Role of HER2-neu as a prognostic factor for survival and relapse in pT1a–bN0M0 breast cancer: a systematic review of the literature with a pooled-analysis
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
High levels of human epidermal growth receptor 2 (HER2) expression are associated with recurrence and death in breast cancer (BC) patients. We have performed a systematic review and meta-analysis in order to evaluate the prognosis for HER2+ pT1a–bN0M0 BC patients. A search of PubMed and Embase was performed. Studies were included if they reported hazard ratios (HRs) with a 95% confidence interval (CI) for multivariate analyses of relapse or survival in pT1a–bN0M0, HER2+ BC patients treated with surgery and chemotherapy and/or endocrine therapy, but not with trastuzumab. A total of 764 patients from seven studies were included in the meta-analysis. In the pooled analysis, HER2 had a detrimental effect on relapse-free (HR 4.68, 95% CI 3.05–7.18; p < 0.00001) and distant relapse-free survival, with a HR of 5.6 (95% CI 2.65–11.85; p < 0.00001). HER2+ status was also linked to increased risk of death (HR 3.4, 95% CI 0.86–13.41; p = 0.08) and worst BC-specific survival (HR 2.61, 95% CI 1.51–4.51; p = 0.0006), but these data were presented in few studies. HER2+ pT1a–bN0M0 BC is associated with a dismal prognosis. In these patients, HER2 has to be taken into account when deciding on adjuvant therapy, and trastuzumab should be considered.
- Chia SK, Speers CH, Bryce CJ, Hayes MM, Olivotto IA. Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies. J Clin Oncol. 2004;22(9):1630–7. CrossRef
- Hanrahan EO, Valero V, Gonzalez-Angulo AM, Hortobagyi GN. Prognosis and management of patients with node-negative invasive breast carcinoma that is 1 cm or smaller in size (stage 1; T1a, bN0M0): a review of the literature. J Clin Oncol. 2006;24(13):2113–22. CrossRef
- Press MF, Bernstein L, Thomas PA, et al. Her-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol. 1997;15(8):2894–904.
- Joensuu H, Isola J, Lundin M, et al. Amplification of erbB2 and erbB2 expression are superior to estrogen receptor status as risk factors for distant recurrence in pT1N0M0 breast cancer: a nationwide population-based study. Clin Cancer Res. 2003;9(3):223–30.
- Joensuu H, Bono P, Kataja V, et al. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009;27(34):5685–92. CrossRef
- Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12(3):236–44. CrossRef
- Ramond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable Her 2-positive breast cancer. N Engl J Med. 2005;353:1673–84. CrossRef
- Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83. CrossRef
- Higgins JPT, Green S (eds). Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated Mar 2011]. The Cochrane collaboration. 2011. Available from http://www.cochrane-handbook.org.
- DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. CrossRef
- Livi L, Meattini I, Saieva C, et al. Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer. Cancer. 2011; in press.
- Cancello G, Maisonneuve P, Rotmensz N, et al. Prognosis in women with small (T1mic, T1a, T1b) node-negative operable breast cancer by immunohistochemically selected subtypes. Breast Cancer Res Treat. 2011;127(3):713–20. CrossRef
- Sanpaolo P, Barbieri V, Pedicini P, Fusco V. Her-2 prognostic value in very early-stage breast cancer: a single-institution retrospective analysis. Med Oncol. 2011. doi:10.1007/s12032-011-9869-0.
- Park YH, Kim ST, Cho EY, et al. A risk stratification by hormonal receptors (ER, PgR) and HER-2 status in small (≤1 cm) invasive breast cancer: who might be possible candidates for adjuvant treatment? Breast Cancer Res Treat. 2010;119(3):653–61. CrossRef
- Curigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol. 2009;27(34):5693–9. CrossRef
- Theriault RL, Litton JK, Mittendorf EA, et al. Age and survival estimates in patients who have node-negative T1ab breast cancer by breast cancer subtype. Clin Breast Cancer. 2011;11(5):325–31. CrossRef
- Wong F, Tuan J, Chua ET. Her2-neu positivity prognosticates for poor disease control in Asian women with small, node negative breast cancer treated with conservation therapy. Int J Radiat Oncol Biol Phys. 2010;78(3 suppl 1):S228. CrossRef
- Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177. CrossRef
- Paik S, Hazan R, Fisher ER, et al. Pathologic findings from the national surgical adjuvant breast and bowel project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol. 1990;8:103.
- van de Vijver MJ, Mooi WJ, Wisman P, et al. Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA. Oncogene. 1988;2:175.
- Gilcrease MZ, Woodward WA, Nicolas MM, et al. Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer. Am J Surg Pathol. 2009;33:759. CrossRef
- Taucher S, Rudas M, Mader RM, et al. Do we need HER-2/neu testing for all patients with primary breast carcinoma? Cancer. 2003;98:2547. CrossRef
- Tandon AK, Clark GM, Chamness GC, et al. HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol. 1989;7:1120.
- Gusterson BA, Gelber RD, Goldhirsch A, et al. Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) breast cancer study group. J Clin Oncol. 1992;10:1049.
- Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol. 2000;18:3651.
- Kröger N, Milde-Langosch K, Riethdorf S, et al. Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients. Clin Cancer Res. 2006;12:159. CrossRef
- Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26:5697. CrossRef
- Wiechmann L, Jacks L, Patil S, et al. Impact of molecular subtype on presenting characteristics of T1a, b tumors. J Clin Oncol. 2009; 27:15s (abstr 11111).
- Rodrigues MJ, Wassermann J, Albiges-Sauvin L, et al. Treatment of node-negative infracentimetric HER2+ invasive breast carcinomas: a joint AERIO/REMAGUS study. J Clin Oncol. 2009;27:15s (abstr 517).
- Wassermann J, Albiges L, Rodrigues MJ, et al. Treatment of small node-negative HER2+ invasive breast carcinomas: 40-month update of the joint Aerio/Remagus study. J Clin Oncol. 2011;29:85–96 (abstr 557).
- Chew HK, Brown M. Cause-specific and all-cause mortality of HER2-positive, node-negative, T1a and T1b breast cancers. J Clin Oncol. 2010;28:15s (abstr 583).
- Kwon JH, Kim YJ, Lee KW, et al. Triple negativity and young age as prognostic factors in lymph node-negative invasive ductal carcinoma of 1 cm or less. BMC Cancer. 2010;10:557. CrossRef
- Wong FY, Yip CS, Chua ET. Implications of HER2 Amplification in small, node-negative breast cancers: do Asians differ? World J Surg. 2011;36(2):287–94. CrossRef
- Parise C, Bauer K, Caggiano V. Is tumor size important in HER2-positive breast cancer? J Clin Oncol. 2010;28:15s (abstr 1582).
- National Comprehensive Cancer Network (NCCN) guidelines. Available at: http://www.nccn.org (accessed on 12 Nov 2011).
- Role of HER2-neu as a prognostic factor for survival and relapse in pT1a–bN0M0 breast cancer: a systematic review of the literature with a pooled-analysis
Volume 29, Issue 4 , pp 2586-2593
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- HER2 positive
- Breast cancer
- Industry Sectors