Using Kaplan–Meier analysis together with decision tree methods (C&RT, CHAID, QUEST, C4.5 and ID3) in determining recurrence-free survival of breast cancer patients

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.

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Effect of mast cells on efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme b.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.11522 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 11522-11522

Author(s):

Mark Wroblewski ◽

Janna-Lisa Velthaus ◽

Raimund Bauer ◽

Volkmar Müller ◽

Christian Schem ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Granzyme B ◽

Resistance Mechanism ◽

Disease Free Survival ◽

Tissue Microarrays ◽

Breast Cancer Patients ◽

Free Survival ◽

Angiogenic Therapy ◽

Kaplan Meier

11522 Background: Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. As mast cell (MC) density is known to correlate with tumor angiogenesis, we analyzed if inhibition of MC holds potential to increase efficacy of AAT in mice and cancer patients. Methods: C57BL/6J (WT), NSG or MC-deficient KitW-sh(Wsh) mice were subcutaneously injected with Panc02, EL4 or BxPC3 cells with or without bone marrow-derived MC. Tumors were treated with 20 mg/kg of anti-VEGFR2 antibodies (DC101) or 25 mg/kg cromoglicic acid. Tissue microarrays from n = 299 breast cancer patients from the GeparQuinto Phase 3 clinical trial were stained for MC and MC numbers were correlated with clinical data. Results: We observed that absence of MC reduced tumor growth and increased the efficacy of AAT in different tumor models. Intriguingly, AAT only initially reduced microvessel proliferation but this was abrogated over time as a result of MC-mediated resistance. We show that MC secrete increased amounts of granzyme b upon therapy, which mobilizes alternative pro-angiogenic factors from the tumor matrix. These factors act beside the targeted VEGFA-VEGFR2-axis and reinduce angiogenesis despite the presence of AAT. Importantly, MC-mediated resistance could be overcome using the FDA-approved MC inhibitor cromoglicic acid. In line with our preclinical data, high intratumoral MC density correlated with disease progression in HR+ breast cancer patients when Bevacizumab was added to standard neodjuvant chemotherapy (HR 8.45, p = 0.006). Accordingly, Kaplan-Meier curves indicated that disease free survival of patients with high tumoral MC density was numerically shorter in the whole cohort and significantly shorter in the HR+ cohort upon addition of AAT to chemotherapy (p = 0.168 and p = 0.004, respectively). Conclusions: Here we unravel a novel resistance mechanism, by which MC hamper efficacy of AAT in mice and cancer patients. In preclinical models this effect could be overcome by combining AAT with an FDA-approved MC inhibitor indicating high clinical relevance. Thus, combination of FDA-approved MC inhibitors with AAT might be a suitable approach to increase efficacy of AAT in the clinic.

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KIBRA; a novel biomarker predicting recurrence free survival of breast cancer patients receiving adjuvant therapy

BMC Cancer ◽

10.1186/s12885-018-4491-6 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 3

Author(s):

Lakmini Mudduwa ◽

Harshini Peiris ◽

Shania Gunasekara ◽

Deepthika Abeysiriwardhana ◽

Nimsha Liyanage ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Therapy ◽

Cancer Patients ◽

Recurrence Free Survival ◽

Breast Cancer Patients ◽

Free Survival

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Weight control strategies in breast cancer patients: A systematic review.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.3_suppl.179 ◽

2016 ◽

Vol 34 (3_suppl) ◽

pp. 179-179

Author(s):

Nathalie LeVasseur ◽

Mark J. Clemons ◽

Sasha Mazzarello ◽

Lisa Vandermeer ◽

Lee Jones ◽

...

Keyword(s):

Breast Cancer ◽

Waist Circumference ◽

Cancer Patients ◽

Weight Control ◽

Control Strategies ◽

Recurrence Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Exercise Interventions ◽

Weight Control Strategies

179 Background: Obesity remains an underestimated contributor to global cancer incidence and cancer-related mortality. Accumulating evidence suggests excessive energy intake and suboptimal levels of physical activity may be important after the diagnosis of cancer and may influence recurrence and overall survival(OS). Objective: Conduct a systematic review to evaluate data from randomized trials of weight control strategies used in breast cancer patients. Methods: A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials through April 2015 was performed. Randomized trials of weight management strategies in breast cancer patients were sought. Outcomes studied included; change in weight, BMI and waist circumference, disease-free survival, recurrence-free survival and OS survival. Random effects meta-analyses were planned provided that included studies were considered to be clinically and methodologically homogenous. Results: Of 2876 abstracts, 312 were retained for review of the full texts. Overall 43 publications describing 40 studies met inclusion criteria. Of 12,801 enrolled patients, 11,597 had breast cancer. Fifteen studies consisted of dietary interventions, 17 consisted of exercise interventions and 8 consisted of both dietary and exercise interventions. Endpoints included: changes in weight (32 studies, 7,861 pts), BMI (12 studies, 1,886 pts), waist circumference (10 studies, 702 pts), recurrence-free survival (4 studies, 6105 pts) and overall survival (2 studies, 3,330 pts). Network meta-analyses of available data are in progress. Study results suggest that weight control strategies including dietary and exercise interventions were effective at reducing weight, BMI and waist circumference. Two large studies showed statistically significant recurrence-free survival benefits with weight control strategies and one showed OS benefit with an exercise intervention. Conclusions: Data from included trials suggest benefits of weight control strategies to decrease weight, BMI and waist circumference. Few trials have been designed to detect PFS or OS benefits. Larger trials are warranted to better define the role of weight control strategies in the management of breast cancer patients.

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The contribution of axillary lymph node volume to recurrence-free survival status in breast cancer patients with sub-stratification by molecular subtypes and pathological complete response

10.21203/rs.3.rs-57680/v1 ◽

2020 ◽

Author(s):

James Kang ◽

Haifang Li ◽

Renee Cattell ◽

Varsha Talanki ◽

Jules A Cohen ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Cancer Patients ◽

Axillary Lymph Node ◽

Molecular Subtypes ◽

Complete Response ◽

Axillary Lymph ◽

Recurrence Free Survival ◽

Breast Cancer Patients ◽

Free Survival

Abstract Purpose This study sought to examine the contribution of axillary lymph node (LN) volume to recurrence-free survival (RFS) in breast cancer patients with sub-stratification by molecular subtypes, and full or nodal PCR.Methods The largest LN volumes per patient at pre-neoadjuvant chemotherapy on standard clinical breast 1.5-Tesla MRI, 3 molecular subtypes, full, breast, and nodal PCR, and 10-year RFS were tabulated (N = 110 patients from MRIs of I-SPY-1 TRIAL). A volume threshold of two standard deviations was used to categorize large versus small LNs for sub stratification. In addition, “normal” node volumes were determined from a different cohort of 218 axillary LNs.Results LN volume (4.07 ± 5.45 cm3) were significantly larger than normal axillary LN volumes (0.646 ± 0.657 cm3, P = 10− 16). Full and nodal pathologic complete response (PCR) was not dependent on pre-neoadjuvant chemotherapy nodal volume (P > .05). The HR+/HER2– group had smaller axillary LN volumes than the HER2 + and triple-negative groups (P < .05). Survival was not dependent on pre-treatment axillary LN volumes alone (P = .29). However, when substratified by PCR, the large LN group with full (P = .011) or nodal PCR (P = .0026) both showed better recurrence-free survival than the small LN group. There was significant difference in RFS when the small node group was separated by the 3 molecular subtypes (P = .036) but not the large node group (P = .97).Conclusions This study found an interaction of axillary lymph node volume, pathological complete responses, and molecular subtypes that inform recurrence-free survival status. Improved characterization of the axillary lymph nodes has the potential to improve the management of breast cancer patients.

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Comparison of MRI tumor volumetric and diameter measurements for predicting recurrence free survival in breast cancer patients undergoing preoperative chemotherapy.

10.1158/0008-5472.sabcs-6053 ◽

2009 ◽

Author(s):

DC Newitt ◽

J Gibbs ◽

SC Partridge ◽

KL Li ◽

EC Lobo ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Preoperative Chemotherapy ◽

Recurrence Free Survival ◽

Breast Cancer Patients ◽

Free Survival

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Comment on ‘Impact ofCYP2D6*10on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy’

Cancer Science ◽

10.1111/j.1349-7006.2008.00864.x ◽

2008 ◽

Vol 99 (8) ◽

pp. 1706-1707 ◽

Cited By ~ 5

Author(s):

Timothy L. Lash ◽

Thomas P. Ahern ◽

Deirdre Cronin-Fenton ◽

Jens Peter Garne ◽

Stephen Hamilton-Dutoit ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tamoxifen Therapy ◽

Adjuvant Tamoxifen ◽

Recurrence Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Adjuvant Tamoxifen Therapy

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CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy

International Journal of Breast Cancer ◽

10.1155/2018/6945129 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Ashley J. Schlafstein ◽

Allison E. Withers ◽

Soumon Rudra ◽

Diana Danelia ◽

Jeffrey M. Switchenko ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Prognostic Biomarker ◽

Pathologic Complete Response ◽

Complete Response ◽

Recurrence Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Risk Of Death

Failure to achieve pathologic complete response is associated with poor prognosis in breast cancer patients following neoadjuvant chemotherapy (NACT). However, prognostic biomarkers for clinical outcome are unclear in this patient population. Cyclin-dependent kinase 9 (CDK9) is often dysregulated in breast cancer, and its deficiency results in genomic instability. We reviewed the records of 84 breast cancer patients from Emory University’s Winship Cancer Institute who had undergone surgical resection after NACT and had tissue available for tissue microarray analysis (TMA). Data recorded included disease presentation, treatment, pathologic response, overall survival (OS), locoregional recurrence free survival (LRRFS), distant-failure free survival (DFFS), recurrence-free survival (RFS), and event-free survival (EFS). Immunohistochemistry was performed on patient samples to determine CDK9 expression levels after NACT. Protein expression was linked with clinical data to determine significance. In a Cox proportional hazards model, using a time-dependent covariate to evaluate the risk of death between groups beyond 3 years, high CDK9 expression was significantly associated with an increase in OS (HR: 0.26, 95% CI: 0.07-0.98, p=0.046). However, Kaplan-Meier curves for OS, LRRFS, DFFS, RFS, and EFS did not reach statistical significance. The results of this study indicate that CDK9 may have a potential role as a prognostic biomarker in patients with breast cancer following NACT. However, further validation studies with increased sample sizes are needed to help elucidate the prognostic role for CDK9 in the management of these patients.

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