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Serum levels of IGF-1 and IGFBP-3 during adjuvant chemotherapy for primary breast cancer
Thursdq,
1.7 March
Poster Session I. Biology
2003
I P57 L. Szatkowska.
MedicalAcademy:
Introduction: The GABA-ergic constitution plays a considerable role in the development of the oncological process. A higher level of GABA (gammaamino-butyric acid) was observed in many different kinds of neoplasms and research is under way to establish its values in the evaluation of the neoplastic process and the progression of the disease. Objectives The objectives were to evaluate the influence of the GABA levels on the nature of failures in the treatment of breast cancer patients and on their asymptomatic survival time. Material and Methods: Retrospective examination included 94 breast cancer patients in Lublin Oncological Centre in the years of 1996-1997 who had GABA levels determined postoperatively. During the course of a 5-year observation the quantity and quality of failures among the women was being evaluated. Using U-Mann Whitney test the dependence of GABA levels on the period of time to failure emergence as well as on the nature of this failure was determined. The significance level of p=O,O5 was accepted. Results: In the course of the 5-year observation of 94 patients, 20 of them experienced treatment failure: 5 had local recurrence and 15 suffered from distant metastases. Failures occurred within 1 to 58 months after the operation. No significant interdependence between GABA levels and the period of time to failure emergence was seen. However, GABA-level influence on the nature of failure was observed. Theaverage GABA levels in tumor tissue were 99,553(ug/1g) in wholegroup. A significant (p=O,O4) rise in GABA levels, as compared with the group of progression-free patients, was observed in patients with local recurrence. Average GABA level in breast cancer tissue was as follows depending on the group of patients. In the group of progression-free patients .93,626ug/lg; in the group of patients with local recurrence l33,137ug/lg; in the group of patients who suffered from distant metastases 119,098ug/1 g. Conclusion: GABA levels evaluated in the postoperative material of breast carcinoma patients are significantly higher in patients with recurrence.
I
P56
Serum levels of IGF-1 and IGFBP-3 during adjuvant chemotherapy for primary breast cancer
G. Ftirstenberger,
_Effects of ad@fant therapies in breast cancer on bone marrow (bm)
carcinoma A Brzozowska, M. Mazurkiewicz, Oncoiog~ Lublin, Potand
S3 1
R. Morant, B. Bolliger, H.J. Senn
Background: Interest in insulin-like growth factors (IGFs) and their effect on carcinogenesis has increased because high serum concentrations of IGF-1 are associated with an increased risk of breast, prostate, colorectal and lung cancer whereas IGF bmding protein-3 (IGFBP-3) seems to exert a protective effect. Therefore patients may benefit from low IGF-1 levels and high levels of IGFBP-3. The present work was undertaken to determine, if adjuvant anthracycline-containing chemotherapy for primary breast cancer modulates IGF-I or IGFBP-3 serum levels. Methods: In 24 patients undergoing adjuvant treatment for primary breast cancer, IGF-1 and IGFBP-3 serum levels were measured before cycle I3 or 4 of three-weekly chemotheraw regimens of either epirubicin and cyclophosphamide (EC, 12 patients), 5-fluorouracil, epirubicin and cyclophosphamide (FEC, 8 patients) or epirubicin and taxotere (ETXT, 4 patients). IGF1 was measured by a commercially available chemiluminescent immunoassay, IGFBP-3 by a sensitive radioimmunoassay (Nichols Institute Diagnostics). P values were calculated by Wilcoxon’s matched pair test. Results: Median pretreatment values of IGF-1 and IGFBP-3 were 118.4 ng/ml (range 26-248) and 3797 ng/ml (range 1820-5610), respectively. After 3 weeks of treatment (before cycle 2) median values of IGF-1 and IGFBP3 were 114.6 ng/ml (range 33.6-215) and 3585.0 @ml (range 2250-4720). respectively. After IO (8-12) weeks of treatment median values of IGF-1 and IGFBP-3 were 130.5 ng/ml (range 39-273.1) and 4036 nglml (range 21105530). respectively. There were no significant changes of IGF-1 and IGFBP3 serum concentrations after 3 or 10 weeks of treatment and no significant changes of the quotient of IGF-l/IGFBP-3. Conclusion: We found no significant changes of IGF-1 and IGFBP3 serum concentrations during adjuvant anthracycline-containing chemotherapy regimens. In addition, the proportion of IGF-I/IGFBP-3 remained stable during the treatment period. These chemotherapy regimens do not have favourable or unfavourable short term effects on IGF-1 or IGFBP-3 values. The results are consistent with data of a previously published study for FEC and CMF (cyclophosphamide, methotrexate and 5-fluorwracil) (J-H Peyrat, F RBvillion. J Bonneterre. Plasma insulin-like growth factor in primary breast cancer patients treated with adjuvant chemotherapy, Br J Cancer, 1998 May; 77(1O):i669-71 1
F. Schuetz’, K. Ehlertz, f? Beckhove’, I.J. DIeI’, E. Solomayer’ , V. Schirrmacher*. G. Bastert’ ,H.J. Strittmatter’ ‘UniversityClinics Heidelberg, Obstetrks and Gynecology Heidelberg, Germany; ’ German Cancer Research Centec lmmunolog~ Heidelberg* Germany We have previously shown an enrichment of tumor-specific MTC in BM but not in peripheral blood (PB) of breast cancer patients. Upon specific restimulation with dendritic cells (DC) in vitro BM T cells exert specific effector functions like IFN-gamma production and cytotoxicity. Furthermore we have shown in NOD/Scid-mice that reactivated MTC infiltrate autologous and heterologous tumor tissue, proliferate and kill tumor cells by induction of apoptosis. leading to a marked or complete tumor rejection within 21 days after transfer. This effect required appropriate stimulation by tumor associated antigens, since MTC stimulated with irrelevant antigen did not exert anti-tumor effects in vivo. To observe the effects of adjuvant breast cancer therapy on tumor specific MTC we reevaluated 25 patients by doing a BM reaspiration and comparing the number of cells with the primary BM aspiration. 50% of the patients with detected tumor specific MTC at the first BM aspiration who received chemotherapies like CMF, EC and ETC were still positiv: respectively 65% of the patients who receive endocrine therapies like tamoxifen and anastrozol. 50% of patients who had received primary chemotherapies (EC, ET, GEDoc) were positive. We thus suggest a cancer therapy based on BM memory T cells reactivated by autologous DC pulsed with TAA in patients with breast cancer metastases.
R. Nishimura’ , K. Nagao’, H. Miyayama2. ’Kumamoto City Hospital, Surge* Kumamoo Ci& Japan; 2 Kumamoto Ci(y Hospital8 Clinical Patholog): Kumamoto Cit$ Japan Background: The usefulness of combination treatment with 5’-deoxy-5fluorouridine (5’-DFUR), intermediate metabolite of capecitabine, and cy clophosphamide (CPA) was reported in advanced or recurrent breast cancer, and 5’-DFUR is converted to 5FU by Thymidine Phosphorylase (TP). We previously reported that the mean TP levels of primary breast cancer was 140.6 U/ml, and the higher levels significantly correlated with negative ER, aneuploid. and higher proliferation when divided into 3 groups: 170, 70-1210, and 1210;. In this study, the oral combination treatment was compared prospectively with CMF in relation to TP levels in adjuvant setting for primary breast cancer. Methods: Two hundreds and nineteen patients with primary breast cancer were operated on between October 1997 and March 1999 in Kumamoto City Hospital. Of the patients, 178 cases with Stage l/II tumors were enrolled in a prospective study stratified by TP levels and nodal status. Out of these patients, 73 cases with positive nodes were randomized to two treatment groups: CMF (CPA 100 mg/day p.o. for 14 days, methotrexate 40 mg/m2 day I,8 and 5-FU 500 mg/m2 day 1,8) or the oral combination therapy (5’-DFUR 600-800 mg/day and CPA 100 mg/day for I-14 days). TP levels of primary breast cancer were assayed by ELISA method. Results: The characteristics of the eligible patients were balanced between 2 regimens. There was no significant difference of disease-free survival between 2 regimens in median follow-up time of 58 months. In low TP groups, patients with 5’-DFUR and CPA regimen had poorer disease-free survival. However, in high TP group, the disease-free survival rates of patients with 5’-DFUR and CPA were superior to those with CMF, although the difference was not significant. There was no significant difference of adverse events occurring during the study in both arms. Conclusion: An oral combination regimen of 5’-DFUR and CPA is effective as adjuvant therapy in node-positive primary breast cancer with high TP levels. These results suggest that TP levels might be upregulated by CPA and be a predictive factor of the therapeutic effect from 5’-DFUR or capecitabine.
Increased aromatase
inhibitor potency: Correlation
R. Sainsbury. Royal Free and Universi~ College Hospital London, Depatiment of Surgery London, United Kingdom Indirect comparisons show the third-generation aromatase inhibitors (Als) anastrozole (AN), letrozole (L) and exemestane (E) are far more potent than the earlier Als aminoglutethimide (AG), formestane (F) and fadrozole (FZ) in
1.7 March
Poster Session I. Biology
2003
I P57 L. Szatkowska.
MedicalAcademy:
Introduction: The GABA-ergic constitution plays a considerable role in the development of the oncological process. A higher level of GABA (gammaamino-butyric acid) was observed in many different kinds of neoplasms and research is under way to establish its values in the evaluation of the neoplastic process and the progression of the disease. Objectives The objectives were to evaluate the influence of the GABA levels on the nature of failures in the treatment of breast cancer patients and on their asymptomatic survival time. Material and Methods: Retrospective examination included 94 breast cancer patients in Lublin Oncological Centre in the years of 1996-1997 who had GABA levels determined postoperatively. During the course of a 5-year observation the quantity and quality of failures among the women was being evaluated. Using U-Mann Whitney test the dependence of GABA levels on the period of time to failure emergence as well as on the nature of this failure was determined. The significance level of p=O,O5 was accepted. Results: In the course of the 5-year observation of 94 patients, 20 of them experienced treatment failure: 5 had local recurrence and 15 suffered from distant metastases. Failures occurred within 1 to 58 months after the operation. No significant interdependence between GABA levels and the period of time to failure emergence was seen. However, GABA-level influence on the nature of failure was observed. Theaverage GABA levels in tumor tissue were 99,553(ug/1g) in wholegroup. A significant (p=O,O4) rise in GABA levels, as compared with the group of progression-free patients, was observed in patients with local recurrence. Average GABA level in breast cancer tissue was as follows depending on the group of patients. In the group of progression-free patients .93,626ug/lg; in the group of patients with local recurrence l33,137ug/lg; in the group of patients who suffered from distant metastases 119,098ug/1 g. Conclusion: GABA levels evaluated in the postoperative material of breast carcinoma patients are significantly higher in patients with recurrence.
I
P56
Serum levels of IGF-1 and IGFBP-3 during adjuvant chemotherapy for primary breast cancer
G. Ftirstenberger,
_Effects of ad@fant therapies in breast cancer on bone marrow (bm)
carcinoma A Brzozowska, M. Mazurkiewicz, Oncoiog~ Lublin, Potand
S3 1
R. Morant, B. Bolliger, H.J. Senn
Background: Interest in insulin-like growth factors (IGFs) and their effect on carcinogenesis has increased because high serum concentrations of IGF-1 are associated with an increased risk of breast, prostate, colorectal and lung cancer whereas IGF bmding protein-3 (IGFBP-3) seems to exert a protective effect. Therefore patients may benefit from low IGF-1 levels and high levels of IGFBP-3. The present work was undertaken to determine, if adjuvant anthracycline-containing chemotherapy for primary breast cancer modulates IGF-I or IGFBP-3 serum levels. Methods: In 24 patients undergoing adjuvant treatment for primary breast cancer, IGF-1 and IGFBP-3 serum levels were measured before cycle I3 or 4 of three-weekly chemotheraw regimens of either epirubicin and cyclophosphamide (EC, 12 patients), 5-fluorouracil, epirubicin and cyclophosphamide (FEC, 8 patients) or epirubicin and taxotere (ETXT, 4 patients). IGF1 was measured by a commercially available chemiluminescent immunoassay, IGFBP-3 by a sensitive radioimmunoassay (Nichols Institute Diagnostics). P values were calculated by Wilcoxon’s matched pair test. Results: Median pretreatment values of IGF-1 and IGFBP-3 were 118.4 ng/ml (range 26-248) and 3797 ng/ml (range 1820-5610), respectively. After 3 weeks of treatment (before cycle 2) median values of IGF-1 and IGFBP3 were 114.6 ng/ml (range 33.6-215) and 3585.0 @ml (range 2250-4720). respectively. After IO (8-12) weeks of treatment median values of IGF-1 and IGFBP-3 were 130.5 ng/ml (range 39-273.1) and 4036 nglml (range 21105530). respectively. There were no significant changes of IGF-1 and IGFBP3 serum concentrations after 3 or 10 weeks of treatment and no significant changes of the quotient of IGF-l/IGFBP-3. Conclusion: We found no significant changes of IGF-1 and IGFBP3 serum concentrations during adjuvant anthracycline-containing chemotherapy regimens. In addition, the proportion of IGF-I/IGFBP-3 remained stable during the treatment period. These chemotherapy regimens do not have favourable or unfavourable short term effects on IGF-1 or IGFBP-3 values. The results are consistent with data of a previously published study for FEC and CMF (cyclophosphamide, methotrexate and 5-fluorwracil) (J-H Peyrat, F RBvillion. J Bonneterre. Plasma insulin-like growth factor in primary breast cancer patients treated with adjuvant chemotherapy, Br J Cancer, 1998 May; 77(1O):i669-71 1
F. Schuetz’, K. Ehlertz, f? Beckhove’, I.J. DIeI’, E. Solomayer’ , V. Schirrmacher*. G. Bastert’ ,H.J. Strittmatter’ ‘UniversityClinics Heidelberg, Obstetrks and Gynecology Heidelberg, Germany; ’ German Cancer Research Centec lmmunolog~ Heidelberg* Germany We have previously shown an enrichment of tumor-specific MTC in BM but not in peripheral blood (PB) of breast cancer patients. Upon specific restimulation with dendritic cells (DC) in vitro BM T cells exert specific effector functions like IFN-gamma production and cytotoxicity. Furthermore we have shown in NOD/Scid-mice that reactivated MTC infiltrate autologous and heterologous tumor tissue, proliferate and kill tumor cells by induction of apoptosis. leading to a marked or complete tumor rejection within 21 days after transfer. This effect required appropriate stimulation by tumor associated antigens, since MTC stimulated with irrelevant antigen did not exert anti-tumor effects in vivo. To observe the effects of adjuvant breast cancer therapy on tumor specific MTC we reevaluated 25 patients by doing a BM reaspiration and comparing the number of cells with the primary BM aspiration. 50% of the patients with detected tumor specific MTC at the first BM aspiration who received chemotherapies like CMF, EC and ETC were still positiv: respectively 65% of the patients who receive endocrine therapies like tamoxifen and anastrozol. 50% of patients who had received primary chemotherapies (EC, ET, GEDoc) were positive. We thus suggest a cancer therapy based on BM memory T cells reactivated by autologous DC pulsed with TAA in patients with breast cancer metastases.
R. Nishimura’ , K. Nagao’, H. Miyayama2. ’Kumamoto City Hospital, Surge* Kumamoo Ci& Japan; 2 Kumamoto Ci(y Hospital8 Clinical Patholog): Kumamoto Cit$ Japan Background: The usefulness of combination treatment with 5’-deoxy-5fluorouridine (5’-DFUR), intermediate metabolite of capecitabine, and cy clophosphamide (CPA) was reported in advanced or recurrent breast cancer, and 5’-DFUR is converted to 5FU by Thymidine Phosphorylase (TP). We previously reported that the mean TP levels of primary breast cancer was 140.6 U/ml, and the higher levels significantly correlated with negative ER, aneuploid. and higher proliferation when divided into 3 groups: 170, 70-1210, and 1210;. In this study, the oral combination treatment was compared prospectively with CMF in relation to TP levels in adjuvant setting for primary breast cancer. Methods: Two hundreds and nineteen patients with primary breast cancer were operated on between October 1997 and March 1999 in Kumamoto City Hospital. Of the patients, 178 cases with Stage l/II tumors were enrolled in a prospective study stratified by TP levels and nodal status. Out of these patients, 73 cases with positive nodes were randomized to two treatment groups: CMF (CPA 100 mg/day p.o. for 14 days, methotrexate 40 mg/m2 day I,8 and 5-FU 500 mg/m2 day 1,8) or the oral combination therapy (5’-DFUR 600-800 mg/day and CPA 100 mg/day for I-14 days). TP levels of primary breast cancer were assayed by ELISA method. Results: The characteristics of the eligible patients were balanced between 2 regimens. There was no significant difference of disease-free survival between 2 regimens in median follow-up time of 58 months. In low TP groups, patients with 5’-DFUR and CPA regimen had poorer disease-free survival. However, in high TP group, the disease-free survival rates of patients with 5’-DFUR and CPA were superior to those with CMF, although the difference was not significant. There was no significant difference of adverse events occurring during the study in both arms. Conclusion: An oral combination regimen of 5’-DFUR and CPA is effective as adjuvant therapy in node-positive primary breast cancer with high TP levels. These results suggest that TP levels might be upregulated by CPA and be a predictive factor of the therapeutic effect from 5’-DFUR or capecitabine.
Increased aromatase
inhibitor potency: Correlation
R. Sainsbury. Royal Free and Universi~ College Hospital London, Depatiment of Surgery London, United Kingdom Indirect comparisons show the third-generation aromatase inhibitors (Als) anastrozole (AN), letrozole (L) and exemestane (E) are far more potent than the earlier Als aminoglutethimide (AG), formestane (F) and fadrozole (FZ) in