INTRODUCTION: Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the short-term disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype. PATIENTS AND METHODS: Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancer patients primary operated at our institution between 2000 and 2005. Receptors were evaluated using IHC. Steroid receptors were considered positive for any nuclear staining; HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization (FISH). Kaplan-Meier (KM) DFI curves were calculated for any relapse defined as a local, regional, contralateral, or distant breast cancer event for the six predefined breast cancer subgroups: ER + PR + HER-2 - (PPN), ER + PR - HER-2 - (PNN), ER + PR + HER-2 + (PPP), ER - PR - HER-2 - (NNN), ER - PR - HER-2 + (NNP), and ER + PR - HER-2 + (PNP). P-values were calculated for comparison of the six different survival curves using two possible adaptations for multiple testing. A multivariate model for the receptors predicting DFI did incorporate local and systemic adjuvant therapy. RESULTS: Median patient age was 57 years (ranges 26-96) and median FU was 3.35 years. Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a significantly better DFI than others based on multiple testing, especially when the PPN group was compared against the four most frequent subtypes. The multivariate model with local and systemic adjuvant therapy confirmed the prognostic value of ER, PR, and HER-2 for short-term DFI. CONCLUSION: It is possible to distinguish short-term prognostic breast cancer subgroups only on the basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant therapy. While gene expression profiles based on microarray data of over hundreds of genes will probably teach us much about breast cancer biology, heterogeneity, and prognosis, we emphasize the important short-term prognostic value of currently used IHC markers for ER, PR, and HER-2.
INTRODUCTION: Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the short-term disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype. PATIENTS AND METHODS: Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancerpatients primary operated at our institution between 2000 and 2005. Receptors were evaluated using IHC. Steroid receptors were considered positive for any nuclear staining; HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization (FISH). Kaplan-Meier (KM) DFI curves were calculated for any relapse defined as a local, regional, contralateral, or distant breast cancer event for the six predefined breast cancer subgroups: ER + PR + HER-2 - (PPN), ER + PR - HER-2 - (PNN), ER + PR + HER-2 + (PPP), ER - PR - HER-2 - (NNN), ER - PR - HER-2 + (NNP), and ER + PR - HER-2 + (PNP). P-values were calculated for comparison of the six different survival curves using two possible adaptations for multiple testing. A multivariate model for the receptors predicting DFI did incorporate local and systemic adjuvant therapy. RESULTS: Median patient age was 57 years (ranges 26-96) and median FU was 3.35 years. Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a significantly better DFI than others based on multiple testing, especially when the PPN group was compared against the four most frequent subtypes. The multivariate model with local and systemic adjuvant therapy confirmed the prognostic value of ER, PR, and HER-2 for short-term DFI. CONCLUSION: It is possible to distinguish short-term prognostic breast cancer subgroups only on the basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant therapy. While gene expression profiles based on microarray data of over hundreds of genes will probably teach us much about breast cancer biology, heterogeneity, and prognosis, we emphasize the important short-term prognostic value of currently used IHC markers for ER, PR, and HER-2.
Authors: Maija Hollmén; Ping Liu; Kari Kurppa; Hans Wildiers; Irene Reinvall; Thijs Vandorpe; Ann Smeets; Karen Deraedt; Tero Vahlberg; Heikki Joensuu; Daniel J Leahy; Patrick Schöffski; Klaus Elenius Journal: PLoS One Date: 2012-06-22 Impact factor: 3.240
Authors: Rossella Lucá; Michele Averna; Francesca Zalfa; Manuela Vecchi; Fabrizio Bianchi; Giorgio La Fata; Franca Del Nonno; Roberta Nardacci; Marco Bianchi; Paolo Nuciforo; Sebastian Munck; Paola Parrella; Rute Moura; Emanuela Signori; Robert Alston; Anna Kuchnio; Maria Giulia Farace; Vito Michele Fazio; Mauro Piacentini; Bart De Strooper; Tilmann Achsel; Giovanni Neri; Patrick Neven; D Gareth Evans; Peter Carmeliet; Massimiliano Mazzone; Claudia Bagni Journal: EMBO Mol Med Date: 2013-09-16 Impact factor: 12.137