Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

RECIST for Response (Clinical and Imaging) in Neoadjuvant Clinical Trials in Operable Breast Cancer

RECIST for Response (Clinical and Imaging) in Neoadjuvant Clinical Trials in Operable Breast Cancer Abstract Although approximately 70% of breast cancer patients demonstrate a clinical response on neoadjuvant systemic therapy on physical examination or on anatomic radiographic imaging, only 3%–40% achieve a pathologic complete response (pCR). Magnetic resonance imaging (MRI) is superior to physical examination, ultrasound, and mammography in response evaluation during neoadjuvant systemic therapy. The accuracy of breast MRI to predict pCR has a moderate sensitivity, but high specificity. The accuracy of anatomic imaging to assess residual disease and predict pCR depended on anatomic radiographic imaging cancer subtypes. Response monitoring using breast is accurate in triple-negative or HER2-positive tumors. It was inaccurate in estrogen receptor-positive/HER2-negative subtype. Another approach currently under investigation is dynamic contrast-enhanced MRI and diffusion weighted-imaging, (18)F-fluorodeoxyglucose positron emission tomography, fluorodeoxyglucose positron emission tomography/computed tomography. In 1981, the World Health Organization (WHO) published tumor-response criteria for use in trials where tumor response to chemotherapy was the primary endpoint (1). In response to multiple modifications of WHO criteria, an International Working Party was formed in the mid-1990s to standardize and simplify response criteria. New criteria, known as Response Evaluation Criteria in Solid Tumors (RECIST), were published in 2000 (2). The specific response categorization (50% for the WHO bidimensional metric, corresponding to a partial response of 30% by RECIST unidimensional measurement) has remained basically unchanged in the evolution of the response assessment. The imaging modalities used to assess tumor size, however, have evolved substantially, which have led to the development of a revised RECIST guideline (version 1.1) (3). The primary purpose of an imaging endpoint is to serve as an early but accurate indicator of a promising treatment effect. The measure of treatment effect on the phase II endpoint must correlate sufficiently well with the measure of treatment effect on the phase III primary endpoint, which is usually assessed by a difference between two arms on progression-free survival or overall survival. Both clinical objective response and time to development of disease progression (progression-free survival) are important endpoint in phase II clinical trials in advanced breast cancer. However, many clinical trials (4–9) established that pathologic complete response (pCR) is of greater importance for patient outcome than clinical response. Despite the fact that no standardized definition for pCR exists, many trials (7,9–12) selected pCR as a primary endpoint. Several imaging techniques are available to predict the effect of preoperative therapy among patients with breast cancer. In many recent trials, physical examination, mammography, and sonographv are still the primary diagnostic tools for the evaluation of therapy (13). According to revised RECIST guideline (version 1.1), ultrasound examinations should not be used in clinical trials to measure tumor regression or progression of lesions because the examination is subjective and operator dependent (3). The RECIST Working Group and same expert (3,14) did not believe that there is at present sufficient standardization and widespread availability to recommend adoption of functional imaging (18F-fluorodeoxyglucose positron emission tomography, dynamic contrast-enhanced magnetic resonance imaging [MRI]) as alternative assessment methods. However, some studies have shown that MRI can determine response to chemotherapy treatment more accurately than mammography, ultrasound, and clinical examination, and now extensive research has been done on the performance of MRI in evaluating the efficacy of preoperative therapy in patients with breast cancer (11,13,15). Yuan et al. (15) performed a meta-analysis of value MRI in prediction of pathologic complete remission after preoperative therapy. This meta-analysis, which included data from 1212 patients, has shown that contrast-enhanced MRI has high specificity (90.7%) and relative lower sensitivity (63.1%) in predicting pathologic complete remission after preoperative therapy in patients with breast cancer [IIIС]. On the other side, a meta-analysis of preparation MRI for staging the primary breast cancer showed that MRI has high sensitivity (90%) and lower specificity (72%) (16) [IIIС]. In other studies (17–21), it was observed that the accuracy of breast imaging techniques to assess clinical response and predict pCR depended on breast cancer subtypes. It was observed that MRI was able to predict pCR more accurately in patients with HER2-positive tumors when compared with HER2-negative tumors or in patients with triple-negative disease (13,17,20). For example, NeOAdjuvant Herceptin Trial (NOAH)study (22) of locally advanced HER2-positive disease comparing pCR rates with clinical response to chemotherapy plus trasturumab reveals a close correlation between clinical and pathological findings [IIB], so that patients who achieved a clinical CR were more likely to have achieved a pCR than patients who only achieved a clinical partial response (67% vs 19%). It was also observed that the average size discrepancy between MRI and pathology was greater in tumors demonstrating limited Ki-67 staining and high level of estrogen receptor (ER) positivity when compared with tumors demonstrating increased Ki-67 staining and ER-negative status. In ECTO II trial (12), achievement of pCR following three different anthracycline- and taxane-containing neoadjuvant chemotherapy regimens was more common in ER-negative than ER-positive women (45.3% vs 10.4%). Only in group of patients with ER-negative tumors, high rates of clinical response (cCR) translated into a high rates of pCR (pCR/cCR = 82.6%). These and other findings (17,21–24) suggest that breast cancer intrinsic subtype and the type of neoadjuvant systemic therapy influence on achieving cCR and pCR. These data also suggest that it is inappropriate to use pCR as the primary endpoint in neoadjuvant trials testing cytotoxic chemotherapy in patients with low grade (1 or 2) ER-positive tumors (24). Conclusion The goals of neoadjuvant therapy of breast cancer have clinically changed and evolved because it was firstly applied to women with inoperable locally advanced and inflammatory breast cancers in the early 1970s. The extended indication to allow more breast-conserving surgery has widened the application of neoadjuvant treatments and provided evidence for the association between favorable long-term outcome and intermediate endpoints, like pCR after chemotherapy or decreased tumor proliferation measured by Ki-67 after endocrine therapy (25). A key question is whether pCR and Ki-67 can take the role of qualified and validated surrogate markers of drug efficacy. The recent improvements in understanding the molecular basis of breast cancer heterogeneity has provided conceptual framework for interpreting the role of pCR as potential surrogate marker and that different molecular subtypes will require different intermediate surrogate endpoints (8). The validation of the intermediate surrogate markers of efficacy would dramatically change the landscape of development of new drugs for a comparative analysis of the intermediate endpoint instead of the final survival endpoint. References 1. Miller AB Hoogstraten B Staquet M Winkler A . Reporting results of cancer treatment. Cancer . 1981; 47( 1): 207– 214. 2. Therasse P Arbuck SG Eisenhauer EA et al.   New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst . 2000; 92( 3): 205– 216. 3. Eisenhauer EA Therasse P Bogaerts J et al.   . New response evalution criteria in solid tumors: revised REGIST guideline (version I.I.). Eur J Cancer . 2009; 45( 2): 228– 247. 4. Fisher B Bryant J Wolmark N et al.   Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol . 1998; 16( 8): 2672– 2685. 5. Bear HD Anderson S Smith RE et al.   Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol . 2006; 24( 13): 2019– 2027. 6. Gianni L Baselga J Eiermann W et al.   Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol . 2009; 27( 15): 2474– 2481. 7. Baselga J Bradbury I Eidtmann H et al.   ; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet . 2012; 379( 9816): 633– 640. 8. Gianni L Pienkowski T Roman L Tseng L Liu M . Addition of pertuzumab (P) to trastuzumab (H)-based neoadjuvant chemotherapy clinically improves pathological complete response in women with HER2-positive early breast cancer: result of a randomized phase II study (NEOSPHERE). Вrеаst . 2011; 20( suppl 1): 573. 9. Kong X Moran M Zhang M et al.   Meta-analysis confirm achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur J Cancer . 2011; 47(11): 2084– 2090. 10. Esserman LJ Berry DA DeMichele A et al.   Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol . 2012; 30( 26): 3242– 3249. 11. Lobbes M, Prevos R, Smidt M. Response monitoring of breast cancer patients reserving neoadjuvant chemotherapy using breast MRI – a review of cur-rent knowledge. J Cancer Ther Res. 2012; 1: 34. 12. Zambetti M Mansutti M Gomez P et al.   Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design (ECTO II). Breast Cancer Res Treat . 2012; 132( 3): 843– 851. 13. Avril N Sassen S Roylance R . Response to therapy in breast cancer. J Nucl Med . 2009; 50( suppl 1): 55S– 63S. 14. Sargent DJ Rubinstein L Schwartz L et al.   Validation of novel imaging methodologies for use as cancer clinical trial end-points. Eur J Cancer . 2009; 45( 2): 290– 299. 15. Yuan Y Chen X-S Liu S-Y et al.   Accuracy of MRI in prediction of pathologic complete remission in breast cancer after preoperative therapy: a meta-analysis. Am J Radiol . 2010; 195( 1): 260– 268. 16. Peter NH Borel-Rinkes IH Zuithoff NP et al.   Meta-analysis of MR imaging in the diagnosis of breast lesions. Radiology . 2008; 246( 1): 116– 124. 17. Sousa B Cardoso F . Neoadjuvant treatment for HER2-positive and triple-negative breast cancer. Ann Oncol . 2012; 23( suppl 10): 237– 242. 18. Thompson A Moulder-Thompson S . Neoadjuvant treatment of breast cancer. Ann Oncol . 2012; 23( suppl 10): 231– 236. 19. von Minckwitz G Untch M Blohmer JU et al.   Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol . 2012; 30( 15): 1796– 1804. 20. Cortazar P Zhang L Untch M et al.   Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CT NeoBC). Cancer Res . 2012; 72( suppl): s1– s11. Abs. San-Antonio Breast Cancer Symposium; December 4–8, 2012. 21. Colleoni M Viale G Zahrieh D et al.   Expression of ER, PgR, HER1, HER2, and response: a study of preoperative chemotherapy. Ann Oncol . 2008; 19( 3): 465– 472. 22. Gianni L Eiermann W Semiglazov V et al.   Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH Trial (NeOAdjuvant Herceptin Trial)): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet . 2010; 375( 9712): 377– 384. 23. Semiglazov V Eiermann W Zambetti M et al.   Surgery following neoadjuvant therapy in patients with HER2-positive locally advanced or inflammatory breast cancer participating in the NeOAdjuvant Herceptin (NOAH) study. Eur J Surg Oncol . 2011; 37( 10): 856– 863. 24. Schott AF Hayes DF . Defining the benefits of neoadjuvant chemotherapy for breast cancer. J Clin Oncol . 2012; 30( 15): 1747– 1749. 25. Sheri A Dowsett M . Developments in Ki67 and other biomarkers for treatment decision making in breast cancer. Ann Oncol . 2012; 23( suppl 10): 219– 227. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JNCI Monographs Oxford University Press

RECIST for Response (Clinical and Imaging) in Neoadjuvant Clinical Trials in Operable Breast Cancer

Semiglazov, Vladimir
JNCI Monographs , Volume 2015 (51) – Jun 10, 2015
Download PDF
3 pages

Loading next page...
 
/lp/oxford-university-press/recist-for-response-clinical-and-imaging-in-neoadjuvant-clinical-rX11vNcgg6

References (28)

Publisher
Oxford University Press
Copyright
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
ISSN
1052-6773
eISSN
1745-6614
DOI
10.1093/jncimonographs/lgv021
pmid
26063880
Publisher site
See Article on Publisher Site

Abstract

Abstract Although approximately 70% of breast cancer patients demonstrate a clinical response on neoadjuvant systemic therapy on physical examination or on anatomic radiographic imaging, only 3%–40% achieve a pathologic complete response (pCR). Magnetic resonance imaging (MRI) is superior to physical examination, ultrasound, and mammography in response evaluation during neoadjuvant systemic therapy. The accuracy of breast MRI to predict pCR has a moderate sensitivity, but high specificity. The accuracy of anatomic imaging to assess residual disease and predict pCR depended on anatomic radiographic imaging cancer subtypes. Response monitoring using breast is accurate in triple-negative or HER2-positive tumors. It was inaccurate in estrogen receptor-positive/HER2-negative subtype. Another approach currently under investigation is dynamic contrast-enhanced MRI and diffusion weighted-imaging, (18)F-fluorodeoxyglucose positron emission tomography, fluorodeoxyglucose positron emission tomography/computed tomography. In 1981, the World Health Organization (WHO) published tumor-response criteria for use in trials where tumor response to chemotherapy was the primary endpoint (1). In response to multiple modifications of WHO criteria, an International Working Party was formed in the mid-1990s to standardize and simplify response criteria. New criteria, known as Response Evaluation Criteria in Solid Tumors (RECIST), were published in 2000 (2). The specific response categorization (50% for the WHO bidimensional metric, corresponding to a partial response of 30% by RECIST unidimensional measurement) has remained basically unchanged in the evolution of the response assessment. The imaging modalities used to assess tumor size, however, have evolved substantially, which have led to the development of a revised RECIST guideline (version 1.1) (3). The primary purpose of an imaging endpoint is to serve as an early but accurate indicator of a promising treatment effect. The measure of treatment effect on the phase II endpoint must correlate sufficiently well with the measure of treatment effect on the phase III primary endpoint, which is usually assessed by a difference between two arms on progression-free survival or overall survival. Both clinical objective response and time to development of disease progression (progression-free survival) are important endpoint in phase II clinical trials in advanced breast cancer. However, many clinical trials (4–9) established that pathologic complete response (pCR) is of greater importance for patient outcome than clinical response. Despite the fact that no standardized definition for pCR exists, many trials (7,9–12) selected pCR as a primary endpoint. Several imaging techniques are available to predict the effect of preoperative therapy among patients with breast cancer. In many recent trials, physical examination, mammography, and sonographv are still the primary diagnostic tools for the evaluation of therapy (13). According to revised RECIST guideline (version 1.1), ultrasound examinations should not be used in clinical trials to measure tumor regression or progression of lesions because the examination is subjective and operator dependent (3). The RECIST Working Group and same expert (3,14) did not believe that there is at present sufficient standardization and widespread availability to recommend adoption of functional imaging (18F-fluorodeoxyglucose positron emission tomography, dynamic contrast-enhanced magnetic resonance imaging [MRI]) as alternative assessment methods. However, some studies have shown that MRI can determine response to chemotherapy treatment more accurately than mammography, ultrasound, and clinical examination, and now extensive research has been done on the performance of MRI in evaluating the efficacy of preoperative therapy in patients with breast cancer (11,13,15). Yuan et al. (15) performed a meta-analysis of value MRI in prediction of pathologic complete remission after preoperative therapy. This meta-analysis, which included data from 1212 patients, has shown that contrast-enhanced MRI has high specificity (90.7%) and relative lower sensitivity (63.1%) in predicting pathologic complete remission after preoperative therapy in patients with breast cancer [IIIС]. On the other side, a meta-analysis of preparation MRI for staging the primary breast cancer showed that MRI has high sensitivity (90%) and lower specificity (72%) (16) [IIIС]. In other studies (17–21), it was observed that the accuracy of breast imaging techniques to assess clinical response and predict pCR depended on breast cancer subtypes. It was observed that MRI was able to predict pCR more accurately in patients with HER2-positive tumors when compared with HER2-negative tumors or in patients with triple-negative disease (13,17,20). For example, NeOAdjuvant Herceptin Trial (NOAH)study (22) of locally advanced HER2-positive disease comparing pCR rates with clinical response to chemotherapy plus trasturumab reveals a close correlation between clinical and pathological findings [IIB], so that patients who achieved a clinical CR were more likely to have achieved a pCR than patients who only achieved a clinical partial response (67% vs 19%). It was also observed that the average size discrepancy between MRI and pathology was greater in tumors demonstrating limited Ki-67 staining and high level of estrogen receptor (ER) positivity when compared with tumors demonstrating increased Ki-67 staining and ER-negative status. In ECTO II trial (12), achievement of pCR following three different anthracycline- and taxane-containing neoadjuvant chemotherapy regimens was more common in ER-negative than ER-positive women (45.3% vs 10.4%). Only in group of patients with ER-negative tumors, high rates of clinical response (cCR) translated into a high rates of pCR (pCR/cCR = 82.6%). These and other findings (17,21–24) suggest that breast cancer intrinsic subtype and the type of neoadjuvant systemic therapy influence on achieving cCR and pCR. These data also suggest that it is inappropriate to use pCR as the primary endpoint in neoadjuvant trials testing cytotoxic chemotherapy in patients with low grade (1 or 2) ER-positive tumors (24). Conclusion The goals of neoadjuvant therapy of breast cancer have clinically changed and evolved because it was firstly applied to women with inoperable locally advanced and inflammatory breast cancers in the early 1970s. The extended indication to allow more breast-conserving surgery has widened the application of neoadjuvant treatments and provided evidence for the association between favorable long-term outcome and intermediate endpoints, like pCR after chemotherapy or decreased tumor proliferation measured by Ki-67 after endocrine therapy (25). A key question is whether pCR and Ki-67 can take the role of qualified and validated surrogate markers of drug efficacy. The recent improvements in understanding the molecular basis of breast cancer heterogeneity has provided conceptual framework for interpreting the role of pCR as potential surrogate marker and that different molecular subtypes will require different intermediate surrogate endpoints (8). The validation of the intermediate surrogate markers of efficacy would dramatically change the landscape of development of new drugs for a comparative analysis of the intermediate endpoint instead of the final survival endpoint. References 1. Miller AB Hoogstraten B Staquet M Winkler A . Reporting results of cancer treatment. Cancer . 1981; 47( 1): 207– 214. 2. Therasse P Arbuck SG Eisenhauer EA et al.   New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst . 2000; 92( 3): 205– 216. 3. Eisenhauer EA Therasse P Bogaerts J et al.   . New response evalution criteria in solid tumors: revised REGIST guideline (version I.I.). Eur J Cancer . 2009; 45( 2): 228– 247. 4. Fisher B Bryant J Wolmark N et al.   Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol . 1998; 16( 8): 2672– 2685. 5. Bear HD Anderson S Smith RE et al.   Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol . 2006; 24( 13): 2019– 2027. 6. Gianni L Baselga J Eiermann W et al.   Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol . 2009; 27( 15): 2474– 2481. 7. Baselga J Bradbury I Eidtmann H et al.   ; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet . 2012; 379( 9816): 633– 640. 8. Gianni L Pienkowski T Roman L Tseng L Liu M . Addition of pertuzumab (P) to trastuzumab (H)-based neoadjuvant chemotherapy clinically improves pathological complete response in women with HER2-positive early breast cancer: result of a randomized phase II study (NEOSPHERE). Вrеаst . 2011; 20( suppl 1): 573. 9. Kong X Moran M Zhang M et al.   Meta-analysis confirm achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur J Cancer . 2011; 47(11): 2084– 2090. 10. Esserman LJ Berry DA DeMichele A et al.   Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol . 2012; 30( 26): 3242– 3249. 11. Lobbes M, Prevos R, Smidt M. Response monitoring of breast cancer patients reserving neoadjuvant chemotherapy using breast MRI – a review of cur-rent knowledge. J Cancer Ther Res. 2012; 1: 34. 12. Zambetti M Mansutti M Gomez P et al.   Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design (ECTO II). Breast Cancer Res Treat . 2012; 132( 3): 843– 851. 13. Avril N Sassen S Roylance R . Response to therapy in breast cancer. J Nucl Med . 2009; 50( suppl 1): 55S– 63S. 14. Sargent DJ Rubinstein L Schwartz L et al.   Validation of novel imaging methodologies for use as cancer clinical trial end-points. Eur J Cancer . 2009; 45( 2): 290– 299. 15. Yuan Y Chen X-S Liu S-Y et al.   Accuracy of MRI in prediction of pathologic complete remission in breast cancer after preoperative therapy: a meta-analysis. Am J Radiol . 2010; 195( 1): 260– 268. 16. Peter NH Borel-Rinkes IH Zuithoff NP et al.   Meta-analysis of MR imaging in the diagnosis of breast lesions. Radiology . 2008; 246( 1): 116– 124. 17. Sousa B Cardoso F . Neoadjuvant treatment for HER2-positive and triple-negative breast cancer. Ann Oncol . 2012; 23( suppl 10): 237– 242. 18. Thompson A Moulder-Thompson S . Neoadjuvant treatment of breast cancer. Ann Oncol . 2012; 23( suppl 10): 231– 236. 19. von Minckwitz G Untch M Blohmer JU et al.   Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol . 2012; 30( 15): 1796– 1804. 20. Cortazar P Zhang L Untch M et al.   Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CT NeoBC). Cancer Res . 2012; 72( suppl): s1– s11. Abs. San-Antonio Breast Cancer Symposium; December 4–8, 2012. 21. Colleoni M Viale G Zahrieh D et al.   Expression of ER, PgR, HER1, HER2, and response: a study of preoperative chemotherapy. Ann Oncol . 2008; 19( 3): 465– 472. 22. Gianni L Eiermann W Semiglazov V et al.   Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH Trial (NeOAdjuvant Herceptin Trial)): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet . 2010; 375( 9712): 377– 384. 23. Semiglazov V Eiermann W Zambetti M et al.   Surgery following neoadjuvant therapy in patients with HER2-positive locally advanced or inflammatory breast cancer participating in the NeOAdjuvant Herceptin (NOAH) study. Eur J Surg Oncol . 2011; 37( 10): 856– 863. 24. Schott AF Hayes DF . Defining the benefits of neoadjuvant chemotherapy for breast cancer. J Clin Oncol . 2012; 30( 15): 1747– 1749. 25. Sheri A Dowsett M . Developments in Ki67 and other biomarkers for treatment decision making in breast cancer. Ann Oncol . 2012; 23( suppl 10): 219– 227. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Journal

JNCI Monographs – Oxford University Press

Published: Jun 10, 2015

There are no references for this article.