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Published in: Annals of Surgical Oncology 3/2015

01-12-2015 | Breast Oncology

Circulating Tumor Cells After Neoadjuvant Chemotherapy in Stage I–III Triple-Negative Breast Cancer

Authors: Carolyn Hall, PhD, Mandar Karhade, MBBS, MPH, Barbara Laubacher, BSN, Amber Anderson, BS, Henry Kuerer, MD, PhD, Sarah DeSynder, MD, Anthony Lucci, MD

Published in: Annals of Surgical Oncology | Special Issue 3/2015

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Abstract

Background

Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen and progesterone receptor expression and HER-2 gene amplification. Circulating tumor cells (CTCs) can be identified in 25 % of nonmetastatic breast cancer patients, and the identification of ≥1 CTC predicts outcome. This study was designed to determine whether CTCs present after neoadjuvant chemotherapy (NACT) predicted worse outcome in nonmetastatic TNBC patients.

Methods

CTCs were assessed in 57 TNBC patients with nonmetastatic TNBC after the completion of NACT. CTCs (per 7.5 ml blood) were identified using the Cell Search® System (Janssen). Log-rank test and Cox regression analysis were applied to establish the association of CTCs with relapse-free (RFS) and overall survival (OS).

Results

Median follow-up was 30 months, and mean age was 53 years. Fifty-four patients (95 %) had >2-cm tumors, 42 (84 %) were nuclear grade 3, and 42 (74 %) had positive axillary lymph nodes. One or more CTC was identified in 30 % of patients. CTC presence was not associated with primary tumor size, high grade, or lymph node positivity. Multivariate analysis demonstrated that detection of ≥1 CTC predicted decreased RFS (log-rank P = 0.03, HR 5.25, 95 % CI 1.34–20.56) and OS (log-rank P = 0.03, HR 7.04, 95 % CI 1.26–39.35).

Conclusions

One or more CTCs present after NACT predicted relapse and survival in nonmetastatic TNBC patients. This information would be helpful in future clinical trial design of adjuvant treatments for TNBC patients who are at risk for relapse after completing NACT.
Literature
1.
go back to reference Diaz LK, Cryns VL, Symmans WF, Sneige N. Triple negative breast carcinoma and the basal phenotype: from expression profiling to clinical practice. Adv Anat Pathol. 2007;14(6):419–30.PubMedCrossRef Diaz LK, Cryns VL, Symmans WF, Sneige N. Triple negative breast carcinoma and the basal phenotype: from expression profiling to clinical practice. Adv Anat Pathol. 2007;14(6):419–30.PubMedCrossRef
2.
go back to reference Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.PubMedCrossRef Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.PubMedCrossRef
3.
go back to reference Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.PubMedCrossRef Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.PubMedCrossRef
4.
go back to reference Dawood S, Broglio K, Esteva FJ, et al. Survival among women with triple receptor-negative breast cancer and brain metastases. Ann Oncol. 2009;20(4):621–7.PubMedPubMedCentralCrossRef Dawood S, Broglio K, Esteva FJ, et al. Survival among women with triple receptor-negative breast cancer and brain metastases. Ann Oncol. 2009;20(4):621–7.PubMedPubMedCentralCrossRef
5.
go back to reference Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–7.PubMedCrossRef Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–7.PubMedCrossRef
6.
go back to reference Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27(8):1168–76.PubMedPubMedCentralCrossRef Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27(8):1168–76.PubMedPubMedCentralCrossRef
7.
go back to reference Kaufmann M, von Minckwitz G, Bear HD, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18(12):1927–34.PubMedCrossRef Kaufmann M, von Minckwitz G, Bear HD, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18(12):1927–34.PubMedCrossRef
8.
go back to reference Sachelarie I, Grossbard ML, Chadha M, Feldman S, Ghesani M, Blum RH. Primary systemic therapy of breast cancer. Oncologist. 2006;11(6):574–89.PubMedCrossRef Sachelarie I, Grossbard ML, Chadha M, Feldman S, Ghesani M, Blum RH. Primary systemic therapy of breast cancer. Oncologist. 2006;11(6):574–89.PubMedCrossRef
9.
go back to reference Bonnefoi H, Litiere S, Piccart M, et al. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Ann Oncol. 2014;25(6):1128–36.PubMedPubMedCentralCrossRef Bonnefoi H, Litiere S, Piccart M, et al. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Ann Oncol. 2014;25(6):1128–36.PubMedPubMedCentralCrossRef
10.
go back to reference Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.PubMedCrossRef Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.PubMedCrossRef
11.
go back to reference Esserman LJ, Berry DA, DeMichele A, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30(26):3242–9.PubMedPubMedCentralCrossRef Esserman LJ, Berry DA, DeMichele A, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30(26):3242–9.PubMedPubMedCentralCrossRef
12.
go back to reference von Minckwitz G. Neoadjuvant chemotherapy in breast cancer-insights from the German experience. Breast cancer. 2012;19(4):282–8.CrossRef von Minckwitz G. Neoadjuvant chemotherapy in breast cancer-insights from the German experience. Breast cancer. 2012;19(4):282–8.CrossRef
13.
go back to reference Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778–85.PubMedCrossRef Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778–85.PubMedCrossRef
14.
go back to reference Smith BL. Neoadjuvant versus adjuvant systemic therapy for operable breast cancer: equivalent outcomes? Ann Surg. 2013;257(2):180–1.PubMedCrossRef Smith BL. Neoadjuvant versus adjuvant systemic therapy for operable breast cancer: equivalent outcomes? Ann Surg. 2013;257(2):180–1.PubMedCrossRef
15.
go back to reference Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol. 2009;6(6):339–51.PubMedCrossRef Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol. 2009;6(6):339–51.PubMedCrossRef
16.
go back to reference Naume B, Borgen E, Beiske K, et al. Immunomagnetic techniques for the enrichment and detection of isolated breast carcinoma cells in bone marrow and peripheral blood. J Hematother. 1997;6(2):103–14.PubMedCrossRef Naume B, Borgen E, Beiske K, et al. Immunomagnetic techniques for the enrichment and detection of isolated breast carcinoma cells in bone marrow and peripheral blood. J Hematother. 1997;6(2):103–14.PubMedCrossRef
17.
go back to reference Bidard FC, Mathiot C, Delaloge S, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol. 2010;21(4):729–33.PubMedCrossRef Bidard FC, Mathiot C, Delaloge S, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol. 2010;21(4):729–33.PubMedCrossRef
18.
go back to reference Rack B, Schindlbeck C, Juckstock J, et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. 2014;106(5). Rack B, Schindlbeck C, Juckstock J, et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. 2014;106(5).
19.
go back to reference Franken B, de Groot MR, Mastboom WJ, et al. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res. 2012;14(5):R133.PubMedPubMedCentralCrossRef Franken B, de Groot MR, Mastboom WJ, et al. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res. 2012;14(5):R133.PubMedPubMedCentralCrossRef
20.
go back to reference van Dalum G, van der Stam GJ, Tibbe AG, et al. Circulating tumor cells before and during follow-up after breast cancer surgery. Int J Oncol. 2015;46(1):407–13.PubMed van Dalum G, van der Stam GJ, Tibbe AG, et al. Circulating tumor cells before and during follow-up after breast cancer surgery. Int J Oncol. 2015;46(1):407–13.PubMed
21.
go back to reference Lucci A, Hall CS, Lodhi AK, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. 2012;13(7):688–95.PubMedCrossRef Lucci A, Hall CS, Lodhi AK, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. 2012;13(7):688–95.PubMedCrossRef
22.
go back to reference Edge SB. AJCC cancer staging manual. 7th ed. New York: Springer; 2010. Edge SB. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.
23.
go back to reference Black MM, Speer FD. Nuclear structure in cancer tissues. Surg Gynecol Obstet. 1957;105(1):97–102.PubMed Black MM, Speer FD. Nuclear structure in cancer tissues. Surg Gynecol Obstet. 1957;105(1):97–102.PubMed
24.
go back to reference Krishnamurthy S, Cristofanilli M, Singh B, et al. Detection of minimal residual disease in blood and bone marrow in early stage breast cancer. Cancer. 2010;116(14):3330–7.PubMedCrossRef Krishnamurthy S, Cristofanilli M, Singh B, et al. Detection of minimal residual disease in blood and bone marrow in early stage breast cancer. Cancer. 2010;116(14):3330–7.PubMedCrossRef
25.
go back to reference Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.PubMedCrossRef Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.PubMedCrossRef
26.
go back to reference McShane LM, Altman DG, Sauerbrei W, et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). Eur J Cancer. 2005;41(12):1690–6.PubMedCrossRef McShane LM, Altman DG, Sauerbrei W, et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). Eur J Cancer. 2005;41(12):1690–6.PubMedCrossRef
27.
go back to reference Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127–32.PubMedCrossRef Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127–32.PubMedCrossRef
28.
go back to reference Pierga JY, Bidard FC, Mathiot C, et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res. 2008;14(21):7004–10.PubMedCrossRef Pierga JY, Bidard FC, Mathiot C, et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res. 2008;14(21):7004–10.PubMedCrossRef
29.
go back to reference Wulfing P, Borchard J, Buerger H, et al. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res. 2006;12(6):1715–20.PubMedCrossRef Wulfing P, Borchard J, Buerger H, et al. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res. 2006;12(6):1715–20.PubMedCrossRef
30.
go back to reference Karhade M, Hall C, Mishra P, et al. Circulating tumor cells in non-metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2014;147(2):325–33.PubMedPubMedCentralCrossRef Karhade M, Hall C, Mishra P, et al. Circulating tumor cells in non-metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2014;147(2):325–33.PubMedPubMedCentralCrossRef
31.
go back to reference Muller V, Stahmann N, Riethdorf S, et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res. 2005;11(10):3678–85.PubMedCrossRef Muller V, Stahmann N, Riethdorf S, et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res. 2005;11(10):3678–85.PubMedCrossRef
32.
go back to reference Gazzaniga P, Naso G, Gradilone A, et al. Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors. Int J Cancer. 2010;126(10):2437–47.PubMed Gazzaniga P, Naso G, Gradilone A, et al. Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors. Int J Cancer. 2010;126(10):2437–47.PubMed
33.
go back to reference Gradilone A, Naso G, Raimondi C, et al. Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization. Ann Oncol. 2011;22(1):86–92.PubMedCrossRef Gradilone A, Naso G, Raimondi C, et al. Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization. Ann Oncol. 2011;22(1):86–92.PubMedCrossRef
34.
go back to reference Apostolaki S, Perraki M, Pallis A, et al. Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance. Ann Oncol. 2007;18(5):851–8.PubMedCrossRef Apostolaki S, Perraki M, Pallis A, et al. Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance. Ann Oncol. 2007;18(5):851–8.PubMedCrossRef
35.
go back to reference Fehm T, Muller V, Aktas B, et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat. 2010;124(2):403–12.PubMedCrossRef Fehm T, Muller V, Aktas B, et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat. 2010;124(2):403–12.PubMedCrossRef
37.
go back to reference Meng S, Tripathy D, Shete S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci U S A. 2004;101(25):9393–8.PubMedPubMedCentralCrossRef Meng S, Tripathy D, Shete S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci U S A. 2004;101(25):9393–8.PubMedPubMedCentralCrossRef
38.
go back to reference Riethdorf S, Muller V, Zhang L, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res. 2010;16(9):2634–45.PubMedCrossRef Riethdorf S, Muller V, Zhang L, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res. 2010;16(9):2634–45.PubMedCrossRef
39.
go back to reference Tewes M, Aktas B, Welt A, et al. Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res Treat. 2009;115(3):581–90.PubMedCrossRef Tewes M, Aktas B, Welt A, et al. Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res Treat. 2009;115(3):581–90.PubMedCrossRef
40.
go back to reference Nadal R, Fernandez A, Sanchez-Rovira P, et al. Biomarkers characterization of circulating tumour cells in breast cancer patients. Breast Cancer Res. 2012;14(3):R71.PubMedPubMedCentralCrossRef Nadal R, Fernandez A, Sanchez-Rovira P, et al. Biomarkers characterization of circulating tumour cells in breast cancer patients. Breast Cancer Res. 2012;14(3):R71.PubMedPubMedCentralCrossRef
Metadata
Title
Circulating Tumor Cells After Neoadjuvant Chemotherapy in Stage I–III Triple-Negative Breast Cancer
Authors
Carolyn Hall, PhD
Mandar Karhade, MBBS, MPH
Barbara Laubacher, BSN
Amber Anderson, BS
Henry Kuerer, MD, PhD
Sarah DeSynder, MD
Anthony Lucci, MD
Publication date
01-12-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4600-6

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