Tamoxifen Archives - Revista Brasileira de Ginecologia e Obstetrícia
, , , , , Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2021;43(3):185-189
, , , , , The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer.
This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017.
From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, ‘disease progression’ was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, ‘presence of side effects’ was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities.
The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2021;43(3):185-189
, , , , , The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer.
This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017.
From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, ‘disease progression’ was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, ‘presence of side effects’ was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities.
The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2018;40(12):794-799
Tamoxifen (TMX) is the main drug used both in pre and postmenopausal women as adjuvant treatment for hormone receptor-positive breast cancer. An important barrier to the use of TMXis the development ofdrug resistance causedby molecular processes related to genetic and epigenetic mechanisms, such as the actions of cytochrome P450 2D6 (CYP2D6) polymorphisms and of its metabolites. The present study aimed to review recent findings related to the impact of CYP2D6 polymorphisms and how they can affect the results of TMX in breast cancer treatment. The keywords CYP2D6, tamoxifen, and breast cancer were searched in the PubMed, Scopus, The Cochrane Library, Scielo, and Bireme databases. Studies related to other types of neoplasms or based on other isoenzymes from cytochrome P450, but not on CYP2D6, were excluded. The impact of CYP2D6 polymorphisms in the TMX resistance mechanism remains unclear. The CYP2D6 gene seems to contribute to decreasing the efficacy of TMX, while the main mechanism responsible for therapy failure, morbidity, and mortality is the progression of the disease.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2018;40(12):794-799
Tamoxifen (TMX) is the main drug used both in pre and postmenopausal women as adjuvant treatment for hormone receptor-positive breast cancer. An important barrier to the use of TMXis the development ofdrug resistance causedby molecular processes related to genetic and epigenetic mechanisms, such as the actions of cytochrome P450 2D6 (CYP2D6) polymorphisms and of its metabolites. The present study aimed to review recent findings related to the impact of CYP2D6 polymorphisms and how they can affect the results of TMX in breast cancer treatment. The keywords CYP2D6, tamoxifen, and breast cancer were searched in the PubMed, Scopus, The Cochrane Library, Scielo, and Bireme databases. Studies related to other types of neoplasms or based on other isoenzymes from cytochrome P450, but not on CYP2D6, were excluded. The impact of CYP2D6 polymorphisms in the TMX resistance mechanism remains unclear. The CYP2D6 gene seems to contribute to decreasing the efficacy of TMX, while the main mechanism responsible for therapy failure, morbidity, and mortality is the progression of the disease.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2016;38(12):615-622
Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HRþ) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemo-therapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2þ) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HRþ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2016;38(12):615-622
Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HRþ) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemo-therapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2þ) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HRþ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2009;31(3):131-137
DOI 10.1590/S0100-72032009000300005
PURPOSE: to evaluate the effects of tamoxifen on the expression of TGF-β and p27 proteins in polyps and adjacent endometrium of women after menopause. METHODS: prospective study with 30 post-menopausal women with diagnosis of breast cancer, taking tamoxifen (20 mg/day), presenting diagnosis of suspect endometrial polyps through transvaginal ultrasonography, and submitted to diagnostic and surgical hysterectomy to withdraw the polyps and adjacent endometrium. A immunohistochemical study has been done to verify the expression of the TGF-β and p27 proteins in the polyps and adjacent endometrium. These proteins' quantification has been done by morphometry. RESULTS: the patients' average age was 61.7 years old; their average age at the menopause onset was 49.5; and the average of using tamoxifen was 25.3 months. The average concentration of positive cells for TGF-β protein in the glandular and stroma polyp epithelium was 62.6±4.5 cells/mm². For the p27, in the glandular polyp epithelium, it was 24.2±18.6 cells/mm² and for the stroma, 19.2±15.2 cells/mm². There was no significant difference between the expression of TGF-β and p27 in the glandular epithelial form the polyps and the adjacent endometrium. The expression of proteins in the polyp and adjacent endometrium with its respective glandular and stroma epithelium showed a significant difference for the p27 protein (r=0.9, p<0.05). CONCLUSIONS: we have concluded that the TGF-β expression is not related to the effect of tamoxifen on the growing of endometrial polyps, but the absence of polyps' malignization by tamoxifen may be explained by the high expression of p27 protein in its glandular epithelium.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2009;31(3):131-137
DOI 10.1590/S0100-72032009000300005
PURPOSE: to evaluate the effects of tamoxifen on the expression of TGF-β and p27 proteins in polyps and adjacent endometrium of women after menopause. METHODS: prospective study with 30 post-menopausal women with diagnosis of breast cancer, taking tamoxifen (20 mg/day), presenting diagnosis of suspect endometrial polyps through transvaginal ultrasonography, and submitted to diagnostic and surgical hysterectomy to withdraw the polyps and adjacent endometrium. A immunohistochemical study has been done to verify the expression of the TGF-β and p27 proteins in the polyps and adjacent endometrium. These proteins' quantification has been done by morphometry. RESULTS: the patients' average age was 61.7 years old; their average age at the menopause onset was 49.5; and the average of using tamoxifen was 25.3 months. The average concentration of positive cells for TGF-β protein in the glandular and stroma polyp epithelium was 62.6±4.5 cells/mm². For the p27, in the glandular polyp epithelium, it was 24.2±18.6 cells/mm² and for the stroma, 19.2±15.2 cells/mm². There was no significant difference between the expression of TGF-β and p27 in the glandular epithelial form the polyps and the adjacent endometrium. The expression of proteins in the polyp and adjacent endometrium with its respective glandular and stroma epithelium showed a significant difference for the p27 protein (r=0.9, p<0.05). CONCLUSIONS: we have concluded that the TGF-β expression is not related to the effect of tamoxifen on the growing of endometrial polyps, but the absence of polyps' malignization by tamoxifen may be explained by the high expression of p27 protein in its glandular epithelium.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):335-339
DOI 10.1590/S0100-72032007000700002
PURPOSE: to evaluate the effect of raloxifene on breast cancer angiogenesis of menopausal women. METHODS: sixteen menopausal women with stage II (>3 cm) estrogen receptor positive operable breast cancer were enrolled in this study. Following confirmation of the diagnosis by incisional biopsy, the patients received 60 mg raloxifene daily for 28 days prior to the definitive surgery. Immunohistochemical study was performed on the sample tumors obtained during the biopsy for the diagnosis and evaluation of the status of estrogen receptor and during the definitive surgery. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. The vascular unit was considered as any endothelial cell or group of cells of a brownish color, clearly separated from adjacent microvessels, tumor cells or other connective tissue, forming or not lumen. Microvessel count was performed in ten fields of each slide using a 40X objective lens (400X magnification). A microscope coupled to a system of capture and analysis of image was used (Imagelab®). Statistical analysis of data was carried out using the paired Student t-test and significance level was established at p<0.05. RESULTS: mean numbers of anti-CD34 antibody-stained microvessels before and after raloxifene treatment were 44.4±3.5 and 22.6±1.6, respectively. A significant reduction in the number of microvessels following raloxifene therapy was observed (p<0.001). CONCLUSIONS: when administered as primary therapy for menopausal women with breast carcinoma, raloxifene significantly reduced tumoral angiogenesis.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):335-339
DOI 10.1590/S0100-72032007000700002
PURPOSE: to evaluate the effect of raloxifene on breast cancer angiogenesis of menopausal women. METHODS: sixteen menopausal women with stage II (>3 cm) estrogen receptor positive operable breast cancer were enrolled in this study. Following confirmation of the diagnosis by incisional biopsy, the patients received 60 mg raloxifene daily for 28 days prior to the definitive surgery. Immunohistochemical study was performed on the sample tumors obtained during the biopsy for the diagnosis and evaluation of the status of estrogen receptor and during the definitive surgery. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. The vascular unit was considered as any endothelial cell or group of cells of a brownish color, clearly separated from adjacent microvessels, tumor cells or other connective tissue, forming or not lumen. Microvessel count was performed in ten fields of each slide using a 40X objective lens (400X magnification). A microscope coupled to a system of capture and analysis of image was used (Imagelab®). Statistical analysis of data was carried out using the paired Student t-test and significance level was established at p<0.05. RESULTS: mean numbers of anti-CD34 antibody-stained microvessels before and after raloxifene treatment were 44.4±3.5 and 22.6±1.6, respectively. A significant reduction in the number of microvessels following raloxifene therapy was observed (p<0.001). CONCLUSIONS: when administered as primary therapy for menopausal women with breast carcinoma, raloxifene significantly reduced tumoral angiogenesis.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 1998;20(9):533-536
DOI 10.1590/S0100-72031998000900007
Purpose: to evaluate the effects of tamoxifen (TAM) on plasma levels of estradiol, progesterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and steroid hormone-binding globulin (SHBG) when given to premenopausal women in the doses of 10 and 20 mg/day for 22 days. Patients and Methods: a randomized double-blind study was performed with 43 premenopausal eumenorrheic women. The patients were divided into three groups: A (N = 15, placebo); B (N = 15, TAM 10 mg/day) and C (N = 13, 20 mg/day). They started taking an oral dose of TAM or placebo on the very first day of the menstrual cycle. Two hormone determinations were performed, both on the 22nd day of the menstrual cycle: the first in the cycle that preceded the use of the drug and the second, in the following cycle, after 22 days of using the medication. We used the Levine and Student tests in order to evaluate the homogeneity of the sample and the variation of the hormone determinations respectively. Results:serum levels of estradiol, progesterone and SHBG increased significantly in groups B and C. In group C, we also observed increase in serum level of FSH (p < 0.0045) and a fall in prolactin level (p < 0.0055). Conclusions: TAM promoted a significant increase in serum concentrations of estradiol, progesterone and SHBG either in the doses of 10 or 20 mg/day. However, significant increase in FSH and decrease in prolactin were obtained only with the dose of 20 mg/day.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 1998;20(9):533-536
DOI 10.1590/S0100-72031998000900007
Purpose: to evaluate the effects of tamoxifen (TAM) on plasma levels of estradiol, progesterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and steroid hormone-binding globulin (SHBG) when given to premenopausal women in the doses of 10 and 20 mg/day for 22 days. Patients and Methods: a randomized double-blind study was performed with 43 premenopausal eumenorrheic women. The patients were divided into three groups: A (N = 15, placebo); B (N = 15, TAM 10 mg/day) and C (N = 13, 20 mg/day). They started taking an oral dose of TAM or placebo on the very first day of the menstrual cycle. Two hormone determinations were performed, both on the 22nd day of the menstrual cycle: the first in the cycle that preceded the use of the drug and the second, in the following cycle, after 22 days of using the medication. We used the Levine and Student tests in order to evaluate the homogeneity of the sample and the variation of the hormone determinations respectively. Results:serum levels of estradiol, progesterone and SHBG increased significantly in groups B and C. In group C, we also observed increase in serum level of FSH (p < 0.0045) and a fall in prolactin level (p < 0.0055). Conclusions: TAM promoted a significant increase in serum concentrations of estradiol, progesterone and SHBG either in the doses of 10 or 20 mg/day. However, significant increase in FSH and decrease in prolactin were obtained only with the dose of 20 mg/day.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2003;25(3):185-191
DOI 10.1590/S0100-72032003000300007
PURPOSE: to quantitatively analyze the immunoreaction of monoclonal antibody Ki-67 in the mammary epithelium adjacent to fibroadenoma of premenopausal women treated with tamoxifen, for 50 days, at doses of 5, 10 and 20 mg/day. METHODS: we studied, prospectively, the effects of tamoxifen administered for 50 days, at doses of 5, 10 e 20 mg/day, by the immunoreaction of the Ki-67 (clone Ki-S5) monoclonal antibody on mammary epithelium adjacent to fibroadenoma in premenopausal women. We studied 58 patients in a double-blind trial who were divided into four groups: Group A (n=13; placebo), Group B (n=16; 5 mg/day tamoxifen), Group C (n=14; 10 mg/day) and Group D (n=15; 20 mg/day). All patients received the medication from the first day on of the menstrual cycle and biopsy was performed on the last day of the treatment. Cells stained and not stained by the immunoreagent were counted by optical microscopy (400X) with a digital image capturing system and image analysis. RESULTS: the average percentage of stained nuclei was calculated for all groups: Group A was 2.0 with a standard error (SE) of 0.3. In Group B it was 0.7 (SE=0.2); in Group C it was 0.4 (SE=0,2) and in Group D it was 0.1 (SE=0). Statistical analysis showed significant reductions between the groups (p<0.001), and Tukey's pairwise comparison test confirmed that there was a significant increase in the immunoreaction of the monoclonal Ki-67 antibody in groups B, C and D. CONCLUSIONS: tamoxifen, administered at doses of 5, 10 and 20 mg/day for 50 days, significantly reduced the immunoreaction of monoclonal Ki-67 in the mammary epithelium of premenopausal patients and there was no significant difference between the groups that received 5, 10 and 20 mg/day tamoxifen.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2003;25(3):185-191
DOI 10.1590/S0100-72032003000300007
PURPOSE: to quantitatively analyze the immunoreaction of monoclonal antibody Ki-67 in the mammary epithelium adjacent to fibroadenoma of premenopausal women treated with tamoxifen, for 50 days, at doses of 5, 10 and 20 mg/day. METHODS: we studied, prospectively, the effects of tamoxifen administered for 50 days, at doses of 5, 10 e 20 mg/day, by the immunoreaction of the Ki-67 (clone Ki-S5) monoclonal antibody on mammary epithelium adjacent to fibroadenoma in premenopausal women. We studied 58 patients in a double-blind trial who were divided into four groups: Group A (n=13; placebo), Group B (n=16; 5 mg/day tamoxifen), Group C (n=14; 10 mg/day) and Group D (n=15; 20 mg/day). All patients received the medication from the first day on of the menstrual cycle and biopsy was performed on the last day of the treatment. Cells stained and not stained by the immunoreagent were counted by optical microscopy (400X) with a digital image capturing system and image analysis. RESULTS: the average percentage of stained nuclei was calculated for all groups: Group A was 2.0 with a standard error (SE) of 0.3. In Group B it was 0.7 (SE=0.2); in Group C it was 0.4 (SE=0,2) and in Group D it was 0.1 (SE=0). Statistical analysis showed significant reductions between the groups (p<0.001), and Tukey's pairwise comparison test confirmed that there was a significant increase in the immunoreaction of the monoclonal Ki-67 antibody in groups B, C and D. CONCLUSIONS: tamoxifen, administered at doses of 5, 10 and 20 mg/day for 50 days, significantly reduced the immunoreaction of monoclonal Ki-67 in the mammary epithelium of premenopausal patients and there was no significant difference between the groups that received 5, 10 and 20 mg/day tamoxifen.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2002;24(4):233-239
DOI 10.1590/S0100-72032002000400004
Purpose: to analyze sensitivity, specificity, positive and negative predictive values and the likelihood ratio of transvaginal ultrasound and hysteroscopy when compared with the histopathologic examination of the endometrium in women with breast cancer who have been treated with tamoxifen. Methods: transversal study with 30 women in whom transvaginal ultrasound evaluated the echogenic pattern of endometrial echo and its thickness. Hyteroscopy was performed and described as normal (normal or atrophic endometrium) or abnormal (thickening, polyps, leiomyoma, synechia). Material for histopathology was obtained from endometrial biopsy and the findings were considered normal (irregular endometrial maturation and/or atrophy) or abnormal (polyps, simple or complex hyperplasia, leiomyoma or endometrial carcinoma). Results: the general diagnosis of endometrial modifications was present in 36.6% of patients. The most frequent results were cystic atrophy (46.6%) and endometrial polyps (26.6%). Through the ROC curve the best cutoff of 8 mm of endometrial thickness measure was determined. This measure showed sensitivity of 72.7%, specificity of 72.9%, positive predictive value of 66.6%, negative predictive value of 83.3% and likelihood ratio of 3.4. Hysteroscopy showed sensitivity of 90.9%, specificity of 68.4%, positive predictive value of 62.5%, negative prediction value of 92.8% and likelihood ratio of 2.8. Conclusions: the most frequent endometrial modifications were cystic atrophy followed by polyps. Transvaginal ultrasound showed a higher rate of false-positive (42.1%), when the cutoff for the thickness of the endometrium was 5 mm; however acuracy improved when the measure of 8 mm was used. The cutoff of 8 mm was determined through the ROC curve.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2002;24(4):233-239
DOI 10.1590/S0100-72032002000400004
Purpose: to analyze sensitivity, specificity, positive and negative predictive values and the likelihood ratio of transvaginal ultrasound and hysteroscopy when compared with the histopathologic examination of the endometrium in women with breast cancer who have been treated with tamoxifen. Methods: transversal study with 30 women in whom transvaginal ultrasound evaluated the echogenic pattern of endometrial echo and its thickness. Hyteroscopy was performed and described as normal (normal or atrophic endometrium) or abnormal (thickening, polyps, leiomyoma, synechia). Material for histopathology was obtained from endometrial biopsy and the findings were considered normal (irregular endometrial maturation and/or atrophy) or abnormal (polyps, simple or complex hyperplasia, leiomyoma or endometrial carcinoma). Results: the general diagnosis of endometrial modifications was present in 36.6% of patients. The most frequent results were cystic atrophy (46.6%) and endometrial polyps (26.6%). Through the ROC curve the best cutoff of 8 mm of endometrial thickness measure was determined. This measure showed sensitivity of 72.7%, specificity of 72.9%, positive predictive value of 66.6%, negative predictive value of 83.3% and likelihood ratio of 3.4. Hysteroscopy showed sensitivity of 90.9%, specificity of 68.4%, positive predictive value of 62.5%, negative prediction value of 92.8% and likelihood ratio of 2.8. Conclusions: the most frequent endometrial modifications were cystic atrophy followed by polyps. Transvaginal ultrasound showed a higher rate of false-positive (42.1%), when the cutoff for the thickness of the endometrium was 5 mm; however acuracy improved when the measure of 8 mm was used. The cutoff of 8 mm was determined through the ROC curve.
