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1
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Shin DS, Ryu JM, Lee SK, Yu J, Lee JE, Kim SW, Nam SJ, Chae BJ. Nonsentinel lymph node metastases in cases of micrometastasis detected by sentinel lymph node biopsy after neoadjuvant chemotherapy. Cancer 2025; 131:e35567. [PMID: 39305113 DOI: 10.1002/cncr.35567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 01/03/2025]
Abstract
BACKGROUND There is a clinical need to omit axillary lymph node dissection (ALND) when residual disease in sentinel lymph nodes (SLNs) is low after neoadjuvant chemotherapy (NAC). This study aimed to clarify the relationship between micrometastasis in SLNs after NAC and additional non-SLN metastases by analyzing SLN biopsy results followed by ALND. METHODS This retrospective study reviewed clinical records of patients who underwent breast cancer surgery between January 2010 and June 2022 after NAC at Samsung Medical Center. Of 3944 patients, 806 underwent SLN biopsy followed by ALND. Intraoperative frozen SLN biopsy results were examined, including the number and size of metastases in SLNs, and further investigated the number of additional non-SLN metastases. RESULTS Among the 806 patients, 95 (11.8%) had micrometastasis on SLNs in frozen sections, of which 89 (93.7%) had clinically node-positive (cN1-3) breast cancer before NAC. Twenty-three patients (24.2%) exhibited positive additional non-SLNs after ALND. The presence of lymphovascular invasion (vs. absence; odds ratio [OR] = 4.02, p = .0151) and having two or more SLNs with micrometastasis (vs. a positive SLN; OR = 3.65, p = .0301) were significantly associated with additional non-SLN metastases. Tumor subtypes and breast pathological complete response after NAC showed no correlation with the additional non-SLN metastases. CONCLUSION The study identified a 24.2% possibility of additional non-SLN metastasis if micrometastases was detected in the SLN after NAC. This rate is significant, indicating that ALND cannot be omitted if low volume residual disease, such as micrometastasis, is identified in the SLN after NAC.
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Affiliation(s)
- Dong Seung Shin
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
| | - Jai Min Ryu
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
| | - Se Kyung Lee
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
| | - Jonghan Yu
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
| | - Jeong Eon Lee
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
| | - Seok Won Kim
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
| | - Seok Jin Nam
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
| | - Byung Joo Chae
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University of Medicine, Seoul, South Korea
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Houvenaeghel G, Heinemann M, Classe JM, Bouteille C, Gimbergues P, Azuar AS, Martino M, Tallet A, Cohen M, de Nonneville A. Omission of Completion Axillary Lymph Node Dissection for Patients with Breast Cancer Treated by Upfront Mastectomy and Sentinel Node Isolated Tumor Cells or Micrometastases. Cancers (Basel) 2024; 16:2666. [PMID: 39123393 PMCID: PMC11312260 DOI: 10.3390/cancers16152666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 08/12/2024] Open
Abstract
Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is debated due to potential under-treatment, with non-sentinel node (NSN) involvement detected in 7% to 18% of patients. This study evaluated the survival impact of cALND omission in a cohort of breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 early BC patients (391 pN1mi, 163 ITC), the NSN involvement rate was 13.2% (49/371). With a median follow-up of 66.46 months, multivariate analysis revealed significant associations between cALND omission and overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly affected by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative BC, DFS, OS, recurrence-free survival (RFS), and MFS were significantly associated with cALND omission (DFS HR: 2.358, p = 0.043; OS HR: 3.317; RFS HR: 2.538; MFS HR: 2.756). For 161 patients aged ≤50 years with ER-positive/Her2-negative cancer, OS and breast cancer-specific survival (BCSS) were notably impacted by cALND omission (OS HR: 103.47, p = 0.004; BCSS HR: 50.874, p = 0.035). These findings suggest a potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Further randomized trials are needed.
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Affiliation(s)
- Gilles Houvenaeghel
- Aix-Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, Department of Surgical Oncology, CRCM, 13009 Marseille, France
| | | | - Jean-Marc Classe
- Institut René Gauducheau, Site Hospitalier Nord, 44800 St Herblain, France;
| | - Catherine Bouteille
- Institut Paoli-Calmettes, Department of Surgical Oncology, CRCM, 13009 Marseille, France; (C.B.); (M.C.)
| | - Pierre Gimbergues
- Centre Jean Perrin, 58 rue Montalembert, 63003 Clermont Ferrand, France;
| | | | - Marc Martino
- Hôpital Saint Joseph, 26 Bd de Louvain, 13008 Marseille, France;
| | - Agnès Tallet
- Institut Paoli-Calmettes, Department of Radiotherapy, CRCM, 13009 Marseille, France;
| | - Monique Cohen
- Institut Paoli-Calmettes, Department of Surgical Oncology, CRCM, 13009 Marseille, France; (C.B.); (M.C.)
| | - Alexandre de Nonneville
- Aix-Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, Department of Medical Oncology, CRCM, 13009 Marseille, France;
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Yang H, Sun Y, Wang P, Qiao J, Wang C, Liu Z. The Impact of Sentinel Lymph Node Biopsy on Female Patients With T3-4c Breast Cancer and 1-2 Positive Lymph Nodes: A Population-Based Cohort Study. Clin Breast Cancer 2024; 24:e126-e137.e3. [PMID: 38114365 DOI: 10.1016/j.clbc.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 11/13/2023] [Indexed: 12/21/2023]
Abstract
PURPOSE This study aimed to evaluate the efficacy of sentinel lymph node biopsy (SLNB) in patients diagnosed with cT3-4c breast cancer with no more than 2 positive sentinel lymph nodes. METHODS Using data from the Surveillance, Epidemiology, and End Results (SEER) database, this retrospective study identified patients diagnosed with T3-4c breast cancer between 2010 and 2015. These patients were then categorized into 2 groups: the SLNB group, which underwent examination of 1-5 regional lymph nodes and the axillary lymph node dissection (ALND) group, which underwent examination of ≥10 regional lymph nodes. Propensity score matching analysis was used to assess the efficacy of SLNB in cT3-4c patients. RESULTS A total of 1139 patients were included in the analysis, with 423 and 716 patients in the SLNB and ALND groups, respectively. The 10-year overall survival (OS) and breast cancer-specific survival (BCSS) rates in the SLNB group were 66.1% and 76.3%, respectively, compared with 66.0% and 73.8%, respectively. Statistical analysis revealed no significant differences between the 2 groups in terms of OS (HR = 1.00, 95% CI = 0.80-1.25, P = .997) and BCSS (HR = 1.08, 95% CI = 0.83-1.41, P = .551). Even after 1:1 propensity score matching, there were no significant differences in OS (HR = 0.87, 95% CI = 0.65-1.16, P = .341) and BCSS (HR = 0.82, 95% CI = 0.59-1.16, P = .266) between the 2 groups. CONCLUSION This study demonstrates that SLNB does not adversely affect the survival of cT3-4c breast cancer patients with 1-2 sentinel lymph node metastases.
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Affiliation(s)
- Hanzhao Yang
- Department of Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Yadong Sun
- Department of Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Peili Wang
- Department of Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Jianghua Qiao
- Department of Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Chengzheng Wang
- Department of Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Zhenzhen Liu
- Department of Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
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Houvenaeghel G, de Nonneville A, Chopin N, Classe JM, Mazouni C, Chauvet MP, Reyal F, Tunon de Lara C, Jouve E, Rouzier R, Daraï E, Gimbergues P, Coutant C, Azuar AS, Villet R, Crochet P, Rua S, Bannier M, Cohen M, Boher JM. The need to tailor the omission of axillary lymph node dissection to patients with good prognosis and sentinel node micro-metastases. Cancer Med 2023; 12:4023-4032. [PMID: 36127853 PMCID: PMC9972015 DOI: 10.1002/cam4.5257] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 09/05/2022] [Accepted: 09/06/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Results of IBCSG-23-01-trial which included breast cancer patients with involved sentinel nodes (SN) by isolated-tumor-cells or micro-metastases supported the non-inferiority of completion axillary-lymph-node-dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN-micro-metastases. METHODS To investigate the impact of cALND omission on disease-free-survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients <75 years old with SN-micro-metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan-Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission. RESULTS Weighted log-rank tests comparing adjusted Kaplan-Meier survival curves showed significant differences in OS (p-value = 0.002) and borderline significant differences in DFS (p-value = 0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR = 2.77, CI95% = 1.36-5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND. CONCLUSIONS Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time.
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Affiliation(s)
- Gilles Houvenaeghel
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - Alexandre de Nonneville
- Department of Medical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | | | - Jean-Marc Classe
- Institut René Gauducheau, Site hospitalier Nord, St Herblain, France
| | | | | | | | | | - Eva Jouve
- Centre Claudius Regaud, Toulouse, France
| | | | | | | | | | | | | | | | - Sandrine Rua
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - Marie Bannier
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - Monique Cohen
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - Jean-Marie Boher
- Department of Biostatistics and Methodology, Institut Paoli Calmettes, 13009 and Aix-Marseille University, Unité Mixte de Recherche S1252, Institut de Recherche pour le Développement, Marseille, France
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5
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Meng L, Zheng T, Wang Y, Li Z, Xiao Q, He J, Tan J. Development of a prediction model based on LASSO regression to evaluate the risk of non-sentinel lymph node metastasis in Chinese breast cancer patients with 1-2 positive sentinel lymph nodes. Sci Rep 2021; 11:19972. [PMID: 34620978 PMCID: PMC8497590 DOI: 10.1038/s41598-021-99522-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/24/2021] [Indexed: 12/27/2022] Open
Abstract
This study aimed to develop an intraoperative prediction model to evaluate the risk of non-sentinel lymph node (NSLN) metastasis in Chinese breast cancer patients with 1–2 positive sentinel lymph nodes (SLNs). The clinicopathologic data of 714 patients with 1–2 positive SLNs were investigated. Univariate and multivariate analyses were performed to identify the risk factors of NSLN metastasis. A new mathematical prediction model was developed based on LASSO and validated in an independent cohort of 131 patients. The area under the receiver operating characteristic curve (AUC) was used to quantify performance of the model. Patients with NSLN metastasis accounted for 37.3% (266/714) and 34.3% (45/131) of the training and validation cohorts, respectively. A LASSO regression-based prediction model was developed and included the 13 most powerful factors (age group, clinical tumour stage, histologic type, number of positive SLNs, number of negative SLNs, number of SLNs dissected, SLN metastasis ratio, ER status, PR status, HER2 status, Ki67 staining percentage, molecular subtype and P53 status). The AUCs of training and validation cohorts were 0.764 (95% CI 0.729–0.798) and 0.777 (95% CI 0.692–0.862), respectively. We presented a new prediction model with excellent clinical applicability and diagnostic performance for use by clinicians as an intraoperative clinical tool to predict risk of NSLN metastasis in Chinese breast cancer patients with 1–2 positive SLNs and make the final decisions regarding axillary lymph node dissection.
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Affiliation(s)
- Lei Meng
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ting Zheng
- Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
| | - Yuanyuan Wang
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhao Li
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qi Xiao
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junfeng He
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jinxiang Tan
- Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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6
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Andersson Y, Bergkvist L, Frisell J, de Boniface J. Omitting completion axillary lymph node dissection after detection of sentinel node micrometastases in breast cancer: first results from the prospective SENOMIC trial. Br J Surg 2021; 108:1105-1111. [PMID: 34010418 DOI: 10.1093/bjs/znab141] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 04/03/2021] [Indexed: 11/14/2022]
Abstract
BACKGROUND Completion axillary lymph node dissection has been abandoned widely among patients with breast cancer and sentinel lymph node micrometastases, based on evidence from prospective RCTs. Inclusion in these trials has been subject to selection bias, with patients undergoing mastectomy being under-represented. The aim of the SENOMIC (omission of axillary lymph node dissection in SENtinel NOde MICrometases) trial was to confirm the safety of omission of axillary lymph node dissection in patients with breast cancer and sentinel lymph node micrometastases, and including patients undergoing mastectomy. METHODS The prospective SENOMIC multicentre cohort trial enrolled patients with breast cancer and sentinel lymph node micrometastases who had breast-conserving surgery or mastectomy at one of 23 Swedish hospitals between October 2013 and March 2017. No completion axillary lymph node dissection was performed. The primary endpoint was event-free survival, with a trial accrual target of 452 patients. Survival proportions were based on Kaplan-Meier survival estimates. RESULTS The trial included 566 patients. Median follow-up was 38 (range 7-67) months. The 3-year event-free survival rate was 96.2 per cent, based on 26 reported breast cancer recurrences, including five isolated axillary recurrences. The unadjusted 3-year event-free survival rate was higher than anticipated, but differed between patients who had mastectomy and those who underwent breast-conserving surgery (93.8 versus 97.8 per cent respectively; P = 0.011). Patients who underwent mastectomy had significantly worse tumour characteristics. On univariable Cox proportional hazards regression analysis, patients who had mastectomy without adjuvant radiotherapy had a significantly higher risk of recurrence than those who underwent breast-conserving surgery (hazard ratio 2.91, 95 per cent c.i. 1.25 to 6.75). CONCLUSION After 3 years, event-free survival was excellent in patients with breast cancer and sentinel node micrometastases despite omission of axillary lymph node dissection. Long-term follow-up and continued enrolment of patients having mastectomy, especially those not receiving adjuvant radiotherapy, are of utmost importance.
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Affiliation(s)
- Y Andersson
- Department of Surgery, Västmanland County Hospital, Västerås, Sweden.,Centre for Clinical Research Uppsala University, Västmanland County Hospital, Västerås, Sweden
| | - L Bergkvist
- Department of Surgery, Västmanland County Hospital, Västerås, Sweden.,Centre for Clinical Research Uppsala University, Västmanland County Hospital, Västerås, Sweden
| | - J Frisell
- Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden.,Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - J de Boniface
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Surgery, Capio St Göran's Hospital, Stockholm, Sweden
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7
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Karanlik H, Igci A. Surgical Approach in Invasive Breast Cancer. Breast Cancer 2019. [DOI: 10.1007/978-3-319-96947-3_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Bouquet de Jolinière J, Major A, Khomsi F, Ben Ali N, Guillou L, Feki A. The Sentinel Lymph Node in Breast Cancer: Problems Posed by Examination During Surgery. A Review of Current Literature and Management. Front Surg 2018; 5:56. [PMID: 30488035 PMCID: PMC6247078 DOI: 10.3389/fsurg.2018.00056] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 08/16/2018] [Indexed: 11/24/2022] Open
Abstract
The presence of tumor cells can be identified in the lymph node when metastasis has occurred from the primary cancer site into the lymph node (1) If the sentinel lymph node ganglion is negative for the presence of tumor cells at the time of histological examination, the other lymph nodes are also negative in 99% of cases. If no tumor cells are identified in the sentinel lymph node ganglion by histological examination, the other lymph nodes are also negative for the presence of tumor cells in 99% of cases. The sentinel lymph node advantageously replaces axillary dissection as a staging method in breast cancer T1 and T2 (2). Approximately 40% of breast cancers metastasize to axillary lymph nodes and metastatic extension depends on disease stage. Sentinel lymph nodes are affected in the following stages: T1a (4.3%), T1b (19.5%), T1c (23.8%), T2 (48.9%), T3 (66.7%).
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Affiliation(s)
| | - A. Major
- Department of Gynecology Obstetrics, Cantonal Hospital, HFR, Fribourg, Switzerland
| | - F. Khomsi
- Department of Gynecology Obstetrics, Cantonal Hospital, HFR, Fribourg, Switzerland
| | - N. Ben Ali
- Department of Gynecology Obstetrics, Cantonal Hospital, HFR, Fribourg, Switzerland
| | - L. Guillou
- Argotlab and Synlab Laboratories, Department of Pathology, Lausanne, Switzerland
| | - A. Feki
- Department of Gynecology Obstetrics, Cantonal Hospital, HFR, Fribourg, Switzerland
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9
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Moo TA, Edelweiss M, Hajiyeva S, Stempel M, Raiss M, Zabor EC, Barrio A, Morrow M. Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection? Ann Surg Oncol 2018; 25:1488-1494. [PMID: 29572705 DOI: 10.1245/s10434-018-6429-2] [Citation(s) in RCA: 111] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND/OBJECTIVE Intraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND). METHODS Patients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined. RESULTS From July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND. CONCLUSION Low-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.
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Affiliation(s)
- Tracy-Ann Moo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Marcia Edelweiss
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sabina Hajiyeva
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michelle Stempel
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Monica Raiss
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Emily C Zabor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Barrio
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Monica Morrow
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Abstract
CONTEXT -Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. OBJECTIVE -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. DATA SOURCES -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. CONCLUSIONS -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.
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Affiliation(s)
| | - Edi Brogi
- From the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
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11
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Houvenaeghel G, Boher JM, Reyal F, Cohen M, Garbay JR, Classe JM, Rouzier R, Giard S, Faure C, Charitansky H, Tunon de Lara C, Daraï E, Hudry D, Azuar P, Gimbergues P, Villet R, Sfumato P, Lambaudie E. Impact of completion axillary lymph node dissection in patients with breast cancer and isolated tumour cells or micrometastases in sentinel nodes. Eur J Cancer 2016; 67:106-118. [PMID: 27640137 DOI: 10.1016/j.ejca.2016.08.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 07/21/2016] [Accepted: 08/04/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Omission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion. METHODS A retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts. FINDINGS Among 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36-4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74-2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46-5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90-2.73). INTERPRETATION A separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.
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Affiliation(s)
- G Houvenaeghel
- Institut Paoli Calmettes and CRCM, 232 Bd Ste Marguerite, Marseille, France; Aix Marseille Université, France.
| | - J M Boher
- Department of Biostatistics and Methodology, Institut Paoli Calmettes, 13009, France; Aix-Marseille University, Unité Mixte de Recherche S912, Institut de Recherche pour le Développement, 13385, Marseille, France
| | - F Reyal
- Institut Curie, 26 rue d'Ulm, 75248, Paris, France
| | - M Cohen
- Institut Paoli Calmettes and CRCM, 232 Bd Ste Marguerite, Marseille, France
| | - J R Garbay
- Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif, France
| | - J M Classe
- Institut René Gauducheau, Site hospitalier Nord, St Herblain, France
| | - R Rouzier
- Centre René Huguenin, 35 rue Dailly, Saint Cloud, France
| | - S Giard
- Centre Oscar Lambret, 3 rue Frédéric Combenal, Lille, France
| | - C Faure
- Centre Léon Bérard, 28 rue Laennec, Lyon, France
| | - H Charitansky
- Centre Claudius Regaud, 20-24 rue du Pont St Pierre, Toulouse, France
| | | | - E Daraï
- Hôpital Tenon, 4 rue de la Chine, Paris, France
| | - D Hudry
- Centre Georges François Leclerc, 1 rue du Professeur Marion, Dijon, France
| | - P Azuar
- Hôpital de Grasse, Chemin de Clavary, Grasse, France
| | - P Gimbergues
- Centre Jean Perrin, 58 rue Montalembert, Clermont Ferrand, France
| | - R Villet
- Hôpital des Diaconnesses, 18 rue du Sergent Bauchat, Paris, France
| | - P Sfumato
- Department of Biostatistics and Methodology, Institut Paoli Calmettes, 13009, France; Aix-Marseille University, Unité Mixte de Recherche S912, Institut de Recherche pour le Développement, 13385, Marseille, France
| | - E Lambaudie
- Institut Paoli Calmettes and CRCM, 232 Bd Ste Marguerite, Marseille, France
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Tallet A, Lambaudie E, Cohen M, Minsat M, Bannier M, Resbeut M, Houvenaeghel G. Locoregional treatment of early breast cancer with isolated tumor cells or micrometastases on sentinel lymph node biopsy. World J Clin Oncol 2016; 7:243-252. [PMID: 27081647 PMCID: PMC4826970 DOI: 10.5306/wjco.v7.i2.243] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 08/14/2015] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
The advent of sentinel lymph-node technique has led to a shift in lymph-node staging, due to the emergence of new entities namely micrometastases (pN1mi) and isolated tumor cells [pN0(i+)]. The prognostic significance of this low positivity in axillary lymph nodes is currently debated, as is, therefore its management. This article provides updates evidence-based medicine data to take into account for treatment decision-making in this setting, discussing the locoregional treatment in pN0(i+) and pN1mi patients (completion axillary dissection, axillary irradiation with or without regional nodes irradiation, or observation), according to systemic treatment, with the goal to help physicians in their daily practice.
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13
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Maguire A, Brogi E. Sentinel lymph nodes for breast carcinoma: an update on current practice. Histopathology 2016; 68:152-67. [PMID: 26768036 PMCID: PMC5027880 DOI: 10.1111/his.12853] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 08/26/2015] [Indexed: 12/12/2022]
Abstract
Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1-T2 disease and cN0 who undergo breast-conserving surgery and whole-breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2 mm). Gross sectioning of SLNs at 2-mm intervals and microscopic examination of one haematoxylin and eosin-stained section from each SLN block is the preferred method for pathological evaluation of SLNs. The role and timing of SLN biopsy for patients who have received neoadjuvant chemotherapy is controversial, and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists.
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Affiliation(s)
- Aoife Maguire
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Edi Brogi
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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14
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Mazouni C, Fina F, Romain S, Bonnier P, Ouafik L, Martin PM. Post-operative nomogram for predicting freedom from recurrence after surgery in localised breast cancer receiving adjuvant hormone therapy. J Cancer Res Clin Oncol 2015; 141:1083-8. [PMID: 25433507 DOI: 10.1007/s00432-014-1889-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 11/25/2014] [Indexed: 12/29/2022]
Abstract
PURPOSE To develop a prognostic nomogram to predict freedom from recurrence for patients treated with adjuvant hormonal therapy (HT) for localised breast cancer (BC). METHODS We performed a retrospective analysis of 142 patients treated with adjuvant HT between 1996 and 2000. Clinical and pathological parameters were analysed. RESULTS A nomogram that predicts the probability of remaining free of recurrence for 5 years after surgery with adjuvant HT was developed using a Cox proportional hazards regression model. The progesterone receptor status (p < 0.001), nodal status (p = 0.008) and cathepsin-D (p < 0.001) were retained to construct the nomogram (C-index 0.734). CONCLUSIONS The nomogram we developed may be useful for estimating the probability of successful treatment 5 years after surgery for localised BC.
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Affiliation(s)
- Chafika Mazouni
- Laboratoire de Transfert d'oncologie Biologique, Faculté de Médecine Nord, Assistance Publique - Hôpitaux de Marseille, Marseille, France,
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15
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Houvenaeghel G, Cohen M, Jauffret-Fara C, Bannier M, Chéreau-Ewald É, Rua Ribeiro S, Lambaudie É. [Regional treatment for axillary lymph node micrometastases of breast cancer]. Cancer Radiother 2015; 19:276-83. [PMID: 26006761 DOI: 10.1016/j.canrad.2015.02.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 02/25/2015] [Indexed: 12/26/2022]
Abstract
In patients with breast cancer, axillary lymph node micrometastasis detection has been more frequent with a better definition since the introduction of the sentinel node procedure. In this review, we focus on pN1mi micrometastasis and review the literature in order to determine factors involved in making the decision of a regional treatment.
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Affiliation(s)
- G Houvenaeghel
- Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France; Centre de recherche en cancérologie de Marseille (CRCM), BP 30059, 13009 Marseille cedex, France; Aix Marseille université, jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille cedex 07, France.
| | - M Cohen
- Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France; Centre de recherche en cancérologie de Marseille (CRCM), BP 30059, 13009 Marseille cedex, France; Aix Marseille université, jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille cedex 07, France
| | - C Jauffret-Fara
- Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France; Centre de recherche en cancérologie de Marseille (CRCM), BP 30059, 13009 Marseille cedex, France; Aix Marseille université, jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille cedex 07, France
| | - M Bannier
- Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France; Centre de recherche en cancérologie de Marseille (CRCM), BP 30059, 13009 Marseille cedex, France; Aix Marseille université, jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille cedex 07, France
| | - É Chéreau-Ewald
- Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France; Centre de recherche en cancérologie de Marseille (CRCM), BP 30059, 13009 Marseille cedex, France; Aix Marseille université, jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille cedex 07, France
| | - S Rua Ribeiro
- Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France; Centre de recherche en cancérologie de Marseille (CRCM), BP 30059, 13009 Marseille cedex, France; Aix Marseille université, jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille cedex 07, France
| | - É Lambaudie
- Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille, France; Centre de recherche en cancérologie de Marseille (CRCM), BP 30059, 13009 Marseille cedex, France; Aix Marseille université, jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille cedex 07, France
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Boutros C, Mazouni C, Lerebours F, Stevens D, Lei X, Gonzalez-Angulo AM, Delaloge S. A preoperative nomogram to predict the risk of synchronous distant metastases at diagnosis of primary breast cancer. Br J Cancer 2015; 112:992-7. [PMID: 25668007 PMCID: PMC4366891 DOI: 10.1038/bjc.2015.34] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Revised: 01/07/2015] [Accepted: 01/12/2015] [Indexed: 01/13/2023] Open
Abstract
Background: The detection of synchronous metastases at primary diagnosis of breast cancer (BC) affects its initial management. A risk calculator that incorporates many factors to evaluate an individual's risk of harbouring synchronous metastases would be useful to adapt cancer management. Patients and Methods: Patients with primary diagnosis of BC were identified from three institutional databases sharing homogeneous work-up recommendations. A risk score for synchronous metastases was estimated and a nomogram was constructed using the first database. Its performance was assessed by receiver characteristic (ROC) analysis. The nomogram was externally validated in the two independent cohorts. Results: A preoperative nomogram based on the clinical tumour size (P<0.001), clinical nodal status (P<0.001), oestrogen (P=0.17) and progesterone receptors (P=0.04) was developed. The nomogram accuracy was 87.3% (95% confidence interval (CI), 84.45–90.2%). Overall, the area under the ROC curve (AUC) was 86.1% for the validation set from the Institut Curie-René Huguenin, and 63.8% for the MD Anderson validation set. The negative predictive value (NPV) was high in the three cohorts (97–99%). Conclusions: We developed and validated a strong metastasis risk calculator that can evaluate with high accuracy an individual's risk of harbouring synchronous metastases at diagnosis of primary BC. Condensed abstract: A nomogram to predict synchronous metastases at diagnosis of breast cancer was developed and externally validated. This tool allows avoiding unnecessary expensive work-up.
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Affiliation(s)
- C Boutros
- Department of Breast and Medical Oncology, Institut Gustave Roussy, Villejuif 94805, France
| | - C Mazouni
- Department of Surgery, Division of Breast and Plastic Surgery, Institut Gustave Roussy, Villejuif 94805, France
| | - F Lerebours
- Department of Breast and Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France
| | - D Stevens
- Department of Breast and Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France
| | - X Lei
- Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA
| | - A M Gonzalez-Angulo
- Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - S Delaloge
- Department of Breast and Medical Oncology, Institut Gustave Roussy, Villejuif 94805, France
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Cserni G, Maráz R. Regional Disease Control in Selected Patients with Sentinel Lymph Node Involvement and Omission of Axillary Lymph Node Dissection. Pathol Oncol Res 2015; 21:861-6. [DOI: 10.1007/s12253-015-9899-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 01/06/2015] [Indexed: 01/10/2023]
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Liu M, Wang S, Pan L, Yang D, Xie F, Liu P, Guo J, Zhang J, Zhou B. A new model for predicting non-sentinel lymph node status in Chinese sentinel lymph node positive breast cancer patients. PLoS One 2014; 9:e104117. [PMID: 25111296 PMCID: PMC4128817 DOI: 10.1371/journal.pone.0104117] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Accepted: 07/04/2014] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Our goal is to validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Stanford Online Calculator (SOC) for predicting non-sentinel lymph node (NSLN) metastasis in Chinese patients, and develop a new model for better prediction of NSLN metastasis. METHODS The MSKCC nomogram and SOC were used to calculate the probability of NSLN metastasis in 120 breast cancer patients. Univariate and multivariate analyses were performed to evaluate the relationship between NSLN metastasis and clinicopathologic factors, using the medical records of the first 80 breast cancer patients. A new model predicting NSLN metastasis was developed from the 80 patients. RESULTS The MSKCC and SOC predicted NSLN metastasis in a series of 120 patients with an area under the receiver operating characteristic curve (AUC) of 0.688 and 0.734, respectively. For predicted probability cut-off points of 10%, the false-negative (FN) rates of MSKCC and SOC were both 4.4%, and the negative predictive value (NPV) 75.0% and 90.0%, respectively. Tumor size, Kiss-1 expression in positive SLN and size of SLN metastasis were independently associated with NSLN metastasis (p<0.05). A new model (Peking University People's Hospital, PKUPH) was developed using these three variables. The MSKCC, SOC and PKUPH predicted NSLN metastasis in the second 40 patients from the 120 patients with an AUC of 0.624, 0.679 and 0.795, respectively. CONCLUSION MSKCC nomogram and SOC did not perform as well as their original researches in Chinese patients. As a new predictor, Kiss-1 expression in positive SLN correlated independently with NSLN metastasis strongly. PKUPH model achieved higher accuracy than MSKCC and SOC in predicting NSLN metastasis in Chinese patients.
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Affiliation(s)
- Miao Liu
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Shu Wang
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Lu Pan
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Deqi Yang
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Fei Xie
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Peng Liu
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Jiajia Guo
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Jiaqing Zhang
- Breast Disease Center, Peking University People's Hospital, Beijing, China
| | - Bo Zhou
- Breast Disease Center, Peking University People's Hospital, Beijing, China
- * E-mail:
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García JMC, Muñoz AP, Vicente AMG, Londoño GAJ, León Martín AA, García RP, Castrejón ÁS. Comparison of Different Predictive Tools of Axillary Status in Breast Cancer with Micrometastatic Sentinel Node. TUMORI JOURNAL 2014. [DOI: 10.1177/1636.17898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Tvedskov TF, Meretoja TJ, Jensen MB, Leidenius M, Kroman N. Cross-validation of three predictive tools for non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node. Eur J Surg Oncol 2014; 40:435-41. [PMID: 24534362 DOI: 10.1016/j.ejso.2014.01.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 01/14/2014] [Accepted: 01/23/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND We cross-validated three existing models for the prediction of non-sentinel node metastases in patients with micrometastases or isolated tumor cells (ITC) in the sentinel node, developed in Danish and Finnish cohorts of breast cancer patients, to find the best model to identify patients who might benefit from further axillary treatment. MATERIAL AND METHOD Based on 484 Finnish breast cancer patients with micrometastases or ITC in sentinel node a model has been developed for the prediction of non-sentinel node metastases. Likewise, two separate models have been developed in 1577 Danish patients with micrometastases and 304 Danish patients with ITC, respectively. The models were cross-validated in the opposite cohort. RESULTS The Danish model for micrometatases was accurate when tested in the Finnish cohort, with a slight change in AUC from 0.64 to 0.63. The AUC of the Finnish model decreased from 0.68 to 0.58 when tested in the Danish cohort, and the AUC of the Danish model for ITC decreased from 0.73 to 0.52, when tested in the Finnish cohort. The Danish micrometastatic model identified 14-22% of the patients as high-risk patients with over 30% risk of non-sentinel node metastases while less than 1% was identified by the Finish model. In contrast, the Finish model predicted a much larger proportion of patients being in the low-risk group with less than 10% risk of non-sentinel node metastases. CONCLUSION The Danish model for micrometastases worked well in predicting high risk of non-sentinel node metastases and was accurate under external validation.
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Affiliation(s)
- T F Tvedskov
- Department of Breast Surgery, Copenhagen University Hospital, Afsnit 4124, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - T J Meretoja
- Breast Surgery Unit, Helsinki University Central Hospital, P.O. Box 140, 00029 HUS, Helsinki, Finland
| | - M B Jensen
- Danish Breast Cancer Cooperative Group, Copenhagen University Hospital, Afsnit 2501, Blegdamsvej 9, Copenhagen, Denmark
| | - M Leidenius
- Breast Surgery Unit, Helsinki University Central Hospital, P.O. Box 140, 00029 HUS, Helsinki, Finland
| | - N Kroman
- Department of Breast Surgery, Copenhagen University Hospital, Afsnit 4124, Blegdamsvej 9, 2100 Copenhagen, Denmark
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Cserni G. Sentinel lymph node status and axillary lymph node dissection in the surgical treatment of breast cancer. Orv Hetil 2014; 155:203-15. [DOI: 10.1556/oh.2014.29816] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Axillary lymph node dissection has been traditionally perceived as a therapeutic and a staging procedure and unselectively removes all axillary lymph nodes. There still remains some controversy as concerns the survival benefit associated with axillary clearance. Sentinel lymph node biopsy removes the most likely sites of regional metastases, the lymph nodes directly connected with the primary tumour. It allows a more accurate staging and a selective indication for clearing the axilla, restricting this to patients who may benefit of it. Axillary dissection was performed in all patients during the learning phase of sentinel lymphadenectomy, but later only patients with metastasis to a sentinel node underwent this operation. Currently, even some patients with minimal sentinel node involvement, including some with macrometastasis may skip axillary clearance. This review summarizes the changes that have occurred in the surgical management of the axilla, the evidences and controversies behind these changes, along with current recommendations. Orv. Hetil., 2014, 155(6), 203–215.
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Affiliation(s)
- Gábor Cserni
- Bács-Kiskun Megyei Kórház Patológiai Osztály Kecskemét Nyíri út 49. 6000
- Szegedi Tudományegyetem, Általános Orvostudományi Kar Patológiai Intézet Szeged Állomás u. 2. 6725
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22
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Tvedskov TF, Jensen MB, Balslev E, Kroman N. Robust and validated models to predict high risk of non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node. Acta Oncol 2014; 53:209-15. [PMID: 23772767 DOI: 10.3109/0284186x.2013.806993] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Benefit from axillary lymph node dissection in sentinel node positive breast cancer patients is under debate. Based on data from 1820 Danish breast cancer patients operated in 2002-2008, we have developed two models to predict high risk of non-sentinel node metastases when micrometastases or isolated tumor cells are found in sentinel node. The aim of this study was to validate these models in an independent Danish dataset. MATERIAL AND METHODS We included 720 breast cancer patients with micrometastases and 180 with isolated tumor cells in sentinel node operated in 2009-2010 from the Danish Breast Cancer Cooperative Group database. Accuracy of the models was tested in this cohort by calculating area under the receiver operating characteristic curve (AUC) as well as sensitivity and specificity. RESULTS AUC for the model for patients with micrometastases was comparable to AUC in the original cohort: 0.63 and 0.64, respectively. The sensitivity and specificity for predicting risk of non-sentinel node metastases over 30% was 0.36 and 0.81, respectively, in the validation cohort. AUC for the model for patients with isolated tumor cells decreased from 0.73 in the original cohort to 0.60 in the validation cohort. When dividing patients with isolated tumor cells into high and low risk of non-sentinel node metastases according to number of risk factors present, 37% in the high-risk group had non-sentinel node metastases. Specificity and sensitivity was 0.48 and 0.88, respectively, in the validation cohort when using this cut-point. CONCLUSION In this independent dataset, the model for patients with micrometastases was robust with accuracy similar to the original cohort, while the model for patients with isolated tumor cells was less accurate. The models may be used to identify patients where axillary lymph node dissection should still be considered.
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Affiliation(s)
- Tove F Tvedskov
- Department of Breast Surgery, Copenhagen University Hospital , Copenhagen , Denmark
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Bargehr J, Edlinger M, Hubalek M, Marth C, Reitsamer R. Axillary Lymph Node Status in Early-Stage Breast Cancer Patients with Sentinel Node Micrometastases (0.2-2 mm). Breast Care (Basel) 2014; 8:187-91. [PMID: 24415968 DOI: 10.1159/000352090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Omission of axillary lymph node dissection (ALND) is increasingly becoming the new standard of care for patients with sentinel lymph node micrometastases (SNMMs). However, a formidable proportion of patients is afflicted with non-sentinel node (NSN) macrometastatic tumor burden. METHODS Over 1 decade 5,000 patients underwent sentinel node biopsies (SNB) at 2 certified breast cancer centers in Austria. All available cases of SNMM during this time period were reviewed. Clinical, tumor and lymph node parameters were analyzed using univariate and multivariate analysis to retrieve predictors for further NSN involvement. RESULTS We identified 216 patients with SNMMs, of whom 181 subsequently underwent ALND. Of the latter patients, 16% (n = 29/181) presented with NSN axillary metastases. ALND revealed NSN macrometastases in 10.5% (n = 19/181) of all the investigated patients, and 66% of the NSN-positive patients (n = 19/29). In 28% (n = 8/29) of the NSN-positive patients, more than 1 macrometastasis was detected. The number of removed sentinel nodes was found to be a significant predictor (p = 0.007) for NSN involvement. CONCLUSION In this retrospective investigation of breast cancer patients with SNMMs, a substantial proportion exhibited involvement of NSNs. Macrometastases accounted for the largest fraction of NSN tumor burden. Refraining from ALND in the face of SNMMs may entail substantial micro- and macrometastatic tumor burden in the remaining axillary lymph node basin.
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Affiliation(s)
- Johannes Bargehr
- Breast Center, Paracelsus Medical University Salzburg, Austria ; Department of Obstetrics and Gynecology, Innsbruck Medical University, Austria
| | - Michael Edlinger
- Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Austria
| | - Michael Hubalek
- Department of Obstetrics and Gynecology, Innsbruck Medical University, Austria
| | - Christian Marth
- Department of Obstetrics and Gynecology, Innsbruck Medical University, Austria
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L’exploration et le traitement de la région axillaire des tumeurs infiltrantes du sein (RPC 2013). ONCOLOGIE 2013. [DOI: 10.1007/s10269-013-2337-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Chaudhry A, Williams S, Cook J, Jenkins M, Sohail M, Calder C, Winters ZE, Rayter Z. The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using One Step Nucleic Acid Amplification (OSNA) and implications for clinical decision-making. Eur J Surg Oncol 2013; 40:150-7. [PMID: 24378008 DOI: 10.1016/j.ejso.2013.12.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 11/29/2013] [Accepted: 12/06/2013] [Indexed: 01/16/2023] Open
Abstract
INTRODUCTION One Step Nucleic Acid Amplification (OSNA) method for the intraoperative analysis of sentinel lymph nodes (SLNs) in breast cancer, obviates a second operation to the axilla and thereby expedites progression to adjuvant therapy. Recent NICE guidelines have approved OSNA as a method of sentinel node diagnosis to support the above case.(1) METHOD: This is a single centre prospective cohort analysis of all patients undergoing breast cancer surgery including sentinel node biopsy from February 2010 to June 2012. Patients with negative SLN(s) on OSNA had no further axillary surgery. A validation phase was performed prior to using OSNA routinely. Those with micrometastases underwent a level 1 clearance, and >one SLN with macrometastases, underwent treatment by level 2 axillary dissection. The length of time from sentinel node retrieval to OSNA result was recorded. RESULTS Four hundred and forty nodes were analysed in 212 patients with a mean age of 55 years (range 24-98). The sensitivity and specificity of OSNA was 93% and 94% respectively in cases of macrometastases. The process required additional median anaesthesia time of 20 min (range -48 to +65 min). Non-sentinel node positivity was 5% and 48% for micrometastasis and macrometastasis respectively. CONCLUSION OSNA identified 62 of 212 patients with at least one positive sentinel node, thereby sparing 29% from a second procedure to clear the axilla subsequently. The median waiting time of 20 min for node results from completion of breast procedure is acceptable and allows for an efficient operating list. OSNA can be incorporated into routine practice and with improved methods of imaging preoperatively, can be an excellent adjunct to the breast cancer patient pathway of care.
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Affiliation(s)
- A Chaudhry
- Department of Breast Surgery, University Hospitals Bristol NHS Trust, United Kingdom.
| | - S Williams
- Department of Breast Surgery, University Hospitals Bristol NHS Trust, United Kingdom
| | - J Cook
- Department of Breast Surgery, University Hospitals Bristol NHS Trust, United Kingdom
| | - M Jenkins
- Department of Histopathology, University Hospitals Bristol NHS Trust, United Kingdom
| | - M Sohail
- Department of Histopathology, University Hospitals Bristol NHS Trust, United Kingdom
| | - C Calder
- Department of Histopathology, University Hospitals Bristol NHS Trust, United Kingdom
| | - Z E Winters
- Department of Breast Surgery, University Hospitals Bristol NHS Trust, United Kingdom; School of Clinical Sciences, University of Bristol, Level 7, Research and Teaching, United Kingdom
| | - Z Rayter
- Department of Breast Surgery, University Hospitals Bristol NHS Trust, United Kingdom
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Santaballa A, De La Cueva H, Salvador C, García-Martínez AM, Guarín MJ, Lorente D, Palomar L, Aznar I, Dobón F, Bello P. Advantages of one step nucleic acid amplification (OSNA) whole node assay in sentinel lymph node (SLN) analysis in breast cancer. SPRINGERPLUS 2013; 2:542. [PMID: 24255842 PMCID: PMC3824711 DOI: 10.1186/2193-1801-2-542] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Accepted: 09/18/2013] [Indexed: 11/10/2022]
Abstract
BACKGROUND The purpose of this study is to present our first results of sentinel node analysis (SLN) by one step nucleic acid amplification (OSNA) in routine clinical practice in our centre and compare them with the results of classic histopathological analysis in a historical cohort from our same institution. METHODS 407 patients (total study population) with early breast cancer and no clinical nodal involvement underwent SLN biopsy in our institution. The SLN was analysed by OSNA in 164 biopsies. OSNA results were compared with the conventional histopathology study of 244 patients who had undergone SLN biopsy previously. The characteristics of the patients in both groups were evaluated and a comparison was made of the rate of metastases detected by both methods and of the surgical procedures needed in each group. We also investigated the state of non-sentinel lymph nodes if micrometastases where found in SLN. RESULTS SLN biopsy result was considered as positive in 45 patients (28%) in the OSNA group and in 58 in the historical group (24%). There was no difference in the rate of macrometastases (16,5% for OSNA, 20% for HE) but we found differences in the rate of micrometastases (11% for OSNA and 3,6% for HE p = 0.0007). Axillary lymphadenectomy (ALND) was performed in 43/45 cases in the OSNA group and in 51/58 of the historical group. In all patients diagnosed by OSNA, ALND was performed during the initial surgical procedure. In the historical cohort ALND was performed during the initial surgical procedure in 41 patients and in a second surgical procedure in 10 patients. Patients from both groups with micrometastases in the SLN had no metastases in other nodes when the ALND was performed. CONCLUSIONS OSNA analysis allows the detection of SLN metastases as precisely as conventional pathology with an increased detection of micrometastases. The OSNA method can reduce the need of a deferred lymphadenectomy.
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Affiliation(s)
- Ana Santaballa
- Medical Oncology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
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Validation of a breast cancer nomogram for predicting nonsentinel node metastases after minimal sentinel node involvement: Validation of the Helsinki breast nomogram. Breast 2013; 22:787-92. [DOI: 10.1016/j.breast.2013.02.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2012] [Revised: 12/28/2012] [Accepted: 02/06/2013] [Indexed: 11/21/2022] Open
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Modèles prédictifs d’envahissement du ganglion non sentinelle en cas de ganglion sentinelle positif dans le cancer du sein. ONCOLOGIE 2013. [DOI: 10.1007/s10269-013-2292-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay. Eur J Surg Oncol 2013; 39:766-73. [PMID: 23607911 DOI: 10.1016/j.ejso.2013.03.011] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 03/04/2013] [Accepted: 03/13/2013] [Indexed: 01/01/2023] Open
Abstract
INTRODUCTION The one-step nucleic acid amplification (OSNA) is a molecular procedure that yields a semiquantitative result for detection of nodal metastasis. Size of metastasis in the sentinel lymph node (SLN) by conventional histology has been described as a predictive factor for additional axillary metastasis. The objective of this study is to quantify intraoperatively the total tumoral load (TTL) in the positive SLNs assessed by OSNA and to determine whether this TTL predicts non-SLN metastasis in patients with clinically node negative early stage breast cancer. METHODS 306 patients with cT1-3N0 invasive breast cancer who had undergone intraoperative SLN evaluation by OSNA were included. TTL was defined as the addition of CK19 mRNA copies of each positive SLN (copies/μL). RESULTS TTL was a predictive factor of additional non-SLN metastasis in the complete axillary lymph node dissection (cALND) (OR, 1.67; 95% CI, 1.18-2.35). In the multivariate analysis, the TTL was a predictor of non-SLN metastasis in HR positive patients (OR, 1.69; 95% CI, 1.19-2.41). In our cohort of patients, with a TTL ≤1.2 × 10(5) copies/μL, there was a specificity of 85.3% and negative predictive value (NPV) of 80%. If we consider only the HR positive patients, with a TTL ≤5 × 10(5) copies/μL there was a specificity of 86.7% and NPV of 83.7%. CONCLUSIONS TTL assessed by OSNA assay predicts for additional non-SLN metastasis and this intraoperative tool can help guiding decisions on performing a cALND in breast cancer patients.
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Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients. Breast Cancer Res Treat 2013; 139:87-93. [DOI: 10.1007/s10549-013-2524-z] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Accepted: 04/03/2013] [Indexed: 02/06/2023]
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Meretoja TJ, Audisio RA, Heikkilä PS, Bori R, Sejben I, Regitnig P, Luschin-Ebengreuth G, Zgajnar J, Perhavec A, Gazic B, Lázár G, Takács T, Kővári B, Saidan ZA, Nadeem RM, Castellano I, Sapino A, Bianchi S, Vezzosi V, Barranger E, Lousquy R, Arisio R, Foschini MP, Imoto S, Kamma H, Tvedskov TF, Jensen MB, Cserni G, Leidenius MHK. International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases. Breast Cancer Res Treat 2013; 138:817-27. [DOI: 10.1007/s10549-013-2468-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Accepted: 02/25/2013] [Indexed: 01/06/2023]
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Abstract
Micrometastases or sub-micrometastases can be detected by standard histopathological method sometimes associated with immunohistochemistry in lymph nodes, bone marrow and blood. The consequence of these small size involvement may be prognostic and therapeutic. Two factors are necessary to assess this kind of involvement: the rate of involvement of non-sentinel lymph node after axillary lymph node dissection and significative difference of survivals. The rate of involvement of non-sentinel lymph node in case of micrometastases or sub-micrometastases is different from the rate of involvement in case of no lymph node metastases (7 to 8%) or in case of macrometases (30 to 50%). Micrometastase is an important factor to determine the rate of involvement of non-sentinel lymph node, the overall or disease free survival and to assess the need of radiotherapy and chemotherapy. In conclusion, micrometastases and sub-micrometastases have a clinical impact even if complementary axillary lymph node dissection is still discussed.
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Meretoja TJ, Leidenius MHK, Heikkilä PS, Boross G, Sejben I, Regitnig P, Luschin-Ebengreuth G, Žgajnar J, Perhavec A, Gazic B, Lázár G, Takács T, Vörös A, Saidan ZA, Nadeem RM, Castellano I, Sapino A, Bianchi S, Vezzosi V, Barranger E, Lousquy R, Arisio R, Foschini MP, Imoto S, Kamma H, Tvedskov TF, Kroman N, Jensen MB, Audisio RA, Cserni G. International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer. J Natl Cancer Inst 2012; 104:1888-96. [PMID: 23117131 DOI: 10.1093/jnci/djs455] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Axillary treatment of breast cancer patients is undergoing a paradigm shift, as completion axillary lymph node dissections (ALNDs) are being questioned in the treatment of patients with tumor-positive sentinel nodes. This study aims to develop a novel multi-institutional predictive tool to calculate patient-specific risk of residual axillary disease after tumor-positive sentinel node biopsy. METHODS Breast cancer patients with a tumor-positive sentinel node and a completion ALND from five European centers formed the original patient series (N = 1000). Statistically significant variables predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other centers. All statistical tests were two-sided. RESULTS Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series. CONCLUSIONS We present a novel, international, multicenter, predictive tool to assess the risk of additional axillary metastases after tumor-positive sentinel node biopsy in breast cancer. The predictive model performed well in internal and external validation but needs to be further studied in each center before application to clinical use.
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Affiliation(s)
- Tuomo J Meretoja
- Helsinki University Central Hospital, Breast Surgery Unit, PO Box 140, FI-00029 HUS, Finland.
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Cserni G, Bezsenyi I, Markó L. Patients' choice on axillary lymph node dissection following sentinel lymph node micrometastasis--first report on prospective use of a nomogram in very low risk patients. Pathol Oncol Res 2012; 19:211-6. [PMID: 23070585 DOI: 10.1007/s12253-012-9571-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Accepted: 09/18/2012] [Indexed: 10/27/2022]
Abstract
The optimal locoregional treatment of patients diagnosed with sentinel node (SN) micrometastasis is controversial. A previously reported and validated nomogram was used to calculate the risk of non-SN metastasis in patients with SN micrometastasis over a period of 2 years. Patients were given detailed information about the risk, consequences and treatment options of non-SN involvement, the risk and potential complications of unnecessary completion axillary lymph node dissection (ALND), the imperfectness of the nomogram, and other factors that may influence their selection of further treatment. They also received a questionnaire to monitor factors influencing their decisions. Of the 25 patients participating in the study, 10 have opted for ALND. The only factor that seemed to influence their choice was fear from disease recurrence. Giving detailed information to SN micrometastatic patients is a patient-centered alternative to current recommendations on performing ALND in all such patients or omitting ALND in all of them.
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Affiliation(s)
- Gábor Cserni
- Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyíri út 38., 6000, Kecskemét, Hungary.
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Multi-Institutional Comparison of Non-sentinel Lymph Node Predictive Tools in Breast Cancer Patients with High Predicted Risk of Further Axillary Metastasis. Pathol Oncol Res 2012; 19:95-101. [DOI: 10.1007/s12253-012-9553-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2012] [Accepted: 06/26/2012] [Indexed: 01/17/2023]
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Cserni G, Boross G, Maráz R, Leidenius M, Meretoja T, Heikkila P, Regitnig P, Luschin-Ebengreuth G, Zgajnar J, Perhavec A, Gazic B, Lázár G, Takács T, Vörös A, Audisio R. Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer. Surg Oncol 2012; 21:59-65. [DOI: 10.1016/j.suronc.2011.12.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2011] [Revised: 12/01/2011] [Accepted: 12/02/2011] [Indexed: 01/17/2023]
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Mazouni C, Spyratos F, Romain S, Fina F, Bonnier P, Ouafik LH, Martin PM. A nomogram to predict individual prognosis in node-negative breast carcinoma. Eur J Cancer 2012; 48:2954-61. [PMID: 22658808 DOI: 10.1016/j.ejca.2012.04.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Revised: 03/22/2012] [Accepted: 04/27/2012] [Indexed: 11/17/2022]
Abstract
BACKGROUND Currently, the benefit of chemotherapy (CT) in node-negative breast carcinoma (NNBC) is discussed. The evaluation of classical clinical and histological factors is limited to assess individual outcome. A statistical model was developed to improve the prognostic accuracy of NNBC. METHODS A total of 305 node-negative breast carcinomas who underwent surgery (+/- radiotherapy) but no adjuvant treatment were selected. Putative prognosis factors including age, tumour size, oestrogen receptor (ER), progesterone receptor (PgR), Scarff-Bloom-Richardon (SBR) grading, urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) and thymidine kinase (TK) were evaluated. The developed model was internally validated using Harrell's concordance index. A prognosis index (PI) was proposed and compared with Adjuvant! Online program. RESULTS Age (p < 0.001), pathological tumour size (pT) (p < 0.001), PgR (p = 0.02), and PAI-1 (p ≤ 0.001) were included in the Cox regression model predicting Breast cancer specific survival (BCSS) at 5-years. Internal validation revealed a concordance index of 0.71. A PI score was derived from our nomogram. The PI score was significantly associated with BCSS (hazard ratio (HR): 4.1 for intermediate, p=0.02, HR: 8.8, p < 0.001 for high group) as compared to Adjuvant! Online score (HR: 1.4, p=0.14). CONCLUSION A nomogram can be used to predict probability survival curves for individual breast cancer patients.
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Affiliation(s)
- C Mazouni
- Laboratoire de transfert d'oncologie biologique, Assistance Publique - Hôpitaux de Marseille, Faculté de Médecine Nord, Marseille, France.
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Tvedskov TF, Jensen MB, Lisse IM, Ejlertsen B, Balslev E, Kroman N. High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node. Int J Cancer 2012; 131:2367-75. [PMID: 22344558 DOI: 10.1002/ijc.27499] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2011] [Accepted: 01/20/2012] [Indexed: 12/21/2022]
Abstract
Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002-2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases.
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Andersson Y, Frisell J, de Boniface J, Bergkvist L. Prediction of non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastases: evaluation of the tenon score. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2012; 6:31-8. [PMID: 22346360 PMCID: PMC3273320 DOI: 10.4137/bcbcr.s8642] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Current guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SLN) metastasis larger than 0.2 mm. However, in 50%-65% of these patients, the non-SLNs contain no further metastases and cALND provides no benefit. Several nomograms and scoring systems have been suggested to predict the risk of metastases in non-SLNs. We have evaluated the Tenon score. PATIENTS AND METHODS In a retrospective review of the Swedish Sentinel Node Multicentre Cohort Study, risk factors for additional metastases were analysed in 869 SLN-positive patients who underwent cALND, using uni- and multivariate logistic regression models. A receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity of the Tenon score, and the area under the curve (AUC) was calculated. RESULTS Non-SLN metastases were identified in 270/869 (31.1%) patients. Tumour size and grade, SLN status and ratio between number of positive SLNs and total number of SLNs were significantly associated with non-SLN status in multivariate analyses. The area under the curve for the Tenon score was 0.65 (95% CI 0.61-0.69). In 102 patients with a primary tumour <2 cm, Elston grade 1-2 and SLN metastases ≤2 mm, the risk of non SLN metastasis was less than 10%. CONCLUSION The Tenon score performed inadequately in our material and we could, based on tumour and SLN characteristics, only define a very small group of patients in which negative non-sentinel nodes could be predicted.
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Affiliation(s)
- Y Andersson
- Department of Surgery, Central Hospital, Västerås, Sweden
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Chen K, Zhu L, Jia W, Rao N, Fan M, Huang H, Shan Q, Han J, Song E, Zeng Y, Su F. Validation and comparison of models to predict non-sentinel lymph node metastasis in breast cancer patients. Cancer Sci 2011; 103:274-81. [DOI: 10.1111/j.1349-7006.2011.02148.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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Houvenaeghel G, Bannier M, Nos C, Giard S, Mignotte H, Jacquemier J, Martino M, Esterni B, Belichard C, Classe JM, Tunon de Lara C, Cohen M, Payan R, Blanchot J, Rouanet P, Penault-Llorca F, Bonnier P, Fournet S, Agostini A, Marchal F, Garbay JR. Non sentinel node involvement prediction for sentinel node micrometastases in breast cancer: nomogram validation and comparison with other models. Breast 2011; 21:204-9. [PMID: 22014859 DOI: 10.1016/j.breast.2011.09.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2011] [Revised: 09/12/2011] [Accepted: 09/18/2011] [Indexed: 01/13/2023] Open
Abstract
PURPOSE The risk of non sentinel node (NSN) involvement varies in function of the characteristics of sentinel nodes (SN) and primary tumor. Our aim was to determine and validate a statistical tool (a nomogram) able to predict the risk of NSN involvement in case of SN micro or sub-micrometastasis of breast cancer. We have compared this monogram with other models described in the literature. METHODS We have collected data on 905 patients, then 484 other patients, to build and validate the nomogram and compare it with other published scores and nomograms. RESULTS Multivariate analysis conducted on the data of the first cohort allowed us to define a nomogram based on 5 criteria: the method of SN detection (immunohistochemistry or by standard coloration with HES); the ratio of positive SN out of total removed SN; the pathologic size of the tumor; the histological type; and the presence (or not) of lympho-vascular invasion. The nomogram developed here is the only one dedicated to micrometastasis and developed on the basis of two large cohorts. The results of this statistical tool in the calculation of the risk of NSN involvement is similar to those of the MSKCC (the similarly more effective nomogram according to the literature), with a lower rate of false negatives. CONCLUSION this nomogram is dedicated specifically to cases of SN involvement by metastasis lower or equal to 2 mm. It could be used in clinical practice in the way to omit ALND when the risk of NSN involvement is low.
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Orsoni M, Clerc J, Golfier F, Cortet M, Raudrant D, Krauth JS. Axillary lymph node dissection in the case of sentinel lymph node micrometastatic invasion: evaluation of three predictive models. Eur J Obstet Gynecol Reprod Biol 2011; 158:334-7. [DOI: 10.1016/j.ejogrb.2011.05.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2010] [Revised: 11/16/2010] [Accepted: 05/19/2011] [Indexed: 10/18/2022]
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Chen JJ, Wu J. Management strategy of early-stage breast cancer patients with a positive sentinel lymph node: With or without axillary lymph node dissection. Crit Rev Oncol Hematol 2011; 79:293-301. [DOI: 10.1016/j.critrevonc.2010.06.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2010] [Revised: 06/13/2010] [Accepted: 06/25/2010] [Indexed: 01/17/2023] Open
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Sauer G, Schneiderhan-Marra N, Muche R, Koretz K, Kazmaier C, Kreienberg R, Joos T, Deissler H. Molecular indicators of non-sentinel node status in breast cancer determined in preoperative biopsies by multiplexed sandwich immunoassays. J Cancer Res Clin Oncol 2011; 137:1175-84. [PMID: 21516507 DOI: 10.1007/s00432-011-0982-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2011] [Accepted: 03/30/2011] [Indexed: 01/17/2023]
Abstract
PURPOSE Purpose of this study was to determine the accuracy of prediction of non-sentinel lymph node (NSLN) involvement in sentinel node (SLN)-positive breast cancer patients based on protein concentrations measured in lysates from initially taken breast biopsies. METHODS Data on protein expression, previously generated by multiplexed bead-based immunoassays, were analysed by multivariate logistic regression to define parameter sets of value to predict NSLN involvement. Receiver-operator characteristics (ROCs) were calculated as indicators of diagnostic significance. RESULTS Analyses of data from all patients (n = 99) resulted in parameter sets that allowed direct prediction of the NSLN status with a ROC area under the curve (AUC) of 0.83. The clinically most relevant prediction of NSLN status in SLN-positive patients (n = 37) based on only seven parameters (including TIMP-2 as the most relevant single value) was possible with high accuracy indicated by an AUC of 0.89. CONCLUSIONS Parallel assessment of protein concentrations in breast biopsies is a highly promising approach to predict nodal involvement and even the NSLN status in SLN-negative breast cancer patients. Such diagnostic information could substantially reduce the number of completion axillary lymph node dissections in clinical practice.
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Affiliation(s)
- Georg Sauer
- Department of Obstetrics and Gynaecology, University of Ulm, Prittwitzstr. 43, 89075 Ulm, Germany
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Meretoja TJ, Strien L, Heikkilä PS, Leidenius MHK. A simple nomogram to evaluate the risk of nonsentinel node metastases in breast cancer patients with minimal sentinel node involvement. Ann Surg Oncol 2011; 19:567-76. [PMID: 21792511 DOI: 10.1245/s10434-011-1882-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND Tumor-positive sentinel node biopsy (SNB) suggests a risk of nonsentinel node metastases in breast cancer. This risk is lower after micrometastasis or isolated tumor cells (ITC) in the sentinel node (SN), and recent studies suggest that completion axillary lymph node dissection (ALND) might not improve outcome in these patients. We aim to validate existing predictive models and to develop a new model for micrometastatic and ITC patients. METHODS A series of 484 patients with micrometastases or ITC in SN followed by ALND was used to evaluate factors affecting nonsentinel node involvement. Logistic regression analysis was performed to construct a predictive model, which was validated by a separate series of 51 patients. RESULTS Only 7.2% of patients had additional metastases on completion ALND. Tumor diameter and multifocality associated with nonsentinel status on multivariate analysis. A predictive model was constructed showing good [area under the curve (AUC) 0.791] discrimination in the validation series. Previously published models performed poorly in our patient population. CONCLUSIONS Nonsentinel node metastases are rare with micrometastasis or ITC in SN. Most published predictive models for nonsentinel node involvement perform poorly in the present patient population. We developed a new predictive model which seems to perform well in discriminating patients with more than 10% risk of additional metastases. However, the presented nomogram needs to be validated with an independent patient series to evaluate its accuracy, especially for high-risk patients.
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Affiliation(s)
- T J Meretoja
- Breast Surgery Unit, Department of Gastrointestinal and General Surgery, Helsinki University Central Hospital, Helsinki, Finland.
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Mazouni C, Bonnier P, Romain S, Martin PM. A nomogram predicting the probability of primary breast cancer survival at 2- and 5-years using pathological and biological tumor parameters. J Surg Oncol 2011; 103:746-50. [PMID: 21544817 DOI: 10.1002/jso.21712] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
PURPOSE Our objective was to develop a nomogram to predict individual overall survival (OS) for primary breast cancer, based on pathological and biological tumor parameters. METHODS A retrospective study in a cohort of 180 patients with primary breast cancer was used to build the nomogram. Pathological factors and tumor proteases measured prospectively in primary tumors were used. A multivariate Cox proportional hazards model was used to explore the relationship with OS, and regression coefficients were used to build the nomogram. The nomogram was internally validated with 200 bootstrap re-samples. RESULTS The final variables included in the nomogram comprised tumor size (P = 0.04), nodal pathological status (P = 0.01), estrogen receptor status (P = 0.04), urokinase plasminogen activator inhibitor-1 (PAI-1; P = 0.02), thymidine kinase (P = 0.03), and cathepsin D (P = 0.004). The predictive accuracy of the nomogram at estimating the probability of OS, at both 2 and 5 years, was respectively 0.874 and 0.832 before and after calibration. CONCLUSION A nomogram to predict 2- and 5-year OS in BC, using histological and biological parameters was successfully developed. This prognostic tool should prove useful in decision-making and therapeutic research.
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Affiliation(s)
- Chafika Mazouni
- Department of Breast Surgery, Institut Gustave Roussy, Villejuif, France.
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Fougo JL, Senra FS, Araújo C, Dias T, Afonso M, Leal C, Dinis-Ribeiro M. Validating the MSKCC nomogram and a clinical decision rule in the prediction of non-sentinel node metastases in a Portuguese population of breast cancer patients. Breast 2011; 20:134-40. [DOI: 10.1016/j.breast.2010.10.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2009] [Revised: 05/17/2010] [Accepted: 10/21/2010] [Indexed: 01/17/2023] Open
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Clinical significance of sentinel lymph node isolated tumour cells in breast cancer. Breast Cancer Res Treat 2011; 127:325-34. [PMID: 21455668 DOI: 10.1007/s10549-011-1476-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2010] [Accepted: 03/19/2011] [Indexed: 12/16/2022]
Abstract
The advent of sentinel lymph node biopsy (SLNB) and improvements in histopathological and molecular analysis have increased the rate at which isolated tumour cells (ITC) are identified. However, their biological and clinical significance has been the subject of much debate. In this article we review the literature concerning SLNB with particular reference to ITC. The controversies regarding histopathological assessment, clinical relevance and management implications are explored. The literature review was facilitated by Medline, PubMed, Embase and Cochrane databases. Published studies have reported divergent results regarding the biological significance and clinical implications of ITC in general and SLN ITC in particular. Some studies demonstrate no associations, whilst others have found these to be indicators of poor prognosis, associated with non-SLN involvement, in addition to local recurrence and distant disease. Absolute consensus regarding the optimal analytical technique for SLN has yet to be reached, particularly concerning immunohistochemical (IHC) techniques targeting cytokeratins and contemporary molecular analysis. The clinical relevance of ITC within the SLN should be primarily determined by the magnitude of their impact on patient management and outcome measures. The modest up-staging within current classification systems is justified and reflects the marginally poorer prognosis for women with SLN ITC. Management need not be altered where further axillary treatment with surgical clearance or radiotherapy and systemic adjuvant treatment are already indicated. However, in the absence of level-1 guidance, each case requires discussion with regard to other tumour and patient related factors in the context of the multidisciplinary team. The identification of ITC remains highly dependent on the analytical technique employed and there exists potential for stage migration and impact on management decisions. Evidence supporting the routine analysis of deeper tissue sections by IHC is lacking and molecular technologies should be restricted to research purposes at present.
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Hindié E, Groheux D, Brenot-Rossi I, Rubello D, Moretti JL, Espié M. The sentinel node procedure in breast cancer: nuclear medicine as the starting point. J Nucl Med 2011; 52:405-14. [PMID: 21321267 DOI: 10.2967/jnumed.110.081711] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Axillary node status is a major prognostic factor in early breast cancer. Staging with sentinel node biopsy (SNB) leads to a substantial reduction in surgical morbidity. Recent multiinstitutional studies revealed SNB false-negative rates ranging from 5.5% to 16.7%, higher than the target (<5%) set by the 2005 guidelines of the American Society of Clinical Oncology. These alarming data point to the necessity of optimization. Dual mapping with radiotracer and blue dye, combining 2 different injection sites, and routinely using lymphoscintigraphy may improve accuracy. Factors associated with decreased sensitivity, such as prior excisional biopsy or neoadjuvant chemotherapy, should be recognized. The use of SNB in situations with a high prevalence of node positivity (large tumor, multifocality) is controversial. The risk of missed disease after negative SNB ranges from 1% to 4% in patients with T1 tumor and up to 15% in patients with T3. With peritumoral injection, internal mammary drainage is seen in about 20% of cases. Patients combining internal mammary drainage with a positive axillary sentinel node have close to a 50% probability of internal mammary involvement. Lymphoscintigraphy might thus be helpful in selecting patients for whom internal mammary radiation has a high benefit-to-risk ratio.
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Affiliation(s)
- Elif Hindié
- Nuclear Medicine, Saint-Louis Hospital, University of Paris VII, Paris, France.
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