Tamoxifen In Breast Cancer Research Articles

Analysis of the complications of endocrine therapy with tamoxifen in breast cancer: clinical and pharmacogenetic aspects. Prospective pharmacogenetic cohort study

Background. Tamoxifen is the drug of choice in ER-positive breast cancer (BC) therapy for perimenopausal women and one of the endocrine therapy options for menopausal patients. The pharmacological effect of tamoxifen can be influenced by the activity of cytochrome P450 (CYP) enzymes and P-glycoprotein transporters (Pg), and the genes encoding them have broad polymorphism, affecting serum concentrations of active metabolites. This article presents the overall results of a prospective population-based study of the clinical significance of genetic polymorphism of tamoxifen metabolic enzymes and transporters in breast cancer patients after radical treatment receiving adjuvant endocrine therapy with tamoxifen in outpatient settings during 2018-2019. The study was approved by the Research Ethics Committee of the Russian Medical Academy of Continuing Professional Education.
 Aim. To analyze the clinical presentation of endocrine therapy with tamoxifen in the adjuvant regimen and to assess the association of polymorphisms of genes encoding cytochrome P450 enzymes and drug transporter proteins with adverse events in BC patients.
 Materials and methods. One hundred and four women with stage I-III luminal breast cancer receiving adjuvant tamoxifen were examined for the presence of CYP2D6, CYP2C, and the following CYP3A gene polymorphisms: CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, as well as the ABCB1 gene polymorphic marker (C3435T) encoding the P-glycoprotein. The allelic variants were identified using the real-time polymerase chain reaction; the test was performed in the Research Center of the Russian Medical Academy of Continuing Professional Education. The study material was buccal epithelium (double sampling) taken after informed consent signing.
 Results. Association analysis showed the association of different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9, and ABCB1 with tamoxifen adverse drug reactions, indicating the clinical significance of these polymorphisms.
 Conclusion. With the implementation of genetic testing of the studied polymorphisms into the routine clinical practice of oncologists prescribing tamoxifen and gynecologists involved in the follow-up of breast cancer patients receiving endocrine therapy in the adjuvant mode, there will be an opportunity for more effective and safer pharmacotherapy.

Impact of organic anion transporting polypeptide, P-glycoprotein, and breast cancer resistance protein transporters on observed tamoxifen and endoxifen concentration and adverse effects.

Drug transporters are important determinants of drug disposition and response. Tamoxifen is an antiestrogen for breast cancer therapy known for adverse drug reactions (ADRs). In this study, the involvement of OATP transporters in tamoxifen and endoxifen transport was studied in vitro while the impact of single nucleotide variation (SNV) in OATP and efflux transporters P-glycoprotein ( ABCB1 ) and Breast Cancer Resistance Protein ( ABCG2 ) on ADRs during tamoxifen therapy were assessed. Patients receiving tamoxifen for breast cancer, who were CYP2D6 normal metabolizers were enrolled ( n = 296). Patients completed a survey that captured ADRs and a blood sample was collected. Tamoxifen and endoxifen plasma concentration were measured, while DNA was genotyped for SNVs in ABCB1, ABCG2, SLCO1A2, SLCO1B1 , and SLCO2B1 . HEK293T cells were used to determine the extent of OATP-mediated transport of tamoxifen and endoxifen. Common SNVs of ABCB1, ABCG2, SLCO1A2 , and SLCO1B1 were not associated with tamoxifen or endoxifen concentration. However, tamoxifen concentration was significantly higher in carriers of SLCO2B1 c.935G>A (129.8 ng/mL) compared to wildtype (114.9 ng/mL; P = 0.036). Interestingly, subjects who carried SLCO1A2 c.38A>G reported significantly less dizziness ( P = 0.016). In-vitro analysis demonstrated increased cellular accumulation of tamoxifen in cells overexpressing OATP1A2 and 1B1, but endoxifen uptake was not effected in OATP overexpressing cells. We showed that OATP1A2 , a transporter known to be expressed at the blood-brain barrier, is capable of tamoxifen transport. Additionally, OATP1A2 c.38A>G was associated with reduced ADRs. Taken together, our findings suggest genetic variation in OATP transporters may be an important predictor of tamoxifen ADRs.

Effect of vitamins C and E on cancer survival; a systematic review.

Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival. Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies. We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp. Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm. CRD42020152795.

Effects of Cimicifuga racemosa (L.) Nutt on sexual function in women receiving tamoxifen for breast cancer

To assess the effects of Cimicifuga racemosa (L.) Nutt on climacteric symptoms and sexual function in women receiving tamoxifen after breast cancer treatment. A prospective study of women treated at the Mastology Outpatient Clinic of the Department of Obstetrics and Gynecology of the Santa Casa de Sao Paulo School of Medical Science of the hospital was conducted between 2018 and 2021. Patients diagnosed with breast cancer that underwent surgical, radiotherapy and chemotherapy treatment more than one year prior, receiving tamoxifen, exhibited climacteric symptoms and were sexually active were selected. Total of 34 women were recruited and during outpatient visits completed sociodemographic questionnaire, Blatt-Kupperman Index (KI) and Female Sexual Function Index (FSFI). The group showed improvements in climacteric symptoms (p<.001) and sexual function (p=.011) after the 6-month follow-up. Cimicifuga racemosa (L.) Nutt promoted improvements in climacteric symptoms and sexual function in women surgically treated for breast cancer. Clinical Trials.gov ID: NCT02467686. Impact Statement What is already known on this subject? The medications used for the treatment of breast cancer can lead to important complaints of vasomotor manifestations with a negative impact on the success of their treatment, and cases have been described until their interruption. Cimicifuga racemosa (L.) Nutt. is described in several works as a therapy to alleviate these symptoms. Numerous works in the literature present climatic symptoms and sexual function with a selective approach to the themes. What do the results of this study add? Our study evaluated a group of women who were treated for breast cancer after menopause taking into account the following aspects: climacteric symptoms and sexual function. When we reviewed the literature, we did not find, so far, work similar to ours. What are the implications of these findings for clinical practice and/or further research? In clinical practice, assessing vasomotor symptoms and sexual response of breast cancer patients can contribute towards improving the lives of this patient group. Prescribing Cimicifuga racemosa (L.) Nutt in cases with climacteric complaints and poor sexual response can relieve distress and promote better health and life status for these women. Although the present investigation has generated important data on female breast cancer survivors, there are limitations regarding the number of participants. We recommend further clinical research with expansion of the sample studied and the results presented.

Interactions Between Natural Products and Tamoxifen in Breast Cancer: A Comprehensive Literature Review.

Introduction: Tamoxifen (TAM) is the most commonly used hormone therapeutic drug for the treatment of estrogen receptor-positive (ER+) breast cancer. 30%–70% of clinical breast cancer patients use natural products, which may increase the likelihood of drug interactions. Objective: To evaluate the evidence for the interactions between natural products and TAM in breast cancer. Methods: Electronic databases, including PubMed, CINAHL Plus (via EbscoHost), European PMC, Medline, and Google Scholar, were searched for relevant publications. The search terms include complementary and alternative medicine, natural products, plant products, herbs, interactions, tamoxifen, breast cancer, and their combinations. Results: Various in vitro and in vivo studies demonstrated that the combined use of natural products with TAM produced synergistic anti-cancer effects, including improved inhibition of tumor cell growth and TAM sensitivity and reduced side effects or toxicity of TAM. In contrast, some natural products, including Angelica sinensis (Oliv.) Diels [Apiaceae], Paeonia lactiflora Pall., Rehmannia glutinosa (Gaertn.) DC., Astragalus mongholicus Bunge, and Glycyrrhiza glabra L. [Fabaceae], showed estrogen-like activity, which may reduce the anti-cancer effect of TAM. Some natural products, including morin, silybin, epigallocatechin gallate (EGCG), myricetin, baicalein, curcumin, kaempferol, or quercetin, were found to increase the bioavailability of TAM and its metabolites in vivo. However, three are limited clinical studies on the combination of natural products and TAM. Conclusion: There is evidence for potential interactions of various natural products with TAM in pre-clinical studies, although the relevant clinical evidence is still lacking. Further studies are warranted to evaluate the potential interactions of natural products with TAM in clinical settings.

Abstract #1185237: Tamoxifen Induced pancreatitis in a non-diabetic patient with hypertriglyceridemia

Tamoxifen is a selective estrogen receptor modulator (SERM) used in breast cancer treatment. It interferes with triglyceride metabolism causing hypertriglyceridemia and can precipitate pancreatitis. We report a case of a non- diabetic middle-aged woman with a history of mild hypertriglyceridemia who presented with acute pancreatitis while on chronic tamoxifen treatment for breast cancer.

A new survival analysis model in adjuvant Tamoxifen-treated breast cancer patients using manifold-based semi-supervised learning

Breast cancer researchers are very interested in studying and analyzing the survival time of patients. However, choosing the appropriate model for survival time analysis is the main challenge in the survival analysis of these patients. Using a dataset of patients with breast cancer, a new survival analysis model is proposed in this study. First, using the Cox-PH model, the whole selected data was categorized into high-risk and low-risk groups. The classified data was given to the AFT model in the next step to estimate the survival time. In some instances, the value of the metabolic status of the Tamoxifen feature was missing. Next, using the information obtained from the first and second steps, in the proposed Manifold-based semi-supervised learning module, the value of missing data was estimated. Using all labeled data, the final survival analysis was performed, and the relative hazard obtained. The comparison of the proposed model via other previous models in survival analysis demonstrates that the proposed model is 26% more accurate than when only the Cox-PH model was used and 28% more accurate than when only the AFT model was used in the testing set. Furthermore, the findings demonstrate that when the Manifold-based SSL model was used in the learning module, the accuracy was 19% higher than the Co-training SSL method and 12% higher than the SVMSSL method. The advantages of the proposed survival analysis method are high capability for identifying the survival risk classes of the patient and high predictive accuracy for the relative hazard.

Identification of the estrogen receptor beta as a possible new tamoxifen-sensitive target in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Despite the proven efficacy of combined immunochemotherapy (R-CHOP) in the majority of patients, ~40% of DLBCL patients do not respond or will relapse and consequently have a very poor prognosis. The development of targeted therapies has not improved patient survival, underscoring the need for new treatment approaches. Using an unbiased genome-wide CD20 guilt-by-association approach in more than 1800 DLBCL patients, we previously identified the estrogen receptor beta (ERβ) as a new target in DLBCL. Here, we demonstrate that ERβ is expressed at significantly higher levels in DLBCL compared to normal B cells, and ERβ plays a role in the protection against apoptosis in DLBCL. Targeting of the ERβ with the selective estrogen receptor modulator tamoxifen reduces cell viability in all tested DLBCL cell lines. Tamoxifen-induced cell death was significantly decreased in an ERβ knock-out cell line. The activity of tamoxifen was confirmed in a xenograft human lymphoma model, as tumor growth decreased, and survival significantly improved. Finally, tamoxifen-treated breast cancer (BC) patients showed a significantly reduced risk of 38% for DLBCL compared to BC patients who did not receive tamoxifen. Our findings provide a rationale to investigate tamoxifen, a hormonal drug with a good safety profile, in DLBCL patients.

Indoleamine 2,3-dioxygenase 1 regulates breast cancer tamoxifen resistance through interleukin-6/signal transducer and activator of transcription

Breast cancer is the primary cause of cancer-related deaths in women. Tamoxifen (TAM) is the preferred drug for treating premenopausal luminal-type breast cancer, but TAM resistance restricts its ability to benefit patients. To date, the mechanism of this resistance remains unclear, and there is currently no effective treatment for reversing it. The expression of indoleamine 2,3-dioxygenase 1 (IDO1) has been shown to be elevated in various malignancies. Here, we aimed to investigate the role of IDO1 in TAM-resistant breast cancer. We confirmed that IDO1 is strongly expressed in TAM-resistant breast cancer, and it mediates drug-resistant cell proliferation, metastasis, and TAM resistance in vivo and in vitro through interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3). We also found that the mechanism by which TAM upregulates IDO1 is dependent on STAT1 activation. In summary, IDO1 regulates TAM resistance and can serve as a novel target for treatment of TAM-resistant breast cancer.

Is screening for endometrial cancer necessary in asymptomatic women treated with tamoxifen for breast cancer?

Objective: This study aimed to investigate the endometrial pathology findings and to determine the appropriate diagnostic approach to assess for potential endometrial malignancy or premalignant pathology in women treated with tamoxifen for breast cancer. Methods: We retrospectively reviewed the medical records of 162 patients taking tamoxifen and who underwent endometrial biopsy. We compared the clinical features of the patients with endometrial intraepithelial neoplasia or cancer (EIN/EC group) and the patients with other pathologic results (others group). Results: EIN or EC was found in ten patients (6.2%). While 70.0% of EIN/EC group received tamoxifen treatment for more than 3 years, 71.7% of the others group received less than 3 years (p &lt; 0.001). Regardless of the presence of vaginal bleeding, EIN/EC was not found in patients with endometrial thickness (ET) &lt;5 mm on transvaginal ultrasonography (TV-US). When ET was ≥5 mm, the incidence rates of EIN/EC were only 2.9% in asymptomatic patients and 11.6% in symptomatic patients, respectively (p = 0.002). When ET was ≥8 mm, the incidence rates of EIN/EC were 3.8% in asymptomatic patients and 12.0% in symptomatic patients, respectively (p = 0.002). When ET was &lt;8 mm, EIN/EC was not found in patients without vaginal bleeding, while EIN/EC was found in 7.1% of patients with vaginal bleeding. Conclusions: Indiscriminate endometrial evaluation should be avoided in women treated with tamoxifen for breast cancer. Patients taking tamoxifen who experience vaginal bleeding and have a thick endometrium (≥5 mm) on TV-US, they should undergo endometrial biopsy.

Efficacy of sonohysterography and hysteroscopy for evaluation of endometrial lesions in tamoxifen treated patients: a systematic review

Objective: This review aims to evaluate the incidence of endometrial lesions in tamoxifen-treated breast cancer patients identified by hysteroscopy (HS) and sonohysterography (SIS) and the diagnostic accuracy of the two methods to detect them. Methods: A systematic review of the literature concerning the role of HS and SIS for evaluation of the endometrium in tamoxifen-treated breast cancer patients was performed. We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library). The search terms used were “hysteroscopy”, “hysterosonography”, “sonohysterography” combined with “tamoxifen”; 89 citations were identified and selected in the initial screening. Results: 28 studies were included in the systematic review. There were 61 citations excluded because they were review articles (n = 9) or case report (n = 5) and non-English articles (n = 8), and had too little information in the full text (n = 39). Similar accuracy between SIS and HS in detection of endometrial tamoxifen-related lesions was found. Conclusions: SIS may represent a minimally invasive, simple, safe, well-tolerated and cost-effective alternative to HS, associated with few contraindications and no potential complications.

Hysteroscopic Endometrial Resection in Women Treated With Tamoxifen for Breast Cancer Provides Definitive Diagnosis and Effective Long-Term Therapy

We evaluated resectoscopic surgery for definitive diagnosis and long-term therapy in 16 symptomatic tamoxifen-treated women with breast cancer who presented with abnormal uterine bleeding and/or intrauterine anomalies. Seven pre-menopausal women had benign pre- and post-operative endometrial biopsy, and 4 had benign polyps. At a median of 7 years of follow-up (range 2–8 y), all remained amenorrheic. Of 9 post-menopausal women, pre-operative biopsy was inadequate in 4, benign endometrium was found in 4, and non-atypical endometrial hyperplasia was found in 1. Post-operatively, all had benign pathology, 8 having polyp and 1 leiomyoma. At a median follow-up of 7 years (range 2–13 y), all were amenorrheic, with no recurrence of breast cancer or uterine pathology.

Functional relationship of SNP (Ala490Thr) of an epigenetic gene EZH2 results in the progression and poor survival of ER+/tamoxifen treated breast cancer patients

EZH2 is a classic histone methyltransferase that causes the trimethylation of H3K27 and consequently suppresses the cancer preventive genes. The role of elevated levels of EZH2 expression in breast cancer aggressiveness and poor prognosis is very well established. The present study focusses on the insight of the clinically important SNPs of EZH2 gene in determining the structure-function relationship towards breast cancer susceptibility. For this purpose the EZH2 SNPs (rs41277434A>C and rs201135441C>T (A490T)) were computationally explored and further the prediction outcomes were validated by performing population-based association and pharmacogenetic study in north Indian region of Punjab. The results of the present analysis provided the novel insight of rs201135441C>T (A490T) mutation, that A>T change i.e. nonpolar amino acid to polar amino acid stabilizes the enzyme-substrate (EZH2-Histone) complex which in turn promotes trimethylation over histone 3 (H3) at lysine residue 27 (H3K27me3) and this might be leading to the methylation of the promoter region of various cancer preventive genes, hence may increase the risk of breast cancer susceptibility. Further the association based study of SNP rs201135441C>T (A490T) support the in silico outcomes by revealing that the T mutant allele of rs201135441 has significantly increased the risk of breast cancer susceptibility and also reduce the overall survival and progression free survival of ER+/tamoxifen treated breast cancer patients and triple negative breast cancer (TNBC) patients, respectively. To the best of our knowledge, this is the first study on EZH2 polymorphism with breast cancer. In conclusion, these findings suggest that these variations in the EZH2 gene may have strong clinical significance as they can be targeted for prognosis, prevention and in drug development.

Impact of systemic adjuvant therapy and CYP2D6 activity on mammographic density in a cohort of tamoxifen-treated breast cancer patients

PurposeChange in mammographic density has been suggested to be a proxy of tamoxifen response. We investigated the effect of additional adjuvant systemic therapy and CYP2D6 activity on MD change in a cohort of tamoxifen-treated pre- and postmenopausal breast cancer patients.MethodsSwedish breast cancer patients (n = 699) operated 2006–2014, genotyped for CYP2D6, having at least three months postoperative tamoxifen treatment, a baseline, and at least one follow-up digital mammogram were included in the study. Other systemic adjuvant treatment included chemotherapy, goserelin, and aromatase inhibitors. Change in MD, dense area, was assessed using the automated STRATUS method. Patients were stratified on baseline characteristics, treatments, and CYP2D6 activity (poor, intermediate, extensive, and ultrarapid). Relative density change was calculated at year 1, 2, and 5 during follow-up in relation to treatments and CYP2D6 activity.ResultsMean relative DA decreased under the follow-up period, with a more pronounced MD reduction in premenopausal patients. No significant effect of chemotherapy, aromatase inhibitors, goserelin, or CYP2D6 activity on DA change was found. DA did not revert to baseline levels after tamoxifen discontinuation.ConclusionOur results indicate that other systemic adjuvant therapy does not further reduce MD in tamoxifen-treated breast cancer patients. We could not confirm the previously suggested association between CYP2D6 activity and MD reduction in a clinical setting with multimodality adjuvant treatment. No rebound effect on MD decline after tamoxifen discontinuation was evident.

A combination approach of pseudotime analysis and mathematical modeling for understanding drug-resistant mechanisms

Cancer cells acquire drug resistance through the following stages: nonresistant, pre-resistant, and resistant. Although the molecular mechanism of drug resistance is well investigated, the process of drug resistance acquisition remains largely unknown. Here we elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing indicates that tamoxifen-resistant cells can be subgrouped into two, one showing altered gene expression related to metabolic regulation and another showing high expression levels of adhesion-related molecules and histone-modifying enzymes. Pseudotime analysis showed a cell transition trajectory to the two resistant subgroups that stem from a shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted and experimentally validated that inhibition of transition to both resistant subtypes would prevent the appearance of tamoxifen resistance.

Abstract 990: Differential immunoregulatory effects of decitabine on lipid metabolism in doxurobicin versus tamoxifen treated breast cancer cells

Abstract Background: The treatment of hormonal positive breast cancer is still based on hormonal tamoxifen (TAM) based regimens in early stages, while based on chemotherapeutic doxorubicin (DOX) based regimens in late stages. DNA methyl transferase inhibitor (decitabine: DEC) is an epigenetic modulator with synergistic anticancer activity when combined with either TAM or DOX. Aims: The cytotoxic synergistic combinations of DEC with either DOX or TAM were examined for their effects on immunomodulation and lipid metabolism in hormonal positive breast cancer cells (MCF7). Material and Methods: Sulphorhodamine-B cytotoxic assay, flow cytometric analysis of cell cycle and apoptosis along with the florescent uptake of Rhodamine123 were adopted for testing the sensitivity of MCF7 cells to the drug combinations. Real time PCR was utilized to measure the genetic expression of immunoregulatory markers (FOXP3, TNFα, IFNγ and IL-6), lipid metabolism regulatory markers (FASN, CPT1, MLYCD, ACCα and AMPK) and apoptosis markers (BAX, BCL2, Caspase-8, AKT, mTOR). Western Blotting was used for the determination of EGFR, CK7, LC3B proteins expressions. Results: The combination with 500nM DEC caused synergistic 50% growth inhibition of MCF7 cells, in which the concentration required for DOX was reduced from 0.501 µM into 0.264µM, while in TAM, the concentration was reduced from 18µM into 12.4µM. The concentration of 500nM DEC induced the uptake of Rhodamine 123 and the expression of Caspase-8, IFNγ, IL-6 and AMPK in the combination with 20µM TAM or 0.25µM DOX compared with their respective single treatment concentrations. Also, both DEC combinations reduced the expressions of BAX/BCl2, EGFR, CK7, aromatase, LC3B and ACCα, but caused insignificant effect on FASN expression. The combination of 500nM DEC with 20µM TAM demonstrated significant accumulation of cells in the G0/G1 phase of the cell cycle (4.22%), and in the early apoptosis (8.97%), along with the increase of mTOR but decrease of CPT1A, MLYCD, TNFα genes expressions. On the other hand, the combination of 500nM DEC with 0.25µM DOX caused accumulation of 94.73% of cells in the late apoptosis, inhibition of the AKT and FOXP3 expressions, but induction of CPT1A. Conclusions: Epigenetic modifier (DEC) showed different synergistic immunomodulatory effects on lipid metabolism regulation markers when combined with chemotherapy (DOX) rather than hormonal therapy (TAM) in hormonal positive breast cancer cells. DEC induces extrinsic late apoptosis through the induction of CPT1A- mediated lipid metabolism along with FOXP3 and AKT inhibition in DOX treated cells, while it induces extrinsic early apoptosis through the inhibition of MLYCD, CPT1A and TNFα in TAM treated cells. Citation Format: Mariam Fouad, Mohammed Sayed-Ahmed. Differential immunoregulatory effects of decitabine on lipid metabolism in doxurobicin versus tamoxifen treated breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 990.

Diagnostic Accuracy of Transvaginal Ultrasound Versus Hysteroscopy in Evaluation of Endometrial Pathology in Breast Cancer Women Receiving Tamoxifen: Correlation with Histopathological Examination

ABSTRACT Background: Multiple endometrial lesions have been reported in tamoxifen -treated breast cancer patients. As a consequence, a thorough uterine cavity examination is often necssary. Objective: To compare the efficacy of transvaginal ultrasound versus hysteroscopy in detecting the endometrial changes in tamoxifen-treated breast cancer patients, and to correlate the findings of both methods with histopathological examination of endometrial biopsies. Patients and methods: Twenty seven patients who had mastactomies for breast cancer and receiving tamoxifen (TAM) were enrolled in this prospective study. They subjected to transvaginal ultrasonography (TVUS) and hysteroscopy for endometrial assessment. Endometrial biopsy was taken from all participants for hitstopathological examination. The ultrasongraphic and hysteroscopic findings were compared and correlated with the histopathological results. Results: The diagnostic accuracy of TVUS versus hysteroscopy in detecting endometrial changes in breast cancer TAM treated women was as follows;TVUS had a sensitivity (82.4%), specificity (30.0%), PPV (66.7%), NPV (50.0%) and accuracy (63%) ;while, the hysteroscope had sensitivity (94.1%), specificity (60.0%), PPV (80.0%), NPV (85.7%) and accuracy (81.5%). Conclusion: Because of certain discrepancies between TVUS and histopathological results in TAM treated women, TVUS is not the best tool for evaluating the endometrium in those patients. The utility of the hysteroscopic image processing helps in the triage of women who require endometrial surveillance, so it will reduce the pathologist's workload and the patient's apprehension while waiting for histopathology result. Nevertheless hysteroscope cannot establish a conclusive diagnosis of premalignant or malignant lesions, but it provides a direct view for targeted biopsies to create a definitive diagnosis.

Adverse effects of adjuvant tamoxifen treatment on bone mineral density in premenopausal breast cancer patients: A systematic review and meta-analysis.

e12500 Background: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreases bone loss. However, the adverse effect of adjuvant tamoxifen therapy for bone mineral density (BMD) in premenopausal breast cancer patients remains uncertain. This meta-analysis aimed to assess the effects of adjuvant tamoxifen therapy on BMD changes in premenopausal women with primary breast cancer. Methods: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen were collected from EMBASE and PubMed. The pooled analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. Results: A total of 1,432 premenopausal patients from eight studies were included in the pooled analysis. After 3 years of median follow up, adjuvant tamoxifen therapy decreased BMD by as much as SMD of -0.79 [95% confidence interval (CI); -1.25 to -0.33, P &lt; 0.01] at lumbar spines and -0.38 at hip (95%CI; -0.88 to 0.12, P &gt; 0.05). Compared with patients received tamoxifen alone, patients who received combination therapy with chemotherapy or ovarian function suppression (OFS) showed decreased bone loss at lumbar spine (SMD -1.17 with 95%CI -1.59 to -0.75, -0.43 with 95%CI -2.26 to 1.40, and -0.75 with 95%CI -1.38 to -0.13, respectively). Conclusions: Our meta-analysis revealed that premenopausal women who received adjuvant tamoxifen treatment showed significant bone loss over a period of time, especially at lumbar spine. However, tamoxifen attenuated bone loss in those who received tamoxifen after chemotherapy or along with OFS.[Table: see text]

Estrogen Receptor and Her2 Pathway related Genes (PIK3CA, GSK3 β)

Background: PIK3CA and GSK-3β have important role(s) in the resistance of estrogen receptor positive (+ER) breast cancer (BC) patients to hormonal therapy. The aim of the current study was to assess the role of PIK3CA and GSK-3β in predicting response to Tamoxifen in BC patients.Methods: PIK3CA and GSK-3β expression levels were assessed in formalin fixed paraffin embedded tissue (FFPE) sections of 58 hormonal positive BC females, using quantitative real time PCR (RT-qPCR). The data were correlated to clinico-pathological features of the patients, response to Tamoxifen and survival outcome. Results: The median PIK3CA expression increased significantly in non-responders to tamoxifen compared to responders [2.94 (IQR=7.5) and 0.72 (IQR=0.9); respectively, P= 0.017]. However, there was no significant difference in GSK-3β expression between responders and non-responders BC patients [1.5 (IQR=3.8) and 1.2 (IQR=2.8); respectively, P= 0.27]. PIK3CA expression associated with low ER expression, presence of distant metastasis and shorter disease free survival (DFS) rate (P=0.032, 0.026 and 0.043; respectively). GSK-3β expression increased significantly in negative LN metastasis and low-expression of progesterone receptors (P=0.01 and 0.006; respectively). There was significant correlation between the expression levels of GSK-3B and PIK3CA in BC patients (r=0.88, P

Evaluating human epidermal growth factor receptor 2 roles in the efficacy of Tamoxifen treatment in breast cancer, a systematic review.

Hormone therapy with Tamoxifen is an effective treatment that can decrease recurrence rate and mortality. Numerous molecular mechanisms can modify the response to Tamoxifen. The objectiveof this studywas to determine Tamoxifen efficacy on patients' recurrence and mortality rates, according to the human epidermal growth factor receptor 2 (HER2) status. In this meta-analysis of published studies, relapse and death rates were measured in both HER2 negative and positive patients treated with Tamoxifen. Besides, the relative risk of treatment with Tamoxifen compared to no Tamoxifen treatment was evaluated in both HER2 positive and negative patients. There was an increased risk of recurrence in HER2 positive patients who received Tamoxifen compared with HER2 negative ones (RR = 1.63, p value < 0.001). Tamoxifen treatment is associated with decreased relapse rate (RR = 0.70, p value < 0.001); however, it did not effect on HER2 positive ones (RR = 1, p value = 0.99). According to the analysis result, the relapse rate in breast cancer patients who were treated with Tamoxifen depends on the HER2 situation. Despite the limited sample size, it is revealed that Tamoxifen can decrease the relapse rate only in HER2 negative patients.