Axillary Node-negative Breast Carcinomas Research Articles

Assessment of the efficacy and safety of methylene blue dye for sentinel lymph node mapping in early breast cancer with clinically negative axilla

Background : The benefits of sentinel lymph node (SLN) biopsy in breast cancer patients with clinically negative axillary nodes are now well established. SLN biopsy has been performed using different techniques including injection of isosulfan blue dye (IBD), radioactive colloid, and methylene blue. The aim of this study was to assess the safety and efficacy of methylene blue dye (MBD) as a mapping agent for SLN biopsy in axillary node negative breast carcinoma. Materials and Methods: Between February 2010-2012, a total of 27 female patients of 18 years and above, with established diagnosis of breast carcinoma with clinically negative ipsilateral axillary lymph nodes were studied. After induction of anesthesia, 5 ml of 1% methylene blue was infiltrated into the subareolar tissue on the affected side. The lymph nodes receiving the blue dye were excised as the SLN. Modified radical mastectomy (MRM) was completed and the excised breast with the axillary tissue was sent for histopathological examination to correlate with the findings of the SLN biopsy. Results: The incidence of breast cancer was highest at 41-50 years. Of 27 cases, SLN was identified in 24 cases using MBD. The identification rate was 88.9%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.8, 100, 100, and 86.7%, respectively. Conclusion: This study confirms the safety and efficacy of methylene blue as a mapping agent for SLN biopsy in axillary node negative breast cancer.

The prognostic value of angiogenic activity evaluation with contrast enhanced power doppler imaging in axillary-node-negative breast carcinoma

To determine the value of contrast ultrasound on evaluating tumor angiogenic activity and its prognostic value in axillary-node-negative breast carcinoma (ANNBC). Power doppler imaging (PDI) was used to observe intratumoral vascularization before and post contrast agents injection. Intratumoral blood flow signals were measured and intratumoral vessel positive total areas (VPTA) were analyzed with computer-assisted quantitative assessment. Sections of malignant tumors were analyzed for the intratumoral microvessel density (MVD) by immunohistochemistry using monoclonal antibody to factor VIII-related antigen. The relationships within VPTA, MVD and prognosis were the main outcome measures. There was no significant correlation between VPTA and MVD before contrast agents used while there was a positive correlation between them after that. However, VPTA and MVD had significant correlation with histology grade and tumor recurrence and metastasis while had no correlation with the general clinic pathologic factors. VPTA and MVD were significantly higher in postoperative cases with recurrence or metastasis than those in cases with tumor-free. Total survival rate and tumor-free survival rate of high-VPTA or high-MVD group were significantly lower than those of low-VPTA or low-MVD group. The value of VPTA by contrast enhanced PDI was a beneficial prognostic indicator. High VPTA in ANNBC patients may has worse prognosis and antiangiogenic therapy is strongly suggested on them.

The combination of p53 mutation and neu/erbB-2 amplification is associated with poor survival in node-negative breast cancer.

Increases in neu/erbB-2 have been implicated in breast cancer prognosis, but do not predict all recurrences. On the basis of evidence that p53 mutation is involved in the development of human neoplasia, we examined the prognostic value of p53 alterations in combination with neu/erbB-2 amplification. A consecutive series of women were observed for recurrence and death (median follow-up of 85 months) and tumors from 543 individuals were analyzed for p53 mutation status and neu/erbB-2 amplification. Exons 4 through 10 of the p53 gene were analyzed by single-stranded conformational polymorphism and mutations were confirmed by DNA sequencing. The association of p53 mutation status and neu/erbB-2 amplification with risk of recurrence and death was examined in survival analyses with traditional and histologic markers as prognostic factors. p53 mutations occurred in 24.5% of the axillary node-negative breast carcinomas. Mutations were more frequent in carcinomas with neu/erbB-2 amplification: 38.9% compared with only 20.9% in those without neu/erbB-2 amplification. We found elevated risks of disease recurrence and overall mortality in patients with both p53 mutation and neu/erbB-2 amplification in their tumor compared with patients with neither or only one of the alterations. This increase persisted with adjustment for other prognostic factors (relative risk, 2.32; P =.002 for recurrence; relative risk, 2.22; P =.004 for death). Evaluation of tumors for p53 mutations may be beneficial to identify women at higher risk of disease recurrence and death when the tumor has neu/erbB-2 amplification, but in the absence of neu/erbB-2 amplification, the presence of p53 mutation may not provide additional independent prognostic information.

Cathepsin-D, urokinase plasminogen activator and type-1 plasminogen activator inhibitor in early breast cancer: an immunohistochemical study of prognostic value and relations to tenascin-C and other factors.

Cytosolic determinations of cathepsin-D (cath-D), urokinase plasminogen activator (uPA) and its specific inhibitor PAI-1 have shown an association with adverse prognosis in breast cancer. Our aim was to study the distribution of these markers in small axillary node-negative breast carcinomas using immunohistochemistry and relate the semiquantitative results to known prognostic factors, the expression of tenascin-C (Tn-C) in invasion border of the tumour and prognosis. All the 158 women (159 tumours) were treated with breast conserving surgery and postoperative radiotherapy. Cytoplasmic immunoreactivity for cath-D was seen in carcinoma cells in 47% and in stromal cells in 44%. Nearly all tumours expressed uPA and PAI-1, which were categorized to cytoplasmic expression in carcinoma cells and diffuse stromal expression and quantified – / + / ++ / +++ and further dichotomized for purposes of analysis. Expression of uPA and PAI-1 in stromal fibroblasts was recorded as – / +. Cytoplasmic and stromal cell cath-D contents were associated with grade, proliferation, Tn-C expression in the tumour invasion border and the development of distant metastasis. In multivariate analysis stromal cath-D proved to be an independent prognostic factor for metastasis. Stromal expression of uPA was associated with an increased risk of local recurrence; otherwise high levels of uPA did not associate with other prognostic factors nor with prognosis. Fibroblastic expression of PAI-1 showed an association with both local and distant disease recurrence. However, no consistent association between the immunohistochemically quantified uPA and PAI-1 and prognosis was found. In conclusion, immunohistochemical determination of cath-D seems to be a viable method to predict a higher risk of metastasis but not local recurrence in small axillary node-negative breast carcinomas.© 1999 Cancer Research Campaign

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence.

We have recently demonstrated an association between distant metastasis and the expression of the extracellular matrix glycoprotein tenascin-C (Tn-C) in the invasion border of small axillary node-negative breast carcinomas. Our purpose was to assess the relationship between the expression of Tn-C in the tumour invasion border and several histopathological and biological variables and to compare their usefulness in predicting local and distant disease recurrences. The original patient group consisted of 143 women with axillary node-negative breast cancer (one bilateral) treated with breast-conserving surgery and post-operative radiotherapy, and followed for a median of 8 years. Because of the small number of recurrences an additional group of 15 similarly treated women with recurrent breast cancer was also studied. The size of the tumour, its histology, including a possible intraductal component, and grade were re-evaluated. The expression of erbB-2, p53, Ki-67 and Tn-C was evaluated by immunohistochemistry. Ploidy and S-phase fraction (SPF) were assessed by flow cytometry. The only statistically significant prognostic factor for local recurrence was Tn-C expression in the invasion border. For metastasis Ki-67 positivity, tumour size and Tn-C expression in the invasion border were statistically significant, but Ki-67 positivity was the only independent prognostic factor. Tn-C expression in the invasion border was associated with a higher proliferation rate measured by Ki-67 and SPF, which is consistent with the suggested growth-promoting activity of Tn-C. Tn-C may be a useful marker in selecting patients for adjuvant therapies to reduce the rate of both local and distant cancer recurrences.