Correspondence
registered, have published results or have their results posted. Compliance with mandatory posting of results, as required by the Food and Drug Administration Amendments Act, is low.18,19 Moreover, this law concerns trials performed in the United States, with no similar law in Europe or elsewhere. So, before the ultimate step of data sharing, considerable improvement in transparency could be achieved by all trials being registered and their results available in journals or posted in clinical trial registries, as required by the All Trials campaign.20 In the United States where posting trial results is mandatory, efforts should be made to more rigorously apply the law. Furthermore, we advocate extending the mandatory posting of results for all clinical trials worldwide.
Agnes Dechartres INSERM U738; Universite´ Paris Descartes—Sorbonne Paris Cite´; Assistance Publique-Hoˆpitaux de Paris, Hoˆpital Hoˆtel-Dieu, Centre d’Epide´miologie Clinique, Paris, France
Philippe Ravaud INSERM U738; Universite´ Paris Descartes—Sorbonne Paris Cite´; Assistance Publique-Hoˆpitaux de Paris, Hoˆpital Hoˆtel-Dieu, Centre d’Epide´miologie Clinique; French Cochrane Centre, Paris, France; Columbia University, Mailman School of Public Health, New York, NY
ACKNOWLEDGMENT
Supported by the academic Grant No. DEQ20101221475, program “Equipe espoir de la Recherche,” Fondation pour la Recherche Me´dicale, Paris, France. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
2. Perneger TV: Sharing raw data: Another of Francis Galton’s ideas. BMJ 342:d3035, 2011 3. Galton F: Biometry. Biometrika 1:7-10, 1901 4. Kirwan JR: Making original data from clinical studies available for alternative analysis. J Rheumatol 24:822-825, 1997 5. Vickers AJ: Whose data set is it anyway? Sharing raw data from randomized trials. Trials 7:15, 2006 6. Vickers AJ: Making raw data more widely available. BMJ 342:d2323, 2011 7. Gotzsche PC: Strengthening and opening up health research by sharing our raw data. Circ Cardiovasc Qual Outcomes 5:236-237, 2012 8. Godlee F, Groves T: The new BMJ policy on sharing data from drug and device trials. BMJ 345:e7888, 2012 9. Groves T: Sharing the raw data from medical research [corrected]. BMJ 338:b1252, 2009 10. Savage CJ, Vickers AJ: Empirical study of data sharing by authors publishing in PLoS journals. PLoS One 4:e7078, 2009 11. Ross JS, Krumholz HM: Ushering in a new era of open science through data sharing: The wall must come down. JAMA 309:1355-1356, 2013 12. Zarin DA: Participant-level data and the new frontier in trial transparency. N Engl J Med 369:468-469, 2013 13. European Medicines Agency. Release of data from clinical trials. http:// www.ema.europa.eu/ema/index.jsp?curl⫽pages/special_topics/general/ general_content_000556.jsp 14. Nisen P, Rockhold F: Access to patient-level data from GlaxoSmithKline clinical trials. N Engl J Med 369:475-478, 2013 15. Hrynaszkiewicz I, Norton ML, Vickers AJ, et al: Preparing raw clinical data for publication: Guidance for journal editors, authors, and peer reviewers. BMJ 340:c181, 2010 16. Mello MM, Francer JK, Wilenzick M, et al: Preparing for responsible sharing of clinical trial data. N Engl J Med 369:1651-1658, 2013 17. Zarin DA, Tse T: Medicine: Moving toward transparency of clinical trials. Science 319:1340-1342, 2008 18. Nguyen TA, Dechartres A, Belgherbi S, et al: Public availability of results of trials assessing cancer drugs in the United States. J Clin Oncol 31:2998-3003, 2013 19. Prayle AP, Hurley MN, Smyth AR: Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: Cross sectional study. BMJ 344:d7373, 2012 20. Sense About Science: All Trials Registered/All Results Reported. 2013 www.alltrials.net
REFERENCES 1. Read W: Public database of federally funded clinical trials data. J Clin Oncol 32:603, 2014
DOI: 10.1200/JCO.2013.53.7217; published online ahead of print at www.jco.org on January 6, 2014
■ ■ ■
Reply to W. Read We read with interest the proposal from Read1 regarding his proposal for a National Clinical Trials Database containing mature datasets from clinical trials with federal funding after his reading of the article from Nguyen et al2 and our accompanying editorial.3 Currently, these datasets are maintained by a dizzying number of organizations and individual researchers.4 While we agree that data funded by public dollars should be made publically available, the ideal shape, structure, and format of such a database are not entirely intuitive and require foresight, planning, and thought.5 The ability to query, search and download the multiple different data sets is not an inconsequential task and a standard format would need to be considered to facilitate use of such a tool. In addition, protection of patient confidentiality remains essential to study participants. Read1 notes the example of the SEER database as an analogous endeavor, but like other government-sponsored data sets including the National Health Interview Survey, Medical Expenditure Panel Survey, and the Health Care Cost and Utilization Project, SEER benefits from central budgets, organization, and effort. We would offer the example of the development of the Human Genome Project as a model of publically shared and easily navigable Big Data generated 604
© 2014 by American Society of Clinical Oncology
from public and private endeavors. Currently, DNA sequencing data is available to anyone on the Internet through the unrestricted public GenBank database,6 and many for-profit and nonprofit organizations have developed tools to search and interpret these data to optimize utility. While public and private databases represent separate challenges, this distinction is likely to be smaller in the future. For example, publication of individual patient data from clinical trials where the relevant information is held by the European Medicines Agency (EMA) is moving forward, with advocates requesting open access to these data based on the patients’ altruism and skepticism over the completeness of published trial information.7 In June 2013, the EMA proposed a draft policy making patient-level data in the possession of the EMA publicly accessible.8 The importance of full reporting has been emphasized in a recent study noting that unpublished clinical study reports provide significantly more information regarding patient-related benefits and harms compared with journal publications or registry reports.9 The EMA reports that access to full data sets of completed trials will lead to improved design of subsequent trials, facilitate reporting of comprehensive meta-analyses of patient-level databases, improve a drug’s value in the marketplace, facilitate comparative effectiveness research efforts, and minimize the likelihood of JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Thammasat University Libraries on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 203.131.222.5
Correspondence
conducting trials that duplicate efforts that were previously unsuccessful.7 The US Food and Drug Administration has similarly proposed expansion of access to data submitted in regulatory applications.10 Mello et al5 recently proposed a framework for broad sharing of participant-level data from clinical trials and related documents. Four possible data-sharing models are proposed, varying in who the decision maker would be for releasing these data. As of October 25, 2013, over 154,000 studies have been listed on clinicaltrials.gov. This represents millions of clinical trial participants whose impact on health care is only magnified by the opportunity for additional gains from their efforts. We wholeheartedly agree with the sentiments of Read,1 although, as the US Food and Drug Administration and EMA outline, these databases will undoubtedly include privately and publicly funded clinical trial data. The devil is in the details.
Sandip M. Prasad Medical University of South Carolina, Charleston, SC
Oliver Sartor Tulane University School of Medicine, New Orleans, LA
Charles L. Bennett South Carolina College of Pharmacy, Medical University of South Carolina and the University of South Carolina, Columbia, SC
REFERENCES 1. Read W: Public database of federally funded clinical trials data. J Clin Oncol 32:603, 2014 2. Nguyen TA, Dechartres A, Belgherbi S, et al: Public availability of results of trials assessing cancer drugs in the United States. J Clin Oncol 31:2998-3003, 2013 3. Prasad SM, Bennett CL: Finishing the picture: Problems with public reporting of clinical trials. J Clin Oncol 31:2981-2982, 2013 4. Bradley CJ, Penberthy L, Devers KJ, et al: Health services research and data linkages: Issues, methods, and directions for the future. Health Serv Res 45:1468-1488, 2010 5. Mello MM, Francer JK, Wilenzick M, et al: Preparing for responsible sharing of clinical trial data. N Engl J Med 369:1651-1658, 2013 6. National Institutes of Health: GenBank. 2013 http://www.ncbi.nlm.nih.gov/ genbank/ 7. Eichler HG, Pe´tavy F, Pignatti F, et al: Access to patient-level trial data: A boon to drug developers. N Engl J Med 369:1577-1579, 2013 8. European Medicines Agency: Publication and access to clinical trial data. 2013 http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/06/ WC500144730.pdf 9. Wieseler B, Wolfram N, McGauran N, et al: Completeness of reporting of patient-relevant clinical trial outcomes: Comparison of unpublished clinical study reports with publicly available data. PLoS Med 10:e1001526, 2013 10. US Food and Drug Administration: Availability of masked and de-identified non-summary safety and efficacy data; request for comments. 2013 https:// www.federalregiter.gov/articles/2013/06/04/2013-13083/availability-of-maskedand-deidentified-non-summary-safety-and-efficacy-data-request-for-comments? utm_campaign⫽subscription⫹mailing⫹list&utm_medium⫽e-mail:&utm_source⫽ federalregister.gov
DOI: 10.1200/JCO.2013.53.7225; published online ahead of print at www.jco.org on January 6, 2014
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
■ ■ ■
Are Dose-Dense and Triplet Chemotherapy Regimens Optimal Adjuvant Therapy in the Majority of Women With Node-Positive Early Breast Cancer? TO THE EDITOR: In their report of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 trial, Swain et al1 state that dose-dense chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel is considered an optimal adjuvant regimen for node-positive primary breast cancer. The authors also assert that docetaxel, doxorubicin, and cyclophosphamide “is an optimal docetaxel-based regimen.” In the demographics of the NSABP study population, only 20% of participants were more than 60 years of age. By contrast, based on the SEER Cancer Statistics Review 2006 to 2010,2 66.4% of patients with breast cancer are more than 55 years of age. This represents a significant sample bias toward younger patients who are capable of tolerating more intensive chemotherapy regimens. The question arises, for whom do the NSABP B38 data apply? The authors report that the “toxicity from protocol therapy was acceptable for the adjuvant setting and typical of the regimens used.” We are concerned that the application of these chemotherapy regimens across the broad spectrum of patients with breast cancer, especially those older patients with comorbidities, will result in substantially higher rates of treatment-related morbidity and mortality. We would also chalwww.jco.org
lenge the proposition that triplet or dose-dense chemotherapy is “optimal” chemotherapy for all patients with node-positive breast cancer. A meta-analysis of phase III randomized trials to compare treatment outcomes for patients with early-stage breast cancer receiving adjuvant chemotherapy with sequential or concurrent anthracyclines and taxanes concluded that the sequential schedule adds significant benefit in both disease-free survival and overall survival over concurrent regimens.3 Among three eligible trials included in the meta-analysis, significant differences in favor of the sequential regimen were seen in disease-free survival (relative risk, 0.90; 95% CI, 0.84 to 0.98; P ⫽ .01) and in overall survival (relative risk, 0.88; 95% CI, 0.79 to 0.98; P ⫽ .02).4 In 2010, Bonilla et al4 reported the results of a systematic review and meta-analysis of randomized controlled trials of dose-dense chemotherapy in nonmetastatic breast cancer. The authors reported that although patients who received dose-dense chemotherapy had a better overall survival (hazard ratio of death, 0.84; 95% CI, 0.72 to 0.98; P ⫽ .03) than those on the conventional schedule, no benefit was observed in the hormone receptor–positive tumors. In the NSABP B-38 study, 80% of patients were hormone receptor positive, and one could argue that these patients were overtreated with these more intensive chemotherapy regimens. It is interesting to note that the only trend toward progression-free survival benefit in the B-38 study was in the hormone receptor–negative cohort. We completely agree with the B-38 study authors that we need to turn to biology for greater success in breast cancer therapy. It would therefore be beneficial to see the results analyzed by tumor subtype as promulgated by the St Gallen Early Breast Cancer Guidelines, © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Thammasat University Libraries on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 203.131.222.5
605
registered, have published results or have their results posted. Compliance with mandatory posting of results, as required by the Food and Drug Administration Amendments Act, is low.18,19 Moreover, this law concerns trials performed in the United States, with no similar law in Europe or elsewhere. So, before the ultimate step of data sharing, considerable improvement in transparency could be achieved by all trials being registered and their results available in journals or posted in clinical trial registries, as required by the All Trials campaign.20 In the United States where posting trial results is mandatory, efforts should be made to more rigorously apply the law. Furthermore, we advocate extending the mandatory posting of results for all clinical trials worldwide.
Agnes Dechartres INSERM U738; Universite´ Paris Descartes—Sorbonne Paris Cite´; Assistance Publique-Hoˆpitaux de Paris, Hoˆpital Hoˆtel-Dieu, Centre d’Epide´miologie Clinique, Paris, France
Philippe Ravaud INSERM U738; Universite´ Paris Descartes—Sorbonne Paris Cite´; Assistance Publique-Hoˆpitaux de Paris, Hoˆpital Hoˆtel-Dieu, Centre d’Epide´miologie Clinique; French Cochrane Centre, Paris, France; Columbia University, Mailman School of Public Health, New York, NY
ACKNOWLEDGMENT
Supported by the academic Grant No. DEQ20101221475, program “Equipe espoir de la Recherche,” Fondation pour la Recherche Me´dicale, Paris, France. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
2. Perneger TV: Sharing raw data: Another of Francis Galton’s ideas. BMJ 342:d3035, 2011 3. Galton F: Biometry. Biometrika 1:7-10, 1901 4. Kirwan JR: Making original data from clinical studies available for alternative analysis. J Rheumatol 24:822-825, 1997 5. Vickers AJ: Whose data set is it anyway? Sharing raw data from randomized trials. Trials 7:15, 2006 6. Vickers AJ: Making raw data more widely available. BMJ 342:d2323, 2011 7. Gotzsche PC: Strengthening and opening up health research by sharing our raw data. Circ Cardiovasc Qual Outcomes 5:236-237, 2012 8. Godlee F, Groves T: The new BMJ policy on sharing data from drug and device trials. BMJ 345:e7888, 2012 9. Groves T: Sharing the raw data from medical research [corrected]. BMJ 338:b1252, 2009 10. Savage CJ, Vickers AJ: Empirical study of data sharing by authors publishing in PLoS journals. PLoS One 4:e7078, 2009 11. Ross JS, Krumholz HM: Ushering in a new era of open science through data sharing: The wall must come down. JAMA 309:1355-1356, 2013 12. Zarin DA: Participant-level data and the new frontier in trial transparency. N Engl J Med 369:468-469, 2013 13. European Medicines Agency. Release of data from clinical trials. http:// www.ema.europa.eu/ema/index.jsp?curl⫽pages/special_topics/general/ general_content_000556.jsp 14. Nisen P, Rockhold F: Access to patient-level data from GlaxoSmithKline clinical trials. N Engl J Med 369:475-478, 2013 15. Hrynaszkiewicz I, Norton ML, Vickers AJ, et al: Preparing raw clinical data for publication: Guidance for journal editors, authors, and peer reviewers. BMJ 340:c181, 2010 16. Mello MM, Francer JK, Wilenzick M, et al: Preparing for responsible sharing of clinical trial data. N Engl J Med 369:1651-1658, 2013 17. Zarin DA, Tse T: Medicine: Moving toward transparency of clinical trials. Science 319:1340-1342, 2008 18. Nguyen TA, Dechartres A, Belgherbi S, et al: Public availability of results of trials assessing cancer drugs in the United States. J Clin Oncol 31:2998-3003, 2013 19. Prayle AP, Hurley MN, Smyth AR: Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: Cross sectional study. BMJ 344:d7373, 2012 20. Sense About Science: All Trials Registered/All Results Reported. 2013 www.alltrials.net
REFERENCES 1. Read W: Public database of federally funded clinical trials data. J Clin Oncol 32:603, 2014
DOI: 10.1200/JCO.2013.53.7217; published online ahead of print at www.jco.org on January 6, 2014
■ ■ ■
Reply to W. Read We read with interest the proposal from Read1 regarding his proposal for a National Clinical Trials Database containing mature datasets from clinical trials with federal funding after his reading of the article from Nguyen et al2 and our accompanying editorial.3 Currently, these datasets are maintained by a dizzying number of organizations and individual researchers.4 While we agree that data funded by public dollars should be made publically available, the ideal shape, structure, and format of such a database are not entirely intuitive and require foresight, planning, and thought.5 The ability to query, search and download the multiple different data sets is not an inconsequential task and a standard format would need to be considered to facilitate use of such a tool. In addition, protection of patient confidentiality remains essential to study participants. Read1 notes the example of the SEER database as an analogous endeavor, but like other government-sponsored data sets including the National Health Interview Survey, Medical Expenditure Panel Survey, and the Health Care Cost and Utilization Project, SEER benefits from central budgets, organization, and effort. We would offer the example of the development of the Human Genome Project as a model of publically shared and easily navigable Big Data generated 604
© 2014 by American Society of Clinical Oncology
from public and private endeavors. Currently, DNA sequencing data is available to anyone on the Internet through the unrestricted public GenBank database,6 and many for-profit and nonprofit organizations have developed tools to search and interpret these data to optimize utility. While public and private databases represent separate challenges, this distinction is likely to be smaller in the future. For example, publication of individual patient data from clinical trials where the relevant information is held by the European Medicines Agency (EMA) is moving forward, with advocates requesting open access to these data based on the patients’ altruism and skepticism over the completeness of published trial information.7 In June 2013, the EMA proposed a draft policy making patient-level data in the possession of the EMA publicly accessible.8 The importance of full reporting has been emphasized in a recent study noting that unpublished clinical study reports provide significantly more information regarding patient-related benefits and harms compared with journal publications or registry reports.9 The EMA reports that access to full data sets of completed trials will lead to improved design of subsequent trials, facilitate reporting of comprehensive meta-analyses of patient-level databases, improve a drug’s value in the marketplace, facilitate comparative effectiveness research efforts, and minimize the likelihood of JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Thammasat University Libraries on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 203.131.222.5
Correspondence
conducting trials that duplicate efforts that were previously unsuccessful.7 The US Food and Drug Administration has similarly proposed expansion of access to data submitted in regulatory applications.10 Mello et al5 recently proposed a framework for broad sharing of participant-level data from clinical trials and related documents. Four possible data-sharing models are proposed, varying in who the decision maker would be for releasing these data. As of October 25, 2013, over 154,000 studies have been listed on clinicaltrials.gov. This represents millions of clinical trial participants whose impact on health care is only magnified by the opportunity for additional gains from their efforts. We wholeheartedly agree with the sentiments of Read,1 although, as the US Food and Drug Administration and EMA outline, these databases will undoubtedly include privately and publicly funded clinical trial data. The devil is in the details.
Sandip M. Prasad Medical University of South Carolina, Charleston, SC
Oliver Sartor Tulane University School of Medicine, New Orleans, LA
Charles L. Bennett South Carolina College of Pharmacy, Medical University of South Carolina and the University of South Carolina, Columbia, SC
REFERENCES 1. Read W: Public database of federally funded clinical trials data. J Clin Oncol 32:603, 2014 2. Nguyen TA, Dechartres A, Belgherbi S, et al: Public availability of results of trials assessing cancer drugs in the United States. J Clin Oncol 31:2998-3003, 2013 3. Prasad SM, Bennett CL: Finishing the picture: Problems with public reporting of clinical trials. J Clin Oncol 31:2981-2982, 2013 4. Bradley CJ, Penberthy L, Devers KJ, et al: Health services research and data linkages: Issues, methods, and directions for the future. Health Serv Res 45:1468-1488, 2010 5. Mello MM, Francer JK, Wilenzick M, et al: Preparing for responsible sharing of clinical trial data. N Engl J Med 369:1651-1658, 2013 6. National Institutes of Health: GenBank. 2013 http://www.ncbi.nlm.nih.gov/ genbank/ 7. Eichler HG, Pe´tavy F, Pignatti F, et al: Access to patient-level trial data: A boon to drug developers. N Engl J Med 369:1577-1579, 2013 8. European Medicines Agency: Publication and access to clinical trial data. 2013 http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/06/ WC500144730.pdf 9. Wieseler B, Wolfram N, McGauran N, et al: Completeness of reporting of patient-relevant clinical trial outcomes: Comparison of unpublished clinical study reports with publicly available data. PLoS Med 10:e1001526, 2013 10. US Food and Drug Administration: Availability of masked and de-identified non-summary safety and efficacy data; request for comments. 2013 https:// www.federalregiter.gov/articles/2013/06/04/2013-13083/availability-of-maskedand-deidentified-non-summary-safety-and-efficacy-data-request-for-comments? utm_campaign⫽subscription⫹mailing⫹list&utm_medium⫽e-mail:&utm_source⫽ federalregister.gov
DOI: 10.1200/JCO.2013.53.7225; published online ahead of print at www.jco.org on January 6, 2014
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
■ ■ ■
Are Dose-Dense and Triplet Chemotherapy Regimens Optimal Adjuvant Therapy in the Majority of Women With Node-Positive Early Breast Cancer? TO THE EDITOR: In their report of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 trial, Swain et al1 state that dose-dense chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel is considered an optimal adjuvant regimen for node-positive primary breast cancer. The authors also assert that docetaxel, doxorubicin, and cyclophosphamide “is an optimal docetaxel-based regimen.” In the demographics of the NSABP study population, only 20% of participants were more than 60 years of age. By contrast, based on the SEER Cancer Statistics Review 2006 to 2010,2 66.4% of patients with breast cancer are more than 55 years of age. This represents a significant sample bias toward younger patients who are capable of tolerating more intensive chemotherapy regimens. The question arises, for whom do the NSABP B38 data apply? The authors report that the “toxicity from protocol therapy was acceptable for the adjuvant setting and typical of the regimens used.” We are concerned that the application of these chemotherapy regimens across the broad spectrum of patients with breast cancer, especially those older patients with comorbidities, will result in substantially higher rates of treatment-related morbidity and mortality. We would also chalwww.jco.org
lenge the proposition that triplet or dose-dense chemotherapy is “optimal” chemotherapy for all patients with node-positive breast cancer. A meta-analysis of phase III randomized trials to compare treatment outcomes for patients with early-stage breast cancer receiving adjuvant chemotherapy with sequential or concurrent anthracyclines and taxanes concluded that the sequential schedule adds significant benefit in both disease-free survival and overall survival over concurrent regimens.3 Among three eligible trials included in the meta-analysis, significant differences in favor of the sequential regimen were seen in disease-free survival (relative risk, 0.90; 95% CI, 0.84 to 0.98; P ⫽ .01) and in overall survival (relative risk, 0.88; 95% CI, 0.79 to 0.98; P ⫽ .02).4 In 2010, Bonilla et al4 reported the results of a systematic review and meta-analysis of randomized controlled trials of dose-dense chemotherapy in nonmetastatic breast cancer. The authors reported that although patients who received dose-dense chemotherapy had a better overall survival (hazard ratio of death, 0.84; 95% CI, 0.72 to 0.98; P ⫽ .03) than those on the conventional schedule, no benefit was observed in the hormone receptor–positive tumors. In the NSABP B-38 study, 80% of patients were hormone receptor positive, and one could argue that these patients were overtreated with these more intensive chemotherapy regimens. It is interesting to note that the only trend toward progression-free survival benefit in the B-38 study was in the hormone receptor–negative cohort. We completely agree with the B-38 study authors that we need to turn to biology for greater success in breast cancer therapy. It would therefore be beneficial to see the results analyzed by tumor subtype as promulgated by the St Gallen Early Breast Cancer Guidelines, © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Thammasat University Libraries on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 203.131.222.5
605
