Dataset Information

Vessel size as a marker of survival in estrogen receptor positive breast cancer.

ABSTRACT:

Purpose

Angiogenesis is crucial for tumor growth and is one of the hallmarks of cancer. In this study, we analyzed microvessel density, vessel median size, and perivascular a-SMA expression as prognostic biomarkers in breast cancer.

Methods

Dual IHC staining was performed where alpha-SMA antibodies were used together with antibodies against the endothelial cell marker CD34. Digital images of stainings were analyzed to extract quantitative data on vessel density, vessel size, and perivascular alpha-SMA status.

Results

The analyses in the discovery cohort (n = 108) revealed a statistically significant relationship between large vessel size and shorter disease-specific survival (p = 0.007, log-rank test; p = 0.01, HR 3.1; 95% CI 1.3-7.4, Cox-regression analyses). Subset analyses indicated that the survival association of vessel size was strengthened in ER + breast cancer. To consolidate these findings, additional analyses were performed on a validation cohort (n = 267) where an association between large vessel size and reduced survival was also detected in ER + breast cancer (p = 0.016, log-rank test; p = 0.02; HR 2.3, 95% CI 1.1-4.7, Cox-regression analyses).

Conclusion

Alpha-SMA/CD34 dual-IHC staining revealed breast cancer heterogeneity regarding vessel size, vessel density, and perivascular a-SMA status. Large vessel size was linked to shorter survival in ER + breast cancer.

SUBMITTER: Milosevic V

PROVIDER: S-EPMC10241708 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vessel size as a marker of survival in estrogen receptor positive breast cancer.

Milosevic Vladan V Edelmann Reidunn J RJ Winge Ingeborg I Strell Carina C Mezheyeuski Artur A Knutsvik Gøril G Askeland Cecilie C Wik Elisabeth E Akslen Lars A LA Östman Arne A

Breast cancer research and treatment 20230524 2

<h4>Purpose</h4>Angiogenesis is crucial for tumor growth and is one of the hallmarks of cancer. In this study, we analyzed microvessel density, vessel median size, and perivascular a-SMA expression as prognostic biomarkers in breast cancer.<h4>Methods</h4>Dual IHC staining was performed where alpha-SMA antibodies were used together with antibodies against the endothelial cell marker CD34. Digital images of stainings were analyzed to extract quantitative data on vessel density, vessel size, and p ...[more]

PMID: 37222874

Similar Datasets

Project description:BackgroundAmong women, breast cancer is the leading cause of cancer-related death worldwide. Estrogen receptor α-positive (ERα+) breast cancer accounts for 70% of all breast cancer subtypes. Although ERα+ breast cancer initially responds to estrogen deprivation or blockade, the emergence of resistance compels the use of more aggressive therapies. While ERα is a driver in ERα+ breast cancer, ERβ plays an inhibitory role in several different cancer types. To date, the lack of highly selective ERβ agonists without ERα activity has limited the exploration of ERβ activation as a strategy for ERα+ breast cancer.MethodsWe measured the expression levels of ESR1 and ESR2 genes in immortalized mammary epithelial cells and different breast cancer cell lines. The viability of ERα+ breast cancer cell lines upon treatments with specific ERβ agonists, including OSU-ERb-12 and LY500307, was assessed. The specificity of the ERβ agonists, OSU-ERb-12 and LY500307, was confirmed by reporter assays. The effects of ERβ agonists on cell proliferation, cell cycle, apoptosis, colony formation, cell migration, and expression of tumor suppressor proteins were analyzed. The expression of ESR2 and genes containing ERE-AP1 composite response elements was examined in ERα+ human breast cancer samples to determine the correlation between ESR2 expression and overall survival and that of putative ESR2-regulated genes.ResultsIn this study, we demonstrate the efficacy of highly selective ERβ agonists in ERα+ breast cancer cell lines and drug-resistant derivatives. ERβ agonists blocked cell proliferation, migration, and colony formation and induced apoptosis and S and/or G2/M cell-cycle arrest of ERα+ breast cancer cell lines. Also, increases in the expression of the key tumor suppressors FOXO1 and FOXO3a were noted. Importantly, the strong synergy between ERβ agonists and ERα antagonists suggested that the efficacy of ERβ agonists is maximized by combination with ERα blockade. Lastly, ESR2 (ERβ gene) expression was negatively correlated with ESR1 (ERα gene) and CCND1 RNA expression in human metastatic ERα+/HER2- breast cancer samples.ConclusionOur results demonstrate that highly selective ERβ agonists attenuate the viability of ERα+ breast cancer cell lines in vitro and suggest that this therapeutic strategy merits further evaluation for ERα+ breast cancer.

Project description:ImportanceBreast cancer risk and comorbidities increase with age. Data are lacking on the association of adjuvant chemotherapy with survival in elderly patients with multiple comorbidities and node-positive breast cancer.ObjectiveTo examine the association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer.Design, setting, and participantsThis retrospective cohort study included patients in the US National Cancer Database who were 70 years or older; had a Charlson/Deyo comorbidity score of 2 or 3; had estrogen receptor-positive, ERBB2 (formerly HER2 or HER2/neu)-negative breast cancer; and underwent surgery for pathologic node-positive breast cancer from January 1, 2010, to December 31, 2014. Propensity scores were used to match patients receiving adjuvant chemotherapy with those not receiving adjuvant chemotherapy based on age, comorbidity score, facility type, facility location, pathologic T and N stage, and receipt of adjuvant endocrine and radiation therapy. Data analysis was performed from December 13, 2018, to April 28, 2020.ExposuresChemotherapy.Main outcomes and measuresThe association of adjuvant chemotherapy with overall survival was estimated using a double robust Cox proportional hazards regression model.ResultsOf a total of 2 445 870 patients in the data set, 1592 patients (mean [SD] age, 77.5 [5.5] years; 1543 [96.9%] female) met the inclusion criteria and were included in the initial nonmatched analysis. Of these patients, 350 (22.0%) received chemotherapy and 1242 (78.0%) did not. Compared with patients who did not receive chemotherapy, patients who received chemotherapy were younger (mean age, 74 vs 78 years; P < .001), had larger primary tumors (pT3/T4 tumors: 72 [20.6%] vs 182 [14.7%]; P = .005), and had higher pathologic nodal burden (75 [21.4%] vs 81 [6.5%] with stage pN3 disease and 182 [52.0%] vs 936 [75.4%] with stage pN1 disease; P < .001). More patients who received chemotherapy also received other adjuvant treatments, including endocrine therapy (309 [88.3%] vs 1025 [82.5%]; P = .01) and radiation therapy (236 [67.4%] vs 540 [43.5%]; P < .001). In the matched cohort, with a median follow-up of 43.1 months (95% CI, 39.6-46.5 months), no statistically significant difference was found in median overall survival between the chemotherapy and no chemotherapy groups (78.9 months [95% CI, 78.9 months to not reached] vs 62.7 months [95% CI, 56.2 months to not reached]; P = .13). After adjustment for potential confounding factors, receipt of chemotherapy was associated with improved survival (hazard ratio, 0.67; 95% CI, 0.48-0.93; P = .02).Conclusions and relevanceThis cohort study found that in node-positive, estrogen receptor-positive elderly patients with breast cancer and multiple comorbidities, receipt of chemotherapy was associated with improved overall survival. Despite attempts to adjust for selection bias, these findings suggest that physicians carefully selected patients likely to derive treatment benefit from adjuvant chemotherapy based on certain unmeasured variables. A standardized, multidisciplinary approach to care may be associated with long-term treatment outcomes in this subset of the population.

Dataset Information

Vessel size as a marker of survival in estrogen receptor positive breast cancer.

Purpose

Methods

Results

Conclusion

Publications

Vessel size as a marker of survival in estrogen receptor positive breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets