Effects Of Tamoxifen In Patients Research Articles

Effect of tamoxifen in patients with thin endometrium who underwent frozen-thawed embryo transfer cycles: a retrospective study.

Thin endometrium leads to an impaired implantation rate. The aim of the study is to compare the clinical outcomes of tamoxifen (TAM) and hormone replacement therapy (HRT) used in patients with thin endometrium (<7mm) in frozen-thawed embryo transfer (FET)cycles. A total of 176 FET cycles with thin endometrium were retrospectively analyzed in our center from Jan 2020 to May 2022. According to patients' own will, 112 patients were allocated to the HRT group and 64 patients chose the TAM protocol. Clinical outcomes were compared between two groups. The duration of treatment was shorter in the TAM group(12.03±2.34d) than the HRT group (16.07±2.52 d), which was statistically different (p<0.05). The endometrial thickness on the transfer day of the TAM group (7.32±1.28 mm) was significantly thicker than that of the HRT group (6.85±0.89mm, p<0.05). The clinical pregnancy rate of the TAM group (50.0%) was higher than that of the HRT group (36.6%), but there was no significant difference (p >0.05). The early miscarriage rate was significantly lower in the TAM group compared with the HRT group (5.9% Vs 26.8%, adjusted OR 0.10, p<0.05), while the live birth rate was higher in the TAM group (46.9% Vs 26.8%, adjusted OR 2.24, p<0.05) compared with the HRT group. For patients with thin endometrium, TAM effectively improved the endometrial thickness and increased the live birth rate. TAM can be used as an alternative protocol for patients with thin endometrium.

Tamoxifen in Recurrent Thin Endometrium

To evaluate the effects of tamoxifen in patients with repeated unresponsive thin endometrium (

The Effect of Tamoxifen on Thin Endometrium in Patients Undergoing Frozen-Thawed Embryo Transfer.

Tamoxifen has played a vital role in endocrine therapy for the treatment of estrogen receptor-positive breast cancer. We examined the effect of tamoxifen in patients with a thin endometrium in frozen-thawed embryo transfer (FET) cycles and compared the improvement in endometrial thickness (EMT) and pregnancy outcomes stratified by different etiologies of thin endometrium. A total of 226 women were recruited for a new tamoxifen protocol; all had an EMT of less than 7.5 mm in previous cycles, including natural cycle (NC), hormone replacement treatment (HRT), and ovulation induction (OI) cycles. Compared with previous cycles, tamoxifen cycles showed a significantly increased EMT (from 6.11 ± 0.98 mm to 7.87 ± 1.48 mm in the NC group, from 6.24 ± 1.01 mm to 8.22 ± 1.67 mm in the HRT group, and from 6.34 ± 1.03 mm to 8.05 ± 1.58 mm in the OI group; all P < .001). Patients were further divided into 3 groups based on the causes of their thin endometrium: (1) history of intrauterine adhesion (n = 34), (2) history of uterine curettage (n = 141), and (3) polycystic ovary syndrome (PCOS; n = 51). Patients with PCOS obtained the thickest EMT (9.31 ± 1.55 mm), the lowest cycle cancellation rate (11.76%), and the highest rate of clinical pregnancy (60%) and live birth (55.56%) per transfer ( P < .001). Multivariable regression analysis showed that EMT was related to live birth (odds ratio: 1.487; 95% confidence interval: 1.172-1.887). A tamoxifen protocol improves EMT in patients after NC, HRT, and OI cycles during FET. Patients with PCOS show the most benefit from tamoxifen and achieve better pregnancy outcomes.

Abstract P4-15-06: Low dose tamoxifen lowers recurrences after mastectomy for in situ neoplasia. Ten-year results of a monoinstitutional study

Abstract There is no agreement upon the need of a preventive treatment after breast mastectomy for in situ neoplasia. Low-dose tamoxifen (5 mg/day) has comparable antiproliferative effect than the standard dose of 20 mg/day in biomarker trials and has been shown to halve ipsilateral recurrence in a large cohort of postmenopausal ER positive DCIS treated with breast conserving surgery (Guerrieri-Gonzaga et al., Int J Cancer 2016). Here we investigated the effect of low dose tamoxifen in patients treated with mastectomy for an in situ neoplasia and followed-up in a single Institution for a median of 10 years. Our cohort consists of 404 consecutive premenopausal (n=281) or postmenopausal (n=123) women who underwent unilateral mastectomy at the European Institute of Oncology (IEO), with or without nipple preservation, between 1996 and 2011. Patients had a diagnosis of pure LCIS (n=12) or ER positive (ER&amp;gt;1%) DCIS (n=363) or both (n=29) and were treated with tamoxifen 5 mg/day (n=162) or no treatment (n=242) upon medical judgment, patient preference and/or clinical trial assignment. The main subject and tumor characteristics are reported in table 1. Patient and tumor characteristics No tam (n=242)Low dose tam (n=162)P-valueMedian age, years (IQR)46 (41, 54)47 (42, 51)0.65Premenopausal status (n, %)160 (66)121 (75)0.07Median BMI (kg/m2, IQR)22 (20, 25)22 (20, 24)0.7Breast cancer family history (%)29320.44Histology (LCIS, DCIS, both; %)4/92/42/86/120.01Grading (G1,G2,G3;%)11/59/2918/61/200.04Median ER (%, IQR)90 (70, 95)90 (80, 95)0.005Median PgR (%, IQR)40 (5, 80)68 (25, 90)0.0002Median Ki67 (%, IQR)15 (10, 23)14 (10, 20)0.03Radiotherapy (n, %)95 (39)76 (47)0.13 After a median follow-up of 10 years (range 4-21 years) and a median low dose tamoxifen treatment of 4.9 years (IQR 2.7, 5.0), a total of 85 events were observed (28 in situ, 40 invasive breast cancers, 3 metastatic diseases, 12 other primary cancers, 2 deaths). A total of 36 ipsilateral breast events (23 versus 13 in the no tam versus tam group, respectively), 32 contralateral breast events (22 versus 10 in the no tam versus tam, respectively) and 17 other events (11 versus 6 in the no tam versus tam, respectively) occurred. Overall, eleven deaths (3%) occurred and no endometrial cancers were observed. A time-dependent competing risk model was applied for tamoxifen use and we have shown that low-dose tamoxifen was associated with a 48% reduction on all breast events (adjusted HR=0.52, 95% CI: 0.31–0.88, p=0.01), adjusting for radiotherapy and age. Although limited by the observational nature of the study, we show for the first time that treatment with low dose tamoxifen is effective and safe in women who underwent mastectomy for non-invasive breast neoplasms and should be taken into consideration as a risk reduction strategy for premenopausal and postmenopausal women with breast intraepithelial neoplasia. Citation Format: Guerrieri-Gonzaga A, Gandini S, Serrano D, Lazzeroni M, Pruneri G, Varricchio C, Cazzaniga M, Leonardi MC, Galimberti V, Viale G, De Censi A, Bonanni B. Low dose tamoxifen lowers recurrences after mastectomy for in situ neoplasia. Ten-year results of a monoinstitutional study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-06.

BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo

BackgroundTamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer.MethodsCell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry.ResultsOur data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer.ConclusionBD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.

Abstract P1-12-17: Mature data (&amp;gt; 25 years) on 2 years adjuvant tamoxifen treatment in premenopausal women with breast cancer: Time to re-emphasize the progesterone receptor as predictive factor?

Abstract Background In 2011 The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) reported that five years of adjuvant tamoxifen (TAM) significantly reduces the 15-year risks of breast cancer recurrence and death. Moreover, the estrogen receptor (ER) was considered the clinically most relevant predictive factor for efficacy of TAM treatment. In premenopausal patients participating in a randomized trial of 2 years of adjuvant TAM, we have previously reported on increased recurrence free survival in patients with ER- and PR-positive disease and a trend for increased overall survival in patients with PR-positive tumors. The median follow-up time was 13.9 years for patients without events. Since the effect on mortality may increase beyond year 10, we investigated more mature of data. Aims To investigate the long-term effect of 2 years adjuvant TAM in premenopausal patients choosing cumulative mortality (CM) and cumulative breast cancer mortality (CBCM) as end-points. Methods Premenopausal patients (n=564) with stage II breast cancer were included in a Swedish randomized multicenter trial between 1986-1991 and allocated to 2 years of TAM (n=276) or no treatment (n=288). The hormone receptor status of the tumor was known for 541 (96%) of the patients included, determined by immunohistochemistry or cytosol-based methods. Less than 2% were treated with adjuvant chemotherapy and they were equally distributed between the two groups. Median follow-up time was 26.3 years (22.7-29.7). Mortality data was obtained from the Swedish Cause of Death Register. Results Death from any cause was recorded among 312 (55%) of the patients, and 265 (47%) of the deaths were due to breast cancer. Two years of TAM decreased CM and CBCM in all patients irrespective of hormonal receptor status (n=564) (CM: HR 0.81; 95% CI: 0.65-1.02, p=0.070; CBCM: HR 0.79; 95% CI: 0.61-1.01, p=0.058), as well as in patients with ER-positive disease (n=346) (CM: HR 0.77; 95% CI: 0.57-1.03, p=0.077; CBCM: HR 0.72; 95% CI: 0.52-1.01, p=0.051), however not strictly significant. Importantly, in patients with PR-positive tumors, TAM significantly reduced CM and CBCM (CM: HR 0.73; 95% CI: 0.55-0.98, p=0.037; CBCM: HR 0.68; 95% CI: 0.49-0.94, p=0.020). Moreover, in patients with ER- and PR positive tumors TAM decreased CM (HR 0.74; 95% CI: 0.55-1.01, p=0.057) and CBCM (HR 0.69; 95% CI: 0-49-0.97, p=0.033), whereas there was no effect of TAM in patients with ER-positive and PR-negative tumors (p=0.97 and p=0.99, respectively). Conclusions The present study demonstrates that 2 years of adjuvant TAM as monotherapy significantly reduced CM and CBCM in premenopausal women with PR-positive tumors as well as CBCM in ER- and PR-positive tumors, after &amp;gt; 25 years of follow-up. Five years of adjuvant TAM have been proven to reduce mortality rates at 15 years, but we herein show that also 2 years of TAM yields a survival benefit at 25 years. In the latest meta-analysis from EBCTCG, PR did not add predictive information in patients with ER-positive tumors, but according to our results the significance of PR, as a predictive factor for TAM efficacy, should be re-emphasized in premenopausal women. Citation Format: Maria Ekholm, Pär-Ola Bendahl, Mårten Fernö, Bo Nordenskjöld, Olle Stål, Lisa Rydén. Mature data (&amp;gt; 25 years) on 2 years adjuvant tamoxifen treatment in premenopausal women with breast cancer: Time to re-emphasize the progesterone receptor as predictive factor? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-17.

Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer

The mechanism of tamoxifen action in the treatment of breast cancer is believed to be via active metabolites that act as potent estrogen receptor antagonists. Attempts to identify relationships between active metabolite concentrations and clinical outcomes have produced mixed results. Since anti-estrogenic effects may be brought about not only by estrogen antagonism, but also by reduced estrogen synthesis, we tested the ability of tamoxifen and its principal metabolites to inhibit aromatase in vitro. The activity of human aromatase in both recombinant and placental microsomal preparations was measured using the rate of generation of a fluorescent metabolite in the presence and absence of multiple concentrations of tamoxifen, endoxifen, N-desmethyl-tamoxifen, and Z-4-hydroxy-tamoxifen. Aromatase inhibition was further characterized by measuring the inhibition of testosterone metabolism to estradiol. The biochemical mechanisms of inhibition were documented and their inhibitory potency was compared. Using recombinant human aromatase, endoxifen, and N-desmethyl-tamoxifen were able to inhibit aromatase activity with K (i) values of 4.0 and 15.9μM, respectively. Detailed characterization of inhibition by endoxifen and N-desmethyl-tamoxifen indicated non-competitive kinetics for both inhibitors. Similarly, endoxifen-inhibited testosterone metabolism via a non-competitive mechanism. No appreciable inhibition by tamoxifen or Z-4-hydroxy-tamoxifen was observed at similar concentrations. The relative inhibitory potency was: endoxifen>N-desmethyl-tamoxifen>>>Z-4-hydroxy-tamoxifen>tamoxifen. Similar data were obtained in human placental microsomes. Endoxifen and N-desmethyl-tamoxifen were found to be potent inhibitors of aromatase. Inhibition by these tamoxifen metabolites may contribute to the variability in clinical effects of tamoxifen in patients with breast cancer. Relationships between tamoxifen metabolite concentrations and clinical outcomes may be complex, and the biologic mechanisms that underlie these relationships may include aromatase inhibition.

Tamoxifen is safe and effective in gynecological cancer patients with renal dysfunction

Tamoxifen has been found to be safe and effective in gynecological cancer patients with normal renal function. However, to our knowledge, no data exist regarding its effectiveness and toxicity in gynecological cancer patients with chronic kidney disease (CKD). Therefore, we retrospectively evaluated the effects of tamoxifen in patients with recurrent gynecological cancer and CKD. We collected clinical and demographic data for all patients. CKD was defined as a creatinine clearance (CrCl) level of less than 90 mL/min/1.73 m2, in accordance with the National Kidney Foundation Kidney and Dialysis Outcomes Quality Initiative, and further categorized as mild, moderate, or severe (CrCl levels of 60–89, 30–59, and &lt; 30 mL/min/1.73 m2, respectively). Twenty-nine patients were included in the study— 22 with epithelial ovarian cancer, 4 with peritoneal cancer, and 3 with fallopian tube cancer. Thirteen patients had mild CKD, 13 had moderate, and 3 had severe. Most patients had been treated with 20 mg/day of tamoxifen every 4 weeks. The median duration of treatment was 5 months (range, 1–52 months). The overall complete response, partial response, stable disease, and disease progression rates were 0%, 10%, 41%, and 48%, respectively. Twenty-one percent of patients experienced hot flashes, and 7% experienced nausea. No major adverse reactions occurred. These findings were similar to those for gynecological cancer patients with normal renal function. In conclusion, 20 mg/day of tamoxifen is safe and effective in gynecological cancer patients with CKD.

Tamoxifen is safe and effective in gynecological cancer patients with renal dysfunction

Tamoxifen has been found to be safe and effective in gynecological cancer patients with normal renal function. However, to our knowledge, no data exist regarding its effectiveness and toxicity in gynecological cancer patients with chronic kidney disease (CKD). Therefore, we retrospectively evaluated the effects of tamoxifen in patients with recurrent gynecological cancer and CKD. We collected clinical and demographic data for all patients. CKD was defined as a creatinine clearance (CrCl) level of less than 90 mL/min/1.73 m(2), in accordance with the National Kidney Foundation Kidney and Dialysis Outcomes Quality Initiative, and further categorized as mild, moderate, or severe (CrCl levels of 60-89, 30-59, and <30 mL/min/1.73 m(2), respectively). Twenty-nine patients were included in the study--22 with epithelial ovarian cancer, 4 with peritoneal cancer, and 3 with fallopian tube cancer. Thirteen patients had mild CKD, 13 had moderate, and 3 had severe. Most patients had been treated with 20 mg/day of tamoxifen every 4 weeks. The median duration of treatment was 5 months (range, 1-52 months). The overall complete response, partial response, stable disease, and disease progression rates were 0%, 10%, 41%, and 48%, respectively. Twenty-one percent of patients experienced hot flashes, and 7% experienced nausea. No major adverse reactions occurred. These findings were similar to those for gynecological cancer patients with normal renal function. In conclusion, 20 mg/day of tamoxifen is safe and effective in gynecological cancer patients with CKD.

PP-5-13 Radical radiotherapy and effects of tamoxifen in patients with histologically positive stumps after breast preservation operations

PP-5-13 Radical radiotherapy and effects of tamoxifen in patients with histologically positive stumps after breast preservation operations