IU Indianapolis ScholarWorks :: Browsing by Author "Sledge, George W."

Browsing by Author "Sledge, George W."

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Assessment of Racial Disparity in Survival Outcomes for Early Hormone Receptor–Positive Breast Cancer After Adjusting for Insurance Status and Neighborhood Deprivation
(American Medical Association, 2022) Sadigh, Gelareh; Gray, Robert J.; Sparano, Joseph A.; Yanez, Betina; Garcoa, Sofia F.; Timsina, Lava R.; Obeng-Gyasi, Samilia; Gareen, Ilana; Sledge, George W.; Whelan, Timothy J.; Cella, David; Wagner, Lynne I.; Carlos, Ruth C.; Surgery, School of Medicine
Importance: Racial disparities in survival outcomes among Black women with hormone receptor-positive breast cancer have been reported. However, the association between individual-level and neighborhood-level social determinants of health on such disparities has not been well studied. Objective: To evaluate the association between race and clinical outcomes (ie, relapse-free interval and overall survival) adjusting for individual insurance coverage and neighborhood deprivation index (NDI), measured using zip code of residence, in women with breast cancer. Design, setting, and participants: This was a post hoc analysis of 9719 women with breast cancer in the Trial Assigning Individualized Options for Treatment, a randomized clinical trial conducted from April 7, 2006, to October 6, 2010. All participants received a diagnosis of hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer. The present data analysis was conducted from April 1 to October 22, 2021. Main outcomes and measures: A multivariate model was developed to evaluate the association between race and relapse-free interval and overall survival adjusting for insurance and NDI level at study entry, early discontinuation of endocrine therapy 4 years after initiation, and clinicopathologic characteristics of cancer. Median follow-up for clinical outcomes was 96 months. Results: A total of 9719 women (4.2% [n = 405] Asian; 7.1% [n = 693] Black; 84.3% [n = 8189] White; 4.4% [n = 403] others/not specified) were included; 9.1% of included women [n = 889] were Hispanic or Latino. Median (SD) age was 56 (9.2) years. In multivariate models, Black race compared with White race was associated with statistically significant shorter relapse-free interval (hazard ratio [HR], 1.39; 95% CI, 1.05-1.84; P = .02) and overall survival (HR, 1.49; 95% CI, 1.10-2.99; P = .009), adjusting for insurance and NDI level at study entry and other factors. Although uninsured status was not associated with clinical outcomes, patients with Medicare (HR, 1.30; 95% CI, 1.01-1.68; P = .04) and Medicaid (HR, 1.44; 95% CI, 1.01-2.05; P = .05) had shorter overall survival compared with those with private insurance. Participants living in neighborhoods in the highest NDI quartile experienced shorter overall survival compared with those in the lowest quartile (HR, 1.34; 95% CI, 1.01-1.77; P = .04), regardless of self-identified race. Conclusions and relevance: The findings of this post hoc analysis of a randomized clinical trial suggest that Black women with breast cancer have significantly shorter relapse-free interval and overall survival compared with White women. Early discontinuation of endocrine therapy, clinicopathologic characteristics, insurance coverage, and NDI do not fully explain the observed disparity.
Breast Cancer Patients’ Insurance Status and Residence Zip Code Correlates with Early Discontinuation of Endocrine Therapy: Analysis of ECOG-ACRIN TAILORx Trial
(Wiley, 2021) Sadigh, Gelareh; Gray, Robert J.; Sparano, Joseph A.; Yanez, Betina; Garcia, Sofia F.; Timsina, Lava R.; Sledge, George W.; Cella, David; Wagner, Lynne I.; Carlos, Ruth C.; Surgery, School of Medicine
Background: Early discontinuation is a substantial barrier to the delivery of endocrine therapies (ETs) and may influence recurrence and survival. The authors investigated the association between early discontinuation of ET and social determinants of health, including insurance coverage and the neighborhood deprivation index (NDI), which was measured on the basis of patients' zip codes, in breast cancer. Methods: In this retrospective analysis of a prospective randomized clinical trial (Trial Assigning Individualized Options for Treatment), women with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who started ET within a year of study entry were included. Early discontinuation was calculated as stopping ET within 4 years of its start for reasons other than distant recurrence or death via Kaplan-Meier estimates. A Cox proportional hazards joint model was used to analyze the association between early discontinuation of ET and factors such as the study-entry insurance and NDI, with adjustments made for other variables. Results: Of the included 9475 women (mean age, 55.6 years; White race, 84%), 58.0% had private insurance, whereas 11.7% had Medicare, 5.8% had Medicaid, 3.8% were self-pay, and 19.1% were treated at international sites. The early discontinuation rate was 12.3%. Compared with those with private insurance, patients with Medicaid (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.23-1.92) and self-pay patients (HR, 1.65; 95% CI, 1.25-2.17) had higher early discontinuation. Participants with a first-quartile NDI (highest deprivation) had a higher probability of discontinuation than those with a fourth-quartile NDI (lowest deprivation; HR, 1.34; 95% CI, 1.11-1.62). Conclusions: Patients' insurance and zip code at study entry play roles in adherence to ET, with uninsured and underinsured patients having a high rate of treatment nonadherence. Early identification of patients at risk may improve adherence to therapy. Lay summary: In this retrospective analysis of 9475 women with breast cancer participating in a clinical trial (Trial Assigning Individualized Options for Treatment), Medicaid and self-pay patients (compared with those with private insurance) and those in the highest quartile of neighborhood deprivation scores (compared with those in the lowest quartile) had a higher probability of early discontinuation of endocrine therapy. These social determinants of health assume larger importance with the expected increase in unemployment rates and loss of insurance coverage in the aftermath of the coronavirus disease 2019 pandemic. Early identification of patients at risk and enrollment in insurance optimization programs may improve the persistence of therapy.
Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing
(Springer, 2014-01) Radovich, Milan; Clare, Susan E.; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A.; Solzak, Jeffrey P.; Kassem, Nawal; Mathieson, Theresa; V. Storniolo, Anna Maria; Rufenbarger, Connie; Lillemoe, Heather A.; Blosser, Rachel J.; Choi, Mi Ran; Sauder, Candice A.; Doxey, Diane; Henry, Jill E.; Hilligoss, Eric E.; Sakarya, Onur; Hyland, Fiona C.; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W.; Schneider, Bryan P.; Department of Surgery, IU School of Medicine
Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer
(Massachusetts Medical Society, 2019-06-20) Sparano, Joseph A.; Gray, Robert J.; Ravdin, Peter M.; Makower, Della F.; Pritchard, Kathleen I.; Albain, Kathy S.; Hayes, Daniel F.; Geyer, Charles E.; Dees, Elizabeth C.; Goetz, Matthew P.; Olson, John A.; Lively, Tracy; Badve, Sunil S.; Saphner, Thomas J.; Wagner, Lynne I.; Whelan, Timothy J.; Ellis, Matthew J.; Paik, Soonmyung; Wood, William C.; Keane, Maccon M.; Gomez Moreno, Henry L.; Reddy, Pavan S.; Goggins, Timothy F.; Mayer, Ingrid A.; Brufsky, Adam M.; Toppmeyer, Deborah L.; Kaklamani, Virginia G.; Berenberg, Jeffrey L.; Abrams, Jeffrey; Sledge, George W.; Pathology and Laboratory Medicine, School of Medicine
BACKGROUND The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy.
Consequences of telomerase inhibition and telomere dysfunction in BRCA1 mutant cancer cells
(2014-03-12) Phipps, Elizabeth Ann; Herbert, Brittney-Shea; Grimes, Brenda R.; Sledge, George W.; Turchi, John; White, Kenneth E.
Telomere maintenance is a critical component of genomic stability. An increasing body of evidence suggests BRCA1, a tumor suppressor gene with a variety of functions including DNA repair and cell cycle regulation, plays a role in telomere maintenance. Mutations in BRCA1 account for approximately half of all hereditary breast and ovarian cancers, and the gene is silenced via promoter methylation and loss of heterozygosity in a proportion of sporadic breast and ovarian cancers. The objective of this study was to determine whether GRN163L, a telomerase inhibitor, currently in clinical trials for the treatment of cancer, has enhanced anti-cancer activity in BRCA1 mutant breast/ovarian cancer cell lines compared to wild-type cancer cells. BRCA1 mutant cancer cells were observed to have shorter telomeres and increased sensitivity to telomerase inhibition, compared to cell lines with wild-type BRCA1. Importantly, GRN163L treatment was synergistic with DNA-damaging drugs, suggesting potential synthetic lethality of the BRCA1 cancer subtype and telomerase inhibition In a related study to examine the roles of BRCA1/2 in telomere maintenance, DNA and RNA extracted from peripheral blood were used to investigate the age-adjusted telomere lengths and telomere-related gene expression profiles of BRCA1 and BRCA2 individuals compared to individuals who developed sporadic cancer and healthy controls. BRCA1 mutation carriers and breast cancer patients showed the shortest average telomere lengths compared to the other groups. In addition, distinct genomic profiles of BRCA mutation carriers were obtained regarding overexpression of telomere-related genes compared to individuals who developed sporadic or familial breast cancer. In summary, telomerase inhibition may be a viable treatment option in BRCA1 mutant breast or ovarian cancers. These data also provides insights into further investigations on the role of BRCA1 in the biology underlying telomere dysfunction in cancer development.
Cytochrome P450 Oxidoreductase (POR) Associated with Severe Paclitaxel-Induced Peripheral Neuropathy in Patients of European Ancestry from ECOG-ACRIN E5103
(American Association for Cancer Research, 2023) Shen, Fei; Jiang, Guanglong; Philips, Santosh; Gardner, Laura; Xue, Gloria; Cantor, Erica; Ly, Reynold C.; Osei, Wilberforce; Wu, Xi; Dang, Chau; Northfelt, Donald; Skaar, Todd; Miller, Kathy D.; Sledge, George W.; Schneider, Bryan P.; Medicine, School of Medicine
Purpose: Paclitaxel is a widely used anticancer therapeutic. Peripheral neuropathy is the dose-limiting toxicity and negatively impacts quality of life. Rare germline gene markers were evaluated for predicting severe taxane-induced peripheral neuropathy (TIPN) in the patients of European ancestry. In addition, the impact of Cytochrome P450 (CYP) 2C8, CYP3A4, and CYP3A5 metabolizer status on likelihood of severe TIPN was also assessed. Experimental design: Whole-exome sequencing analyses were performed in 340 patients of European ancestry who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Patients who experienced grade 3-4 (n = 168) TIPN were compared to controls (n = 172) who did not experience TIPN. For the analyses, rare variants with a minor allele frequency ≤ 3% and predicted to be deleterious by protein prediction programs were retained. A gene-based, case-control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of severe TIPN. CYP star alleles for CYP2C8, CYP3A4, and CYP3A5 were called. An additive logistic regression model was performed to test the association of CYP2C8, CYP3A4, and CYP3A5 metabolizer status with severe TIPN. Results: Cytochrome P450 oxidoreductase (POR) was significantly associated with severe TIPN (P value = 1.8 ×10-6). Six variants were predicted to be deleterious in POR. There were no associations between CYP2C8, CYP3A4, or CYP3A5 metabolizer status with severe TIPN. Conclusions: Rare variants in POR predict an increased risk of severe TIPN in patients of European ancestry who receive paclitaxel.
Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103)
(American Society of Clinical Oncology, 2018-09) Miller, Kathy D.; O’Neill, Anne; Gradishar, William; Hobday, Timothy J.; Goldstein, Lori J.; Mayer, Ingrid A.; Bloom, Stuart; Brufsky, Adam M.; Tevaarwerk, Amye J.; Sparano, Joseph A.; Le-Lindqwister, Nguyet Anh; Hendricks, Carolyn B.; Northfelt, Donald W.; Dang, Chau T.; Sledge, George W.; Medicine, School of Medicine
Purpose Bevacizumab improves progression-free survival but not overall survival in patients with metastatic breast cancer. E5103 tested the effect of bevacizumab in the adjuvant setting in patients with human epidermal growth factor receptor 2-negative disease. Patients and Methods Patients were assigned 1:2:2 to receive placebo with doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (arm A), bevacizumab only during AC and paclitaxel (arm B), or bevacizumab during AC and paclitaxel followed by bevacizumab monotherapy for 10 cycles (arm C). Random assignment was stratified and bevacizumab dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with bevacizumab in arm C. The primary end point was invasive disease-free survival (IDFS). Results Four thousand nine hundred ninety-four patients were enrolled. Median age was 52 years; 64% of patients were estrogen receptor positive, 27% were lymph node negative, and 78% received dose-dense AC. Chemotherapy-associated adverse events including myelosuppression and neuropathy were similar across all arms. Grade ≥ 3 hypertension was more common in bevacizumab-treated patients, but thrombosis, proteinuria, and hemorrhage were not. The cumulative incidence of clinical congestive heart failure at 15 months was 1.0%, 1.9%, and 3.0% in arms A, B, and C, respectively. Bevacizumab exposure was less than anticipated, with approximately 24% of patients in arm B and approximately 55% of patients in arm C discontinuing bevacizumab before completing planned therapy. Five-year IDFS was 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C. Conclusion Incorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy does not improve IDFS or overall survival in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer. Longer duration bevacizumab therapy is unlikely to be feasible given the high rate of early discontinuation.
Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108)
(American Society of Clinical Oncology, 2022) Khan, Seema A.; Zhao, Fengmin; Goldstein, Lori J.; Cella, David; Basik, Mark; Golshan, Mehra; Julian, Thomas B.; Pockaj, Barbara A.; Lee, Christine A.; Razaq, Wajeeha; Sparano, Joseph A.; Babiera, Gildy V.; Dy, Irene A.; Jain, Sarika; Silverman, Paula; Fisher, Carla S.; Tevaarwerk, Amye J.; Wagner, Lynne I.; Sledge, George W.; Surgery, School of Medicine
Purpose: Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. Methods: Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. Results: Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. Conclusion: Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.
Effects of HIV Protease Inhibitor Ritonavir on Akt-Regulated Cell Proliferation in Breast Cancer
(American Association for Cancer Research, 2006-03-15) Srirangam, Anjaiah; Mitra, Ranjana; Wang, Mu; Gorski, J. Christopher; Badve, Sunil; Baldridge, Lee Ann; Hamilton, Justin; Kishimoto, Hiromitsu; Hawes, John; Li, Lang; Orschell, Christie M.; Srour, Edward F.; Blum, Janice S.; Donner, David; Sledge, George W.; Nakshatri, Harikrishna; Potter, David A.
Purpose These studies were designed to determine whether ritonavir inhibits breast cancer in vitro and in vitro and, if so, how. Experimental Design Ritonavir effects on breast cancer cell growth were studied in the estrogen receptor (ER)-positive lines MCF7 and T47D and in the ER-negative lines MDA-MB-436 and MDA-MB-231. Effects of ritonavir on Rb-regulated and Akt-mediated cell proliferation were studied. Ritonavir was tested for inhibition of a mammary carcinoma xenograft. Results ER-positive estradiol-dependent lines (IC50, 12–24 µmol/L) and ER-negative (IC50, 45 µmol/L) lines exhibit ritonavir sensitivity. Ritonavir depletes ER-α levels notably in ER-positive lines. Ritonavir causes G1 arrest, depletes cyclin-dependent kinases 2, 4, and 6 and cyclin D1 but not cyclin E, and depletes phosphorylated Rb and Ser473 Akt. Ritonavir induces apoptosis independent of G1 arrest, inhibiting growth of cells that have passed the G1 checkpoint. Myristoyl-Akt, but not activated K-Ras, rescues ritonavir inhibition. Ritonavir inhibited a MDA-MB-231 xenograft and intratumoral Akt activity at a clinically attainable serum Cmax of 22 ± 8 µmol/L. Because heat shock protein 90 (Hsp90) substrates are depleted by ritonavir, ritonavir effects on Hsp90 were tested. Ritonavir binds Hsp90 (KD, 7.8 µmol/L) and partially inhibits its chaperone function. Ritonavir blocks association of Hsp90 with Akt and, with sustained exposure, notably depletes Hsp90. Stably expressed Hsp90α short hairpin RNA also depletes Hsp90, inhibiting proliferation and sensitizing breast cancer cells to low ritonavir concentrations. Conclusions Ritonavir inhibits breast cancer growth in part by inhibiting Hsp90 substrates, including Akt. Ritonavir may be of interest for breast cancer therapeutics and its efficacy may be increased by sustained exposure or Hsp90 RNA interference.
Gene Expression Analysis Reveals Distinct Pathways of Resistance to Bevacizumab in Xenograft Models of Human ER-Positive Breast Cancer
(Ivyspring, 2014) Gökmen-Polar, Yesim; Goswami, Chirayu P.; Toroni, Rachel A.; Sanders, Kerry L.; Mehta, Rutika; Sirimalle, Usha; Tanasa, Bogdan; Shen, Changyu; Li, Lang; Ivan, Mircea; Badve, Sunil S.; Sledge, George W.; Pathology and Laboratory Medicine, School of Medicine
Bevacizumab, the recombinant antibody targeting vascular endothelial growth factor (VEGF), improves progression-free but not overall survival in metastatic breast cancer. To seek further insights in resistance mechanisms to bevacizumab at the molecular level, we developed VEGF and non-VEGF-driven ER-positive MCF7-derived xenograft models allowing comparison of tumor response at different timepoints. VEGF gene (MV165) overexpressing xenografts were initially sensitive to bevacizumab, but eventually acquired resistance. In contrast, parental MCF7 cells derived tumors were de novo insensitive to bevacizumab. Microarray analysis with qRT-PCR validation revealed that Follistatin (FST) and NOTCH were the top signaling pathways associated with resistance in VEGF-driven tumors (P<0.05). Based on the presence of VEGF, treatment with bevacizumab resulted in altered patterns of metagenes and PAM50 gene expression. In VEGF-driven model after short and long-term bevacizumab treatments, a change in the intrinsic subtype (luminal to myoepithelial/basal-like) was observed in association with increased expression of genes implicated with cancer stem cell phenotype (P<0.05). Our results show that the presence or absence of VEGF expression affects the response to bevacizumab therapy and gene pathways. In particular, long-term bevacizumab treatment shifts the cancer cells to a more aggressive myoepithelial/basal subtype in VEGF-expressing model, but not in non-VEGF model. These findings could shed light on variable results to anti-VEGF therapy in patients and emphasize the importance of patient stratification based on the VEGF expression. Our data strongly suggest consideration of patient subgroups for treatment and designing novel combinatory therapies in the clinical setting.

Browsing by Author "Sledge, George W."

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