Lani
05-19-2011, 09:14 PM
status may end up being helpful
RAD51 and brain metastases (BM) in patients (pts) with HER2+ breast cancer.
Sub-category:
HER2+
Category:
Breast Cancer - HER2/ER
Meeting:
2011 ASCO Annual Meeting
Abstract No:
634
Citation:
J Clin Oncol 29: 2011 (suppl; abstr 634)
Attend this session at the
ASCO Annual Meeting!
Session: Breast Cancer - HER2/ER
Type: General Poster Session
Time: Monday June 6, 1:00 PM to 5:00 PM
Location: McCormick Place Hall A
Author(s): R. Duchnowska, J. Jassem, E. Szutowicz, W. Biernat, T. Jankowski, W. Och, R. Staszkiewicz, M. Chudzik, W. Rogowski, N. Flores, S. Woditschka, L. Li, C. Goswami, M. A. Thorat, Y. Gokmen-Polar, G. W. Sledge, P. S. Steeg, D. Palmieri, S. S. Badve; Military Institute of Medicine, Warsaw, Poland; Medical University of Gdansk, Gdansk, Poland; Medical University, Gdansk, Poland; Regional Cancer Center, Lublin, Poland; Regional Hospital, Olsztyn, Poland; Regional Oncology Center, Olsztyn, Poland; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD; Indiana University School of Medicine, Indianapolis, IN; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN; Wolfson Institute of Preventive Medicine, CRUK Centre for Epidemiology, London, United Kingdom; Indiana University Simon Cancer Center, Indianapolis, IN
Abstract Disclosures
Abstract:
Background: BM is a common occurrence in HER2‑positive breast cancer pts. If the pts most likely to develop BM could be identified, prophylactic strategies might prevent or delay occurrence of this failure. Our previous work focusing on clinical and pathological factors coupled with gene expression analysis identified a 13 gene signature that together could predict the likelihood brain metastases within the first 3 years (early vs. late occurrence) after diagnosis (J Clin Oncol 2008; 26: 45s). More specifically, it suggested that a number of proteins involved in DNA double strand break repair are overexpressed in untreated primary breast tumors from patients who developed BM within 3 years of diagnosis. Methods: To determine the impact of DNA repair genes in early breast tumorigenesis, a 3D culture model system of immortal, nontumorigenic human MCF10A breast cells was used, with and without ectopic expression of HER2 and the DNA repair genes BARD1 and RAD51 from the signature. The number and morphology of breast acini were scored using indirect immunofluorescence and confocal microscopy. Results: Overexpression of HER2 increased the proportion of acini showing invasion into the extracellular matrix by 4.2-fold (P=0.05). Overexpression of RAD51, with or without concomitant HER2 overexpression, more strongly promoted invasive growth, with increases of 6.5-fold and 6.8-fold, respectively, over control transfectants (P=0.03 and 0.004, respectively). BARD1 overexpression promoted invasive growth 2.5-fold over control transfectants (P=0.04) but did not exceed or interact with HER2 overexpression. Conclusions: These data indicate that RAD51 overexpression occurs early in carcinogenesis and that it may accelerate the invasion process. This may underlie the proclivity of patients with RAD51 overexpressing tumors to develop brain metastases.
RAD51 and brain metastases (BM) in patients (pts) with HER2+ breast cancer.
Sub-category:
HER2+
Category:
Breast Cancer - HER2/ER
Meeting:
2011 ASCO Annual Meeting
Abstract No:
634
Citation:
J Clin Oncol 29: 2011 (suppl; abstr 634)
Attend this session at the
ASCO Annual Meeting!
Session: Breast Cancer - HER2/ER
Type: General Poster Session
Time: Monday June 6, 1:00 PM to 5:00 PM
Location: McCormick Place Hall A
Author(s): R. Duchnowska, J. Jassem, E. Szutowicz, W. Biernat, T. Jankowski, W. Och, R. Staszkiewicz, M. Chudzik, W. Rogowski, N. Flores, S. Woditschka, L. Li, C. Goswami, M. A. Thorat, Y. Gokmen-Polar, G. W. Sledge, P. S. Steeg, D. Palmieri, S. S. Badve; Military Institute of Medicine, Warsaw, Poland; Medical University of Gdansk, Gdansk, Poland; Medical University, Gdansk, Poland; Regional Cancer Center, Lublin, Poland; Regional Hospital, Olsztyn, Poland; Regional Oncology Center, Olsztyn, Poland; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD; Indiana University School of Medicine, Indianapolis, IN; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN; Wolfson Institute of Preventive Medicine, CRUK Centre for Epidemiology, London, United Kingdom; Indiana University Simon Cancer Center, Indianapolis, IN
Abstract Disclosures
Abstract:
Background: BM is a common occurrence in HER2‑positive breast cancer pts. If the pts most likely to develop BM could be identified, prophylactic strategies might prevent or delay occurrence of this failure. Our previous work focusing on clinical and pathological factors coupled with gene expression analysis identified a 13 gene signature that together could predict the likelihood brain metastases within the first 3 years (early vs. late occurrence) after diagnosis (J Clin Oncol 2008; 26: 45s). More specifically, it suggested that a number of proteins involved in DNA double strand break repair are overexpressed in untreated primary breast tumors from patients who developed BM within 3 years of diagnosis. Methods: To determine the impact of DNA repair genes in early breast tumorigenesis, a 3D culture model system of immortal, nontumorigenic human MCF10A breast cells was used, with and without ectopic expression of HER2 and the DNA repair genes BARD1 and RAD51 from the signature. The number and morphology of breast acini were scored using indirect immunofluorescence and confocal microscopy. Results: Overexpression of HER2 increased the proportion of acini showing invasion into the extracellular matrix by 4.2-fold (P=0.05). Overexpression of RAD51, with or without concomitant HER2 overexpression, more strongly promoted invasive growth, with increases of 6.5-fold and 6.8-fold, respectively, over control transfectants (P=0.03 and 0.004, respectively). BARD1 overexpression promoted invasive growth 2.5-fold over control transfectants (P=0.04) but did not exceed or interact with HER2 overexpression. Conclusions: These data indicate that RAD51 overexpression occurs early in carcinogenesis and that it may accelerate the invasion process. This may underlie the proclivity of patients with RAD51 overexpressing tumors to develop brain metastases.