Clinical Focus

  • Cancer
  • Cancer > Breast Cancer
  • Medical Oncology

Academic Appointments

Administrative Appointments

  • Professor, and Chief, Division of Oncology, Stanford University Medical Center (2013 - Present)

Honors & Awards

  • Ballve-Lantero Chair (Endowed Chair), Ballve-Lantero (1996)
  • Listed in "America's Top Doctors", Castle Connolly (2001-2012)
  • Komen Brinker Award for Scientific Distinction, Susan G. Komen Breast Cancer Foundation (2006)
  • Jill Rose Award, Breast Cancer Foundation (2007)
  • William L. McGuire Award, San Antonio Breast Cancer Symposium (2010)
  • Health Care Hero award, Indianapolis Business Journal (2011)
  • APEX Award for Publication Excellence in the category of "Regular Departments & Columns", Oncology Times (2012)
  • Chair, Breast Committee, Eastern Cooperative Oncology Group (ECOG) (2002-2010)
  • Editor-In-Chief, Clinical Breast Cancer (1999-present)
  • President, American Society of Clinical Oncology, American Society of Clinical Oncology (ASCO) (2010-2011)
  • HOPE Funds for Cancer Research 2013 Award of Excellence for Medicine, HOPE Funds, Cancer Research (April 28, 2013)

Professional Education

  • Board Certification: Medical Oncology, American Board of Internal Medicine (1983)
  • Fellowship:The University of Texas at San Antonio (1983) TX
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1980)
  • Residency:St Louis University Hospital (1980) MO
  • Medical Education:Tulane University School of Medicine (1977) LA


All Publications

  • Curing Metastatic Breast Cancer. Journal of oncology practice / American Society of Clinical Oncology Sledge, G. W. 2016; 12 (1): 6-10


    Metastatic breast cancer is generally considered incurable, and this colors doctor-patient interactions for patients with metastatic disease. Although true for most patients, there appear to be important exceptions, instances where long-term disease-free survival occurs. Although these instances are few in number, they suggest the possibility of cure. How will we move toward cure for a much larger population of patients with metastatic disease? This article outlines a potential research agenda that might move us toward that distant goal.

    View details for DOI 10.1200/JOP.2015.008953

    View details for PubMedID 26759458

  • A Call for Viewpoints. JAMA oncology Sledge, G. W., Disis, M. L. 2015; 1 (4): 432-?

    View details for DOI 10.1001/jamaoncol.2015.1238

    View details for PubMedID 26181249

  • Targeted Therapy for Cancer in the Genomic Era CANCER JOURNAL Afghahi, A., Sledge, G. W. 2015; 21 (4): 294-298


    The advent of cancer genomics has led to the development of many highly successful targeted therapies, primarily inhibitors of growth factor receptors and related kinases, including imatinib for chronic myeloid leukemia and trastuzumab for HER2-positive breast cancer. This approach has become highly successful for certain cancers. However, as the list of targeted therapies expands, their efficacy becomes more limited, and toxicity accumulates. What we have learned in the past decades is that while the targeted therapeutics approach may be highly successful in less complex tumors, cancers defined by carcinogen-induced genomic chaos, such a UV-induced melanoma or tobacco-induced lung cancer, are driven by a multitude of competing molecular pathways and, as such, are not as successfully managed by a similar approach. Luckily, in the past years, the field of cancer immunotherapy has become more fully developed with the emergence of checkpoint blockade inhibitor therapy. These promising new agents are particularly well suited for tumors with a high mutational burden due to underlying genomic disarray. While still in its infancy, we predict that cancer immunotherapy will offer a better alternative to our current targeted approach and eagerly await the results of several ongoing clinical trials that will elucidate this new direction in cancer therapy.

    View details for DOI 10.1097/PPO.0000000000000135

    View details for Web of Science ID 000359820200010

    View details for PubMedID 26222081

  • "Vertical" Inhibition of HER2 Yields Horizontal Gains in the Clinic. Clinical cancer research Sledge, G. W., Pegram, M. D. 2015; 21 (12): 2663-2665


    HER2-targeted therapy has moved beyond trastuzumab to include other monoclonals targeting the cell surface, receptor tyrosine kinase inhibitors of HER2, and antibody-drug conjugates. Afatinib, a small molecule receptor tyrosine kinase inhibitor, now joins the ranks of HER2-targeting agents in combination with trastuzumab. The combination brings new opportunities and challenges.

    View details for DOI 10.1158/1078-0432.CCR-14-3183

    View details for PubMedID 26078429

  • Everything old is neu again: cellular senescence in HER2-positive breast cancer. Journal of the National Cancer Institute Sledge, G. W., Pegram, M. D. 2015; 107 (5)

    View details for DOI 10.1093/jnci/djv091

    View details for PubMedID 25972602

  • Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant Trastuzumab Trial. Journal of clinical oncology Perez, E. A., Thompson, E. A., Ballman, K. V., Anderson, S. K., Asmann, Y. W., Kalari, K. R., Eckel-Passow, J. E., Dueck, A. C., Tenner, K. S., Jen, J., Fan, J., Geiger, X. J., McCullough, A. E., Chen, B., Jenkins, R. B., Sledge, G. W., Winer, E. P., Gralow, J. R., Reinholz, M. M. 2015; 33 (7): 701-708


    To develop a genomic signature that predicts benefit from trastuzumab in human epidermal growth factor receptor 2-positive breast cancer.DASL technology was used to quantify mRNA in samples from 1,282 patients enrolled onto the Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer (North Central Cancer Treatment Group N9831 [NCCTG-N9831]) adjuvant trastuzumab trial. Cox proportional hazard ratios (HRs), adjusted for significant clinicopathologic risk factors, were used to determine the association of each gene with relapse-free survival (RFS) for 433 patients who received chemotherapy alone (arm A) and 849 patients who received chemotherapy plus trastuzumab (arms B and C). Network and pathway analyses were used to identify key biologic processes linked to RFS. The signature was built by using a voting scheme.Network and functional ontology analyses suggested that increased RFS was linked to a subset of immune function genes. A voting scheme model was used to define immune gene enrichment based on the expression of any nine or more of 14 immune function genes at or above the 0.40 quantile for the population. This model was used to identify immune gene-enriched tumors in arm A and arms B and C. Immune gene enrichment was linked to increased RFS in arms B and C (HR, 0.35; 95% CI, 0.22 to 0.55; P < .001), whereas arm B and C patients who did not exhibit immune gene enrichment did not benefit from trastuzumab (HR, 0.89; 95% CI, 0.62 to 1.28; P = .53). Enriched immune function gene expression as defined by our predictive signature was not associated with increased RFS in arm A (HR, 0.90; 95% CI, 0.60 to 1.37; P = .64).Increased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab.

    View details for DOI 10.1200/JCO.2014.57.6298

    View details for PubMedID 25605861

  • Genomic Analysis Reveals That Immune Function Genes Are Strongly Linked to Clinical Outcome in the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial JOURNAL OF CLINICAL ONCOLOGY Perez, E. A., Thompson, E. A., Ballman, K. V., Anderson, S. K., Asmann, Y. W., Kalari, K. R., Eckel-Passow, J. E., Dueck, A. C., Tenner, K. S., Jen, J., Fan, J., Geiger, X. J., McCullough, A. E., Chen, B., Jenkins, R. B., Sledge, G. W., Winer, E. P., Gralow, J. R., Reinholz, M. M. 2015; 33 (7)
  • Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients JOURNAL OF NEURO-ONCOLOGY Duchnowska, R., Jassem, J., Goswami, C. P., Dundar, M., Goekmen-Polar, Y., Li, L., Woditschka, S., Biernat, W., Sosinska-Mielcarek, K., Czartoryska-Arlukowicz, B., Radecka, B., Tomasevic, Z., Stepniak, P., Wojdan, K., Sledge, G. W., Steeg, P. S., Badve, S. 2015; 122 (1): 205-216


    The overexpression or amplification of the human epidermal growth factor receptor 2 gene (HER2/neu) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4-22.3; p < 0.001; Cohort B: HR 6.1, 95 % CI 1.5-25.6; p = 0.01] and the lack of trastuzumab administration in the metastatic setting (Cohort A: HR 5.0, 95 % CI 1.4-10.0; p = 0.009; Cohort B: HR 10.0, 95 % CI 2.0-100.0; p = 0.008). A profile including 13 genes was associated with early (?36 months) symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene classifier (RAD51, HDGF, TPR) highly predictive of early BM (HR 5.3, 95 % CI 1.6-16.7; p = 0.005; multivariate analysis). However, predictive value of the classifier was not confirmed in the independent validation Cohort B. The presence of visceral metastases and the lack of trastuzumab administration in the metastatic setting apparently increase the likelihood of early BM in advanced HER2-positive breast cancer.

    View details for DOI 10.1007/s11060-014-1704-y

    View details for Web of Science ID 000351091500023

    View details for PubMedID 25559688

  • The future of breast cancer systemic therapy: the next 10 years JOURNAL OF MOLECULAR MEDICINE-JMM Telli, M. L., Sledge, G. W. 2015; 93 (2): 119-125


    Over the past 50 years, substantial progress has been made in the systemic treatment of early-stage and advanced breast cancer. The use of chemotherapy in the adjuvant and metastatic settings has demonstrated proven efficacy and it has been clearly demonstrated that targeting the estrogen receptor and human growth factor receptor 2 (HER2) is efficacious in early and advanced disease. Despite these advances, vexing clinical challenges remain particularly related to the treatment of triple-negative breast cancer (TNBC; estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, and HER2-negative) where little progress has been made therapeutically in more than a decade. While recurrences of hormone-responsive breast cancer are overall less common, late relapses after cessation of endocrine therapy are a more frequent occurrence in modern times and reflect the problem of underlying tumor dormancy that as yet has not been overcome. Multiple molecular tools are now available to interrogate the biology of breast cancer, though exactly how to make this information meaningful in the clinic has proven challenging, and molecularly driven clinical trials have faced feasibility challenges. In parallel, focus has expanded from tumor to host with the ability to ascertain underlying germline alterations, such as inherited BRCA1 and BRCA2 mutations, which may be responsible for breast cancer carcinogenesis and, importantly, may have implications for treatment. These clinical advances in germline genetics, made possible by both scientific investigation as well as the courts, still face challenges related to increasing encounters with variants of unknown significance and difficulty in predicting risks associated with less well-characterized inherited cancer predisposition syndromes. In this paper, we attempt to predict the next 10 years of breast cancer, in particular focusing on how the past serves as prologue to the future in this disease.

    View details for DOI 10.1007/s00109-014-1238-y

    View details for Web of Science ID 000349288800002

  • Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial. Journal of clinical oncology Stearns, V., Chapman, J. W., Ma, C. X., Ellis, M. J., Ingle, J. N., Pritchard, K. I., Budd, G. T., Rabaglio, M., Sledge, G. W., Le Maitre, A., Kundapur, J., Liedke, P. E., Shepherd, L. E., Goss, P. E. 2015; 33 (3): 265-271


    Treatment-emergent symptoms with adjuvant tamoxifen and aromatase inhibitors (AIs) have been associated with superior recurrence-free survival (RFS). We hypothesized that MA.27 anastrozole- or exemestane-treated patients with new or worsening vasomotor and/or joint symptoms would have improved RFS.MA.27 randomly assigned 7,576 postmenopausal women with breast cancer to 5 years of anastrozole or exemestane. Patient-reported symptoms were collected using the Common Terminology Criteria for Adverse Events version 3.0 at protocol-specified baseline and 6- and 12-month clinical visits. Symptoms were considered present with either vasomotor and/or joint complaints. Associations between symptoms and baseline patient characteristics were examined with ?(2) and Fisher's exact tests. Subsequent effects of new or worsening symptoms on RFS were examined with landmark analyses and stratified univariable and multivariable Cox models. We examined the effects of 3-month symptoms arising from unplanned clinic visits as a result of severe toxicity.Patients were assessable if eligible for the MA.27 trial, received some trial therapy, and had no disease recurrence at the end of a symptom assessment period; 96% of patients (n = 7,306 patients) were included at 6 months, and 96% (n = 7,246) were included at 12 months. Thirty-four percent of patients had baseline symptoms. For patients without baseline symptoms, 25% and 52% had new symptoms by 6 and 12 months, respectively. Neither treatment-emergent nor baseline symptoms significantly impacted RFS (P > .10) in patients with or without baseline symptoms.In MA.27, anastrozole or exemestane treatment-emergent symptoms were not associated with improved RFS. Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms.

    View details for DOI 10.1200/JCO.2014.57.6926

    View details for PubMedID 25512454

  • Treatment-Associated Musculoskeletal and Vasomotor Symptoms and Relapse-Free Survival in the NCIC CTG MA.27 Adjuvant Breast Cancer Aromatase Inhibitor Trial JOURNAL OF CLINICAL ONCOLOGY Stearns, V., Chapman, J. W., Ma, C. X., Ellis, M. J., Ingle, J. N., Pritchard, K. I., Budd, G. T., Rabaglio, M., Sledge, G. W., Le Maitre, A., Kundapur, J., Liedke, P. E., Shepherd, L. E., Goss, P. E. 2015; 33 (3): 265-U163
  • Anti-vascular endothelial growth factor therapy in breast cancer: game over? Journal of clinical oncology Sledge, G. W. 2015; 33 (2): 133-135

    View details for DOI 10.1200/JCO.2014.58.1298

    View details for PubMedID 25349299

  • Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831 JOURNAL OF CLINICAL ONCOLOGY Perez, E. A., Romond, E. H., Suman, V. J., Jeong, J., Sledge, G., Geyer, C. E., Martino, S., Rastogi, P., Gralow, J., Swain, S. M., Winer, E. P., Colon-Otero, G., Davidson, N. E., Mamounas, E., Zujewski, J. A., Wolmark, N. 2014; 32 (33): 3744-?
  • Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. Journal of clinical oncology Perez, E. A., Romond, E. H., Suman, V. J., Jeong, J., Sledge, G., Geyer, C. E., Martino, S., Rastogi, P., Gralow, J., Swain, S. M., Winer, E. P., Colon-Otero, G., Davidson, N. E., Mamounas, E., Zujewski, J. A., Wolmark, N. 2014; 32 (33): 3744-3752


    Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2) -positive breast cancer were first reported in 2005. One of these reports, the joint analysis of North Central Cancer Treatment Group NCCTG N9831 (Combination Chemotherapy With or Without Trastuzumab in Treating Women With HER2-Overexpressing Breast Cancer) and the National Surgical Adjuvant Breast and Bowel Project NSABP B-31 (Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2), was updated in 2011. We now report the planned definitive overall survival (OS) results from this joint analysis along with updates on the disease-free survival (DFS) end point.In all, 4,046 patients with HER2-positive operable breast cancer were enrolled to receive doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in both trials. The required number of events for the definitive statistical analysis for OS (710 events) was reached in September 2012. Updated analyses of overall DFS and related subgroups were also performed.Median time on study was 8.4 years. Adding trastuzumab to chemotherapy led to a 37% relative improvement in OS (hazard ratio [HR], 0.63; 95% CI, 0.54 to 0.73; P < .001) and an increase in 10-year OS rate from 75.2% to 84%. These results were accompanied by an improvement in DFS of 40% (HR, 0.60; 95% CI, 0.53 to 0.68; P < .001) and increase in 10-year DFS rate from 62.2% to 73.7%. All patient subgroups benefited from addition of this targeted anti-HER2 agent.The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence.

    View details for DOI 10.1200/JCO.2014.55.5730

    View details for PubMedID 25332249

  • Decade in review-targeted therapy: successes, toxicities and challenges in solid tumours. Nature reviews. Clinical oncology Neal, J. W., Sledge, G. W. 2014; 11 (11): 627-628

    View details for DOI 10.1038/nrclinonc.2014.171

    View details for PubMedID 25286974

  • Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100 BRITISH JOURNAL OF CANCER Schneider, B. P., Li, L., Shen, F., Miller, K. D., Radovich, M., O'Neill, A., Gray, R. J., Lane, D., Flockhart, D. A., Jiang, G., Wang, Z., Lai, D., Koller, D., Pratt, J. H., Dang, C. T., Northfelt, D., Perez, E. A., Shenkier, T., Cobleigh, M., Smith, M. L., Railey, E., Partridge, A., Gralow, J., Sparano, J., Davidson, N. E., Foroud, T., Sledge, G. W. 2014; 111 (6): 1241-1248
  • Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. British journal of cancer Schneider, B. P., Li, L., Shen, F., Miller, K. D., Radovich, M., O'Neill, A., Gray, R. J., Lane, D., Flockhart, D. A., Jiang, G., Wang, Z., Lai, D., Koller, D., Pratt, J. H., Dang, C. T., Northfelt, D., Perez, E. A., Shenkier, T., Cobleigh, M., Smith, M. L., Railey, E., Partridge, A., Gralow, J., Sparano, J., Davidson, N. E., Foroud, T., Sledge, G. W. 2014; 111 (6): 1241-1248


    Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension.A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160?mm?Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3-5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100.When using the phenotype of SBP>160?mm?Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10(-8); OR=3.3) and in the cumulative dose model (P=4.7 × 10(-8); HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3-5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037; OR=2.4).A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials.

    View details for DOI 10.1038/bjc.2014.430

    View details for PubMedID 25117820

  • Improving the quality of cancer care in America through health information technology JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION Feeley, T. W., Sledge, G. W., Levit, L., Ganz, P. A. 2014; 21 (5): 772-775


    A recent report from the Institute of Medicine titled Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis, identifies improvement in information technology (IT) as essential to improving the quality of cancer care in America. The report calls for implementation of a learning healthcare IT system: a system that supports patient-clinician interactions by providing patients and clinicians with the information and tools necessary to make well informed medical decisions and to support quality measurement and improvement. While some elements needed for a learning healthcare system are already in place for cancer, they are incompletely implemented, have functional deficiencies, and are not integrated in a way that creates a true learning healthcare system. To achieve the goal of a learning cancer care delivery system, clinicians, professional organizations, government, and the IT industry will have to partner, develop, and incentivize participation.

    View details for DOI 10.1136/amiajnl-2013-002346

    View details for Web of Science ID 000340581400003

    View details for PubMedID 24352553

  • Heterogeneity and Cancer ONCOLOGY-NEW YORK Allison, K. H., Sledge, G. W. 2014; 28 (9): 772-778
  • Past, Present, and Future Challenges in Breast Cancer Treatment JOURNAL OF CLINICAL ONCOLOGY Sledge, G. W., Mamounas, E. P., Hortobagyi, G. N., Burstein, H. J., Goodwin, P. J., Wolff, A. C. 2014; 32 (19): 1979-1986
  • Past, present, and future challenges in breast cancer treatment. Journal of clinical oncology Sledge, G. W., Mamounas, E. P., Hortobagyi, G. N., Burstein, H. J., Goodwin, P. J., Wolff, A. C. 2014; 32 (19): 1979-1986

    View details for DOI 10.1200/JCO.2014.55.4139

    View details for PubMedID 24888802

  • DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer. Journal of the National Cancer Institute Woditschka, S., Evans, L., Duchnowska, R., Reed, L. T., Palmieri, D., Qian, Y., Badve, S., Sledge, G., Gril, B., Aladjem, M. I., Fu, H., Flores, N. M., Gökmen-Polar, Y., Biernat, W., Szutowicz-Zielinska, E., Mandat, T., Trojanowski, T., Och, W., Czartoryska-Arlukowicz, B., Jassem, J., Mitchell, J. B., Steeg, P. S. 2014; 106 (7)


    Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood.Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis-specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group).Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression.BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species-mediated genotoxic stress in the metastatic brain.

    View details for DOI 10.1093/jnci/dju145

    View details for PubMedID 24948741

  • Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women with breast cancer participating in E5103 BREAST CANCER RESEARCH AND TREATMENT Ruddy, K. J., O'Neill, A., Miller, K. D., Schneider, B. P., Baker, E., Sparano, J. A., Dang, C., Northfelt, D. W., Sledge, G. W., Partridge, A. H. 2014; 144 (3): 591-597


    This study aimed to investigate whether pre-chemotherapy anti-mullerian hormone (AMH) is a biomarker for chemotherapy-related amenorrhea (CRA) in breast cancer patients. A multicenter randomized controlled trial, ECOG5103, assigned patients with early stage breast cancer to standard doxorubicin-cyclophosphamide followed by paclitaxel with either placebo or one of two durations of bevacizumab therapy. Five hundred ninety-one patients were part of the decision-making/quality of life substudy, in which there were surveys from baseline through 18-month follow-up. One hundred twenty-four women were included in this analysis of menses data because they were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy. One hundred of the 124 also responded to the 18-month survey. Median age was 45 years (range 25-55), and median serum AMH level was 0.11 ng/mL (range 0.01-8.63) prior to treatment. Eighty-two percent had CRA at 12 months, and 81 % at 18 months. In multivariate analyses, older age (p = 0.0003) was the only statistically significant predictor of 12-month CRA, but at 18-months, lower pre-chemotherapy AMH (p = 0.04) and older age (p = 0.008) were both statistically significant predictors of CRA. Race, bevacizumab therapy, and tamoxifen use were not statistically significantly associated with CRA after adjustment for AMH and age. Pre-chemotherapy AMH level is a potential novel biomarker for CRA in premenopausal women with early stage breast cancer. Further research to evaluate the clinical utility of AMH testing is warranted.

    View details for DOI 10.1007/s10549-014-2891-0

    View details for Web of Science ID 000333360700014

    View details for PubMedID 24584876

  • Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing BREAST CANCER RESEARCH AND TREATMENT Radovich, M., Clare, S. E., Atale, R., Pardo, I., Hancock, B. A., Solzak, J. P., Kassem, N., Mathieson, T., Storniolo, A. M., Rufenbarger, C., Lillemoe, H. A., Blosser, R. J., Choi, M. R., Sauder, C. A., Doxey, D., Henry, J. E., Hilligoss, E. E., Sakarya, O., Hyland, F. C., Hickenbotham, M., Zhu, J., Glasscock, J., Badve, S., Ivan, M., Liu, Y., Sledge, G. W., Schneider, B. P. 2014; 143 (1): 57-68


    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.

    View details for DOI 10.1007/s10549-013-2780-y

    View details for Web of Science ID 000329295500006

    View details for PubMedID 24292813

  • Gene Expression Analysis Reveals Distinct Pathways of Resistance to Bevacizumab in Xenograft Models of Human ER-Positive Breast Cancer JOURNAL OF CANCER Goekmen-Polar, Y., Goswami, C. P., Toroni, R. A., Sanders, K. L., Mehta, R., Sirimalle, U., Tanasa, B., Shen, C., Li, L., Ivan, M., Badve, S., Sledge, G. W. 2014; 5 (8): 633-645

    View details for DOI 10.7150/jca.8466

    View details for Web of Science ID 000345216400003

  • ASCO's approach to a learning health care system in oncology. Journal of oncology practice / American Society of Clinical Oncology Sledge, G. W., Hudis, C. A., Swain, S. M., Yu, P. M., Mann, J. T., Hauser, R. S., Lichter, A. S. 2013; 9 (3): 145-148


    The promise of emerging science and the challenges confronting today's health care system can both be addressed by fully embracing the IoM's vision of a learning health care system. ASCO's initial foray into realizing this vision for oncology shows great promise.

    View details for DOI 10.1200/JOP.2013.000957

    View details for PubMedID 23942494

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