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RELATIONSHIP BETWEEN PREOPERATIVE SERUM CEA AND CA 15-3 AND RISK OF BREAST CANCER RECURRENCE IN POSTMENOPAUSAL ELDERLY WOMEN
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
HRT. Progesterone (P) combined with estradiol (E2) could be safer than synthetic progestins (SP). The reasons of this discrepancy are unknown. P and SP effects are mediated through the progesterone receptor but SP have mixed pharmacological properties. We compared the effect of P and medroxyprogesterone acetate (MPA), on two breast cancer cell lines (MCF-7 and T47-D cells) and on cultures of normal breast cells. The results confirmed that P and MPA decreased PRA and PRB expression (without any effect on the PRA/PRB ratio) but E2+MPA treatment maintained a stronger decrease of PR expression. Consequences of these differences were evaluated on cell proliferation and differentiation. In MCF-7 but not in T47-D cells, MPA antagonised the E2 mediated proliferation. It was associated with a decrease of cyclin D1 and an increase of p21 transcriptions. Transfection experiments with MMTV-luc suggested an important glucocorticoid effect of MPA in MCF-7 cells. There was also an increase in transcription of proteins involved in cell differentiation as fatty acid synthetase and Wisp2 in both cell lines. Experiments on normal human breast epithelial cells provided opposite results on proliferation and differentiation. Indeed in these cells, E2+P treatment seemed to have a more beneficial effect than E2+MPA treatment. In conclusions, our results showed opposite effect of P and MPA in normal and in beast cancer cells. In combined treatment, P was safer than MPA in normal breast cells but not in breast cancer cell lines.
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after 3 months levels of 2-OHE1 and 16α-OHE1 and their ratio were similar in group 1 and group 2. During transdermal therapy level of 2-OHE1 haven’t significantly changed while level of 16α-OHE1 have increased 2-fold and 2/16α ratio decreased for 40,9% in group 2 and 44,2% in group 1 (p<0,05). Oral therapy stimulated synthesis of both metabolites: 2-OHE1 increased for 223,1% and 16α-OHE1 for 500,0%, 2/16α ratio decreased for 55,6% (p<0,05). In combined groups, both transdermal and oral, 2/16α ratio were similar after 3 months. Conclusions: The way of estrogen administration defines the ways of hydroxymetabolism changes. Oral estrogen therapy increases the amount of circulating estrogen metabolites which can perform negative impact on target-cells in women with high risk of breast cancer and prevailing 16α-hydroxylating processes. Further longitudinal studies are needed to confirm these changes. Keywords: Estrogen metabolites, breast cancer, hormone replacement therapy.
182 BREAST CANCER SURGERY AND COSMESIS E. Kouskos 1 , C. Markopoulos 2 . 1 Vostanio Hospital of Mytilene, Surgical Department, Mytilene, Greece; 2 Laiko Hospital, Breast Unit, 2nd SurgicalDepartment, Athens, Greece
180 EFFECT OF HEALTH COUNSELING ON FEMALES’ AWARENESS TOWARDS BREAST CANCER S.H. Kavari. Semnan Medical University, Faculty of Health, Semnan, Iran, Islamic Republic of Objectives: The aim of this study was to determine the effect of health counseling on the females’ awareness towards methods of prevention of breast cancers. Methods: This study was a quasi experimental design. The aim of the study was to determine the difference of the subjects’ awareness about methods of prevention of breast cancer at pre intervention and post intervention in a medical health center of medical Shiraz University. The mean & standard deviation of the achieved scores related to the awareness were calculated. The sample size was 1200 subjects who were attending in health counseling program in selected health centers. The sampling method was consequence and the study tool was a questionnaire. Results: showed that the mean and standard deviation of samples’ age was 23.72±4.84 and 49.4%. The majority of the subjects had a level of high school degree in education and, 76.6% were housewives. The differences between the mean of their scores of the subjects’ awareness in the two groups (who participated in the counseling and who did not) were significant (P<0.0001). Conclusion: Considering the importance of prevention methods of breast cancer, the researchers suggest to conduct a prospective study for assessing the effect of premarital health counseling program on females’ practice. The study findings showed, a high efficacy of the health counseling regarding the subjects awareness about prevention methods of breast cancer. Keywords: Health counseling, Methods prevention, Breast cancer.
181 IMPACT OF HORMONE REPLACEMENT THERAPY ON ENDOGENOUS ESTRADIOL HYDROXYMETABOLISM IN RUSSIAN POSTMENOPAUSAL WOMEN V. Konovalova, V. Smetnik. Research Center for Obstetrics, Gynecology and Perinatology, Gynecologic Endocrinology, Moscow, Russian Federation Objectives: Changes in endogenous estradiol metabolism may play an important role in breast cancer pathophysioligy. Women with low 2/16α ratio can be at higher risk of breast cancer. We examined impact of exogenous estradiol therapy on estrogen metabolism in postmenopausal women with no history of breast cancer. Methods: 58 women were divided into 3 groups: transdermal estradiol monotherapy (n=21), transdermal estradiol and progesterone in continious combined regimen (n=15) and oral (estradiol and dydrogesterone) combined regimen (n=22). Initially and after 3 months estrogen metabolites were measured by ESTRAMET 2/16α in urine samples. Results: We found that progestins do not influence estrogen metabolites:
Objectives: Presentation of our breast cancer patients’ evaluation about the cosmetic result in relation to their specific surgical management. Methods: A total of 302 breast cancer patients who had been treated by modified radical mastectomy (MRM, n: 144), wide local excision and axillary clearance (breast conserving surgery, BCS, n: 126), and mastectomy followed by delayed reconstruction (breast reconstruction, BR, n: 32) self rated their own cosmetic satisfaction via a questionnaire. Results: The majority of BCS patients and many of those with BR appeared happy with the outcome of their surgery. More than 78% of BCS patients are very satisfied by their body image and the outcome of their operation, not facing dressing problems, fitting well in their new health status and feeling safe by conserving surgery. On the other hand, 75% of BR women have a satisfactory sexual life. The worst results were achieved by MRM patients. Among BCS women, only 20 (15.9%) described significant difference between their two breasts, while 118 (93.7%) are feeling quite and very safe even though their breast was not excised and 120 (95.2%) are still in fond of conserving treatment instead of mastectomy. Most of MRM patients (110, 76.4%) are not choosing a breast reconstruction and almost all (142, 98.6%) are feeling quite and very safe with mastectomy. Conclusions: The study reveals very good cosmetic outcome and patients’ satisfaction for BCS women, followed by the BR ones. Keywords: Breast cancer, mastectomy, reconstruction, cosmesis.
183 RELATIONSHIP BETWEEN PREOPERATIVE SERUM CEA AND CA 15-3 AND RISK OF BREAST CANCER RECURRENCE IN POSTMENOPAUSAL ELDERLY WOMEN F. Lumachi 1 , S.M.M. Basso 2 , M. Bonamini 2 , G.B. Chiara 2 , B. Marzano 2 , E. Milan 2 , B.U. Waclaw 2 . 1 University of Padua, School of Medicine, Department of Surgical & Gastroenterological Siences, Padova, Italy; 2 S.M. degli Angeli Hospital, Unità Operativa Chirurgia 1, Pordenone, Italy Objectives: The purpose of this study was to investigate whether the preoperative CEA and CA 15-3 serum levels can predict which patients with breast cancer (BC) are likely to have a shorter disease free survival interval following surgery. Methods: We evaluated the prognostic value of these parameters in a series of 363 consecutive postmenopausal women (median age 63 years) with pT1-2, N0-1 BC for progression-free survival. There were 203 (55.9%) patients aged 47-64 (Group A), and 160 (44.1%) >64 years (Group B). The size of the tumor (19.9±13.6 vs. 22.7±14.0 mm, p=0.06) did not differ between Groups, while the mean baseline serum CEA (2.7±8.5 vs. 4.8±11.0 ng/mL, p=0.04), and CA 15-3 (19.0±14.3 vs. 24.9±27.3 U/L, p=0.01) levels were higher in Group B. Results: At long-term follow-up (3-5 years) 301 patients (82.9%) were disease-free (subgroup 1), and 62 (17.1%) patients (Group A = 41, 20.2%; Group B=20, 12.5%) developed local recurrence or distant metastases (subgroup 2). Overall, the mean serum marker levels did not differ (p=NS)
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8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
between subgroups. In Group A, the mean CA 15-3 levels were significantly (p<0.01) higher between subgroups, while in disease-free Group B patients the preoperative serum tumor levels were higher than in those with relapse. Conclusions: In patients with BC high baseline serum CA 15-3 levels is usually considered a predictive factor for relapse. However, our findings indicate that a relationship between baseline serum marker levels and progression-free survival in elderly patients with BC does not exist. Keywords: Breast cancer, menupause, CEA, CA 15-3.
for 5 years carried a higher OR (2·15; 1·72-2·68) than the sequential EPT use (1·17; 0·86-1·61). Use of levonorgestrel releasing intrauterine system (LNG-IUS) alone (n=154) (1·45; 1·97-1·77) or as a complement to oestradiol (n=137) (2·15; 1·72-2·68) was also associated with an increased risk for breast cancer. Conclusions: The association between HT use and the risk for breast cancer shows a large variation between various forms of HT, and also the use of LNG-IUS may carry a risk. Keywords: Postmenopausal hormone therapy, breast cancer
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ORAL CONTRACEPTIVES USE AND HORMONE REPLACEMENT THERAPY TOGETHER AS A RISK OF BREAST CANCER AMONG POSTMENOPAUSAL WOMEN
RENIN ANGIOTENSIN SYSTEM-REGULATING AMINOPEPTIDASE ACTIVITIES IN SERUM OF PRE- AND POST- MENOPAUSAL WOMEN WITH BREAST CANCER
F. Lumachi 1 , S.M.M. Basso 2 , M. Bonamini 2 , G.B. Chiara 2 , M. Ermani 3 , B. Marzano 2 , E. Milan 2 , B.U. Waclaw 2 . 1 University of Padua, School of Medicine, Department of Surgical & Gastroenterological Siences, Padova, Italy; 2 Unità Operativa Chirurgia 1, S.M. degli Angeli Hospital, Pordenone, Italy; 3 Biostatistics Unit, Department of Neurosciences, University of Padua, School of Medicine, Padova, Italy
J.M. Martinez-Martos 1 , M.P. Carrera-Gonzalez 1, B. Dueñas 2 , M.J. Ramirez-Exposito 1 . 1 University of Jaen, Health Sciences, Jaen, Spain; 2 Complejo Hospitalario de Jaen, Jaen, Spain
Objectives: The aim of this study was to determine the effects of oral contraceptive (OC) use and hormone replacement therapy (HRT) in postmenopausal women on the risk of breast cancer (BC). Methods: This is a case-control study among 552 postmenopausal women (median age 59 years, range 48-72) who underwent OC (N=121, 21.9%) and HRT (N=229, 41.5%) administration. Cases were 283 patients with confirmed pT1-2 pN0-1 BC, and controls were 269 age-matched women with no history of cancer or hormone-related diseases, followed prospectively for at least 2 years. The χ2 test and the Student’s t-test were used, and the relative odds ratios (OR) calculation at 95% confidence interval (CI) was also obtained. Results: A total of 73 (17.8%) cases and 48 (17.8%) controls (p=0.008) were former user of OC, while the HRT users were 138 (48.8%) and 91 (33.9%), respectively (p<0.001). The duration of therapy was (cases vs. controls) 22.5±20.5 vs. 35.1±40.2 months; p=0.08) for OC, and 43.7±30.2 vs. 30.6±23.5 months; p<0.001) for HRT. The relative OR was 1.72 (95% CI 1.12-2.22), and 1.91 (95% CI 1.34-2.62) for OC and HRT users, respectively, while the cumulative risk in patients who underwent both OC and HRT therapy was 4.39 (95% CI 2.35-4.56). Conclusions: Although our results must be cautiously interpreted, due to small number of patients, both duration of HRT and common exposure to OC and HRT could have potential impact in increasing risk of BC in postmenopausal women. Keywords: Breast cancer, oral contraceptives, hormone replacement therapy, risk factors.
Objectives: Angiotensin peptides are involved in the control of cellular growth, proliferation and differentiation as well as angiogenesis. Angiotensin II stimulates angiogenesis and tumour growth. Angiotensin II degradation begins with the action of aminopeptidase A (APA) and aspartyl aminopeptidase (AspAP) activities to produce angiotensin III. Angiotensin III is catabolized by aminopeptidase N (APN) and aminopeptidase B (APB) to produce angiotensin IV. Here we analyse APN, APB, APA and AspAP activities in serum of pre- and post- menopausal women with breast cancer to evaluate their putative value as biological markers of the initiation and promotion processes. Methods: We measured fluorometrically serum APN, APB, APA and AspAP activities using aminoacyl-beta-naphthylamide as substrates in women diagnosed with ductal infiltrating carcinomas. Results: Both pre- and postmenopausal women with breast cancer showed higher values of APN and APB activities than controls, being postmenopausal women who showed the highest values. On the contrary, a significant decrease was found in AspAP activity in premenopausal women with breast cancer. No differences were found between groups in APA activity. Conclusions: Our findings of a decrease in AspAP activity and an increase in APN and APB activities suggest that the metabolism of Angiotensin II to Angiotensin III is slow, whereas the metabolism of Angiotensin III to Angiotensin IV is rapid. As a result, Angiotensin II action predominates. An imbalance in the signals activated by Angiotensin II may produce abnormal vascular growth with different response between pre- and postmenopausal women due to their hormonal differences. Keywords: Renin-angiotensin system; Angiotensin; Angiogenesis.
187 185 A CASE-CONTROL STUDY ON HORMONE THERAPY AS A RISK FACTOR FOR BREAST CANCER IN FINLAND H. Lyytinen 1 , T. Dyba 2 , O. Ylikorkala 1 , E. Pukkala 2 . 1 Helsinki University Central Hospital, Department of Obstetrics and Gynaecology, Helsinki, Finland; 2 Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland Objectives: To evaluate the association between postmenopausal hormone therapy (HT) and the risk for breast cancer in recently postmenopausal Finnish women. Methods: All Finnish women with first invasive breast cancer diagnosed between the ages of 50-60 during 1995-2004 (n= 5798) were identified from the Finnish Cancer Registry. For each case, three controls of the same age were retrieved from the Finnish Population Register. The cases and controls were linked to the national medical reimbursement register to assess the use of HT. The odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer were calculated with conditional logistic regression analysis, adjusting for parity, age at the first birth and health care district. Results: Oestradiol-only therapy (557 users with breast cancer, n) or oral progestagen (n=91) were not accompanied by an increased risk. Oestradiol-progestagen therapy (EPT) (n=1004) was associated with an elevated risk in the whole series (OR 1·31; 95% CI 1·20-1·43). The risk became detectable in less than 3 years of use. The continuous EPT regimen
THE RATIO OF THE ESTRADIOL METABOLITES 2-HYDROXYESTRONE (2-OHE1) AND 16-HYDROXYESTRONE (16-OHE1) IN POSTMENOPAUSAL WOMEN WITH AND WITHOUT BREAST CANCER A. Mueck 1 , J. Huober 2 , H. Seeger 1 . 1 University Women’s Hospital, Section of Endocrinology and Menopause, Tübingen, Germany; 2 Breast Center, St. Gallen, Switzerland Objectives: Estradiol is in the human body mainly metabolised by oxidative processes to estrone. Further metabolism occurs irreversibly in two different ways, i.e.hydroxylation at the A-ring or at the D-ring. These metabolites have different biological behaviour with tumorigenic features of 16-OHE1 and antiproliferative characteristics of 2-OHE1. We investigated the ratio of these estradiol metabolites in patients with breast cancer (BC) and with benign diseases. Patients and methods: From 2001 to 2003 urine samples of 207 postmenopausal pts with and without BC (n=206) were collected prior to surgery and stored at -20C. 2-OHE1 and 16-OHE1 were measured by ELISA (Estramet, Immuna Care, Bethlehem, USA). Results: Factors like age, height, weight, BMI and smoking were not significantly different in controls and cases. Log ratio was 0.22 (CI 0.17;0.26) and 0.11 (CI 0.07;0.15) in controls and cases respectively and was statistically significant lower (p=0.0002) in BC pts suggesting a relative outweigh of the tumorigenic metabolite 16-OHE1 in BC patients. In multiple linear regression test log ratio was significantly influenced by BMI. In these pts
HRT. Progesterone (P) combined with estradiol (E2) could be safer than synthetic progestins (SP). The reasons of this discrepancy are unknown. P and SP effects are mediated through the progesterone receptor but SP have mixed pharmacological properties. We compared the effect of P and medroxyprogesterone acetate (MPA), on two breast cancer cell lines (MCF-7 and T47-D cells) and on cultures of normal breast cells. The results confirmed that P and MPA decreased PRA and PRB expression (without any effect on the PRA/PRB ratio) but E2+MPA treatment maintained a stronger decrease of PR expression. Consequences of these differences were evaluated on cell proliferation and differentiation. In MCF-7 but not in T47-D cells, MPA antagonised the E2 mediated proliferation. It was associated with a decrease of cyclin D1 and an increase of p21 transcriptions. Transfection experiments with MMTV-luc suggested an important glucocorticoid effect of MPA in MCF-7 cells. There was also an increase in transcription of proteins involved in cell differentiation as fatty acid synthetase and Wisp2 in both cell lines. Experiments on normal human breast epithelial cells provided opposite results on proliferation and differentiation. Indeed in these cells, E2+P treatment seemed to have a more beneficial effect than E2+MPA treatment. In conclusions, our results showed opposite effect of P and MPA in normal and in beast cancer cells. In combined treatment, P was safer than MPA in normal breast cells but not in breast cancer cell lines.
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after 3 months levels of 2-OHE1 and 16α-OHE1 and their ratio were similar in group 1 and group 2. During transdermal therapy level of 2-OHE1 haven’t significantly changed while level of 16α-OHE1 have increased 2-fold and 2/16α ratio decreased for 40,9% in group 2 and 44,2% in group 1 (p<0,05). Oral therapy stimulated synthesis of both metabolites: 2-OHE1 increased for 223,1% and 16α-OHE1 for 500,0%, 2/16α ratio decreased for 55,6% (p<0,05). In combined groups, both transdermal and oral, 2/16α ratio were similar after 3 months. Conclusions: The way of estrogen administration defines the ways of hydroxymetabolism changes. Oral estrogen therapy increases the amount of circulating estrogen metabolites which can perform negative impact on target-cells in women with high risk of breast cancer and prevailing 16α-hydroxylating processes. Further longitudinal studies are needed to confirm these changes. Keywords: Estrogen metabolites, breast cancer, hormone replacement therapy.
182 BREAST CANCER SURGERY AND COSMESIS E. Kouskos 1 , C. Markopoulos 2 . 1 Vostanio Hospital of Mytilene, Surgical Department, Mytilene, Greece; 2 Laiko Hospital, Breast Unit, 2nd SurgicalDepartment, Athens, Greece
180 EFFECT OF HEALTH COUNSELING ON FEMALES’ AWARENESS TOWARDS BREAST CANCER S.H. Kavari. Semnan Medical University, Faculty of Health, Semnan, Iran, Islamic Republic of Objectives: The aim of this study was to determine the effect of health counseling on the females’ awareness towards methods of prevention of breast cancers. Methods: This study was a quasi experimental design. The aim of the study was to determine the difference of the subjects’ awareness about methods of prevention of breast cancer at pre intervention and post intervention in a medical health center of medical Shiraz University. The mean & standard deviation of the achieved scores related to the awareness were calculated. The sample size was 1200 subjects who were attending in health counseling program in selected health centers. The sampling method was consequence and the study tool was a questionnaire. Results: showed that the mean and standard deviation of samples’ age was 23.72±4.84 and 49.4%. The majority of the subjects had a level of high school degree in education and, 76.6% were housewives. The differences between the mean of their scores of the subjects’ awareness in the two groups (who participated in the counseling and who did not) were significant (P<0.0001). Conclusion: Considering the importance of prevention methods of breast cancer, the researchers suggest to conduct a prospective study for assessing the effect of premarital health counseling program on females’ practice. The study findings showed, a high efficacy of the health counseling regarding the subjects awareness about prevention methods of breast cancer. Keywords: Health counseling, Methods prevention, Breast cancer.
181 IMPACT OF HORMONE REPLACEMENT THERAPY ON ENDOGENOUS ESTRADIOL HYDROXYMETABOLISM IN RUSSIAN POSTMENOPAUSAL WOMEN V. Konovalova, V. Smetnik. Research Center for Obstetrics, Gynecology and Perinatology, Gynecologic Endocrinology, Moscow, Russian Federation Objectives: Changes in endogenous estradiol metabolism may play an important role in breast cancer pathophysioligy. Women with low 2/16α ratio can be at higher risk of breast cancer. We examined impact of exogenous estradiol therapy on estrogen metabolism in postmenopausal women with no history of breast cancer. Methods: 58 women were divided into 3 groups: transdermal estradiol monotherapy (n=21), transdermal estradiol and progesterone in continious combined regimen (n=15) and oral (estradiol and dydrogesterone) combined regimen (n=22). Initially and after 3 months estrogen metabolites were measured by ESTRAMET 2/16α in urine samples. Results: We found that progestins do not influence estrogen metabolites:
Objectives: Presentation of our breast cancer patients’ evaluation about the cosmetic result in relation to their specific surgical management. Methods: A total of 302 breast cancer patients who had been treated by modified radical mastectomy (MRM, n: 144), wide local excision and axillary clearance (breast conserving surgery, BCS, n: 126), and mastectomy followed by delayed reconstruction (breast reconstruction, BR, n: 32) self rated their own cosmetic satisfaction via a questionnaire. Results: The majority of BCS patients and many of those with BR appeared happy with the outcome of their surgery. More than 78% of BCS patients are very satisfied by their body image and the outcome of their operation, not facing dressing problems, fitting well in their new health status and feeling safe by conserving surgery. On the other hand, 75% of BR women have a satisfactory sexual life. The worst results were achieved by MRM patients. Among BCS women, only 20 (15.9%) described significant difference between their two breasts, while 118 (93.7%) are feeling quite and very safe even though their breast was not excised and 120 (95.2%) are still in fond of conserving treatment instead of mastectomy. Most of MRM patients (110, 76.4%) are not choosing a breast reconstruction and almost all (142, 98.6%) are feeling quite and very safe with mastectomy. Conclusions: The study reveals very good cosmetic outcome and patients’ satisfaction for BCS women, followed by the BR ones. Keywords: Breast cancer, mastectomy, reconstruction, cosmesis.
183 RELATIONSHIP BETWEEN PREOPERATIVE SERUM CEA AND CA 15-3 AND RISK OF BREAST CANCER RECURRENCE IN POSTMENOPAUSAL ELDERLY WOMEN F. Lumachi 1 , S.M.M. Basso 2 , M. Bonamini 2 , G.B. Chiara 2 , B. Marzano 2 , E. Milan 2 , B.U. Waclaw 2 . 1 University of Padua, School of Medicine, Department of Surgical & Gastroenterological Siences, Padova, Italy; 2 S.M. degli Angeli Hospital, Unità Operativa Chirurgia 1, Pordenone, Italy Objectives: The purpose of this study was to investigate whether the preoperative CEA and CA 15-3 serum levels can predict which patients with breast cancer (BC) are likely to have a shorter disease free survival interval following surgery. Methods: We evaluated the prognostic value of these parameters in a series of 363 consecutive postmenopausal women (median age 63 years) with pT1-2, N0-1 BC for progression-free survival. There were 203 (55.9%) patients aged 47-64 (Group A), and 160 (44.1%) >64 years (Group B). The size of the tumor (19.9±13.6 vs. 22.7±14.0 mm, p=0.06) did not differ between Groups, while the mean baseline serum CEA (2.7±8.5 vs. 4.8±11.0 ng/mL, p=0.04), and CA 15-3 (19.0±14.3 vs. 24.9±27.3 U/L, p=0.01) levels were higher in Group B. Results: At long-term follow-up (3-5 years) 301 patients (82.9%) were disease-free (subgroup 1), and 62 (17.1%) patients (Group A = 41, 20.2%; Group B=20, 12.5%) developed local recurrence or distant metastases (subgroup 2). Overall, the mean serum marker levels did not differ (p=NS)
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8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
between subgroups. In Group A, the mean CA 15-3 levels were significantly (p<0.01) higher between subgroups, while in disease-free Group B patients the preoperative serum tumor levels were higher than in those with relapse. Conclusions: In patients with BC high baseline serum CA 15-3 levels is usually considered a predictive factor for relapse. However, our findings indicate that a relationship between baseline serum marker levels and progression-free survival in elderly patients with BC does not exist. Keywords: Breast cancer, menupause, CEA, CA 15-3.
for 5 years carried a higher OR (2·15; 1·72-2·68) than the sequential EPT use (1·17; 0·86-1·61). Use of levonorgestrel releasing intrauterine system (LNG-IUS) alone (n=154) (1·45; 1·97-1·77) or as a complement to oestradiol (n=137) (2·15; 1·72-2·68) was also associated with an increased risk for breast cancer. Conclusions: The association between HT use and the risk for breast cancer shows a large variation between various forms of HT, and also the use of LNG-IUS may carry a risk. Keywords: Postmenopausal hormone therapy, breast cancer
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ORAL CONTRACEPTIVES USE AND HORMONE REPLACEMENT THERAPY TOGETHER AS A RISK OF BREAST CANCER AMONG POSTMENOPAUSAL WOMEN
RENIN ANGIOTENSIN SYSTEM-REGULATING AMINOPEPTIDASE ACTIVITIES IN SERUM OF PRE- AND POST- MENOPAUSAL WOMEN WITH BREAST CANCER
F. Lumachi 1 , S.M.M. Basso 2 , M. Bonamini 2 , G.B. Chiara 2 , M. Ermani 3 , B. Marzano 2 , E. Milan 2 , B.U. Waclaw 2 . 1 University of Padua, School of Medicine, Department of Surgical & Gastroenterological Siences, Padova, Italy; 2 Unità Operativa Chirurgia 1, S.M. degli Angeli Hospital, Pordenone, Italy; 3 Biostatistics Unit, Department of Neurosciences, University of Padua, School of Medicine, Padova, Italy
J.M. Martinez-Martos 1 , M.P. Carrera-Gonzalez 1, B. Dueñas 2 , M.J. Ramirez-Exposito 1 . 1 University of Jaen, Health Sciences, Jaen, Spain; 2 Complejo Hospitalario de Jaen, Jaen, Spain
Objectives: The aim of this study was to determine the effects of oral contraceptive (OC) use and hormone replacement therapy (HRT) in postmenopausal women on the risk of breast cancer (BC). Methods: This is a case-control study among 552 postmenopausal women (median age 59 years, range 48-72) who underwent OC (N=121, 21.9%) and HRT (N=229, 41.5%) administration. Cases were 283 patients with confirmed pT1-2 pN0-1 BC, and controls were 269 age-matched women with no history of cancer or hormone-related diseases, followed prospectively for at least 2 years. The χ2 test and the Student’s t-test were used, and the relative odds ratios (OR) calculation at 95% confidence interval (CI) was also obtained. Results: A total of 73 (17.8%) cases and 48 (17.8%) controls (p=0.008) were former user of OC, while the HRT users were 138 (48.8%) and 91 (33.9%), respectively (p<0.001). The duration of therapy was (cases vs. controls) 22.5±20.5 vs. 35.1±40.2 months; p=0.08) for OC, and 43.7±30.2 vs. 30.6±23.5 months; p<0.001) for HRT. The relative OR was 1.72 (95% CI 1.12-2.22), and 1.91 (95% CI 1.34-2.62) for OC and HRT users, respectively, while the cumulative risk in patients who underwent both OC and HRT therapy was 4.39 (95% CI 2.35-4.56). Conclusions: Although our results must be cautiously interpreted, due to small number of patients, both duration of HRT and common exposure to OC and HRT could have potential impact in increasing risk of BC in postmenopausal women. Keywords: Breast cancer, oral contraceptives, hormone replacement therapy, risk factors.
Objectives: Angiotensin peptides are involved in the control of cellular growth, proliferation and differentiation as well as angiogenesis. Angiotensin II stimulates angiogenesis and tumour growth. Angiotensin II degradation begins with the action of aminopeptidase A (APA) and aspartyl aminopeptidase (AspAP) activities to produce angiotensin III. Angiotensin III is catabolized by aminopeptidase N (APN) and aminopeptidase B (APB) to produce angiotensin IV. Here we analyse APN, APB, APA and AspAP activities in serum of pre- and post- menopausal women with breast cancer to evaluate their putative value as biological markers of the initiation and promotion processes. Methods: We measured fluorometrically serum APN, APB, APA and AspAP activities using aminoacyl-beta-naphthylamide as substrates in women diagnosed with ductal infiltrating carcinomas. Results: Both pre- and postmenopausal women with breast cancer showed higher values of APN and APB activities than controls, being postmenopausal women who showed the highest values. On the contrary, a significant decrease was found in AspAP activity in premenopausal women with breast cancer. No differences were found between groups in APA activity. Conclusions: Our findings of a decrease in AspAP activity and an increase in APN and APB activities suggest that the metabolism of Angiotensin II to Angiotensin III is slow, whereas the metabolism of Angiotensin III to Angiotensin IV is rapid. As a result, Angiotensin II action predominates. An imbalance in the signals activated by Angiotensin II may produce abnormal vascular growth with different response between pre- and postmenopausal women due to their hormonal differences. Keywords: Renin-angiotensin system; Angiotensin; Angiogenesis.
187 185 A CASE-CONTROL STUDY ON HORMONE THERAPY AS A RISK FACTOR FOR BREAST CANCER IN FINLAND H. Lyytinen 1 , T. Dyba 2 , O. Ylikorkala 1 , E. Pukkala 2 . 1 Helsinki University Central Hospital, Department of Obstetrics and Gynaecology, Helsinki, Finland; 2 Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland Objectives: To evaluate the association between postmenopausal hormone therapy (HT) and the risk for breast cancer in recently postmenopausal Finnish women. Methods: All Finnish women with first invasive breast cancer diagnosed between the ages of 50-60 during 1995-2004 (n= 5798) were identified from the Finnish Cancer Registry. For each case, three controls of the same age were retrieved from the Finnish Population Register. The cases and controls were linked to the national medical reimbursement register to assess the use of HT. The odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer were calculated with conditional logistic regression analysis, adjusting for parity, age at the first birth and health care district. Results: Oestradiol-only therapy (557 users with breast cancer, n) or oral progestagen (n=91) were not accompanied by an increased risk. Oestradiol-progestagen therapy (EPT) (n=1004) was associated with an elevated risk in the whole series (OR 1·31; 95% CI 1·20-1·43). The risk became detectable in less than 3 years of use. The continuous EPT regimen
THE RATIO OF THE ESTRADIOL METABOLITES 2-HYDROXYESTRONE (2-OHE1) AND 16-HYDROXYESTRONE (16-OHE1) IN POSTMENOPAUSAL WOMEN WITH AND WITHOUT BREAST CANCER A. Mueck 1 , J. Huober 2 , H. Seeger 1 . 1 University Women’s Hospital, Section of Endocrinology and Menopause, Tübingen, Germany; 2 Breast Center, St. Gallen, Switzerland Objectives: Estradiol is in the human body mainly metabolised by oxidative processes to estrone. Further metabolism occurs irreversibly in two different ways, i.e.hydroxylation at the A-ring or at the D-ring. These metabolites have different biological behaviour with tumorigenic features of 16-OHE1 and antiproliferative characteristics of 2-OHE1. We investigated the ratio of these estradiol metabolites in patients with breast cancer (BC) and with benign diseases. Patients and methods: From 2001 to 2003 urine samples of 207 postmenopausal pts with and without BC (n=206) were collected prior to surgery and stored at -20C. 2-OHE1 and 16-OHE1 were measured by ELISA (Estramet, Immuna Care, Bethlehem, USA). Results: Factors like age, height, weight, BMI and smoking were not significantly different in controls and cases. Log ratio was 0.22 (CI 0.17;0.26) and 0.11 (CI 0.07;0.15) in controls and cases respectively and was statistically significant lower (p=0.0002) in BC pts suggesting a relative outweigh of the tumorigenic metabolite 16-OHE1 in BC patients. In multiple linear regression test log ratio was significantly influenced by BMI. In these pts