Breast cancer is characterized by hormone dependency, and endocrine therapy is a key treatment in breast cancer. Recently, targeted therapies such as Trastuzumab treatment for HER2-positive breast cancer has been important. Triple-negative (TN) breast cancer is characterized by lack of expression of estrogen receptor (ER) and progesterone receptor (PgR), and the absence of HER2 protein overexpression, and so there is no targeted therapy for this subtype. In this study, we examined the biological and prognostic characteristics in TN breast cancer.
Patients and methods
Between January 1998 and September 2006, 1,552 patients with primary breast cancer were investigated retrospectively in this study and ER, PgR and HER2 status were evaluated in all cases. Furthermore, p53 overexpression and Ki67 values were examined immunohistochemically.
Patient distribution according to ER, PgR or HER2 status was as follows: ER and PgR positive: 57.9%, and ER and PgR negative: 25.1%. With regards to the HER2 status, HER2 positive was 23.3%, and triple negative (TN) was 14.0%. TN breast cancer has a high proliferation rate, high nuclear grade and frequent p53 overexpression. Patients with TN tumors had a significantly poorer disease-free survival (DFS) than those with non-TN tumors. After recurrence the overall survival (OS) rate in TN cases was significantly lower than that of the non-TN cases. Multivariate analysis revealed that TN was a significant factor for DFS and OS after recurrence.
TN breast cancer is a rare subtype with a high proliferation rate and a high nuclear grade, p53 overexpression, and lower DFS/OS. To improve the prognosis of TN breast cancer, a new effective strategy needs to be developed.
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Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.
Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.
Sørlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.
Kai K, Nishimura R, Arima N, et al. p53 expression status is a significant molecular marker in predicting the time to endocrine therapy failure in recurrent breast cancer: a cohort study. Int J Clin Oncol. 2006;11:426–33.
Umemura S, Kurosumi M, Moriya T, et al. Immunohistochemical evaluation for hormone receptors in breast cancer: a practically useful evaluation system and handling protocol. Breast Cancer. 2006;13:232–5.
Viale G, Regan MM, Maiorano E, et al. Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal women with early breast cancer: results from the BIG 1–98 collaborative groups. J Clin Oncol. 2007;25:3846–52.
Nishimura R, Matsuda M, Miyayama H, et al. Proliferative activity evaluated by MIB-1 predicts the time and type of recurrence in breast cancer. Breast Cancer Res Treat. 2003;82(Suppl 1):S165.
Finnegan TJ, Carey LA. Gene-expression analysis and the basal-like breast cancer subtype. Future Oncol. 2007;3:55–63.
Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8:235–44.
Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina breast cancer study. JAMA. 2006;295:2492–502.
Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005;23:7350–60.
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;10:5367–74.
Matos I, Dufloth R, Alvarenga M, et al. p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch. 2005;447:688–94.
Siziopikou KP, Cobleigh M. The basal subtype of breast carcinomas may represent the group of breast tumors that could benefit from EGFR-targeted therapies. Breast. 2007;16:104–7.
Yehiely F, Moyano JV, Evans JR, et al. Deconstructing the molecular portrait of basal-like breast cancer. Trends Mol Med. 2006;12(11):537–44.
Abd El-Rehim DM, Ball G, Pinder SE, et al. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer. 2005;116:340–50.
Foulkes WD, Brunet JS, Stefansson IM, et al. The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res. 2004;64:830–5.
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;109:1721–8.
Nishimura R, Okumura Y, Arima N. Trastuzumab monotherapy versus combination therapy for treating recurrent breast cancer: time to progression and survival. Breast Cancer 2008;15(1):57–64.
Nishimura R, Nagao K, Miyayama H, et al. An evaluation of predictive factors involved in clinical or pathological response to primary chemotherapy in advanced breast cancer. Breast Cancer. 2002;9:145–52.
Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.
Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85.
Hayes DF, Thor A, Dressler L, et al. HER2 predicts benefit from adjuvant paclitaxel after AC in node positive breast cancer. J Clin Oncol. 2006 (ASCO Annual Meeting Proceedings Part I, vol 24, No. 18S, 20 June Supplement: 510, 2006)
Miller KD, Sledge GW, Burstein HJ. Angiogenesis inhibition in the treatment of breast cancer: a review of studies presented at the 2006 san antonio breast cancer symposium. Clin Adv Hematol Oncol. 2007;5:1–12.
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Nishimura, R., Arima, N. Is triple negative a prognostic factor in breast cancer?. Breast Cancer 15, 303–308 (2008). https://doi.org/10.1007/s12282-008-0042-3