, and therapeutic implications.

P023. Intra-tumoural lipid composition and lymphovascular invasion in breast cancer via non-invasive magnetic Resonance spectroscopy

P023. Intra-tumoural lipid composition and lymphovascular invasion in breast cancer via non-invasive magnetic Resonance spectroscopy

Comparison of ER, PR and HER-2/NEU reactivity pattern with histological grade, type, tumour size, Lymphovascular invasion, mitotic index and lymph node status in breast cancer

Context: Breast cancer prognosis is related to a variety of clinical, pathologic and molecular features which include classical prognostic factors viz. Histological grade, morphological type, tumour size, mitotic index, Lymphovascular invasion and lymph node metastases. Estrogen and progesterone receptors (ER, PR) and more recently, HER-2/neu have with increasing importance influenced the management of the malignancy. The presence of hormone receptors (ER and PR) in the tumour tissue correlates well with the response to hormone therapy and chemotherapy. Aims: To assess ER, PR and Her2neu status in breast cancer and to compare ER, PR and Her2neu status with other prognostic factors like tumour size, pathological type, histological grade, lymph node status, mitotic index and Lymphovascular invasion in breast cancer. Methods and materials: A total of 100 cases of breast cancer reported at pathology department during a period from January 2019 to August 2020 are enrolled in the study. Representative sections with tumour and the adjacent normal breast tissue (internal control) are processed for ER, PR and HER-2/neu immuno-histochemical staining. Tumour size, morphological type, Histological grading, Mitotic index, Lymphovascular invasion, Lymph Node status were studied. Results: Occurrence of breast carcinoma is higher in older women (> 50 years of age). The prevalence of ER, PR, HER-2/neu expression are high (ER-73.0%, PR - 65.0% and HER-2/neu - 28.0%). About 14.0% tumour are triple negative. Increased HER2/neu positivity is noticed in ER and PR negative tumours. Two third (66.0%) tumour’s size is from 2 to 5 cm. Proportion of Grade II (39.0%) and Grade III tumour (37.0%) are high. Most common pathologic type of carcinoma is Infiltrating duct carcinoma, not otherwise specified (85.0%) followed by Mucinous carcinoma (5.0%), Invasive papillary carcinoma (4.0%) and Invasive lobular carcinoma (2.0%). PR positivity is increased with increasing tumour size. (p value = 0.01). PR positivity decreases with the increase in grade. (p value = 0.03). HER/ 2neu expression decreased with rising age. (p value = 0.03). Conclusion: The findings suggest that women in our population more often have histologically less aggressive breast carcinoma with a smaller number of triple negative tumours (14%), so they are likely to be more susceptible to conventional hormonal and targeted antibody treatment.

Intra-tumoural lipid composition and lymphovascular invasion in breast cancer via non-invasive magnetic resonance spectroscopy

ObjectivesDespite improved survival due to new treatments, the 10-year survival rate in patients with breast cancer is approximately 75%. Lymphovascular invasion (LVI), a prognostic marker independent from histological grade and stage, can only be fully determined at final histological examination. Lipid composition is deregulated in tumour via de novo lipogenesis, with alteration in lipogenic genes in LVI. We hypothesise alteration in lipid composition derived from novel non-invasive spectroscopy method is associated with LVI positivity.MethodsThirty female patients (age 39–78) with invasive ductal carcinoma were enrolled, with 13 LVI negative and 17 LVI positive. Saturated, monounsaturated, polyunsaturated fatty acids and triglycerides (SFA, MUFA, PUFA and TRG) were quantified from ex vivo breast tumours freshly excised from patients on a 3 T clinical MRI scanner, and proliferative activity marker Ki-67 and serotonin derived histologically.ResultsThere were significantly lower MUFA (p = 0.0189) in LVI positive (median: 0.37, interquartile range (IQR): 0.25–0.64) than negative (0.63, 0.49–0.96). There were significantly lower TRG (p = 0.0226) in LVI positive (1.32, 0.95–2.43) than negative (2.5, 1.92–4.15). There was no significant difference in SFA (p = 0.6009) or PUFA (p = 0.1641). There was no significant correlation between lipid composition against Ki-67 or serotonin, apart from a borderline negative correlation between PUFA and serotonin (r = - 0.3616, p = 0.0496).ConclusionLipid composition might provide a biomarker to study lymphovascular invasion in breast cancer.Key Points• Monounsaturated fatty acids in lymphovascular invasion (LVI) positive invasive breast carcinoma were significantly lower than that in LVI negative.• Triglycerides in LVI positive invasive breast carcinoma were significantly lower than that in LVI negative.• Lipid composition from MR spectroscopy reflects the rate of de novo lipogenesis and provides a potential biomarker independent from histological grade and stage.

Lymphovascular invasion in breast cancer is associated with gene expression signatures of cell proliferation but not lymphangiogenesis or immune response.

While the prognostic relevance of lymphovascular invasion (LVI) in breast cancer is well known, its molecular biology is poorly understood. We hypothesized that pathologically determined LVI reflects molecular features of tumors and can be discerned from their genomic and transcriptomic profiles. LVI status and Nottingham histological scores of primary breast tumors of The Cancer Genome Atlas (TCGA) project were assessed from pathology reports; other clinical and molecular data were obtained from TCGA data portals and publications. Two independent datasets (GSE5460 and GSE7849) were combined and used for validation. LVI status was determinable for 639 and 196 cases of the TCGA and validation cohorts, among whom LVI incidence was 37.8% and 37.2%, respectively. LVI was associated with high tumor Ki67 expression, advanced pathologic stage, and high Nottingham scores. LVI-positive cases had worse overall and progression-free survival regardless of cancer subtype. Surprisingly, in both cohorts, LVI was not associated with lymphangiogenesis or lymphatic vessel density as estimated from tumor expression of lymphatic endothelium-associated genes. LVI-positive tumors had higher genome copy number aberrations, aneuploidy, and homologous recombination defects, but not single-nucleotide variations or intra-tumor genome heterogeneity. Tumor immune cell composition and cytolytic activity was not associated with LVI status. On the other hand, expression of cell proliferation-related genes was significantly increased in LVI-positive tumors. Our study suggests that breast cancer with LVI is a highly proliferative cancer, and it does not correlate with gene expression markers for lymphangiogenesis or immune response.

Value of digital mammography in predicting lymphovascular invasion of breast cancer

BackgroundLymphovascular invasion (LVI) has never been revealed by preoperative scans. It is necessary to use digital mammography in predicting LVI in patients with breast cancer preoperatively.MethodsOverall 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were enrolled and assigned into the LVI positive group (n = 42) and the LVI negative group (n = 80). Independent t-test and χ2 test were performed.ResultsDifference in Ki-67 between the two groups was statistically significant (P = 0.012). Differences in interstitial edema (P = 0.013) and skin thickening (P = 0.000) were statistically significant between the two groups. Multiple factor analysis showed that there were three independent risk factors for LVI: interstitial edema (odds ratio [OR] = 12.610; 95% confidence interval [CI]: 1.061–149.922; P = 0.045), blurring of subcutaneous fat (OR = 0.081; 95% CI: 0.012–0.645; P = 0.017) and skin thickening (OR = 9.041; 95% CI: 2.553–32.022; P = 0.001).ConclusionsInterstitial edema, blurring of subcutaneous fat, and skin thickening are independent risk factors for LVI. The specificity of LVI prediction is as high as 98.8% when the three are used together.

Development of a risk-stratification scoring system for predicting lymphovascular invasion in breast cancer

BackgroundLymphovascular invasion (LVI) is a vital risk factor for prognosis across cancers. We aimed to develop a scoring system for stratifying LVI risk in patients with breast cancer.MethodsA total of 301 consecutive patients (mean age, 49.8 ± 11.0 years; range, 29–86 years) with breast cancer confirmed by pathological reports were retrospectively evaluated at the authors’ institution between June 2015 and October 2018. All patients underwent contrast-enhanced Magnetic Resonance Imaging (MRI) examinations before surgery. MRI findings and histopathologic characteristics of tumors were collected for analysis. Breast LVI was confirmed by postoperative pathology. We used a stepwise logistic regression to select variables and two cut-points were determined to create a three-tier risk-stratification scoring system. The patients were classified as having low, moderate and high probability of LVI. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the scoring system.ResultsTumor margins, lobulation sign, diffusion-weighted imaging appearance, MRI-reported axillary lymph node metastasis, time to signal intensity curve pattern, and HER-2 were selected as predictors for LVI in the point-based scoring system. Patients were considered at low risk if the score was < 3.5, moderate risk if the score was 3.5 to 6.0, and high risk if the score was ≥6.0. LVI risk was segmented from 0 to 100.0% and was positively associated with an increase in risk scores. The AUC of the scoring system was 0.824 (95% confidence interval [CI]: 0.776--0.872).ConclusionThis study shows that a simple and reliable score-based risk-stratification system can be practically used in stratifying the risk of LVI in breast cancer.

Diagnostic concordance of reporting lymphovascular invasion in breast cancer

AimsThis study aims to assess the diagnostic agreement of lymphovascular invasion (LVI) in invasive breast cancer (BC).MethodsData on LVI were collected from the UK National Health Service Breast Screening Programme...

Rho-GTPase activating-protein 18: a biomarker associated with good prognosis in invasive breast cancer

Background:The prognostic value of lymphovascular invasion (LVI) in breast cancer (BC) has been demonstrated in several independent studies. However, identification of driver molecules for LVI remains a challenging task. Large-scale transcriptomic profiling of histologically validated LVI can potentially identify genes that regulate LVI.Methods:Integrative bio-informatics analyses of the METABRIC study were performed utilising a subset of strictly defined LVI using histological and immunohistochemical (IHC) criteria. ARHGAP18 was among the top differentially expressed genes between LVI+ and LVI− BC with a 1.8-fold change. The prognostic impact of ARHGAP18 gene expression was assessed in the METABRIC data set (n=1980) and externally validated using the online BC gene expression data sets utilising bc-GenExMiner v4.0 (n=2016). Subsequently, ARHGAP18 protein expression was assessed on a large cohort of invasive BC (n=959) with long-term follow-up using IHC.Results:Pooled analysis of ARHGAP18 mRNA expression showed that overexpression was associated with better outcome (P<0.001, hazard ratio (HR)=0.82, 95% CI 0.75–0.90). ARHGAP18 protein was expressed in the cytoplasm and nuclei of the tumour cells and its expression was positively associated with good prognostic variables. Lack of cytoplasmic expression showed associations with LVI (P=0.006), epithelial-mesenchymal transition and the HER+ subtype (P=0.01). Loss of nuclear expression was associated with higher grade, HER2+ and high Ki67LI (P=0.001). Cytoplasmic and nuclear expression showed a positive association with improved survival independent of other variables (P=0.01, HR=0.74, 95% CI 0.60–87).Conclusions:ARHGAP18 expression at transcriptomic and protein levels is associated with improved patients’ outcomes whose deregulation may play a role in tumour progression and the development of LVI in BC. Further assessment of its potential therapeutic value in BC is warranted.

Identification of genes and pathways related to lymphovascular invasion in breast cancer patients: A bioinformatics analysis of gene expression profiles.

Surgery is the most effective treatment for breast cancer patients. However, some patients developed recurrence and distant metastasis after surgery. Adjuvant therapy is considered for high-risk patients depending on several prognostic markers, and lymphovascular invasion has become one of such prognostic markers that help physicians to identify the risk for distant metastasis and recurrence. However, the mechanism of lymphovascular invasion in breast cancer remains unknown. This study aims to unveil the genes and pathways that may involve in lymphovascular invasion in breast cancer. In total, 108 breast cancer samples were collected during surgery and microarray analysis was performed. Significance analysis of the microarrays and limma package for R were used to examine differentially expressed genes between lymphovascular invasion-positive and lymphovascular invasion-negative cases. Network and pathway analyses were mapped using the Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery. In total, 86 differentially expressed genes, including 37 downregulated genes and 49 upregulated genes were identified in lymphovascular invasion-positive patients. Among these genes, TNFSF11, IL6ST, and EPAS1 play important roles in cytokine-receptor interaction, which is the most enriched pathway related to lymphovascular invasion. Moreover, the results also suggested that an imbalance between extracellular matrix components and tumor micro-environment could induce lymphovascular invasion. Our study evaluated the underlying mechanisms of lymphovascular invasion, which may further help to assess the risk of breast cancer progression and identify potential targets of adjuvant treatment.

P069 - Hormone use is associated with lymphovascular invasion in breast cancer

P069 - Hormone use is associated with lymphovascular invasion in breast cancer

Hormone Use is Associated with Lymphovascular Invasion in Breast Cancer.

Risk of developing breast cancer increases with short breastfeeding and the use of hormones. The prognosis of breast cancer is better if the tumours are hormone receptor positive. Since breast feeding affects estrogen and progesterone receptors, we wanted to investigate how such reproductive factors as breastfeeding and the use of hormones interact with known prognostic markers and specific tumour characteristics in women with breast cancer. A total of 250 women treated for breast cancer from a larger cohort completed a questionnaire on breastfeeding, number and age at births and use of hormones. A logistic regression analysis was made to search for connections between known prognostic markers on the one hand (type of cancer, grade, tumor size, estrogen receptor and progesterone receptor, lymphovascular invasion and DNA-ploidy) and reproductive data, breastfeeding, and hormone use on the other. Hormone use, but not breastfeeding, was significantly associated, also on multivariate analysis, with the prognostic variable lymphovascular invasion, connected to a worse prognosis. No other hormone use or breast feeding correlations with prognostic variables were found.

1904 Chromosomal aberrations associated with lymphovascular invasion in breast cancer

1904 Chromosomal aberrations associated with lymphovascular invasion in breast cancer

Lymphovascular invasion: assessment and prognostic impact in melanoma and breast cancer.

The presence of lymphovascular invasion is a recognised poor prognostic factor in a wide range of tumour types. Vascular invasion was historically identified through haematoxylin and eosin staining, however this technique is non-specific and differentiates poorly between blood and lymphatic vessels. Newer techniques using immunohistochemistry allow more sensitive and specific identification of lymphovascular invasion and are able to accurately differentiate between lymphatic and blood vessels. This review will discuss the current methods available for the assessment of lymphovascular invasion. Additionally, it will focus on the role of lymphovascular invasion in breast cancer and melanoma, discussing the relative importance of lymphatic and blood vessel invasion in each tumour type.

Lymphatic Space Invasion is Not an Independent Predictor of Outcomes in Early Stage Breast Cancer Treated by Breast-Conserving Surgery and Radiation

To study the prognostic importance of lymphovascular invasion (LVI) in early stage breast cancer after conservative surgery and radiation. From 2/80 to 8/07, 1,478 patients were treated with breast-conserving surgery and radiation with or without systemic therapy. Study eligibility included breast conservation, whole breast postoperative radiation, T1-T2 disease, and known LVI status. Endpoints were 5- and 10-year actuarial outcomes for local control and survival. LVI was present in 427 patients and absent in 1,051 patients. Median follow-up was 68 and 69 months, respectively. Patients with LVI had a younger median age, were more often pre- or perimenopausal, T2, physically palpable, invasive ductal, node positive, grade 3, and treated with chemotherapy compared with patients without LVI. The 5- and 10-year local-regional recurrence was 4.5% and 9.6% with LVI compared with 1.6% and 5.6% without LVI (p = 0.01). The 5- and 10-year overall survival was 83% and 68% for LVI and 91% and 80% for no LVI, respectively (p < 0.0001). Multivariate analysis showed that LVI was not an independent predictor of local-regional control (p = 0.0697) or survival (p = 0.1184). LVI in breast cancer is found in association with other worse prognostic factors for outcome, is associated with a modest increase in local-regional recurrence, but is not an independent predictor of local-regional recurrence or survival on multivariate analysis.

Calpastatin is associated with lymphovascular invasion in breast cancer

Metastasis of breast cancer is a major contributor to mortality. Histological assessment of vascular invasion (VI) provides important prognostic information and demonstrates that VI occurs predominantly via lymphatics in breast cancer. We sought to examine genes and proteins involved in lymphovascular invasion (LVI) to understand the mechanisms of this key disease process. A gene expression array of 91 breast cancer patients was analysed by an Artificial Neural Network (ANN) approach using LVI to supervise the analysis. 89 transcripts were significantly associated ( p < 0.001) with the presence of LVI. Calpastatin, a specific calpain inhibitor, had the second lowest selection error and was investigated in breast cancer specimens using real-time PCR ( n = 56) and immunohistochemistry ( n = 53). Both calpastatin mRNA and protein levels were significantly associated with the presence of LVI ( p = 0.014 and p = 0.025 respectively). The data supports the hypothesis that calpastatin may play a role in regulating the initial metastatic dissemination of breast cancer.