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Laura J Esserman - One of the best experts on this subject based on the ideXlab platform.
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receptor activator of nuclear factor kappa b rank expression in primary breast cancer correlates with Recurrence Free Survival and development of bone metastases in i spy1 calgb 150007 150012 acrin 6657
Breast Cancer Research and Treatment, 2017Co-Authors: Neelima Vidula, Laura J Esserman, Christina Yau, Hope S RugoAbstract:The receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis may contribute to the development of bone metastases (BM). We studied gene expression in this pathway in primary breast cancer (BC) to determine correlations with clinical characteristics and outcomes in the neoadjuvant I-SPY1 study. We evaluated RANK/RANKL/OPG expression using expression microarrays in I-SPY1 (n = 149). Associations with clinical features were determined using t test and ANOVA. Associations between biomarker high versus low groups (dichotomized at an optimal cutpoint) and Recurrence-Free Survival (RFS) were evaluated using the log-rank test and in a multivariate Cox proportional hazard model. A pooled external neoadjuvant cohort with gene expression data (GSE25066) (Hatzis et al. in JAMA 305(18):1873–1881, 30) (n = 425) was used for validation. Associations with site-specific relapse were evaluated using the t-test and multivariate logistic regression adjusting for hormone receptor (HR) status. RANK was significantly higher in HR negative versus HR positive (p = 0.027), in basal versus non-basal disease (p = 0.004), and in those achieving pathologic complete response (p = 0.038); the associations with HR negative and basal BC were also significant in GSE25066. In both datasets, higher RANK associated with significantly worse RFS (I-SPY1: p = 0.045, GSE25066: p = 0.044). However, this association did not remain significant after adjusting for HR status. In I-SPY1 patients with Recurrence, higher RANK correlated with BM versus non-BM (p = 0.045), even after adjusting for HR status (p = 0.035). RANK is increased in HR negative and basal BC, and correlates with worse RFS and risk of BM. The RANK pathway is a potential therapeutic target in BC.
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pathologic complete response predicts Recurrence Free Survival more effectively by cancer subset results from the i spy 1 trial calgb 150007 150012 acrin 6657
Journal of Clinical Oncology, 2012Co-Authors: Laura J Esserman, Donald A Berry, Angela Demichele, Lisa A Carey, Sarah E Davis, Meredith Buxton, Cliff Hudis, Joe W Gray, Charles M PerouAbstract:Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting Recurrence-Free Survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal gr...
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chemotherapy response and Recurrence Free Survival in neoadjuvant breast cancer depends on biomarker profiles results from the i spy 1 trial calgb 150007 150012 acrin 6657
Breast Cancer Research and Treatment, 2012Co-Authors: Laura J Esserman, Donald A Berry, Angela Demichele, Lisa A Carey, Joe W Gray, Charles M Perou, Maggie C U Cheang, Kathleen Conwaydorsey, Marc E LenburgAbstract:Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on Recurrence-Free Survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of Recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.
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mri measurements of breast tumor volume predict response to neoadjuvant chemotherapy and Recurrence Free Survival
American Journal of Roentgenology, 2005Co-Authors: Savannah C Partridge, Jessica Gibbs, Ying Lu, Laura J Esserman, Debasish Tripathy, Dulcy Wolverton, Hope S Rugo, Shelley E Hwang, Cheryl EwingAbstract:OBJECTIVE. The purpose of this study was to assess the value of MRI measurements of breast tumor size for predicting Recurrence-Free Survival (RFS) in patients undergoing neoadjuvant (preoperative) chemotherapy and to compare the predictive value of MRI with that of established prognostic indicators.SUBJECTS AND METHODS. The study included 62 patients undergoing neoadjuvant chemotherapy. The longest diameter and volume of each tumor were measured on MRI before and after one and four cycles of treatment. Change in diameter on clinical examination, tumor size at pathology, and the number of positive nodes were determined. Each measure of tumor extent was assessed for the ability to predict RFS.RESULTS. Univariate Cox analysis showed initial MRI volume was the strongest predictor of RFS (p = 0.002). Final change in MRI volume (p = 0.015) was more predictive than change in diameter on MRI (p = 0.077) or clinical examination (p = 0.27). Initial diameter on MRI (p = 0.003) and clinical examination (p = 0.033), ...
Joe W Gray - One of the best experts on this subject based on the ideXlab platform.
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pathologic complete response predicts Recurrence Free Survival more effectively by cancer subset results from the i spy 1 trial calgb 150007 150012 acrin 6657
Journal of Clinical Oncology, 2012Co-Authors: Laura J Esserman, Donald A Berry, Angela Demichele, Lisa A Carey, Sarah E Davis, Meredith Buxton, Cliff Hudis, Joe W Gray, Charles M PerouAbstract:Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting Recurrence-Free Survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal gr...
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chemotherapy response and Recurrence Free Survival in neoadjuvant breast cancer depends on biomarker profiles results from the i spy 1 trial calgb 150007 150012 acrin 6657
Breast Cancer Research and Treatment, 2012Co-Authors: Laura J Esserman, Donald A Berry, Angela Demichele, Lisa A Carey, Joe W Gray, Charles M Perou, Maggie C U Cheang, Kathleen Conwaydorsey, Marc E LenburgAbstract:Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on Recurrence-Free Survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of Recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.
Charles M Perou - One of the best experts on this subject based on the ideXlab platform.
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pathologic complete response predicts Recurrence Free Survival more effectively by cancer subset results from the i spy 1 trial calgb 150007 150012 acrin 6657
Journal of Clinical Oncology, 2012Co-Authors: Laura J Esserman, Donald A Berry, Angela Demichele, Lisa A Carey, Sarah E Davis, Meredith Buxton, Cliff Hudis, Joe W Gray, Charles M PerouAbstract:Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting Recurrence-Free Survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal gr...
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chemotherapy response and Recurrence Free Survival in neoadjuvant breast cancer depends on biomarker profiles results from the i spy 1 trial calgb 150007 150012 acrin 6657
Breast Cancer Research and Treatment, 2012Co-Authors: Laura J Esserman, Donald A Berry, Angela Demichele, Lisa A Carey, Joe W Gray, Charles M Perou, Maggie C U Cheang, Kathleen Conwaydorsey, Marc E LenburgAbstract:Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on Recurrence-Free Survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of Recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.
Patrick C. Walsh - One of the best experts on this subject based on the ideXlab platform.
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the significance of a positive bladder neck margin after radical prostatectomy the american joint committee on cancer pathological stage t4 designation is not warranted
The Journal of Urology, 2010Co-Authors: Phillip M Pierorazio, Jonathan I Epstein, Patrick C. Walsh, Elizabeth B Humphreys, Alan W PartinAbstract:Purpose: The American Joint Committee on Cancer currently designates invasion of the bladder neck as a pT4 lesion. However, retrospective analyses have not demonstrated biochemical Recurrence-Free Survival after radical prostatectomy to be consistent with other T4 lesions. We examined biochemical Recurrence-Free Survival and cancer specific Survival in men with a positive bladder neck margin.Materials and Methods: Of nearly 17,000 patients in the Johns Hopkins Institutional radical prostatectomy database (1982 to 2008) 198 (1.2%) were identified with a positive bladder neck margin. Kaplan-Meier analyses were used to evaluate biochemical Recurrence-Free Survival and cancer specific Survival. A multivariate proportional hazards model predicting biochemical Recurrence-Free Survival and cancer specific Survival was fit with prostate specific antigen, Gleason sum and pathological stage to determine the significance of a positive bladder neck margin.Results: Of the 198 men with a positive bladder neck margin 79...
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is it possible to compare psa Recurrence Free Survival after surgery and radiotherapy using revised astro criterion nadir 2
Urology, 2008Co-Authors: Matthew E Nielsen, Danil V Makarov, Elizabeth B Humphreys, Leslie A Mangold, Alan W Partin, Patrick C. WalshAbstract:OBJECTIVES The new American Society for Therapeutic Radiology and Oncology/Radiation Therapy Oncology Group consensus definition of biochemical failure after radiotherapy for prostate cancer is defined as a prostate-specific antigen level at or greater than the absolute nadir PSA level plus 2 ng/mL. Because this definition inevitably will be used to compare cancer control rates after radiotherapy to those after surgery, this study examined the effect of this comparison. METHODS We reviewed the data from 2570 men who had undergone radical prostatectomy from 1985 to 2004. Biochemical failure was defined as any measurable PSA level of 0.2 ng/mL or greater. We evaluated how the nadir+2 definition affected the failure rate when applied to this series. RESULTS The actuarial 5, 10, and 15-year biochemical Recurrence-Free Survival probability with failure defined as a PSA level of 0.2 ng/mL or more and a PSA level of 2 ng/mL or more was 88.6%, 81.2%, and 78.1% and 94.6%, 89.4%, and 84.3%, respectively (P <0.0001). The median time to biochemical progression was 2.8 years for the greater than 0.2 ng/mL definition and 7.9 years for the 2 ng/mL or more definition. The nadir+2 definition systematically overestimated the biochemical Recurrence-Free Survival, even after stratifying patients into standard prognostic risk groups, especially in men who developed local Recurrence. CONCLUSIONS When applied to a mature series of surgically treated patients with localized prostate cancer, the American Society for Therapeutic Radiology and Oncology "nadir+2" definition resulted in a systematic delay in the determination of biochemical failure. Because patients in this series who experienced a detectable PSA level took more than 5 years to progress to a PSA level of 2 ng/mL or greater, the 5-year biochemical control rates with the definition of 0.2 ng/mL or more should be compared with the 10-year biochemical control rates using the nadir+2 definition.
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era specific biochemical Recurrence Free Survival following radical prostatectomy for clinically localized prostate cancer
The Journal of Urology, 2001Co-Authors: Alan Wayne Partin, Steven Piantadosi, Jonathan I Epstein, Patrick C. WalshAbstract:Purpose: We retrospectively reviewed a large series of men with clinically localized prostate cancer who underwent surgery to define the extent of stage migration and its influence on biochemical Recurrence in 3 different eras of prostate cancer management.Materials and Methods: A total of 2,370 men were treated with radical prostatectomy from 1982 to 1998. We analyzed the Freedom from biochemical (prostate specific antigen) progression after radical prostatectomy. We compared the distribution of pathological stage by the year of surgery. We then compared the biochemical Recurrence-Free Survival rate according to the different eras that reflect a change in prostate cancer management.Results: There was a significant downward stage migration of prostate cancer and an increasing proportion of men who presented with organ confined disease in recent years. The actuarial biochemical Recurrence-Free rate was significantly different for patients who underwent surgery between 1982 and 1988, compared with those bet...
Sergij Goerdt - One of the best experts on this subject based on the ideXlab platform.
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p cadherin expression in merkel cell carcinomas is associated with prolonged Recurrence Free Survival
British Journal of Dermatology, 2012Co-Authors: L Vlahova, Yvette Doerflinger, David Schrama, Peter Helmbold, Jürgen C. Becker, Roland Houben, Matthias Goebeler, Christel Weiß, Sergij GoerdtAbstract:Summary Background Merkel cell carcinoma (MCC) is a highly aggressive skin cancer, associated with advanced age, immunosuppression and Merkel cell polyomavirus (MCV) infections. As development and progression of cancer can be promoted by changes in cell adhesion proteins, we have previously analysed homo- and heterotypic cell–cell contacts of normal Merkel cells and MCCs and obtained indications for cadherin switching. Objectives To examine the prevalence and prognostic relevance of E-, N- and P-cadherin in MCCs. Methods Paraffin-embedded MCC samples (n = 148) from 106 different patients were analysed by double-label immunostaining and immunofluorescence microscopy. MCV status was determined by real-time polymerase chain reaction. The cadherin repertoire and MCV status were correlated to clinical data, including tumour stage and Recurrence-Free Survival. Results Ninety-one per cent of all MCC were positive for N-cadherin whereas only 61·6% and 70·3% expressed E- and P-cadherin, respectively. P-cadherin was significantly more frequent in primary tumours than in lymph node metastases (81·9% vs. 40·9%, P = 0·0002). Patients with P-cadherin-positive primary tumours were in earlier tumour stages at initial diagnosis (P = 0·0046). Both in log-rank tests (P = 0·0474) and in multiple Cox regression analysis including age, sex, immunosuppression, stage at initial diagnosis and MCV status (hazard ratio 0·193, P = 0·0373), patients with P-cadherin-positive primary MCCs had significantly prolonged Recurrence-Free Survival (mean 25·2 vs. 10·6 months; median 9·0 vs. 4·0 months). MCV DNA was detected in 78·2% of all MCC, more frequently in P-cadherin-positive MCC (P = 0·0008). Conclusion P-cadherin expression in MCCs predicts prolonged Recurrence-Free Survival and may therefore indicate favourable prognosis.
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p cadherin expression in merkel cell carcinomas is associated with prolonged Recurrence Free Survival
British Journal of Dermatology, 2012Co-Authors: L Vlahova, Yvette Doerflinger, David Schrama, Peter Helmbold, Jürgen C. Becker, Roland Houben, Matthias Goebeler, Christel Weiß, Sergij GoerdtAbstract:Summary Background Merkel cell carcinoma (MCC) is a highly aggressive skin cancer, associated with advanced age, immunosuppression and Merkel cell polyomavirus (MCV) infections. As development and progression of cancer can be promoted by changes in cell adhesion proteins, we have previously analysed homo- and heterotypic cell–cell contacts of normal Merkel cells and MCCs and obtained indications for cadherin switching. Objectives To examine the prevalence and prognostic relevance of E-, N- and P-cadherin in MCCs. Methods Paraffin-embedded MCC samples (n = 148) from 106 different patients were analysed by double-label immunostaining and immunofluorescence microscopy. MCV status was determined by real-time polymerase chain reaction. The cadherin repertoire and MCV status were correlated to clinical data, including tumour stage and Recurrence-Free Survival. Results Ninety-one per cent of all MCC were positive for N-cadherin whereas only 61·6% and 70·3% expressed E- and P-cadherin, respectively. P-cadherin was significantly more frequent in primary tumours than in lymph node metastases (81·9% vs. 40·9%, P = 0·0002). Patients with P-cadherin-positive primary tumours were in earlier tumour stages at initial diagnosis (P = 0·0046). Both in log-rank tests (P = 0·0474) and in multiple Cox regression analysis including age, sex, immunosuppression, stage at initial diagnosis and MCV status (hazard ratio 0·193, P = 0·0373), patients with P-cadherin-positive primary MCCs had significantly prolonged Recurrence-Free Survival (mean 25·2 vs. 10·6 months; median 9·0 vs. 4·0 months). MCV DNA was detected in 78·2% of all MCC, more frequently in P-cadherin-positive MCC (P = 0·0008). Conclusion P-cadherin expression in MCCs predicts prolonged Recurrence-Free Survival and may therefore indicate favourable prognosis.