Prognostic analysis of triple-negative breast cancer patients treated with adjuvant chemotherapy of fluorouracil, epirubicin and cyclophosphamide

Sun,Weiling; Li,Chunhong; Liu,Meiyan; Liu,Wei; Yang,Chunyu; Cai,Li

doi:10.3892/ol.2016.4176

Prognostic analysis of triple-negative breast cancer patients treated with adjuvant chemotherapy of fluorouracil, epirubicin and cyclophosphamide

Authors:
- Weiling Sun
- Chunhong Li
- Meiyan Liu
- Wei Liu
- Chunyu Yang
- Li Cai
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Affiliations: The Department of Endoscopy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150040, P.R. China, The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150040, P.R. China
Published online on: February 2, 2016 https://doi.org/10.3892/ol.2016.4176
Pages: 2320-2326

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Abstract

The aim of the present study was to investigate the association between the clinicopathological and demographic factors, and the survival time of patients with triple‑negative breast cancer (TNBC) in China. The patients had received adjuvant chemotherapy consisting of 5‑fluorouracil, epirubicin and cyclophosphamide (FEC; 500 mg/m2 cyclophosphamide, day 1; 75 mg/m2 epirubicin, day 1; 500 mg/m2 5‑fluorouracil, days 1 and 8; every 3 weeks, for at least 4 cycles). The clinicopathological and demographic factors affecting the outcome of the patients with TNBC that received adjuvant FEC chemotherapy were evaluated. Within these variables, the overall survival (OS) and disease‑free survival (DFS) times were analyzed using the log‑rank test, which was constructed using the multivariate Cox proportional hazards regression model and Kaplan‑Meier analysis. Additionally, Spearman's χ2 test was used to analyze categorical variables. In the univariate statistical analysis, the significant risk factors for TNBC patient survival were the stage of disease and lymph node status, which were associated with the OS and DFS, and the total number of pregnancies, which was associated with the DFS. In the multivariate Cox proportional hazard model, lymph node status was an independent prognostic indicator of OS [P<0.001; hazard ratio (HR), 1.996; 95% confidence interval (CI), 1.465‑2.720] and DFS (P<0.001; HR, 1.824; 95% CI, 1.315‑2.531). By the Kaplan‑Meier method, the stage of disease and lymph node status demonstrated a significant effect on OS and DFS. Patients with the lymph node status N3 and stage III disease possessed a poor prognosis and survival. An association between lymph node status and the tumor recurrence and mortality rate was identified. The area under the curves of the lymph node status for TNBC recurrence and mortality were 0.676 (P=0.002) and 0.685 (P=0.001), respectively. Additionally, the number of pregnancies was associated with tumor size, lymph node status and stages of disease. Lymph node status is an independent prognostic indicator of OS and DFS to TNBC patients with FEC adjuvant chemotherapy.

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1	Alkis N, Durnali AG, Arslan UY, Kocer M, Onder FO, Tokluoglu S, Celenkoglu G, Muallaoglu S, Utkan G, Ulas A, et al: Optimal timing of adjuvant treatment in patients with early breast cancer. Med Oncol. 28:1255–1259. 2011. View Article : Google Scholar : PubMed/NCBI
2	Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI
3	Ono M, Tsuda H, Shimizu C, Yamamoto S, Shibata T, Yamamoto H, Hirata T, Yonemori K, Ando M, Tamura K, et al: Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer. Breast Cancer Res Treat. 132:793–805. 2012. View Article : Google Scholar : PubMed/NCBI
4	Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF, Nicholson RI and Ellis IO: Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol. 203:661–671. 2004. View Article : Google Scholar : PubMed/NCBI
5	Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 295:2492–2502. 2006. View Article : Google Scholar : PubMed/NCBI
6	Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 10:5367–5374. 2004. View Article : Google Scholar : PubMed/NCBI
7	Prat A and Perou CM: Deconstructing the molecular portraits of breast cancer. Mol Oncol. 5:5–23. 2011. View Article : Google Scholar : PubMed/NCBI
8	Dawson SJ, Provenzano E and Caldas C: Triple negative breast cancers: Clinical and prognostic implications. Eur J Cancer. 45(Suppl 1): 27–40. 2009. View Article : Google Scholar : PubMed/NCBI
9	Bauer KR, Brown M, Cress RD, Parise CA and Caggiano V: Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California cancer Registry. Cancer. 109:1721–1728. 2007. View Article : Google Scholar : PubMed/NCBI
10	Irvin WJ Jr and Carey LA: What is triple-negative breast cancer? Eur J Cancer. 44:2799–2805. 2008. View Article : Google Scholar : PubMed/NCBI
11	Pal SK, Childs BH and Pegram M: Triple negative breast cancer: Unmet medical needs. Breast Cancer Res Treat. 125:627–636. 2011. View Article : Google Scholar : PubMed/NCBI
12	Foulkes WD, Smith IE and Reis-Filho JS: Triple-negative breast cancer. N Engl J Med. 363:1938–1948. 2010. View Article : Google Scholar : PubMed/NCBI
13	Metzger-Filho O, Tutt A, de Azambuja E, Saini KS, Viale G, Loi S, Bradbury I, Bliss JM, Azim HA Jr, Ellis P, et al: Dissecting the heterogeneity of triple-negative breast cancer. J Clin Oncol. 30:1879–1887. 2012. View Article : Google Scholar : PubMed/NCBI
14	Gucalp A and Traina TA: Triple-negative breast cancer: Adjuvant therapeutic options. Chemother Res Pract. 2011:6962082011.PubMed/NCBI
15	De Laurentiis M, Cianniello D, Caputo R, Stanzione B, Arpino G, Cinieri S, Lorusso V and De Placido S: Treatment of triple negative breast cancer (TNBC): Current options and future perspectives. Cancer Treat Rev. 36(Suppl 3): S80–S86. 2010. View Article : Google Scholar : PubMed/NCBI
16	Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, et al: Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol. 28:1145–1153. 2010. View Article : Google Scholar : PubMed/NCBI
17	Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF and Ellis IO: Prognostic markers in triple-negative breast cancer. Cancer. 109:25–32. 2007. View Article : Google Scholar : PubMed/NCBI
18	Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P and Narod SA: Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res. 13:4429–4434. 2007. View Article : Google Scholar : PubMed/NCBI
19	Calza S, Hall P, Auer G, Bjöhle J, Klaar S, Kronenwett U, Liu ET, Miller L, Ploner A, Smeds J, et al: Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients. Breast Cancer Res. 8:R342006. View Article : Google Scholar : PubMed/NCBI
20	Mersin H, Yildirim E, Berberoglu U and Gülben K: The prognostic importance of triple negative breast carcinoma. Breast. 17:341–346. 2008. View Article : Google Scholar : PubMed/NCBI
21	Rodríguez-Pinilla SM, Sarrió D, Honrado E, Hardisson D, Calero F, Benitez J and Palacios J: Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas. Clin Cancer Res. 12:1533–1539. 2006. View Article : Google Scholar : PubMed/NCBI
22	Rodríguez-Pinilla SM, Sarrió D, Honrado E, Moreno-Bueno G, Hardisson D, Calero F, Benítez J and Palacios J: Vimentin and laminin expression is associated with basal-like phenotype in both sporadic and BRCA1-associated breast carcinomas. J Clin Pathol. 60:1006–1012. 2007. View Article : Google Scholar : PubMed/NCBI
23	Reis-Filho JS, Milanezi F, Steele D, Savage K, Simpson PT, Nesland JM, Pereira EM, Lakhani SR and Schmitt FC: Metaplastic breast carcinomas are basal-like tumours. Histopathology. 49:10–21. 2006. View Article : Google Scholar : PubMed/NCBI
24	Abdulkarim BS, Cuartero J, Hanson J, Deschênes J, Lesniak D and Sabri S: Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol. 29:2852–2858. 2011. View Article : Google Scholar : PubMed/NCBI
25	Hernandez-Aya LF, Chavez-Macgregor M, Lei X, Meric-Bernstam F, Buchholz TA, Hsu L, Sahin AA, Do KA, Valero V, Hortobagyi GN, et al: Nodal status and clinical outcomes in a large cohort of patients with triple-negative breast cancer. J Clin Oncol. 29:2628–2634. 2011. View Article : Google Scholar : PubMed/NCBI
26	Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL and Massagué J: Genes that mediate breast cancer metastasis to lung. Nature. 436:518–524. 2005. View Article : Google Scholar : PubMed/NCBI
27	Bertucci F, Finetti P, Cervera N, Charafe-Jauffret E, Mamessier E, Adélaïde J, Debono S, Houvenaeghel G, Maraninchi D, Viens P, et al: Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res. 66:4636–4644. 2006. View Article : Google Scholar : PubMed/NCBI
28	Fadare O, Wang SA and Hileeto D: The expression of cytokeratin 5/6 in invasive lobular carcinoma of the breast: Evidence of a basal-like subset? Hum Pathol. 39:331–336. 2008. View Article : Google Scholar : PubMed/NCBI
29	Oakman C, Viale G and Di Leo A: Management of triple negative breast cancer. Breast. 19:312–321. 2010. View Article : Google Scholar : PubMed/NCBI
30	Sihto H, Lundin J, Lundin M, Lehtimäki T, Ristimäki A, Holli K, Sailas L, Kataja V, Turpeenniemi-Hujanen T, Isola J, et al: Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: A nationwide cohort study. Breast Cancer Res. 13:R872011. View Article : Google Scholar : PubMed/NCBI
31	Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, Nielsen TO and Gelmon K: Metastatic behavior of breast cancer subtypes. J Clin Oncol. 28:3271–3277. 2010. View Article : Google Scholar : PubMed/NCBI
32	Colleoni M, Cole BF, Viale G, Regan MM, Price KN, Maiorano E, Mastropasqua MG, Crivellari D, Gelber RD, Goldhirsch A, et al: Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: Results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Clin Oncol. 28:2966–2973. 2010. View Article : Google Scholar : PubMed/NCBI
33	Cheang MC, Voduc KD, Tu D, Jiang S, Leung S, Chia SK, Shepherd LE, Levine MN, Pritchard KI, Davies S, et al: Responsiveness of intrinsic subtypes to adjuvant anthracycline substitution in the NCIC.CTG MA.5 randomized trial. Clin Cancer Res. 18:2402–2412. 2012. View Article : Google Scholar : PubMed/NCBI
34	Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, Dumontet C, Reed J, Krajewska M, Treilleux I, Rupin M, 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. 27:1168–1176. 2009. View Article : Google Scholar : PubMed/NCBI
35	Bhatti AB, Khan AI, Siddiqui N, Muzaffar N, Syed AA, Shah MA and Jamshed A: Outcomes of triple-negative versus non-triple-negative breast cancers managed with breast-conserving therapy. Asian Pac J Cancer Prev. 15:2577–2581. 2014. View Article : Google Scholar : PubMed/NCBI
36	Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W and Toppmeyer D: Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 24:5652–5657. 2006. View Article : Google Scholar : PubMed/NCBI
37	Zhang L, Hao C, Dong G and Tong Z: Analysis of Clinical Features and Outcome of 356 Triple-Negative Breast Cancer Patients in China. Breast Care (Basel). 7:13–17. 2012. View Article : Google Scholar : PubMed/NCBI
38	Tischkowitz M, Brunet JS, Bégin LR, Huntsman DG, Cheang MC, Akslen LA, Nielsen TO and Foulkes WD: Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer. 7:1342007. View Article : Google Scholar : PubMed/NCBI
39	Kandel MJ, Stadler Z, Masciari S, Collins L, Schnitt S, Harris L, Miron A, Richardson A and Garber JE: Prevalence of BRCA1 mutations in triple negative breast cancer (BC). J Clin Oncol. 24(Suppl 18): 5082006.
40	Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML and Perou CM: The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 13:2329–2334. 2007. View Article : Google Scholar : PubMed/NCBI
41	Kaplan HG, Malmgren JA and Atwood M: T1N0 triple negative breast cancer: Risk of recurrence and adjuvant chemotherapy. Breast J. 15:454–460. 2009. View Article : Google Scholar : PubMed/NCBI