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Drugs
Published in: Drugs 17/2010

01-12-2010 | Review Article

Triple-Negative Breast Cancer

Epidemiology and Management Options

Author: Dr Shaheenah Dawood

Published in: Drugs | Issue 17/2010

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Abstract

The triple receptor-negative breast cancer (TNBC) subtype is characterized by the lack of expression of both hormone receptors as well as lack of over-expression and/or lack of gene amplification of human epidermal growth factor receptor 2 (HER2). Approximately 10–15% of breast carcinomas are known to be of the TNBC subtype, which constitutes approximately 80% of all ‘basal-like tumours’. Risk factors for TNBC include young age at breast cancer diagnosis, young age at menarche, high parity, lack of breast feeding, high body mass index and African American ethnicity. The majority of BRCA1 tumours are TNBC. TNBC has a worse prognosis and tends to relapse early compared with other subtypes of breast cancer. Conversely, it displays increased chemosensitivity compared with other breast tumour subtypes. Several agents are currently being investigated as potential therapeutic agents for the treatment of women with TNBC including agents targeted against EGFR, anti-angiogenic agents, multityrosine kinase inhibitors and poly (ADP-ribose) polymerase (PARP) inhibitors. This review focuses on the epidemiology of TNBC, its pathological features, natural history and recurrence patterns as well as current and future management options.
Literature
1.
2.
Berry DA, Inoue L, Shen Y, et al. Modeling the impact of treatment and screening on U.S. breast cancer mortality: a Bayesian approach. J Natl Cancer Inst Monogr 2006; 36: 30–6PubMedCrossRef
3.
Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumors. Nature 2000; 406: 747–52PubMedCrossRef
4.
Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001; 9819: 10869–74CrossRef
5.
Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003; 100: 8418–23PubMedCrossRef
6.
Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004; 10: 5367–74PubMedCrossRef
7.
Livasy CA, Karaca G, Nanda R, et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006; 2: 264–71CrossRef
8.
Dawood S, Broglio K, Buzdar AU, et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 2010; 28: 92–8PubMedCrossRef
9.
Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 2005; 23: 7350–60PubMedCrossRef
10.
Bertucci F, Finetti P, Cervera N, et al. How basal are triple-negative breast cancers? Int J Cancer 2008; 123: 236–40PubMedCrossRef
11.
Kreike B, van Kouwenhove M, Horlings H, et al. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 2007; 9(5): R65PubMedCrossRef
12.
Sotiriou C, Neo SY, McShane LM, et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 2003; 100: 10393–8PubMedCrossRef
13.
Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005; 11: 5678–85PubMedCrossRef
14.
Fan C, Oh DS, Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 2006; 355: 560–9PubMedCrossRef
15.
Hu Z, Fan C, Oh DS, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006; 7: 96PubMedCrossRef
16.
Cheang MC, Voduc D, Bajdik C, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 2008; 14: 1368–76PubMedCrossRef
17.
Viale G, Bottiglieri L. Pathological definition of triple negative breast cancer. Eur J Cancer 2009; 45 Suppl. 1: 5–10PubMedCrossRef
18.
Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene 2006; 25: 5846–53PubMedCrossRef
19.
Anders C, Carey LA. Understanding and treating triple-negative breast cancer. Oncology (Williston Park) 2008; 22: 1233–9
20.
Linn SC, Van ‘t Veer LJ. Clinical relevance of the triple-negative breast cancer concept: genetic basis and clinical utility of the concept. Eur J Cancer 2009; 45 Suppl. 1: 11–26PubMedCrossRef
21.
Collins LC, Martyniak A, Kandel MJ, et al. Basal cytokeratin and epidermal growth factor receptor expression are not predictive of BRCA1 mutation status in women with triple-negative breast cancers. Am J Surg Pathol 2009; 33: 1093–7PubMedCrossRef
22.
Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006; 295: 2492–502PubMedCrossRef
23.
Millikan RC, Newman B, Tse CK, et al. Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 2008; 109: 123–39PubMedCrossRef
24.
Yang XR, Sherman ME, Rimm DL, et al. Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 2007; 16: 439–43PubMedCrossRef
25.
Bauer KR, Brown M, Cress RD, et al. 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 2007; 109: 1721–8PubMedCrossRef
26.
Morris GJ, Naidu S, Topham AK, et al. Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Cancer 2007; 110: 876–84PubMedCrossRef
27.
Anderson WF, Jatoi I, Devesa SS. Distinct breast cancer incidence and prognostic patterns in the NCI’s SEER program: suggesting a possible link between etiology and outcome. Breast Cancer Res Treat 2005; 90: 127–37PubMedCrossRef
28.
Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007; 13: 4429–34PubMedCrossRef
29.
Collett K, Stefansson IM, Eide J, et al. A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors. Cancer Epidemiol Biomarkers Prev 2005; 14: 1108–12PubMedCrossRef
30.
Yang WT, Dryden M, Broglio K, et al. Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Res Treat 2008; 111: 405–10PubMedCrossRef
31.
Wang Y, Ikeda DM, Narasimhan B, et al. Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression. Radiology 2008; 246: 367–75PubMedCrossRef
32.
Kim SH, Seo BK, Lee J, et al. Correlation of ultrasound findings with histology, tumor grade, and biological markers in breast cancer. Acta Oncol 2008; 47: 1531–8PubMedCrossRef
33.
Uematsu T, Kasami M, Yuen S. Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology 2009; 250: 638–47PubMedCrossRef
34.
Basu S, Chen W, Tchou J, et al. Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization. Cancer 2008; 112: 995–1000PubMedCrossRef
35.
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet 2008; 371: 29–40CrossRef
36.
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–717CrossRef
37.
Henderson IC, Berry DA, Demetri GD, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 2003; 21: 976–83PubMedCrossRef
38.
Hayes DF, Thor AD, Dressler LG, et al., Cancer and Leukemia Group B (CALGB) Investigators. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 2007; 357: 1496–506PubMedCrossRef
39.
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: 1168–76PubMedCrossRef
40.
Jacquemier J, Penault-Llorca F, Mnif H, et al. Identification of a basal-like subtype and comparative effect of epirubicin-based chemotherapy and sequential epirubicin followed by docetaxel chemotherapy in the PACS 01 breast cancer trial: 33 markers studied on tissue-microarrays (TMA) [abstract no. 509]. J Clin Oncol 2006; 24 Suppl.: 5S
41.
Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003; 21: 1431–9PubMedCrossRef
42.
Huober J, von Minckwitz G, Denkert C, et al. Neoadjuvant chemotherapy in operable breast cancer with docetaxel, doxorubicin, and cyclophosphamide (TAC) or TAC followed by vinorelbine and capecitabine (NX): final results and analysis of markers predicting response to treatment [abstract no. 524]. J Clin Oncol 2009; 27 Suppl.: 15sCrossRef
43.
Rodríguez-Lescure A, Martín M, Ruiz A, et al. Subgroup analysis of GEICAM 9906 trial comparing six cycles of FE90C (FEC) to four cycles of FE90C followed by 8 weekly paclitaxel administrations (FECP): relevance of HER2 and hormonal status (HR) [abstract no. 10598]. J Clin Oncol 2007; 25 (18S Jun 20 Suppl.): 10598
44.
Loesch DM, Greco F, O’Shaughnessy J, et al. A randomized, multicenter phase III trial comparing doxorubicin + cyclophosphamide followed by paclitaxel or doxorubicin + paclitaxel followed by weekly paclitaxel as adjuvant therapy for high-risk breast cancer [abstract no. 517]. J Clin Oncol 2007; 25 (18S Jun 20 Suppl.): 517CrossRef
45.
Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358: 1663–71PubMedCrossRef
46.
Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 2007; 13: 2329–34PubMedCrossRef
47.
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: 1275–81PubMedCrossRef
48.
Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathological primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999; 17: 460–9PubMed
49.
Pivot XB, Li RK, Thomas ES, et al. Activity of ixabepilone in oestrogen receptor-negative and oestrogen receptor-progesterone receptor-human epidermal growth factor receptor 2-negative metastatic breast cancer. Eur J Cancer 2009; 45: 2940–6PubMedCrossRef
50.
Taniguchi T, Tischkowitz M, Ameziane N, et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 2003; 9: 568–74PubMedCrossRef
51.
Turner N, Tutt A, Ashworth A. Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 2004; 4: 814–9PubMedCrossRef
52.
Garber J, Richardson A, Harris L, et al. Neoadjuvant cisplatin (CDDP) in triple negative breast (BC) [abstract no. 3074]. Breast Cancer Res Treat 2006; 100 Suppl. 1
53.
O’Shaughnessy J, Weckstein D, Vukelja S, et al. Preliminary results of a randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer [abstract no. 308]. Breast Cancer Res Treat 2007; 106 Suppl. 1: S32
54.
Sirohi B, Arnedos M, Popat S, et al. Platinum-based chemotherapy in triple-negative breast cancer. Ann Oncol 2008; 19: 1847–52PubMedCrossRef
55.
Roy V, Pockaj BA, Northfelt DW, et al. N0338 phase II trial of docetaxel and carboplatin administered every two weeks as induction therapy for stage II or III breast cancer [abstract no. 563]. J Clin Oncol 2008; 26 (15S May 20 Suppl.): 563CrossRef
56.
Byrski T, Huzarski T, Dent R, et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 2009; 115: 359–63PubMedCrossRef
57.
Byrski T, Gronwald J, Huzarski T, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 2010; 28: 375–9PubMedCrossRef
58.
Silver DP, Richardson AL, Eklund AC, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol 2010; 28: 1145–53PubMedCrossRef
59.
Torrisi R, Balduzzi A, Ghisini R, et al. Tailored preoperative treatment of locally advanced triple negative (hormone receptor negative and HER2 negative) breast cancer with epirubicin, cisplatin, and infusional fluorouracil followed by weekly paclitaxel. Cancer Chemother Pharmacol 2008 Sep; 62(4): 667–72PubMedCrossRef
60.
Leone JP, Guardiolo V, Venkatraman A, et al. Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): retrospective analysis of 125 patients [abstract no. 625]. J Clin Oncol 2009; 27 (15S May 20 Suppl.): 625
61.
Carey LA, Rugo HS, Marcom PK, et al. TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer [abstract no. 1009]. J Clin Oncol 2008; 26 (15 Suppl.): 43s
62.
Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357: 2666–76PubMedCrossRef
63.
O’Shaughnessy J, Osborne C, Pippen J, et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial [abstract no. 3]. J Clin Oncol 2009; 27 (18s)
64.
Tutt A, Robson M, Garber JE, et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer [abstract no. CRA501]. J Clin Oncol 2009; 27 (18s)
65.
Cancer and Leukemia Group B. Paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide in treating patients with breast cancer that can be removed by surgery [ClinicalTrials. gov identifier NCT00861705]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Sep 11]
66.
Massachusetts General Hospital. Platinum for triple-negative metastatic breast cancer and evaluation of p63/p73 as a biomarker of response [ClinicalTrials.gov identifier NCT00483223]. US National Institutes of Health, Clinical Trials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Sep 11]
67.
Sarah Cannon Research Institute. Panitumumab, gemcita-bine and carboplatin in triple-negative metastatic breast cancer [ClinicalTrials.gov identifier NCT00894504]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Sep 11]
68.
Linderholm BK, Klintman M, Grabau D, et al. Significantly higher expression of vascular endothelial growth factor (VEGF) and shorter survival after recurrences in premeno-pausal node negative patients with triple negative breast cancer [abstract no. 1077]. Cancer Res 2009; 69(2): 128–9SCrossRef
69.
Burstein HJ, Elias AD, Rugo HS, et al. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2008; 26: 1810–6PubMedCrossRef
70.
Guarneri V, Conte P. Metastatic breast cancer: therapeutic options according to molecular subtypes and prior adjuvant therapy. Oncologist 2009; 14: 645–56PubMedCrossRef
71.
Yang XR, Pfeiffer RM, Garcia-Closas M, et al. Hormonal markers in breast cancer: coexpression, relationship with pathologic characteristics, and risk factor associations in a population-based study. Cancer Res 2007; 67: 10608–17PubMedCrossRef
72.
Bradley CJ, Given XW, Roberts C. Race, socioeconomic status, and breast cancer treatment and survival. J Natl Cancer Inst 2002; 94: 490–6PubMedCrossRef
73.
Dawood S, Broglio K, Kau SW, et al. Triple receptor-negative breast cancer: the effect of race on response to primary systemic treatment and survival outcomes. J Clin Oncol 2009; 27: 220–6PubMedCrossRef
74.
Nofech-Mozes S, Trudeau M, Kahn HK, et al. Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers. Breast Cancer Res Treat 2009; 118: 131–7PubMedCrossRef
75.
Smid M, Wang Y, Zhang Y, et al. Subtypes of breast cancer show preferential site of relapse. Cancer Res 2008; 68: 3108–14PubMedCrossRef
76.
77.
Lin NU, Claus E, Sohl J, et al. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer 2008; 113: 2638–45PubMedCrossRef
78.
Heitz F, Harter P, Traut A, et al. Cerebral metastases (CM) in breast cancer (BC) with focus on triple-negative tumors. J Clin Oncol 26: 2008 (May 20 suppl; abstr 1010)
79.
Dawood S, Broglio K, Esteva FJ, et al. Survival among women with triple receptor-negative breast cancer and brain metastases. Ann Oncol 2009; 20: 621–7PubMedCrossRef
Metadata
Title
Triple-Negative Breast Cancer
Epidemiology and Management Options
Author
Dr Shaheenah Dawood
Publication date
01-12-2010
Publisher
Springer International Publishing
Published in
Drugs / Issue 17/2010
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/11538150-000000000-00000

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