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Prediction of axillary response by monitoring with ultrasound and MRI during and after neoadjuvant chemotherapy in breast cancer patients. Eur Radiol 2019; 30:1460-1469. [DOI: 10.1007/s00330-019-06539-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 09/11/2019] [Accepted: 10/23/2019] [Indexed: 12/15/2022]
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Mrkonjic M, Berman HK, Done SJ, Youngson B, Mulligan AM. Breast specimen handling and reporting in the post-neoadjuvant setting: challenges and advances. J Clin Pathol 2019; 72:120-132. [PMID: 30670564 DOI: 10.1136/jclinpath-2018-205598] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 11/28/2018] [Indexed: 12/23/2022]
Abstract
Neoadjuvant systemic therapy is becoming more commonly used in patients with earlier stages of breast cancer. To assess tumour response to neoadjuvant chemotherapy, pathological evaluation is the gold standard. Depending on the treatment response, the pathological examination of these specimens can be quite challenging. However, a uniform approach to evaluate post-neoadjuvant-treated breast specimens has been lacking. Furthermore, there is no single universally accepted or endorsed classification system for assessing treatment response in this setting. Recent initiatives have attempted to create a standardised protocol for evaluation of post-neoadjuvant breast specimens. This review outlines the necessary information that should be collected prior to macroscopic examination of these specimens, the recommended and most pragmatic approach to tissue sampling for microscopic examination, describes the macroscopic and microscopic features of post-therapy breast specimens, summarises two commonly used systems for classifying treatment response and outlines the critical variables that should be included in the final pathology report.
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Affiliation(s)
- Miralem Mrkonjic
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.,Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Hal K Berman
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.,Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Susan J Done
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.,Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Bruce Youngson
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.,Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Anna Marie Mulligan
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada .,Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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3
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Choi M, Park YH, Ahn JS, Im YH, Nam SJ, Cho SY, Cho EY. Evaluation of Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Experience in a Single Institution over a 10-Year Period. J Pathol Transl Med 2016; 51:69-78. [PMID: 28013533 PMCID: PMC5267543 DOI: 10.4132/jptm.2016.10.05] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2016] [Revised: 10/04/2016] [Accepted: 10/05/2016] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with favorable clinical outcome in breast cancer patients. However, the possibility that the prognostic significance of pCR differs among various definitions has not been established. METHODS We retrospectively evaluated the pathologic response after NAC in 353 breast cancer patients and compared the prognoses after applying the following different definitions of pCR: ypT0/is, ypT0, ypT0/is ypN0, and ypT0 ypN0. RESULTS pCR was significantly associated with improved distant disease-free survival (DDFS) regardless of the definition (ypT0/is, p = .002; ypT0, p = .008; ypT0/is ypN0, p < .001; ypT0 ypN0, p = .003). Presence of tumor deposits of any size in the lymph nodes (LNs; ypN ≥ 0(i+)) was associated with worse DDFS (ypT0 ypN0 vs ypT0 ypN ≥ 0(i+), p = .036 and ypT0/is ypN0 vs ypT0/is ypN ≥ 0(i+), p = .015), and presence of isolated tumor cells was associated with decreased overall survival (OS; ypT0/is ypN0 vs ypT0/is ypN0(i+), p = .013). Residual ductal carcinoma in situ regardless of LN status showed no significant difference in DDFS or OS (DDFS: ypT0 vs ypTis, p = .373 and ypT0 ypN0 vs ypTis ypN0, p = .462; OS: ypT0 vs ypTis, p = .441 and ypT0 ypN0 vs ypTis ypN0, p = .758). In subsequent analysis using ypT0/is ypN0, pCR was associated with improved DDFS and OS in triple-negative tumors (p < .001 and p = .003, respectively). CONCLUSIONS Based on our study results, the prognosis and rate of pCR differ according to the definition of pCR and ypT0/is ypN0 might be considered a more preferable definition of pCR.
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Affiliation(s)
- Misun Choi
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yeon Hee Park
- Division of Hematology-Oncology,Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Seok Ahn
- Division of Hematology-Oncology,Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Hyuck Im
- Division of Hematology-Oncology,Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seok Jin Nam
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Youn Cho
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun Yoon Cho
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: development of a specific predictor and study of its utilities using decision curve analysis. Breast Cancer Res Treat 2016; 161:73-81. [PMID: 27807808 DOI: 10.1007/s10549-016-4040-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 10/24/2016] [Indexed: 10/20/2022]
Abstract
PURPOSE The aim of this study was to assess the Institut Gustave Roussy/M.D. Anderson Cancer Center (IGR/MDACC) nomogram in predicting pathologic complete response (pCR) to preoperative chemotherapy in a cohort of human epidermal growth factor receptor 2 (HER2)-positive tumors treated with preoperative chemotherapy with trastuzumab. We then combine clinical and pathological variables associated with pCR into a new nomogram specific to HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. PATIENTS AND METHODS Data from 270 patients with HER2-positive tumors treated with preoperative chemotherapy with trastuzumab at the Institut Curie and at the Georges François Leclerc Cancer Center were used to assess the IGR/MDACC nomogram and to subsequently develop a new nomogram for pCR based on multivariate logistic regression. Model performance was quantified in terms of calibration and discrimination. We studied the utility of the new nomogram using decision curve analysis. RESULTS The IGR/MDACC nomogram was not accurate for the prediction of pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab, with poor discrimination (AUC = 0.54, 95% CI 0.51-0.58) and poor calibration (p = 0.01). After uni- and multivariate analysis, a new pCR nomogram was built based on T stage (TNM), hormone receptor status, and Ki67 (%). The model had good discrimination with an area under the curve (AUC) at 0.74 (95% CI 0.70-0.79) and adequate calibration (p = 0.93). By decision curve analysis, the model was shown to be relevant between thresholds of 0.3 and 0.7. CONCLUSION To the best of our knowledge, ours is the first nomogram to predict pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. To ensure generalizability, this model needs to be externally validated.
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Diaz-Botero S, Espinosa-Bravo M, Gonçalves VR, Esgueva-Colmenarejo A, Peg V, Perez J, Cortes J, Rubio IT. Different Prognostic Implications of Residual Disease After Neoadjuvant Treatment: Impact of Ki 67 and Site of Response. Ann Surg Oncol 2016; 23:3831-3837. [DOI: 10.1245/s10434-016-5339-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Vila J, Mittendorf EA, Farante G, Bassett RL, Veronesi P, Galimberti V, Peradze N, Stauder MC, Chavez-MacGregor M, Litton JF, Huo L, Kuerer HM, Hunt KK, Caudle AS. Nomograms for Predicting Axillary Response to Neoadjuvant Chemotherapy in Clinically Node-Positive Patients with Breast Cancer. Ann Surg Oncol 2016; 23:3501-3509. [PMID: 27216742 DOI: 10.1245/s10434-016-5277-1] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND Many patients with clinically node-positive breast cancer receive neoadjuvant chemotherapy (NAC). Recent trials suggest the potential for limiting axillary surgery in patients who convert to pathologically node-negative disease. The authors developed a nomogram to predict axillary response to NAC in patients with cN1 disease that can assist clinicians in treatment planning. METHODS Patients with cT1-4N1M0 breast cancer who received NAC and underwent axillary lymph node dissection from 2001 through 2013 were identified (n = 584). Uni- and multivariate logistic regression analyses were performed to determine factors predictive of nodal conversion. A nomogram to predict the likelihood of nodal pathologic complete response (pCR) was constructed based on clinicopathologic variables and validated using an external dataset. RESULTS Axillary pCR was achieved for 217 patients (37 %). Patients presenting with high nuclear grade [grade 3 vs. 1, odds ratio (OR) 13.4], human epidermal growth factor receptor 2-positive (OR 4.7), estrogen receptor (ER)-negative (OR 3.5), or progesterone receptor-negative (OR 4.3) tumors were more likely to achieve nodal pCR. These factors, together with clinically relevant factors including presence of multifocal/centric disease, clinical T stage, and extent of nodal disease seen on regional nodal ultrasound at diagnosis were used to create nomograms predicting nodal conversion. The discrimination of the nomogram using ER+ status (>1 % staining) versus ER- status [area under the curve (AUC) 78 %] was improved slightly using the percentage of ER staining (AUC 78.7 %). Both nomograms were validated using an external cohort. CONCLUSION Nomograms incorporating routine clinicopathologic parameters can predict axillary pCR in node-positive patients receiving NAC and may help to inform treatment decisions.
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Affiliation(s)
- Jose Vila
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,The European Institute of Oncology, Milan, Italy
| | | | | | - Roland L Bassett
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | | | | | | | | | | | - Lei Huo
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Henry M Kuerer
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kelly K Hunt
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Abigail S Caudle
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Vugts G, Maaskant-Braat AJG, de Roos WK, Voogd AC, Nieuwenhuijzen GAP. Management of the axilla after neoadjuvant chemotherapy for clinically node positive breast cancer: A nationwide survey study in The Netherlands. Eur J Surg Oncol 2016; 42:956-64. [PMID: 27107791 DOI: 10.1016/j.ejso.2016.03.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 03/04/2016] [Accepted: 03/21/2016] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Axillary pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is achieved in a substantial part of clinically node positive breast cancer patients. Treatment of the axilla after NAC varies widely, and new techniques to spare patients from an axillary lymph node dissection (ALND) are being introduced. METHODS This Dutch nationwide survey regarding treatment of the initially clinically node positive axilla in patients receiving NAC was conducted amongst 148 surgical oncologists during November 2014-June 2015, to survey the diagnostic work-up, axillary mapping and willingness to omit ALND. RESULTS Axillary ultrasound was considered a standard procedure in the diagnostic work-up by 99% of participants. The majority of 70% of participants stated that ALND could possibly be omitted in node positive patients with a favourable response to NAC. A positive correlation was observed between the total amount of patients treated, versus patients receiving NAC (P < 0.01). A total of 93 respondents performed axillary response evaluation after NAC, using imaging (72%), excision of localized lymph nodes (56%) or sentinel node biopsy (SNB; 45%). Decision-making in omitting ALND was influenced by the presence of N2-3 disease, patient age and type of breast surgery. Multivariable analysis showed that clinicians who administered NAC more often, were more likely to omit ALND (P < 0.01). DISCUSSION The majority of surgeons are inclined to omit ALND in case of an axillary pCR. A large variety of techniques is being used to identify a pCR. The lack of consensus on this topic indicates the need for guidelines based on the best available evidence.
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Affiliation(s)
- G Vugts
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands; Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands.
| | | | - W K de Roos
- Department of Surgery, Gelderse Vallei Hospital, Ede, The Netherlands
| | - A C Voogd
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands; Department of Epidemiology, Maastricht University, Maastricht, The Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht, The Netherlands
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Kim TH, Kang DK, Kim JY, Han S, Jung Y. Histologic Grade and Decrease in Tumor Dimensions Affect Axillary Lymph Node Status after Neoadjuvant Chemotherapy in Breast Cancer Patients. J Breast Cancer 2015; 18:394-9. [PMID: 26770247 PMCID: PMC4705092 DOI: 10.4048/jbc.2015.18.4.394] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 11/04/2015] [Indexed: 12/31/2022] Open
Abstract
Purpose The purposes our study was to find out any histologic factors associated with negative conversion of axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC). We also evaluated the association between the decrease in size of primary breast tumor and negative conversion of ALN. Methods From January 2012 to November 2014, we included 133 breast cancer patients who underwent NAC and who had ALN metastases which were confirmed on fine-needle aspiration or core needle biopsy at initial diagnosis. All 133 patients underwent initial magnetic resonance imaging (MRI) at the time of diagnosis and preoperative MRI after completion of NAC. We measured the longest dimension of primary breast cancer on MRI. Results Of 133 patients, 39 patients (29%) showed negative conversion of ALN and of these 39 patients, 25 patients (64%) showed pathologic complete remission of primary breast. On univariate analysis, mean percent decrease in longest dimension, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status and histologic grade were significantly associated with the ALN status after NAC (p<0.001, p=0.001, p< 0.001, p=0.001, p=0.002, respectively). On multivariate logistic regression analysis, percent decrease in longest dimension (odds ratio, 1.026; 95% confidence interval [CI], 1.009-1.044) and histologic grade (odds ratio, 3.964; 95% CI, 1.151-13.657) were identified as being independently associated with the ALN status after NAC. The area under the receiver operating characteristic curve was 0.835 with the best cutoff value of 80% decrease in longest dimension. Combination of high histologic grade and more than 80% decrease in longest dimension showed 64% sensitivity and 92% specificity. Conclusion High histologic grade and more than 80% decrease in primary tumor dimension were associated with negative conversion of ALN after NAC.
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Affiliation(s)
- Tae Hee Kim
- Department of Radiology, Ajou University School of Medicine, Suwon, Korea
| | - Doo Kyoung Kang
- Department of Radiology, Ajou University School of Medicine, Suwon, Korea
| | - Ji Young Kim
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Sehwan Han
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Yongsik Jung
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
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9
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Rubio IT. Sentinel lymph node biopsy after neoadjuvant treatment in breast cancer: Work in progress. Eur J Surg Oncol 2015; 42:326-32. [PMID: 26774943 DOI: 10.1016/j.ejso.2015.11.018] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Accepted: 11/25/2015] [Indexed: 11/19/2022] Open
Abstract
Sentinel lymph node biopsy has replaced axillary lymph node dissection (ALND) in those patients with clinically node negative axilla and nowadays, patients with low burden disease in the SLNs may spare an ALND without compromising their oncologic outcomes. In the last decade, indications of neoadjuvant treatment (NAT) have been extended to patients with operable disease and with the use of targeted therapies, rates of pathologic complete response (pCR) after NAT have increased. In the neoadjuvant setting, SLN after NAT is feasible and accurate in clinically node negative patients and it has been explored in different randomized prospective studies in patients with clinically positive axilla in the continuous effort to avoid the morbidity of ALND. The importance of identifying patients with residual axillary disease may serve not only as indicator for selecting patients with pCR to be spared an ALND but also for selecting patients for additional therapy. Future research is needed to more accurately identify residual axillary disease and the SLN after NAT is the driver for this achievement.
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Affiliation(s)
- I T Rubio
- Hospital Universitario Vall d'hebron, Barcelona, Spain.
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10
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You S, Kang DK, Jung YS, An YS, Jeon GS, Kim TH. Evaluation of lymph node status after neoadjuvant chemotherapy in breast cancer patients: comparison of diagnostic performance of ultrasound, MRI and ¹⁸F-FDG PET/CT. Br J Radiol 2015; 88:20150143. [PMID: 26110204 PMCID: PMC4651396 DOI: 10.1259/bjr.20150143] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective: To evaluate the diagnostic performance of ultrasound, MRI and fluorine-18 fludeoxyglucose positron emission tomography (18F-FDG PET)/CT for the diagnosis of metastatic axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC) and to find out histopathological factors affecting the diagnostic performance of these imaging modalities. Methods: From January 2012 to November 2014, 191 consecutive patients with breast cancer who underwent NAC before surgery were retrospectively reviewed. We included 139 patients with ALN metastasis that was confirmed on fine needle aspiration or core needle biopsy at initial diagnosis. Results: After NAC, 39 (28%) patients showed negative conversion of ALN on surgical specimens of sentinel lymph node (LN) or ALN. The sensitivity of ultrasound, MRI and PET/CT was 50% (48/96), 72% (70/97) and 22% (16/73), respectively. The specificity of ultrasound, MRI and PET/CT was 77% (30/39), 54% (21/39) and 85% (22/26), respectively. The Az value of combination of ultrasound and PET/CT was the highest (0.634) followed by ultrasound (0.626) and combination of ultrasound, MRI and PET/CT (0.617). The size of tumour deposit in LN and oestrogen receptor was significantly associated with the diagnostic performance of ultrasound (p < 0.001 and p = 0.009, respectively) and MRI (p = 0.045 and p = 0.036, respectively). The percentage diameter decrease, size of tumour deposit in LN, progesterone receptor, HER2 and histological grade were significantly associated with the diagnostic performance of PET/CT (p = 0.023, p = 0.002, p = 0.036, p = 0.044 and p = 0.008, respectively). On multivariate logistic regression analysis, size of tumour deposit within LN was identified as being independently associated with diagnostic performance of ultrasound [odds ratio, 13.07; 95% confidence interval (CI), 2.95–57.96] and PET/CT (odds ratio, 6.47; 95% CI, 1.407–29.737). Conclusion: Combination of three imaging modalities showed the highest sensitivity, and PET/CT showed the highest specificity for the evaluation of ALN metastasis after NAC. Ultrasound alone or combination of ultrasound and PET/CT showed the highest positive-predictive value. The size of tumour deposit within ALN was significantly associated with diagnostic performance of ultrasound and PET/CT. Advances in knowledge: This study is about the diagnostic performance of ultrasound, MRI, PET/CT and combination of each imaging modality for the evaluation of metastatic ALN after NAC. Of many histopathological factors, only the size of tumour deposit within ALN was an independent factor associated with the diagnostic performance of ultrasound and PET/CT.
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Affiliation(s)
- S You
- Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - D K Kang
- Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Y S Jung
- Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Y-S An
- Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - G S Jeon
- Department of Radiology, CHA Bundang Medical Center, CHA University, College of Medicine, Seongnam, Republic of Korea
| | - T H Kim
- Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea
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Earl H, Provenzano E, Abraham J, Dunn J, Vallier AL, Gounaris I, Hiller L. Neoadjuvant trials in early breast cancer: pathological response at surgery and correlation to longer term outcomes - what does it all mean? BMC Med 2015; 13:234. [PMID: 26391216 PMCID: PMC4578850 DOI: 10.1186/s12916-015-0472-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 09/01/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Neoadjuvant breast cancer trials are important for speeding up the introduction of new treatments for patients with early breast cancer and for the highly productive translational research which they facilitate. Meta-analysis of trial data shows clear correlation between pathological response at surgery after neoadjuvant chemotherapy and longer-term outcomes at an individual patient level. However, this does not appear to be present on individual trial level analysis, when correlating improved outcome for the investigational arm for the primary endpoint (pathological response) with longer-term outcomes. DISCUSSION The correlation between pathological response and longer-term outcomes in trials is dependent on many factors. These include definitions of pathological response, both complete and partial; assessment methods for pathological response at surgery; subtype and prognosis of breast cancer at diagnosis; number of patients recruited; adjuvant treatments; the mechanism of action of the investigational drug; the length of follow-up at the time of reporting; the definitions used in longer-term outcomes analysis; clonal heterogeneity; and new adaptive trial designs with additional neo/adjuvant treatments. Future developments of neoadjuvant breast cancer trials are discussed. With so many factors influencing the correlation of longer-term outcomes for trial-level data, we conclude that the main focus of neoadjuvant trials should remain the primary endpoint of pathological response. Neoadjuvant breast cancer trials are very important investigational studies that will continue to increase our understanding of the disease and offer the potential of more rapid introduction of new treatments for women with high-risk early breast cancer. In the future, we are likely to see both novel trial designs adopted in the neoadjuvant context and modifications of neo/adjuvant treatments for pathological non-responders within clinical trials. Both of these have the intention of improving longer-term outcomes for patients who do not have a good pathological response to first-line neoadjuvant treatment. If successful, these developments are likely to reduce further any positive correlation between pathological response and longer-term outcomes.
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Affiliation(s)
- Helena Earl
- Department of Oncology, University of Cambridge, Cambridge, UK. .,NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre, Cambridge, UK. .,Cambridge Breast Research Unit, Cambridge, UK. .,Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
| | - Elena Provenzano
- NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre, Cambridge, UK. .,Cambridge Breast Research Unit, Cambridge, UK. .,Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
| | - Jean Abraham
- Department of Oncology, University of Cambridge, Cambridge, UK. .,NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre, Cambridge, UK. .,Cambridge Breast Research Unit, Cambridge, UK. .,Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
| | - Janet Dunn
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.
| | - Anne-Laure Vallier
- Cambridge Breast Research Unit, Cambridge, UK. .,Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
| | - Ioannis Gounaris
- Cambridge University Hospital NHS Foundation Trust, Cambridge, UK. .,Cancer Research UK Cambridge Institute, Cambridge, UK.
| | - Louise Hiller
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.
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van Roozendaal LM, de Wilt JHW, van Dalen T, van der Hage JA, Strobbe LJA, Boersma LJ, Linn SC, Lobbes MBI, Poortmans PMP, Tjan-Heijnen VCG, Van de Vijver KKBT, de Vries J, Westenberg AH, Kessels AGH, Smidt ML. The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07). BMC Cancer 2015; 15:610. [PMID: 26335105 PMCID: PMC4559064 DOI: 10.1186/s12885-015-1613-2] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Accepted: 08/19/2015] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .
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Affiliation(s)
- L M van Roozendaal
- Division of Surgical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands.
- GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
- Department of Surgical Oncology, Maastricht University Medical Centre, P.O. Box 5800 6202 AZ, Maastricht, The Netherlands.
| | - J H W de Wilt
- Division of Surgical Oncology, Radboud university medical centre, Nijmegen, The Netherlands.
| | - T van Dalen
- Division of Surgical Oncology, Diakonessenhuis Hospital, Utrecht, The Netherlands.
| | - J A van der Hage
- Division of Surgical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
| | - L J A Strobbe
- Division of Surgical Oncology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
| | - L J Boersma
- Department of Radiation Oncology, Maastricht University Medical Centre (MAASTRO clinic), Maastricht, The Netherlands.
- GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
| | - S C Linn
- Division of Medical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
| | - M B I Lobbes
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
- GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
| | - P M P Poortmans
- Department of Radiation Oncology, Radboud university medical centre, Nijmegen, The Netherlands.
| | - V C G Tjan-Heijnen
- Division of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands.
- GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
| | - K K B T Van de Vijver
- Department of Pathology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
| | - J de Vries
- Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands.
| | - A H Westenberg
- Radiation Oncology, Arnhem Institute for Radiation Oncology, Arnhem, The Netherlands.
| | - A G H Kessels
- Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.
| | - M L Smidt
- Division of Surgical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands.
- GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
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13
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van Nijnatten TJA, Schipper RJ, Lobbes MBI, Nelemans PJ, Beets-Tan RGH, Smidt ML. The diagnostic performance of sentinel lymph node biopsy in pathologically confirmed node positive breast cancer patients after neoadjuvant systemic therapy: A systematic review and meta-analysis. Eur J Surg Oncol 2015; 41:1278-87. [PMID: 26329781 DOI: 10.1016/j.ejso.2015.07.020] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 07/20/2015] [Accepted: 07/30/2015] [Indexed: 11/25/2022] Open
Abstract
PURPOSE To provide a systematic review and meta-analysis of studies investigating sentinel lymph node biopsy after neoadjuvant systemic therapy in pathologically confirmed node positive breast cancer patients. METHODS Pubmed and Embase databases were searched until June 19th, 2015. All abstracts were read and data extraction was performed by two independent readers. A random-effects model was used to pool the proportion for identification rate, false-negative rate (FNR) and axillary pCR with 95% confidence intervals. Subgroup analyses affirmed potential confounders for identification rate and FNR. RESULTS A total of 997 abstracts were identified and eventually eight studies were included. Pooled estimates were 92.3% (90.8-93.7%) for identification rate, 15.1% (12.7-17.6%) for FNR and 36.8% (34.2-39.5%) for axillary pCR. After subgroup analysis, FNR is significantly worse if one sentinel node was removed compared to two or more sentinel nodes (23.9% versus 10.4%, p = 0.026) and if studies contained clinically nodal stage 1-3, compared to studies with clinically nodal stage 1-2 patients (21.4 versus 13.1%, p = 0.049). Other factors, including single tracer mapping and the definition of axillary pCR, were not significantly different. CONCLUSION Based on current evidence it seems not justified to omit further axillary treatment in every clinically node positive breast cancer patients with a negative sentinel lymph node biopsy after neoadjuvant systemic therapy.
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Affiliation(s)
- T J A van Nijnatten
- Department of Radiology, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
| | - R J Schipper
- Department of Radiology, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - M B I Lobbes
- Department of Radiology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - P J Nelemans
- Department of Epidemiology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - R G H Beets-Tan
- Department of Radiology, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - M L Smidt
- Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
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14
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Caudle AS, Kuerer HM. Targeting and limiting surgery for patients with node-positive breast cancer. BMC Med 2015; 13:149. [PMID: 26109042 PMCID: PMC4481081 DOI: 10.1186/s12916-015-0385-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 06/03/2015] [Indexed: 12/22/2022] Open
Abstract
The presence of axillary nodal metastases has a significant impact on locoregional and systemic treatment decisions. Historically, all node-positive patients underwent complete axillary lymph node dissection; however, this paradigm has changed over the last 10 years. The use of sentinel lymph node dissection has expanded from its initial role as a surgical staging procedure in clinically node-negative patients. Clinically node-negative patients with small volume disease found on sentinel lymph node dissection now commonly avoid more extensive axillary surgery. There is interest in expanding this role to node-positive patients who receive neoadjuvant chemotherapy as a way to restage the axilla in hopes of sparing women who convert to node-negative status from the morbidity of complete nodal clearance. While sentinel lymph node dissection alone may not accomplish this goal, there are novel techniques, such as targeted axillary dissection, that may now allow for reliable nodal staging after chemotherapy.
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Affiliation(s)
- Abigail S Caudle
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit1484, Houston, TX, 77230-1402, USA.
| | - Henry M Kuerer
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit1484, Houston, TX, 77230-1402, USA.
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15
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Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients: Identification rate and influence on axillary treatment. Eur J Cancer 2015; 51:915-21. [DOI: 10.1016/j.ejca.2015.03.014] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Revised: 02/01/2015] [Accepted: 03/19/2015] [Indexed: 02/06/2023]
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16
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Mougalian SS, Soulos PR, Killelea BK, Lannin DR, Abu-Khalaf MM, DiGiovanna MP, Sanft TB, Pusztai L, Gross CP, Chagpar AB. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer 2015; 121:2544-52. [DOI: 10.1002/cncr.29348] [Citation(s) in RCA: 123] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 01/23/2015] [Accepted: 02/10/2015] [Indexed: 11/09/2022]
Affiliation(s)
- Sarah S. Mougalian
- Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Pamela R. Soulos
- Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Brigid K. Killelea
- Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Donald R. Lannin
- Department of Surgery; Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Maysa M. Abu-Khalaf
- Department of Medicine; Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Michael P. DiGiovanna
- Department of Medicine; Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Tara B. Sanft
- Department of Medicine; Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Lajos Pusztai
- Department of Medicine; Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Cary P. Gross
- Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
| | - Anees B. Chagpar
- Cancer Outcomes, Public Policy, and Effectiveness Research Center, Yale Comprehensive Cancer Center, Yale University School of Medicine; New Haven Connecticut
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17
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Kim JY, Kim MK, Lee JE, Jung Y, Bae SY, Lee SK, Kil WH, Kim SW, Kim KS, Nam SJ, Han S. Sentinel lymph node biopsy alone after neoadjuvant chemotherapy in patients with initial cytology-proven axillary node metastasis. J Breast Cancer 2015; 18:22-8. [PMID: 25834607 PMCID: PMC4381119 DOI: 10.4048/jbc.2015.18.1.22] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Accepted: 03/03/2015] [Indexed: 11/30/2022] Open
Abstract
Purpose Neoadjuvant chemotherapy (NAC) has been recently used to downstage breast cancer. However, in patients with initial axillary lymph node (ALN) metastasis, ALN dissection regardless of the NAC response remains the standard treatment. The purpose of this study was to identify the feasibility and accuracy of sentinel lymph node biopsy (SLNB) after NAC in patients with ALN metastasis at diagnosis. Methods From January 2007 to August 2013, data of patients who were diagnosed with invasive breast cancer and ALN metastasis and treated with NAC followed by definitive surgery in two centers were collected retrospectively. A total of 386 patients were enrolled and classified into five groups according to surgical procedure for the ALNs and pathologic results. Results At SLNB after NAC, sentinel lymph nodes (SLNs) that stained blue or were hot, including suspicious nodes, were identified; the SLN identification and false-negative rates was 96% and 10%, respectively. There was no difference in the overall survival among the groups. For patients who revealed a pathologic complete node response, there was a significant difference in the disease-free survival rate between the SLNB only and complete ALN dissection groups (p=0.031). However, the rate of axillary recurrence demonstrated no significant differences among the groups (p>0.050). Conclusion SLNB after NAC in breast cancer patients with initial ALN metastasis may help identify downstaging to negative nodal status and thereby reduce the surgical morbidity by avoiding standard ALN dissection.
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Affiliation(s)
- Ji Young Kim
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | | | - Jeong Eon Lee
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yongsik Jung
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Soo Youn Bae
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Se Kyung Lee
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Ho Kil
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seok Won Kim
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | - Seok Jin Nam
- Department of Surgery, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sehwan Han
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
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18
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Wang-Lopez Q, Chalabi N, Abrial C, Radosevic-Robin N, Durando X, Mouret-Reynier MA, Benmammar KE, Kullab S, Bahadoor M, Chollet P, Penault-Llorca F, Nabholtz JM. Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer? Crit Rev Oncol Hematol 2015; 95:88-104. [PMID: 25900915 DOI: 10.1016/j.critrevonc.2015.02.011] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2014] [Revised: 01/22/2015] [Accepted: 02/09/2015] [Indexed: 10/23/2022] Open
Abstract
Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the "in vivo" efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting. However, pCR remains a subject of controversy in terms of definition and its evaluation methods. In addition, its predictive value for patient outcome in various breast cancer biological subtypes has been under debate. In this review, we will present the existing definitions of pCR, the impact of its evaluation methods on its rate and the assessment of its predictive value for patient outcome in the molecular subtypes of breast cancer (luminal A and B, Triple Negative and HER2-positive).
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Affiliation(s)
- Qian Wang-Lopez
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; Inserm UMR 990, 63000 Clermont-Ferrand, France
| | - Nassera Chalabi
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; ERTICA EA 4677, University of Auvergne, 63000 Clermont-Ferrand, France; CIC 501, UMR 766, 63003 Clermont-Ferrand, France
| | - Catherine Abrial
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; ERTICA EA 4677, University of Auvergne, 63000 Clermont-Ferrand, France; CIC 501, UMR 766, 63003 Clermont-Ferrand, France
| | - Nina Radosevic-Robin
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; ERTICA EA 4677, University of Auvergne, 63000 Clermont-Ferrand, France
| | - Xavier Durando
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; CIC 501, UMR 766, 63003 Clermont-Ferrand, France; CREAT EA 7283, University of Auvergne, 63000 Clermont-Ferrand, France
| | - Marie-Ange Mouret-Reynier
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; ERTICA EA 4677, University of Auvergne, 63000 Clermont-Ferrand, France
| | | | - Sharif Kullab
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France
| | - Mohun Bahadoor
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France
| | - Philippe Chollet
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; Inserm UMR 990, 63000 Clermont-Ferrand, France
| | - Frédérique Penault-Llorca
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; ERTICA EA 4677, University of Auvergne, 63000 Clermont-Ferrand, France.
| | - Jean-Marc Nabholtz
- Jean Perrin Comprehensive Cancer Centre, 63011 Clermont-Ferrand, France; ERTICA EA 4677, University of Auvergne, 63000 Clermont-Ferrand, France
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19
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Cortazar P, Geyer CE. Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol 2015; 22:1441-6. [PMID: 25727556 DOI: 10.1245/s10434-015-4404-8] [Citation(s) in RCA: 176] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Indexed: 11/18/2022]
Abstract
BACKGROUND There has been recent interest in using pathological complete response (pCR) as a potential surrogate endpoint for long-term outcomes in the neoadjuvant treatment of high-risk, early-stage breast cancer. METHODS We review the clinical trials that have contributed to our understanding of the association between pCR and long-term outcomes, describe the various definitions of pCR, describe patient populations in which pCR may predict long-term benefit, and discuss the implications of pCR on drug development and accelerated approval for neoadjuvant treatment of breast cancer. RESULTS Varying definitions of pCR across clinical trials conducted in heterogeneous patient populations make understanding the association of pCR with long-term outcomes challenging. The US Food and Drug Administration established the Collaborative Trials in Neoadjuvant Breast Cancer group to evaluate the potential use of pCR as a regulatory endpoint. The group demonstrated that pCR defined as no residual invasive cancer in the breast and axillary nodes with presence or absence of in situ cancer (ypT0/is ypN0 or ypT0 ypN0) provided a better association with improved outcomes compared to eradication of invasive tumor from the breast alone (ypT0/is). CONCLUSION Even though pCR was not validated as a surrogate endpoint for long-term outcomes, the promising data regarding the strong association of pCR with substantially improved outcomes in individual patients with more aggressive subtypes of breast cancer supported the opening of an accelerated approval pathway for patients with high-risk, early-stage breast cancer.
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Affiliation(s)
- Patricia Cortazar
- Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA,
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20
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Kida K, Ishikawa T, Yamada A, Shimizu D, Tanabe M, Sasaki T, Ichikawa Y, Endo I. A prospective feasibility study of sentinel node biopsy by modified Indigocarmine blue dye methods after neoadjuvant chemotherapy for breast cancer. Eur J Surg Oncol 2015; 41:566-70. [PMID: 25650249 DOI: 10.1016/j.ejso.2014.10.066] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Revised: 10/08/2014] [Accepted: 10/17/2014] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Although sentinel lymph node biopsy (SLNB) is a standard staging method for assessing nodal status of breast cancer patients, SLNB after neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to validate the practicality and accuracy of SLNB by our modified Indigocarmine blue dye methods following NAC. METHODS One hundred consecutive cases with breast cancers treated by NAC were enrolled in this study. After NAC, all patients underwent SLNB performed by our modified Indigocarmine blue dye methods without radioisotope, followed by back-up axillary lymph node dissection (ALND). RESULTS Sentinel nodes (SNs) were identified in 94 cases (identification rate, 94%); the accuracy was 94.7% (89/94 cases); and the false negative rate (FNR) 13.5% (5/37 cases). For cases with vs. without clinically evident metastatic nodes before NAC, the identification rate was 92.4% (61/66 cases) vs. 97.1% (33/34 cases); the accuracy 91.8% (56/61 cases) vs. 97.0% (32/33 cases) and the FNR 16.1% (5/31 cases) vs. 0% (0/6 case), respectively. There were six patients without identified SNs, three of them had metastatic nodes. False negatives occurred in five cases; in four, fewer than two sentinel nodes had been removed. CONCLUSION Following NAC, the accuracy of SLNB by modified Indigocarmine blue dye methods is adequate compared with other tracers. In patients in whom no SNs have been identified, lymphatic metastasis is likely and therefore ALND is recommended. For patients with cN0 prior to NAC, SLNB by modified Indigocarmine blue dye methods is clinically feasible, though controversial for patients with positive nodes.
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Affiliation(s)
- K Kida
- Department of Gastroenterological Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
| | - T Ishikawa
- Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan
| | - A Yamada
- Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan
| | - D Shimizu
- Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan
| | - M Tanabe
- Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan
| | - T Sasaki
- Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan
| | - Y Ichikawa
- Department of Gastroenterological Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan
| | - I Endo
- Department of Gastroenterological Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan
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21
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Li JW, Mo M, Yu KD, Chen CM, Hu Z, Hou YF, Di GH, Wu J, Shen ZZ, Shao ZM, Liu GY. ER-poor and HER2-positive: a potential subtype of breast cancer to avoid axillary dissection in node positive patients after neoadjuvant chemo-trastuzumab therapy. PLoS One 2014; 9:e114646. [PMID: 25504233 PMCID: PMC4263615 DOI: 10.1371/journal.pone.0114646] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 11/12/2014] [Indexed: 02/06/2023] Open
Abstract
PURPOSE The study was to estimate the likelihood of axillary downstaging and to identify the factors predicting a pathologically node negative status after neoadjuvant chemotherapy (NAC) with or without trastuzumab in HER2-positive breast cancer. METHODS Patients with HER2-positive, stage IIa-IIIc breast cancer were enrolled. Axillary status was evaluated by palpation and fine needle aspiration (FNA) before NAC. All patients received 4-6 cycles of PCrb (paclitaxel 80 mg/m2 and carboplatin AUC = 2 d1, 8, and 15 of a 28-day cycle, or paclitaxel 175 mg/m2 and carboplatin AUC = 6 every-3-week) and were non-randomly administered trastuzumab (2 mg/kg weekly or 6 mg/kg every-3-week) or not. After NAC, each patient underwent standard axillary lymph node dissection and breast-conserving surgery or mastectomy. And some patients received sentinel lymph node biopsy (SLNB) before axillary dissection. RESULTS Between November-2007 and June-2013, 255 patients were enrolled. Of them, 157 were confirmed as axillary node positive by FNA (group-A) and 98 as axillary node negative either by FNA or impalpable (group-B). After axillary dissection, the overall pathologically node negative rates (pNNR) were 52.9% in group-A and 69.4% in group-B. The ER-poor/HER2-positive subtype acquired the highest pNNR (79.6% in group-A and 87.9% in group-B, respectively) and the lowest rate of residual with ≥4 nodes involvement (1.9% and 3%, respectively) after PCrb plus trastuzumab. In multivariate analysis, trastuzumab added and ER-poor status were independent factors in predicting a higher pNNR in HER2-positive breast cancer. Forty-six tested patients showed that the ER-poor/HER2-positive subtype acquired a considerable high pNNR and axillary status with SLNB was well macthed with the axillary dissection. CONCLUSIONS ER-poor/HER2-positive subtype of breast cancer is a potential candidate for undergoing sentinel lymph node biopsy instead of regional node dissection for accurate axillary evaluation after effective downstaging by neoadjuvant chemo-trastuzumab therapy.
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Affiliation(s)
- Jian-wei Li
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Miao Mo
- Clinical Statistics Center, Fudan University Shanghai Cancer Center, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Ke-da Yu
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Can-ming Chen
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Zhen Hu
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Yi-feng Hou
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Gen-hong Di
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Jiong Wu
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Zhen-zhou Shen
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Zhi-ming Shao
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Guang-yu Liu
- Department of Breast Surgery, Shanghai Cancer Center/Cancer Institute, Fudan University, Shanghai, P. R. China and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
- * E-mail:
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Schipper RJ, Moossdorff M, Nelemans PJ, Nieuwenhuijzen GA, de Vries B, Strobbe LJ, Roumen RM, van den Berkmortel F, Tjan-Heijnen VC, Beets-Tan RG, Lobbes MB, Smidt ML. A Model to Predict Pathologic Complete Response of Axillary Lymph Nodes to Neoadjuvant Chemo(Immuno)Therapy in Patients With Clinically Node-Positive Breast Cancer. Clin Breast Cancer 2014; 14:315-22. [DOI: 10.1016/j.clbc.2013.12.015] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Revised: 12/31/2013] [Accepted: 12/31/2013] [Indexed: 01/29/2023]
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23
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Choy N, Lipson J, Porter C, Ozawa M, Kieryn A, Pal S, Kao J, Trinh L, Wheeler A, Ikeda D, Jensen K, Allison K, Wapnir I. Initial Results with Preoperative Tattooing of Biopsied Axillary Lymph Nodes and Correlation to Sentinel Lymph Nodes in Breast Cancer Patients. Ann Surg Oncol 2014; 22:377-82. [DOI: 10.1245/s10434-014-4034-6] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Indexed: 11/18/2022]
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25
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Early and delayed prediction of axillary lymph node neoadjuvant response by 18F-FDG PET/CT in patients with locally advanced breast cancer. Eur J Nucl Med Mol Imaging 2014; 41:1309-18. [DOI: 10.1007/s00259-013-2657-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Accepted: 11/28/2013] [Indexed: 11/26/2022]
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Predictors of durable no evidence of disease status in de novo metastatic inflammatory breast cancer patients treated with neoadjuvant chemotherapy and post-mastectomy radiation. SPRINGERPLUS 2014; 3:166. [PMID: 24711988 PMCID: PMC3977020 DOI: 10.1186/2193-1801-3-166] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Accepted: 03/19/2014] [Indexed: 11/10/2022]
Abstract
INTRODUCTION Definitive locoregional therapy including surgery and post-mastectomy radiation therapy (PMRT) has been offered to select IBC patients with de novo metastatic disease. Herein we examined predictive factors for progression-free survival after comprehensive PMRT radiation +/- locoregional treatment of metastatic sites. METHODS Charts of T4d, any N, M1 (de novo) patients who completed PMRT to ≥ 50 Gy from 2006-2011 were reviewed. Patients who received doses <50Gy to the primary site, received radiation at another facility or were treated pre-operatively were excluded. The remaining 36 patients formed the study cohort. Progression-free survival post-PMRT (PFSx) was assessed from the last day of radiation. Median dose to primary fields was 51 Gy. Boost doses ranged from 6-16 Gy. RESULTS Median age at diagnosis was 54 (range 33-70). Median follow up from primary irradiation completion was 31 months. Sixteen patients were Stage IV NED at last follow-up (IR 37-60 mo). Fifteen patients died of disease. Five patients experienced an in-field recurrence, three of which resulted from local recurrence at the medial edge of the field. Actuarial 5 year locoregional control (LRC) was 86%. Median PFSx was 20 months. All sites of gross disease were treated with radiation in 21/36 patients. Location of metastatic disease had no correlation with PFSx. Estrogen receptor (ER)- patients had shorter 5-yr actuarial PFSx (28% vs. 66%, P = 0.03) and 5 year actuarial OSx (37% vs 71%, P = 0.02). Nine patients (25%) developed a pathological complete response (pCR) after chemotherapy and with a median follow-up of 59 months, 7 remained without evidence of disease. CONCLUSIONS Despite the poor prognosis associated with metastatic IBC, our data suggest that select patients may be appropriate candidates for locoregional therapy. Patients who achieve a pCR or those with ER + disease have a favorable PFSx. It remains unclear whether all gross disease needs to be addressed with locoregional therapy to provide benefit.
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Leone JP, Leone J, Vallejo CT, Pérez JE, Romero AO, Machiavelli MR, Romero Acuña L, Domínguez ME, Langui M, Fasce HM, Leone BA, Ortiz E, Iturbe J, Zwenger AO. Sixteen years follow-up results of a randomized phase II trial of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast cancer: GOCS experience. Breast Cancer Res Treat 2013; 143:313-23. [PMID: 24327333 DOI: 10.1007/s10549-013-2806-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 12/03/2013] [Indexed: 11/26/2022]
Abstract
Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival.
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Affiliation(s)
- José Pablo Leone
- Division of Hematology and Oncology, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion Room 463, 5150 Centre Ave, Pittsburgh, PA, 15232, USA,
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Assessing the impact of neoadjuvant chemotherapy on the management of the breast and axilla in breast cancer. Clin Breast Cancer 2013; 14:20-5. [PMID: 24157259 DOI: 10.1016/j.clbc.2013.08.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Revised: 08/28/2013] [Accepted: 08/29/2013] [Indexed: 11/23/2022]
Abstract
BACKGROUND Nodal status is a sensitive prognostic indicator in breast cancer. Axillary metastases may be an indication for neoadjuvant systemic therapy. The aims of this study were to compare pathologic response rates to neoadjuvant chemotherapy (NAC) in the breast and axilla across different molecular subtypes of breast cancer and to compare the predictive value of axillary assessment before and after chemotherapy in determining final nodal status in this cohort of patients. PATIENTS AND METHODS The cohort comprised patients undergoing NAC from 2003 to November 2012. Data regarding patient and tumor characteristics, management, and outcomes were obtained from a prospectively maintained database and analyzed using PASW Statistics, version 18 (SPSS Inc, Chicago, IL). RESULTS Two hundred two cancers were identified in 196 patients. One hundred thirty-one (65%) diagnostic axillary procedures were performed, 105 (80%) before NAC, of which 93 (89%) were positive. In 28 (30%), downstaging was noted before NAC. Human epidermal growth factor receptor 2 (HER2) subtypes had the highest rate of complete pathologic response (n = 11 [61%]) and negative axillary clearance (AXCn) (n = 11 [69%]). Of 177 AXCns, 68 (38%) were negative before NAC. CONCLUSION AXCn in patients undergoing NAC remains controversial. HER2 subtypes are less likely to have axillary involvement after NAC and may demand different management.
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29
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Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, von Minckwitz G, Nekljudova V, Schmatloch S, Schrenk P, Staebler A, Untch M. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol 2013; 14:609-18. [PMID: 23683750 DOI: 10.1016/s1470-2045(13)70166-9] [Citation(s) in RCA: 979] [Impact Index Per Article: 81.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The optimum timing of sentinel-lymph-node biopsy for breast cancer patients treated with neoadjuvant chemotherapy is uncertain. The SENTINA (SENTinel NeoAdjuvant) study was designed to evaluate a specific algorithm for timing of a standardised sentinel-lymph-node biopsy procedure in patients who undergo neoadjuvant chemotherapy. METHODS SENTINA is a four-arm, prospective, multicentre cohort study undertaken at 103 institutions in Germany and Austria. Women with breast cancer who were scheduled for neoadjuvant chemotherapy were enrolled into the study. Patients with clinically node-negative disease (cN0) underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arm A). If the sentinel node was positive (pN1), a second sentinel-lymph-node biopsy procedure was done after neoadjuvant chemotherapy (arm B). Women with clinically node-positive disease (cN+) received neoadjuvant chemotherapy. Those who converted to clinically node-negative disease after chemotherapy (ycN0; arm C) were treated with sentinel-lymph-node biopsy and axillary dissection. Only patients whose clinical nodal status remained positive (ycN1) underwent axillary dissection without sentinel-lymph-node biopsy (arm D). The primary endpoint was accuracy (false-negative rate) of sentinel-lymph-node biopsy after neoadjuvant chemotherapy for patients who converted from cN1 to ycN0 disease during neoadjuvant chemotherapy (arm C). Secondary endpoints included comparison of the detection rate of sentinel-lymph-node biopsy before and after neoadjuvant chemotherapy, and also the false-negative rate and detection rate of sentinel-lymph-node biopsy after removal of the sentinel lymph node. Analyses were done according to treatment received (per protocol). FINDINGS Of 1737 patients who received treatment, 1022 women underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arms A and B), with a detection rate of 99.1% (95% CI 98.3-99.6; 1013 of 1022). In patients who converted after neoadjuvant chemotherapy from cN+ to ycN0 (arm C), the detection rate was 80.1% (95% CI 76.6-83.2; 474 of 592) and false-negative rate was 14.2% (95% CI 9.9-19.4; 32 of 226). The false-negative rate was 24.3% (17 of 70) for women who had one node removed and 18.5% (10 of 54) for those who had two sentinel nodes removed (arm C). In patients who had a second sentinel-lymph-node biopsy procedure after neoadjuvant chemotherapy (arm B), the detection rate was 60.8% (95% CI 55.6-65.9; 219 of 360) and the false-negative rate was 51.6% (95% CI 38.7-64.2; 33 of 64). INTERPRETATION Sentinel-lymph-node biopsy is a reliable diagnostic method before neoadjuvant chemotherapy. After systemic treatment or early sentinel-lymph-node biopsy, the procedure has a lower detection rate and a higher false-negative rate compared with sentinel-lymph-node biopsy done before neoadjuvant chemotherapy. These limitations should be considered if biopsy is planned after neoadjuvant chemotherapy. FUNDING Brustkrebs Deutschland, German Society for Senology, German Breast Group.
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Affiliation(s)
- Thorsten Kuehn
- Interdisciplinary Breast Centre, Department of Gynaecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany.
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Zucchini G, Quercia S, Zamagni C, Santini D, Taffurelli M, Fanti S, Martoni A. Potential utility of early metabolic response by 18F-2-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography in a selected group of breast cancer patients receiving preoperative chemotherapy. Eur J Cancer 2013; 49:1539-45. [DOI: 10.1016/j.ejca.2012.12.024] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2012] [Revised: 12/03/2012] [Accepted: 12/22/2012] [Indexed: 11/29/2022]
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Koolen BB, Valdés Olmos RA, Wesseling J, Vogel WV, Vincent AD, Gilhuijs KGA, Rodenhuis S, Rutgers EJT, Vrancken Peeters MJTFD. Early Assessment of Axillary Response with 18F-FDG PET/CT during Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: Implications for Surgical Management of the Axilla. Ann Surg Oncol 2013; 20:2227-35. [DOI: 10.1245/s10434-013-2902-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Indexed: 12/14/2022]
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Sahoo S, Lester SC. Pathology Considerations in Patients Treated with Neoadjuvant Chemotherapy. Surg Pathol Clin 2012; 5:749-74. [PMID: 26838287 DOI: 10.1016/j.path.2012.06.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Neoadjuvant therapy (NAT) originally reserved for the treatment of inflammatory and locally advanced breast cancers is currently offered to women with earlier-stage and operable breast carcinoma. NAT allows more women to be eligible for breast conservation surgery and provides an opportunity to assess the response of carcinomas to therapy. This review focuses on the predictors of therapeutic response in pretreatment tumor, evaluation of post-treatment breast and lymph node specimens and classification systems to evaluate degree of response to NAT.
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Affiliation(s)
- Sunati Sahoo
- Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
| | - Susan C Lester
- Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
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Koolen BB, Valdés Olmos RA, Elkhuizen PHM, Vogel WV, Vrancken Peeters MJTFD, Rodenhuis S, Rutgers EJT. Locoregional lymph node involvement on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy. Breast Cancer Res Treat 2012; 135:231-40. [PMID: 22872522 DOI: 10.1007/s10549-012-2179-1] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Accepted: 07/17/2012] [Indexed: 12/12/2022]
Abstract
The optimal method for locoregional staging in patients treated with neoadjuvant chemotherapy (NAC), usually ultrasound (US) and pre- or post-chemotherapy sentinel lymph node biopsy (SLNB), remains subject of debate. The aim of this study was to assess the value of 18F-FDG PET/CT for detecting locoregional lymph node metastases in primary breast cancer patients scheduled for NAC. 311 breast cancer patients, scheduled for NAC, underwent PET/CT of the thorax in prone position with hanging breasts. A panel of four experienced reviewers examined PET/CT images, blinded for other diagnostic procedures. FDG uptake in locoregional nodes was determined qualitatively using a 4-point scale (0 = negative, 1 = questionable, 2 = moderately intense, and 3 = very intense). Results were compared with pathology obtained by US-guided fine needle aspiration or SLNB prior to NAC. All FDG-avid extra-axillary nodes were considered metastatic, based on the previously reported high positive predictive value of the technique. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-avid nodes for the detection of axillary metastases (score 2 or 3) were 82, 92, 98, 53, and 84 %, respectively. Of 28 patients with questionable axillary FDG uptake (score 1), 23 (82 %) were node-positive. Occult lymph node metastases in the internal mammary chain and periclavicular area were detected in 26 (8 %) and 32 (10 %) patients, respectively, resulting in changed regional radiotherapy planning in 50 (16 %) patients. In breast cancer patients scheduled for NAC, PET/CT renders pre-chemotherapy SLNB unnecessary in case of an FDG-avid axillary node, enables axillary response monitoring during or after NAC, and leads to changes in radiotherapy for a substantial number of patients because of detection of occult N3-disease. Based on these results, we recommend a PET/CT as a standard staging procedure in breast cancer patients scheduled for NAC.
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Affiliation(s)
- Bas B Koolen
- Department of Nuclear Medicine, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
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Is optimal timing of sentinel lymph node biopsy before neoadjuvant chemotherapy in patients with breast cancer? A literature review. Surg Oncol 2012; 21:252-6. [PMID: 22819780 DOI: 10.1016/j.suronc.2012.06.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2012] [Revised: 06/17/2012] [Accepted: 06/25/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Twenty five percent of women with breast cancer who undergo preoperative chemotherapy do not have axillary metastases. These patients need to withstand sentinel lymph node biopsy (SLNB). The optimal timing of SLNB in patients with neoadjuvant chemotherapy has not yet been defined. METHODS We systematically reviewed the literature for studies concerning the efficacy of sentinel lymph node biopsy before neoadjeuvant chemotherapy. A literature search was performed for the years 1993 through 2011 using the databases MEDLINE and EMBASE. Data that assessed the reliability of sentinel lymph node biopsy before chemotherapy were collected. RESULTS We identified 10 high-quality studies from 387 papers, which are analyzed further in this review. The identification rates reported ranged from 97% to 100%. The sensitivities of sentinel lymph node biopsy were 100%, and the false negative rates were 0%. Use an isotope combined with blue dye was associated with a higher probability of identification than that of using an isotope or blue dye alone (99.5% vs 98.5%). Only two studies compared data based on different timing for the sentinel lymph node biopsy. They achieved a lower false negative rate (0% vs 15.8%) and higher success rate (100% vs 81%) in patients with sentinel lymph node biopsy prior to neoadjuvant chemotherapy. CONCLUSION Sentinel lymph node biopsy prior to chemotherapy potentially gives a more accurate evaluation of axillary status, because it is unaffected by any previous therapeutic intervention.
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Tan SH, Lee SC. An update on chemotherapy and tumor gene expression profiles in breast cancer. Expert Opin Drug Metab Toxicol 2012; 8:1083-113. [DOI: 10.1517/17425255.2012.694867] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Fumagalli D, Bedard PL, Nahleh Z, Michiels S, Sotiriou C, Loi S, Sparano JA, Ellis M, Hylton N, Zujewski JA, Hudis C, Esserman L, Piccart M. A common language in neoadjuvant breast cancer clinical trials: proposals for standard definitions and endpoints. Lancet Oncol 2012; 13:e240-8. [PMID: 22652232 DOI: 10.1016/s1470-2045(11)70378-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Guarneri V, Barbieri E, Conte P. Biomarkers predicting clinical benefit: fact or fiction? J Natl Cancer Inst Monogr 2012; 2011:63-6. [PMID: 22043043 DOI: 10.1093/jncimonographs/lgr021] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Preoperative therapy is increasingly used in operable disease to improve the chance for breast-conservative surgery. Moreover, this strategy allows for a better definition of patient prognosis. Independently from stage at diagnosis and breast cancer subtype, the achievement of a pathological complete response (pCR) is a surrogate marker for long-term outcome. The likelihood of pCR depends on tumor biology, being poorly differentiated tumors with ductal histology, absence of hormone receptors, and high proliferation rate those with a higher chance of achieving a CR. However, pCR is a late efficacy parameter that can be evaluated at the end of the preoperative treatment; moreover, a pCR is achieved in a minority of patients and is not an appropriate efficacy measure for neoadjuvant endocrine therapy. The predictive role of tumor biomarkers such as p53, microtubule-associated tau protein, and poly (ADP-ribose) polymerase will be reviewed along with potential markers of early treatment effect.
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Affiliation(s)
- Valentina Guarneri
- Department of Oncology, Hematology and Respiratory Diseases, University Hospital, University of Modena and Reggio Emilia, Modena 41100, Italy
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Zer A, Rizel S, Braunstein R, Yerushalmi R, Hendler D, Neimann V, Cioreuru N, Sulkes A, Stemmer SM. Tailoring neoadjuvant chemotherapy for locally advanced breast cancer: a historical prospective study. Chemotherapy 2012; 58:95-101. [PMID: 22377846 DOI: 10.1159/000336257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2011] [Accepted: 01/06/2012] [Indexed: 11/19/2022]
Abstract
BACKGROUND Despite the growing number of clinical trials assessing preoperative systemic chemotherapy (PST) for locally advanced breast cancer, the optimal regimen has still to be defined. PURPOSE This was to evaluate the toxicity, operability rate, pathological response rate and disease-free and overall survival associated with a PST regimen consisting of the sequential administration of single agents according to the individual tumor response. METHODS Medical files were reviewed of 102 consecutive patients with breast cancer treated in 2000-2007 with a neoadjuvant sequential regimen of doxorubicin followed by taxane. The number of cycles and the addition of taxane were based on tumor response. RESULTS Seventy percent of the patients had inoperable disease at diagnosis and 29% were given preoperative therapy for breast conservation. All patients underwent surgery, 65% achieved breast conservation. An overall pathological complete response (breast and nodes) was achieved in 14% of the patients, and a complete nodal pathologic response in 34%. At a median follow-up of 54 months, the overall survival rate was 82% and the disease-free survival rate was 70%. There was no treatment-related mortality. Febrile neutropenia occurred in 19% of the patients. CONCLUSIONS A neoadjuvant regimen of doxorubicin with or without a sequential taxane, in which the number of cycles and the sequential administration of taxane are determined according to clinical response, appears to be safe and effective for patients with locally advanced breast cancer and yields a high rate of breast conservation. Tailored PST can spare patients receiving unnecessary chemotherapy.
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Affiliation(s)
- Alona Zer
- Institute of Oncology, Davidoff Center, Rabin Medical Center, Petach Tikva, Israel. alonaz @ clalit.org.il
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D'Angelo-Donovan DD, Dickson-Witmer D, Petrelli NJ. Sentinel lymph node biopsy in breast cancer: a history and current clinical recommendations. Surg Oncol 2012; 21:196-200. [PMID: 22237143 DOI: 10.1016/j.suronc.2011.12.005] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2011] [Revised: 11/29/2011] [Accepted: 12/04/2011] [Indexed: 12/14/2022]
Abstract
The advent of sentinel lymph node biopsy changed the way the surgical community treated breast cancer. It also reduced the post operative morbidity for millions of patients. Now that sentinel lymph node biopsy has become the mainstay of treatment, new clinical questions have arisen and continued research is being done to answer these questions. This report details a brief history of sentinel lymph node biopsy and how it was applied in the treatment a breast cancer. This report also includes a review of the current literature regarding unique clinical scenarios involving sentinel lymph node biopsy in breast cancer including the ACOSOG Z011 trial.
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Affiliation(s)
- Desiree D D'Angelo-Donovan
- Department of Surgery, Christiana Care Health System, MAP II, Suite 2121, 4745 Ogletown-Stanton Road, Newark, DE 19713, USA.
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Comparison of two nomograms to predict pathologic complete responses to neoadjuvant chemotherapy for breast cancer: evidence that HER2-positive tumors need specific predictors. Breast Cancer Res Treat 2011; 132:601-7. [DOI: 10.1007/s10549-011-1897-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 11/22/2011] [Indexed: 10/14/2022]
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Pathological Assessment Following Pre-operative Systemic Therapy. CURRENT BREAST CANCER REPORTS 2011. [DOI: 10.1007/s12609-011-0055-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Chen S, Chen CM, Yu KD, Yang WT, Shao ZM. A prognostic model to predict outcome of patients failing to achieve pathological complete response after anthracycline-containing neoadjuvant chemotherapy for breast cancer. J Surg Oncol 2011; 105:577-85. [DOI: 10.1002/jso.22140] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2011] [Accepted: 10/19/2011] [Indexed: 12/16/2022]
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Are we ready for an early evaluation of the response of axillary lymph node metastases to neoadjuvant therapy? Eur J Nucl Med Mol Imaging 2011; 38:2096-7; author reply 2098-9. [DOI: 10.1007/s00259-011-1921-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Accepted: 08/17/2011] [Indexed: 11/27/2022]
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Wang Z, Wu LC, Chen JQ. Sentinel lymph node biopsy compared with axillary lymph node dissection in early breast cancer: a meta-analysis. Breast Cancer Res Treat 2011; 129:675-689. [PMID: 21743996 DOI: 10.1007/s10549-011-1665-1] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2011] [Accepted: 06/28/2011] [Indexed: 11/30/2022]
Abstract
Sentinel lymph node biopsy (SLNB) has been recommended as the standard performance for negative sentinel lymph node (SLN) patients without axillary lymph node dissection (ALND) in the surgical management of early breast cancer; however, the efficiency of SLNB for patients with positive SLNs is still unclear. We performed this meta-analysis to compare the effectiveness and safety of SLNB with ALND. Randomized controlled trials (RCTs) comparing SLNB with ALND in early breast cancer were identified in Pubmed, Embase, and The Cochrane Library. Overall survival (OS), disease-free survival (DFS), regional lymph node recurrence, postoperative morbidity, and quality of life (QOL) between the two groups were assessed by using the methods provided by the Cochrane Handbook for Systematic Reviews of Interventions. Eight well-designed RCTs (total 8,560 patients; 4,301 for SLNB and 4,259 for ALND) were included. Meta-analysis showed that there was no statistical difference in OS (HR = 1.07, 95% CI: 0.90-1.27), DFS (HR = 1.00, 95% CI: 0.88-1.14), and regional lymph node recurrence (OR = 1.65, 95% CI: 0.77-3.56) between SLNB and ALND group, whether for SLN (+) subgroup or for SLN (-) subgroup. However, SLNB results in a significant reduction of postoperative morbidity and improved QOL. In conclusion, SLNB can be recommended as preferred care for SLN-negative patients and selected patients with SLN-micrometastasis. Despite this, ALND remains the standard management in breast cancer patients with SLN-macrometastasis.
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Affiliation(s)
- Zhen Wang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
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Is 18F-FDG PET accurate to predict neoadjuvant therapy response in breast cancer? A meta-analysis. Breast Cancer Res Treat 2011; 131:357-69. [PMID: 21960111 DOI: 10.1007/s10549-011-1780-z] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Accepted: 09/13/2011] [Indexed: 12/19/2022]
Abstract
Clinical evidence regarding the value of (18)F-FDG PET for therapy responses assessment in breast cancer is increasing. The objective of this study is to evaluate the accuracy of (18)F-FDG PET in predicting responses to neoadjuvant therapies with meta-analysis and explore its optimal regimen for clinical use. Articles in English language relating to the accuracy of (18)F-FDG PET for this utility were retrieved. Methodological quality was assessed by QUADAS tool. Pooled estimation and subgroup analysis data were obtained by statistical analysis. Nineteen studies met the inclusion criteria and involved 920 pathologically confirmed patients in total (mean age 49.8 years, all female). Methodological quality was relatively high. To predict histopathological response in primary breast lesions by PET, the pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio were 84% (95% CI, 78-88%), 66% (95% CI, 62-70%), 50% (95% CI, 44-55%), 91% (95% CI, 87-94%), and 11.90 (95% CI, 6.33-22.36), respectively. In regional lymph nodes, sensitivity and NPV of PET were 92% (95% CI, 83-97%) and 88% (95% CI, 76-95%), respectively. Subgroup analysis showed that performing a post-therapy (18)F-FDG PET early (after the 1st or 2nd cycle of chemotherapy) was significantly better than later (accuracy 76% vs. 65%, P = 0.001). Furthermore, the best correlation with pathology was yielded by employing a reduction rate (RR) cutoff value of standardized uptake value between 55 and 65%. (18)F-FDG PET is useful to predict neoadjuvant therapy response in breast cancer. However, the relatively low specificity and PPV still call for caution. It is suggested to perform PET in an earlier course of therapy and use RR cutoff value between 55 and 65%, which might potentially identify non-responders early. However, further prospective studies are warranted to assess this regimen and adequately position PET in treatment management.
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Ono M, Tsuda H, Shimizu C, Yamamoto S, Shibata T, Yamamoto H, Hirata T, Yonemori K, Ando M, Tamura K, Katsumata N, Kinoshita T, Takiguchi Y, Tanzawa H, Fujiwara Y. Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer. Breast Cancer Res Treat 2011; 132:793-805. [PMID: 21562709 DOI: 10.1007/s10549-011-1554-7] [Citation(s) in RCA: 234] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Accepted: 04/25/2011] [Indexed: 12/18/2022]
Abstract
The purpose of the present study was to identify histological surrogate predictive markers of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC). Among 474 patients who received NAC and subsequent surgical therapy for stage II-III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens obtained before NAC were available. As controls, CNB specimens from 42 tumors of the hormone receptor-negative and HER2-positive (HR-/HER2+) subtype and 46 tumors of the hormone receptor-positive and HER2-negative (HR+/HER2-) subtype were also included. Histopathological examination including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis, and immunohistochemical studies for basal markers were performed, and the correlation of these data with pathological therapeutic effect was analyzed. The rates of pCR at the primary site were higher for TNBC (32%) and the HR-/HER2+ subtype (21%) than for the HR+/HER2- subtype (7%) (P = 0.006). Expression of basal markers and p53, histological grade 3, high TIL scores, and apoptosis were more frequent in TNBC and the HR-/HER2+ subtype than in the HR+/HER2- subtype (P = 0.002 for TIL and P < 0.001 for others). In TNBC, the pCR rates of tumors showing a high TIL score and of those showing a high apoptosis score were 37 and 47%, respectively, and significantly higher or tended to be higher than those of the tumors showing a low TIL score and of the tumors showing a low apoptosis score (16 and 27%, respectively, P = 0.05 and 0.10). In a total of 180 breast cancers, the pCR rates of the tumors showing a high TIL score (34%) and of those showing a high apoptosis score (35%) were significantly higher than those of the tumors showing a low TIL score (10%) and those of the tumors showing a low apoptosis score (19%) (P = 0.0001 and 0.04, respectively). Histological grade and basal marker expression were not correlated with pCR. Although the whole analysis was exploratory, the degree of TIL correlated with immune response appear to play a substantial role in the response to NAC in TNBC.
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MESH Headings
- Adult
- Aged
- Breast Neoplasms/drug therapy
- Breast Neoplasms/metabolism
- Breast Neoplasms/mortality
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/drug therapy
- Carcinoma, Ductal, Breast/metabolism
- Carcinoma, Ductal, Breast/mortality
- Carcinoma, Ductal, Breast/pathology
- Disease-Free Survival
- Female
- Humans
- Kaplan-Meier Estimate
- Logistic Models
- Lymphocytes/pathology
- Lymphocytes/physiology
- Middle Aged
- Neoadjuvant Therapy
- Neoplasm Invasiveness
- Neoplasm Staging
- Receptor, ErbB-2/metabolism
- Receptors, Estrogen/metabolism
- Receptors, Progesterone/metabolism
- Treatment Outcome
- Young Adult
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Affiliation(s)
- Makiko Ono
- Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
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Shimazu K, Noguchi S. Sentinel lymph node biopsy before versus after neoadjuvant chemotherapy for breast cancer. Surg Today 2011; 41:311-6. [DOI: 10.1007/s00595-010-4404-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2010] [Accepted: 06/17/2010] [Indexed: 11/30/2022]
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Rousseau C, Devillers A, Campone M, Campion L, Ferrer L, Sagan C, Ricaud M, Bridji B, Kraeber-Bodéré F. FDG PET evaluation of early axillary lymph node response to neoadjuvant chemotherapy in stage II and III breast cancer patients. Eur J Nucl Med Mol Imaging 2011; 38:1029-36. [DOI: 10.1007/s00259-011-1735-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2010] [Accepted: 12/16/2010] [Indexed: 01/09/2023]
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Chintamani, Tandon M, Mishra A, Agarwal U, Saxena S. Sentinel lymph node biopsy using dye alone method is reliable and accurate even after neo-adjuvant chemotherapy in locally advanced breast cancer--a prospective study. World J Surg Oncol 2011; 9:19. [PMID: 21396137 PMCID: PMC3041688 DOI: 10.1186/1477-7819-9-19] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Accepted: 02/08/2011] [Indexed: 11/23/2022] Open
Abstract
Background Sentinel lymph node biopsy (SLNB) is now considered a standard of care in early breast cancers with N0 axillae; however, its role in locally advanced breast cancer (LABC) after neo-adjuvant chemotherapy (NACT) is still being debated. The present study assessed the feasibility, efficacy and accuracy of sentinel lymph node biopsy (SLNB) using "dye alone" (methylene blue) method in patients with LABC following NACT. Materials and methods Thirty, biopsy proven cases of LABC that had received three cycles of neo-adjuvant chemotherapy (cyclophosphamide, adriamycin, 5-fluorouracil) were subjected to SLNB (using methylene blue dye) followed by complete axillary lymph node dissection (levels I-III). The sentinel node(s) was/were and the axilla were individually assessed histologically. The SLN accuracy parameters were calculated employing standard definitions. The SLN identification rate in the present study was 100%. The sensitivity of SLNB was 86.6% while the accuracy was 93.3%, which were comparable with other studies done using dual lymphatic mapping method. The SLN was found at level I in all cases and no untoward reaction to methylene blue dye was observed. Conclusions This study confirms that SLNB using methylene blue dye as a sole mapping agent is reasonably safe and almost as accurate as dual agent mapping method. It is likely that in the near future, SLNB may become the standard of care and provide a less morbid alternative to routine axillary lymph node dissection even in patients with LABC that have received NACT.
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Affiliation(s)
- Chintamani
- Department of Surgery, Vardhman Mahavir Medical College, Safdarjang Hospital, New Delhi, 110023, India.
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