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Prognostic Value of HER 2 Neu Overexpression and Genetic Category in Patients Age 70 and Older with Breast Cancer
Proceedings of the 51st Annual ASTRO Meeting Results: For the entire cohort of 1,729 patients, the median follow-up was 14.17 years and the mean age at diagnosis was 55.9 years. The MC cohort was more likely to be older ($ 50 years old) than the IDC group (80.4% vs. 65.8%, p = 0.05). The MC and IDC cohorts were of similar T stage, as well as ER positive (p . 0.05) and PR positive (p . 0.05) status. Mucinous histology did not correlate with loco-regional recurrence, method of tumor detection, race, family history, margin status, use of hormonal therapy or chemotherapy (all p . 0.05). At the time of diagnosis, patients in the MC cohort were less likely to be node positive than the IDC group (2.4% vs.19.7%, p = 0.02). Interestingly, nodal recurrence was found in 36/1688 (2.1%) of patients in the IDC control cohort whereas the MC group experienced no nodal recurrences. 15-year breast relapse-free rates were not significantly different in the MC and IDC cohorts (87.3% vs. 79.5%, p = 0.83). In univariate analysis, histology (MC vs. IDC) was not an independent predictor of local relapse (HR=0.88; 95% CI, 0.28 to 2.78; p = 0.84), distant relapse (HR=0.66; 95% CI, 0.24 to 1.77; p = 0.41) or overall survival (HR=0.84; 95% CI, 0.37 to 1.90; p = 0.68) at 15 years. Conclusions: Our data implies that the natural history of MC resembles IDC. Patients with mucinous (colloid) histology have demonstrated less nodal involvement at diagnosis and with fewer nodal recurrences. Local, distant, and overall survival rates are comparable between the two cohorts and these findings suggest that patients diagnosed with MC are appropriate candidates for CS+RT with a relatively favorable long-term prognosis. Author Disclosure: R.R. Parikh, None; N. Taunk, None; M.S. Moran, None; B.G. Haffty, None.
2045
Circulating Tumor Cells during Radiotherapy in Breast Cancer Patients
E. Boelke, H. Bojar, H. Prisack, C. Matuschek, W. Budach, S. Gripp, M. Peiper, B. Dogan University of Duesseldorf, D-40025, Germany Purpose/Objective(s): Circulating tumour cells (CTC) play a major role in determination of prognosis of metastatic cancers. Certain gene expressions in CTC can be used for an accurate detection and quantification of tumour cells in peripheral blood. Materials/Methods: Peripheral blood (PB) samples of 63 Patients with breast cancer of various stages were scanned at the beginning of or during radiotherapy, 14 samples served as control group. After immunomagnetic separation of occult tumour cells and reverse-transcription, we performed multiplex PCR steps using primers for the genes GA733.2, muc-1, and c-erbB2. A quantitative real-time-PCR using probes for mammaglobin1, SPDEF, MMP-11 and c-erbB2, genes determined according to our microarray-based gene expression data. Results: GA733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mammaglobin1 in 9.1% and SPDEF in 12.1%. Due to absence of specificity and high ambient expression in PB c-erbB2 and MMP-11 were excluded from further analysis. Besides single gene analysis we also evaluated significance of gene profiles. Highly significant correlations to staging of breast cancer were found in single gene analysis of GA733.2 and muc-1, in gene profile analysis of GA733.2 muc-1 and GA733.2, muc-1 mammaglobin1 SPDEF. We found further significant correlations to the TNM-status whereas our results did not correlate to tumour grading. Significant results were demonstrated also in context to ELISA-determined Ca 15-3 status. Conclusions: In contrast to other investigators who claimed an independent predictive value of c-erbB2 we demonstrated in our study that c-erbB2 does not have any marker feature. In addition multiplex- and real-time-PCR determined c-erbB2-expression in PB did not show any correlation to the immunohistochemically determined Her2/neu-status. Our study indicates that not single genes but subtle patterns of multiple genes lead to an increasing accuracy combined with no loss of specificity in detection of circulating tumor cells. Author Disclosure: E. Boelke, None; H. Bojar, None; H. Prisack, None; C. Matuschek, None; W. Budach, None; S. Gripp, None; M. Peiper, None; B. Dogan, None.
2046
Prognostic Value of HER 2 Neu Overexpression and Genetic Category in Patients Age 70 and Older with Breast Cancer
G. A. Ferraris1, E. A. Richardet2, M. Diaz Vazquez1, B. Dosoretz3, M. Rafailovici3, M. Filomia3, M. Ferraris4 Instituto Privado de Radioterapia Cuyo, Mendoza, Argentina, 2Instituto Oncologico Co´rdoba, Co´rdoba, Argentina, 3Vidt Centro Medico, Buenos Aires, Argentina, 4Centro Me´dico Dean Funes, Co´rdoba, Argentina
1
Purpose/Objective(s): The purpose of this study is to investigate the prognostic significance of HER 2 Neu status in elderly patients with breast cancer. Materials/Methods: We conducted a retrospective review of 96 consecutive patients age 70 and older diagnosed with invasive breast cancer between January 1998 and December 2002 who had known HER2-Neu status as determined by immunohistochemistry and who received breast surgery and radiation at a single institution. No patient received trastuzumab. We evaluated the association of HER2/Neu status with tumor characteristics using a chi-square metric and with disease-free survival, cause-specific survival, and overall survival using Cox multivariable regression analysis. Analyses were repeated to determine the prognostic significance of tumor subgroups as determined by estrogen receptor (ER), progesterone receptor (PR), and HER2/Neu status as published in Nguyen et al J Clin. Oncol. 2008 May 10;26(14):2373-8. Results: The median follow-up was 5.63 years and the median age was 76. 19.79% of patients were HER-2/neu positive and 80.21% were HER-2/neu negative. Her-2 neu positivity was significantly associated with tumor size T2 vs. T1 (p = 0.027) and the use of chemotherapy (p = 0.03). On univariable analysis, HER-2/Neu overexpression was associated with a significantly poorer disease free survival (Hazard Ratio = 2.6, p =0.018, (95% CI) (1.2; 5,6), but not cause-specific survival (p = 0.6) or overall survival(p = 0.115). On multivariate analysis, the genetic category HER2 (ER- and PR- and HER2+) and Triple Negative (ER-and PR-andHER2-), tumor size T2, and positive axillary lymph nodes were associated with poorer disease-free survival (all p \ 0.05). Conclusions: In elderly patients treated without trastuzumab, HER2 overexpression was associated with a poorer disease-free survival, suggesting that elderly patients with HER2 overexpression may also benefit from the addition of trastuzumab as younger patients do. Concordant results in different patient populations from different continents may increase the importance of this finding. Author Disclosure: G.A. Ferraris, None; E.A. Richardet, None; M. Diaz Vazquez, None; B. Dosoretz, None; M. Rafailovici, None; M. Filomia, None; M. Ferraris, None.
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2045
Circulating Tumor Cells during Radiotherapy in Breast Cancer Patients
E. Boelke, H. Bojar, H. Prisack, C. Matuschek, W. Budach, S. Gripp, M. Peiper, B. Dogan University of Duesseldorf, D-40025, Germany Purpose/Objective(s): Circulating tumour cells (CTC) play a major role in determination of prognosis of metastatic cancers. Certain gene expressions in CTC can be used for an accurate detection and quantification of tumour cells in peripheral blood. Materials/Methods: Peripheral blood (PB) samples of 63 Patients with breast cancer of various stages were scanned at the beginning of or during radiotherapy, 14 samples served as control group. After immunomagnetic separation of occult tumour cells and reverse-transcription, we performed multiplex PCR steps using primers for the genes GA733.2, muc-1, and c-erbB2. A quantitative real-time-PCR using probes for mammaglobin1, SPDEF, MMP-11 and c-erbB2, genes determined according to our microarray-based gene expression data. Results: GA733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mammaglobin1 in 9.1% and SPDEF in 12.1%. Due to absence of specificity and high ambient expression in PB c-erbB2 and MMP-11 were excluded from further analysis. Besides single gene analysis we also evaluated significance of gene profiles. Highly significant correlations to staging of breast cancer were found in single gene analysis of GA733.2 and muc-1, in gene profile analysis of GA733.2 muc-1 and GA733.2, muc-1 mammaglobin1 SPDEF. We found further significant correlations to the TNM-status whereas our results did not correlate to tumour grading. Significant results were demonstrated also in context to ELISA-determined Ca 15-3 status. Conclusions: In contrast to other investigators who claimed an independent predictive value of c-erbB2 we demonstrated in our study that c-erbB2 does not have any marker feature. In addition multiplex- and real-time-PCR determined c-erbB2-expression in PB did not show any correlation to the immunohistochemically determined Her2/neu-status. Our study indicates that not single genes but subtle patterns of multiple genes lead to an increasing accuracy combined with no loss of specificity in detection of circulating tumor cells. Author Disclosure: E. Boelke, None; H. Bojar, None; H. Prisack, None; C. Matuschek, None; W. Budach, None; S. Gripp, None; M. Peiper, None; B. Dogan, None.
2046
Prognostic Value of HER 2 Neu Overexpression and Genetic Category in Patients Age 70 and Older with Breast Cancer
G. A. Ferraris1, E. A. Richardet2, M. Diaz Vazquez1, B. Dosoretz3, M. Rafailovici3, M. Filomia3, M. Ferraris4 Instituto Privado de Radioterapia Cuyo, Mendoza, Argentina, 2Instituto Oncologico Co´rdoba, Co´rdoba, Argentina, 3Vidt Centro Medico, Buenos Aires, Argentina, 4Centro Me´dico Dean Funes, Co´rdoba, Argentina
1
Purpose/Objective(s): The purpose of this study is to investigate the prognostic significance of HER 2 Neu status in elderly patients with breast cancer. Materials/Methods: We conducted a retrospective review of 96 consecutive patients age 70 and older diagnosed with invasive breast cancer between January 1998 and December 2002 who had known HER2-Neu status as determined by immunohistochemistry and who received breast surgery and radiation at a single institution. No patient received trastuzumab. We evaluated the association of HER2/Neu status with tumor characteristics using a chi-square metric and with disease-free survival, cause-specific survival, and overall survival using Cox multivariable regression analysis. Analyses were repeated to determine the prognostic significance of tumor subgroups as determined by estrogen receptor (ER), progesterone receptor (PR), and HER2/Neu status as published in Nguyen et al J Clin. Oncol. 2008 May 10;26(14):2373-8. Results: The median follow-up was 5.63 years and the median age was 76. 19.79% of patients were HER-2/neu positive and 80.21% were HER-2/neu negative. Her-2 neu positivity was significantly associated with tumor size T2 vs. T1 (p = 0.027) and the use of chemotherapy (p = 0.03). On univariable analysis, HER-2/Neu overexpression was associated with a significantly poorer disease free survival (Hazard Ratio = 2.6, p =0.018, (95% CI) (1.2; 5,6), but not cause-specific survival (p = 0.6) or overall survival(p = 0.115). On multivariate analysis, the genetic category HER2 (ER- and PR- and HER2+) and Triple Negative (ER-and PR-andHER2-), tumor size T2, and positive axillary lymph nodes were associated with poorer disease-free survival (all p \ 0.05). Conclusions: In elderly patients treated without trastuzumab, HER2 overexpression was associated with a poorer disease-free survival, suggesting that elderly patients with HER2 overexpression may also benefit from the addition of trastuzumab as younger patients do. Concordant results in different patient populations from different continents may increase the importance of this finding. Author Disclosure: G.A. Ferraris, None; E.A. Richardet, None; M. Diaz Vazquez, None; B. Dosoretz, None; M. Rafailovici, None; M. Filomia, None; M. Ferraris, None.
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