Prognostic factors for early relapse in non-metastatic triple negative breast cancer — real world data

BackgroundTriple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse.Materials and methodsSingle-centre retrospective analysis of 127 women with TNBC, stage II–III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse.ResultsAfter 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3–22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2–6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1–1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively).ConclusionsIn this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.     

Prognostic significance of nuclear morphometry in superficial bladder cancer

OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN: The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody. RESULTS: None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression. CONCLUSION: The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.     

Cytologic diagnosis of axillary lymph node metastasis in breast cancer

OBJECTIVE: To compare imprint cytology with histology as a method for rapid intraoperative diagnosis of axillary lymph node metastasis in breast cancer. STUDY DESIGN: We evaluated imprint cytology, comparing it with histopathology. A sample of 635 axillary lymph nodes was studied by imprint cytology using both Giemsa stain and hematoxylin-eosin. The results were compared with each other and with those of histopathologic examination. RESULTS: The Giemsa stain method, as compared to histopathology, had 94% accuracy, 97% sensitivity, 90% specificity and 94% positive prognostic value. The hematoxylin-eosin stain method was less accurate than the Giemsa stain method as compared to histopathology (accuracy 91%, sensitivity 96%, specificity 83% and positive prognostic value 92%). CONCLUSION: These data confirm the value of imprint cytology as a rapid, reliable method of intraoperative assessment of axillary lymph node metastasis in breast cancer. It results in better staging of the disease. It can be used intraoperatively, as an alternative to frozen section, if a pathology laboratory is not available, to exclude stage I patients from further treatment.     

Prognostic significance of CHAC1 expression in breast cancer

Molecular Biology Reports - An emerging component of Unfolded Protein Response (UPR) pathway, cation transport regulator homolog 1 (CHAC1) has been conferred with the ability to degrade...     

Prognostic significance of CA 15.3 in metastatic breast cancer

We have investigated the possible relation between serum levels of CA 15.3 and disease status in 110 patients after radical mastectomy for breast cancer, with metastatic diffusion. Its persistent elevation was usually related to a very poor prognosis. In patients who died within 18 months the marker was always elevated. In case of progression of the disease, the marker level appeared to be consistently correlated with the general clinical condition. In healthy patients with stable disease the marker remained near the normal range.     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer

The indication of neoadjuvant chemotherapy has been recently extended; it is now applied not only in locally advanced breast cancer but in primarily resecable tumours as well, in order to promote breast conservation. Based on recent clinical results, the reconsideration of traditional lymph node dissection in axillary staging is timely in patients receiving neoadjuvant chemotherapy. Precise axillary staging needs surgical removal of lymph nodes. Based on prospective randomised trials, sentinel lymph node biopsy appears to be appropriate for axillary staging even in tumours requiring neoadjuvant treatment. The extended indication of sentinel lymph node biopsy raises several questions and problems. In the present paper the authors review the results and possible limitations of sentinel lymph node biopsy in relation to neoadjuvant chemotherapy.     

Patterns of DNA copy number changes in sentinel lymph node breast cancer metastases

The sentinel lymph node (SLN) is considered to be the first axillary node that contains malignant cells in metastatic breast tumors, and its positivity is currently used in clinical practice as an indication for axillary lymph node dissection. Therefore, accurate evaluation of the SLN for the presence of breast metastatic cells is essential. The main aim of our study is to characterize the genomic changes present in the SLN metastatic samples with the ultimate goal of improving the predictive value of SLN evaluation. Twenty paired samples of SLN metastases and their corresponding primary breast tumors (PBT) were investigated for DNA copy number changes using comparative genomic hybridization (CGH). Non-random DNA copy number changes were observed in all the lesions analyzed, with gains being more common than losses. In 75% of the cases there was at least one change common to both PBT and SLN. The most frequent changes detected in both lesions were gains of 1pter-->p32, 16, 17, 19, and 20 and losses of 6q13-->q23 and 13q13-->q32. In the PBT group, alterations on chromosomes 1, 16, and 20 were the most frequent, whereas chromosomes 1, 6, and 19 were the ones with the highest number of changes in the SLN metastatic group. A positive correlation was found between the DNA copy number changes per chromosome in each of the groups. Our findings indicate the presence of significant DNA copy number changes in the SLN metastatic lesions that could be used in the future as additional markers to improve the predictive value of SLN biopsy procedure.     

Prognostic significance of aromatase and estrone sulfatase enzymes in human breast cancer

The aromatase and estrone sulfatase enzymes are important sources of local synthesis of biologically active estrogens in human breast cancer. Significant intratumoral aromatase activity was detected in 91/145 (63%) of tumors and estrone sulfatase was detected in 93/104 (89%) of tumors. There was no relationship between aromatase activity and tumor size, site, nodal status, menopousal status or estrogen receptor status. There was a significant correlation between the aromatase activity and histological grade, with an excess of aromatase-positive in the high grade tumors (P = 0.03). There was a marginally inverse correlation between the aromatase activity and time to relapse (P < 0.1), a significant correlation between aromatase activity and survival after relapse (P < 0.05) but not with overall survival (P < 0.1). Intratumoral estrone sulfatase activity was not significantly correlated to any putative prognostic factors, nor with time to relapse nor overall survival time.     

Computerized morphometric image analysis of cytologic nuclear parameters in breast cancer

The value of nuclear morphometry in the preoperative fine needle aspiration (FNA) cytologic diagnosis of mammary lesions was investigated and correlated with the lymph node status of the patients. The subjects consisted of four groups of patients: 49 with invasive ductal carcinomas (18 with no positive nodes, 16 with one to three positive nodes and 15 with four or more positive nodes) and 14 patients with benign lesions. The FNA specimens were smeared onto slides and stained by the May-Grünwald-Giemsa technique. The area, perimeter and maximum diameter of 100 randomly chosen nuclei were both measured with the IBAS image analysis system and semiquantitatively estimated with an eyepiece micrometer. For all three parameters, significant differences were found between benign and malignant lesions. The mean nuclear perimeter allowed the morphometric discrimination between all four groups with statistical significance; nuclear area and maximum diameter did not discriminate patients with invasive carcinoma and one to three positive nodes from those with no positive nodes or more than three positive nodes. Morphometry proved to be far superior to eyepiece measurements with respect to accuracy and reproducibility of the results. The results suggest that nuclear perimeter can be used as an additional parameter not only for the FNA cytologic diagnosis of breast cancer, but also for the estimation of patients' prognosis.     

Methylation of the DFNA5 increases risk of lymph node metastasis in human breast cancer

The pathogenesis of breast cancer involves multiple genetic and epigenetic events. In this study, we report an epigenetic alteration of DFNA5 in human breast cancer. DFNA5 gene was silenced in breast cancer cell lines that were methylated in the DFNA5 promoter, and restored by treatment with the demethylating agent, 5-aza-dC, and gene knock-down of DFNA5 increased cellular invasiveness in vitro. The mRNA expression of DFNA5 in breast cancer tissues was down-regulated as compared to normal tissues. Moreover, the DFNA5 promoter was found to be methylated in primary tumor tissues with high frequency (53%, 18/34). Quantitative methylation-specific PCR of DFNA5 clearly discriminated primary breast cancer tissues from normal breast tissues (15.3%, 2/13). Moreover, methylation status of DFNA5 was correlated with lymph node metastasis in breast cancer patients. Our data implicate DFNA5 promoter methylation as a novel molecular biomarker in human breast cancer.     

Postoperative fever: the potential relationship with prognosis in node negative breast cancer patients

Background

Postoperative fever may serve as an indirect sign to reflect the alterations of the host milieu caused by surgery. It still remains open to investigation whether postoperative fever has a bearing on prognosis in patients with lymph node negative breast cancers.

Methods

We performed a retrospective study of 883 female unilateral patients with lymph node negative breast cancer. Fever was defined as an oral temperature ≥38 in one week postoperation. Survival curves were performed with Kaplan-Meier method, and annual relapse hazard was estimated by hazard function.

Findings

The fever patients were older than those without fever (P<0.0001). Hypertensive patients had a propensity for fever after surgery (P = 0.011). A statistically significant difference was yielded in the incidence of fever among HR+/ERBB2-, ERBB2+, HR-/ERBB2- subgroups (P = 0.012). In the univariate survival analysis, we observed postoperative fever patients were more likely to recur than those without fever (P = 0.0027). The Cox proportional hazards regression analysis showed that postoperative fever (P = 0.044, RR = 1.89, 95%CI 1.02–3.52) as well as the HR/ERBB2 subgroups (P = 0.013, HR = 1.60, 95%CI 1.09–2.31) was an independent prognostic factor for relapse-free survival.

Conclusion

Postoperative fever may contribute to relapse in node negative breast cancer patients, which suggests that changes in host milieu related to fever might accelerate the growth of micro-metastatic foci. It may be more precise to integrate both tumor- and host-related factors for the evaluation of relapse risk.     

Prognostic significance of mean nuclear volume in pancreatic adenocarcinoma

OBJECTIVE: To evaluate the correlation of stereologically estimated mean nuclear volume of tumor cells with other clinicopathologic prognostic features and survival in pancreatic ductal adenocarcinoma. STUDY DESIGN: The study included 27 patients with primary pancreatic ductal adenocarcinoma. A stereologic method proposed by Gundersen et al was used for the estimation of mean nuclear volume in hematoxylin and eosin-stained histologic sections of each case. Mean nuclear volume values were compared statistically with histopathologic prognostic feature groups and survival. RESULTS: The mean nuclear volume values of tumor cells ranged from 296.83 to 982.79 microns 3 (mean, 633.906 +/- 212.310). Higher values of mean nuclear volume were significantly related to advanced tumor stage and the presence of distant metastasis (Kruskal-Wallis, P = .036; Mann-Whitney U, P = .020). In contrast, nodal stage, tumor grade, perineural invasion, lymphatic and blood vessel invasion, and size of tumor showed no statistical relation to mean nuclear volume of tumor cells. Mean nuclear volume was found to be a significant predictor of survival in univariate analysis (P = .016). CONCLUSION: Estimation of mean nuclear volume may help in predicting the extent of disease and clinical behavior in pancreatic adenocarcinoma.