Browse > Article
http://dx.doi.org/10.7314/APJCP.2013.14.4.2401

Predictive Factors Determining Neoadjuvant Chemotherapy Outcomes in Breast Cancer - a Single Center Experience  

Yu, Yang (Department of Breast Surgery, Zhejiang Cancer Hospital)
Xiang, Hua (Department of Pathology, First Affiliated Hospital of College of Medicine, Zhejiang University)
He, Xiang-Ming (Department of Breast Surgery, Zhejiang Cancer Hospital)
Yang, Hong-Jian (Department of Breast Surgery, Zhejiang Cancer Hospital)
Zong, Xiang-Yun (Department of Breast Surgery, Shanghai 6th Hospital, Shanghai Jiaotong University School of Medicine)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.4, 2013 , pp. 2401-2406 More about this Journal
Abstract
From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.
Keywords
Neoadjuvant chemotherapy; invasive breast cancer; hormone receptor; HER2; topoisomerase $II{\alpha}$;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Petrarca CR, Brunetto AT, Duval V, Brondani A, et al (2011). Survivin as a predictive biomarker of complete pathologic response to neoadjuvant chemotherapy in patients with stage II and stage III breast cancer. Clin Breast Cancer, 11, 129-34.   DOI   ScienceOn
2 Rastogi P, Anderson SJ, Bear HD, Geyer CE, et al (2008). Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol, 26, 778-85.   DOI   ScienceOn
3 Untch M, von Minckwitz G (2011). Neoadjuvant chemotherapy: early response as a guide for further treatment: clinical, radiological, and biological. J Natl Cancer Inst Monogr, 43, 138-41.
4 Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B (2001). Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr, 30, 96-102.
5 Wu J, Li S, Jia W, Su F (2011). Response and prognosis of taxanes and anthracyclines neoadjuvant chemotherapy in patients with triple-negative breast cancer. J Cancer Res Clin Oncol, 137, 1505-10.   DOI
6 Zhu L, Li YF, Chen WG, He JR, et al (2008). HER2 and topoisomerase IIalpha: possible predictors of response to neoadjuvant chemotherapy for breast cancer patients. Chin Med J (Engl), 121, 1965-8.
7 Aigner J, Schneeweiss A, Sohn C, Marme F (2011). The role of neoadjuvant chemotherapy in the management of primary breast cancer. Minerva Ginecol, 63, 261-74.
8 Arpino G, Ciocca DR, Weiss H, Allred DC, et al (2005). Predictive value of apoptosis, proliferation, HER-2, and topoisomerase IIalpha for anthracycline chemotherapy in locally advanced breast cancer. Breast Cancer Res Treat, 92, 69-75.   DOI
9 Bonnefoi H, Piccart M, Bogaerts J, Mauriac L, et al (2011). TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial. Lancet Oncol, 12, 527-39.   DOI   ScienceOn
10 Coon JS, Marcus E, Gupta-Burt S, Seelig S, et al (2002). Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res, 8, 1061-7.
11 Di Leo A, Gancberg D, Larsimont D, Tanner M, et al (2002). HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracyclinebased therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res, 8, 1107-16.
12 Di Leo A, Larsimont D, Gancberg D, Jarvinen T, et al (2001). HER-2 and topoisomerase II alpha as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide. Ann Oncol, 12, 1081-9.   DOI   ScienceOn
13 Dowsett M, Nielsen TO, A'hern R, Bartlett J, et al (2011). Assessment of ki67 in breast cancer: recommendations from the international ki67 in breast cancer working group. J Natl Cancer Inst, 103, 1656-64.   DOI   ScienceOn
14 Du Y, Zhou Q, Yin W, Zhou L, et al (2011). The role of topoisomerase II${\alpha}$ in predicting sensitivity to anthracyclines in breast cancer patients: a meta-analysis of published literatures. Breast Cancer Res Treat, 129, 839-48.   DOI   ScienceOn
15 Duffaud F, Therasse P (2000). New guidelines to evaluate the response to treatment in solid tumors. Bull Cancer, 87, 881-6.
16 Fritz P, Cabrera CM, Dippon J, Gerteis A, et al (2005). c-erbB2 and topoisomerase IIalpha protein expression independently predict poor survival in primary human breast cancer: a retrospective study. Breast Cancer Res, 7, R374-84.   DOI   ScienceOn
17 Harris LN, Broadwater G, Abu-Khalaf M, Cowan D, et al (2009). Topoisomerase II{alpha} amplification does not predict benefit from dose-intense cyclophosphamide, doxorubicin, and fluorouracil therapy in HER2-amplified early breast cancer: results of CALGB 8541/150013. J Clin Oncol, 27, 3430-6.   DOI   ScienceOn
18 Generali D, Symmans WF, Berruti A, Fox SB (2011). Predictive immunohistochemical biomarkers in the context of neoadjuvant therapy for breast cancer. J Natl Cancer Inst Monogr, 43, 99-102.
19 Glynn RW, Mahon S, Curran C, Callagy G, et al (2011). TOP2A amplification in the absence of that of HER-2/neu: toward individualization of chemotherapeutic practice in breast cancer. Oncologist, 16, 949-55.   DOI   ScienceOn
20 Gnant M, Harbeck N, Thomssen C (2011). St. Gallen 2011: Summary of the Consensus Discussion. Breast Care (Basel), 6, 136-41.   DOI   ScienceOn
21 Harris LN, Yang L, Liotcheva V, Pauli S, et al (2001). Induction of topoisomerase II activity after ErbB2 activation is associated with a differential response to breast cancer chemotherapy. Clin Cancer Res, 7, 1497-504.
22 Jarvinen TA, Holli K, Kuukasjarvi T, Isola JJ (1998). Predictive value of topoisomerase IIalpha and other prognostic factors for epirubicin chemotherapy in advanced breast cancer. Br J Cancer, 77, 2267-73.   DOI   ScienceOn
23 Jarvinen TA, Liu ET (2003). HER-2/neu and topoisomerase IIalpha in breast cancer. Breast Cancer Res Treat, 78, 299-311.   DOI   ScienceOn
24 Jarvinen TA, Tanner M, Rantanen V, Barlund M, et al (2000). Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. Am J Pathol, 156, 839-47.   DOI   ScienceOn
25 Kurosumi M (2004). Significance of histopathological evaluation in primary therapy for breast cancer--recent trends in primary modality with pathological complete response (pCR) as endpoint. Breast Cancer, 11, 139-47.   DOI
26 Jiang ZF, Wang T (2009). An interpretation of the China edition of National Comprehensive Cancer Network(NCCN) clinical practice guideline for breast cancer. [Article in Chinese] Zhonghua Wai Ke Za Zhi, 47, 485-7.
27 Knoop AS, Knudsen H, Balslev E, Rasmussen BB, et al (2005). retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol, 23, 7483-90.   DOI   ScienceOn
28 Kong X, Moran MS, Zhang N, Haffty B, Yang Q (2011). Metaanalysis confirms achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur J Cancer, 47, 2084-90.   DOI   ScienceOn
29 Kurosumi M (2006). Significance and problems in evaluations of pathological responses to neoadjuvant therapy for breast cancer. Breast Cancer, 13, 254-9.   DOI
30 Leong SP, Shen ZZ, Liu TJ, Agarwal G, et al (2010). Is breast cancer the same disease in Asian and Western countries? World J Surg, 34, 2308-24.   DOI   ScienceOn
31 Munro AF, Cameron DA, Bartlett JM (2010). Targeting anthracyclines in early breast cancer: new candidate predictive biomarkers emerge. Oncogene, 29, 5231-40.   DOI   ScienceOn
32 Li XR, Liu M, Zhang YJ, Wang JD, et al (2011). ER, PgR, HER-2, Ki-67, topoisomerase II${\alpha}$, and nm23-H1 proteins expression as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer. Med Oncol, 1, S48-54.
33 Lips EH, Mulder L, de Ronde JJ, Mandjes IA, et al (2012). Neoadjuvant chemotherapy in ER+ HER2-breast cancer: response prediction based on immunohistochemical and molecular characteristics. Breast Cancer Res Treat, 131, 827-36.   DOI   ScienceOn
34 Moreno-Aspitia A (2012). Neoadjuvant therapy in early-stage breast cancer. Crit Rev Oncol Hematol, 82, 187-99.   DOI   ScienceOn
35 Ng AK, Travis LB (2009). Radiation therapy and breast cancer risk. J Natl Compr Canc Netw, 7, 1121-8.
36 Oshima K, Naoi Y, Kishi K, Nakamura Y, et al (2011). Gene expression signature of TP53 but not its mutation status predicts response to sequential paclitaxel and 5-FU/ epirubicin/cyclophosphamide in human breast cancer. Cancer Lett, 307, 149-57.   DOI   ScienceOn