Adjuvant Therapy For Breast Cancer Research Articles

Lomitapide as a Potential Estrogen Receptor Inhibitor: A Computational Drug Repurposing Study

Objective: Estrogen receptor (ER) inhibitors have significant therapeutic potential for hormone-dependent cancers and related disorders. Tamoxifen, a well-known selective estrogen receptor modulator, has been widely used as adjuvant therapy for estrogen receptor-positive breast cancer. However, tamoxifen may exhibit a tendency to develop resistance with prolonged usage and particularly elevate the risk of uterine cancer. Therefore, there is a need for the discovery and development of new ER modulators or inhibitors. In this study, we identified potential estrogen receptor inhibitors through computational drug repositioning.
 
 Methods: A set of 2048 compounds, encompassing FDA-approved drugs and active metabolites, were subjected to molecular docking, molecular dynamics simulations, and free energy calculations to evaluate their interaction with estrogen receptor α (ERα).
 
 Results: Among the compounds evaluated, conivaptan, atogepant, and lomitapide exhibited the highest affinities for ERα. Lomitapide displayed a superior docking score (-12 kcal/mol) compared to the established ER inhibitor, tamoxifen (-10 kcal/mol). Further investigation using molecular dynamics simulations and free energy calculations disclosed lomitapide's heightened binding affinity of -380.727 kJ/mol, surpassing tamoxifen's binding affinity of -352.029 kJ/mol.
 
 Conclusion: This comprehensive computational exploration underscores lomitapide's potential as a compelling candidate with an envisaged stronger estrogen receptor affinity than the acknowledged standard, tamoxifen. To validate lomitapide's promise as a novel ER inhibitor, essential in vitro and in vivo studies are suggested. These investigations will provide essential insights into lomitapide's reposition in addressing the challenges tied to hormone-dependent cancers and associated maladies.

Epigenetic Effects of Resveratrol on Oncogenic Signaling in Breast Cancer.

The crosstalk between oncogenic signaling pathways plays a crucial role in driving cancer development. We previously demonstrated that dietary polyphenols, specifically resveratrol (RSV) and other stilbenoids, epigenetically target oncogenes for silencing via DNA hypermethylation in breast cancer. In the present study, we identify signal transduction regulators among RSV-hypermethylated targets and investigate the functional role of RSV-mediated DNA hypermethylation in the regulation of Hedgehog and Wnt signaling. Non-invasive ER-positive MCF-7 and highly invasive triple-negative MCF10CA1a human breast cancer cell lines were used as experimental models. Upon 9-day exposure to 15 µM RSV, pyrosequencing and qRT-PCR were performed to assess DNA methylation and expression of GLI2 and WNT4, which are upstream regulators of the Hedgehog and Wnt pathways, respectively. Our results showed that RSV led to a DNA methylation increase within GLI2 and WNT4 enhancers, which was accompanied by decreases in gene expression. Consistently, we observed the downregulation of genes downstream of the Hedgehog and Wnt signaling, including common targets shared by both pathways, CCND1 and CYR61. Further analysis using chromatin immunoprecipitation identified increased H3K27 trimethylation and decreased H3K9 and H3K27 acetylation, along with abolishing OCT1 transcription factor binding. Those changes indicate a transcriptionally silent chromatin state at GLI2 and WNT4 enhancers. The inhibition of the Wnt signal transduction was confirmed using a phospho-antibody array that demonstrated suppression of positive and stimulation of negative Wnt regulators. In conclusion, our results provide scientific evidence for dietary polyphenols as epigenetics-modulating agents that act to re-methylate and silence oncogenes, reducing the oncogenic signal transduction. Targeting such an action could be an effective strategy in breast cancer prevention and/or adjuvant therapy.

The Development and Evaluation of an Educational Video for Breast Cancer Patients Requiring Adjuvant Radiation Therapy

Patient education and informed consent are required prior to adjuvant radiation therapy (RT) for early breast cancer (EBC), and include the role, rationale, potential toxicities and practicalities of the treatment process. Current education of patients about RT is verbal, in the form of a consultation by a radiation oncologist, often supplemented with print or online materials. This approach is limited by its doctor-dependency and non-standardised nature. Video education is being recognised increasingly as an opportunity to remediate this and appeal to patients’ preference for visual learning. The purpose of this study was to design and produce a video as an educational adjunct for EBC patients’ viewing prior to adjuvant RT, and to evaluate its acceptability through content analysis of three online focus group discussions, among ten participants with EBC requiring RT. After qualitative content analysis of the focus group transcripts, data were summarised into three main categories: (1) understanding of RT, (2) ease of engagement with the video and (3) anxiety and preparedness for RT. The 18-min video was positively received by all participants, and discussion feedback was used to inform improvements to the video. This focus group study demonstrated that the video was well understood, informative and acceptable to EBC patients in preparing them for RT. The effectiveness of the video in improving knowledge and alleviating distress in preparation for therapy will be further evaluated in an ethics-approved biphasic quasi-experimental study.

Developing questions to assess and measure patients’ perceived survival benefit from adjuvant endocrine therapy in breast cancer: a mixed methods pilot study

This mixed method study developed multiple question types to understand and measure women’s perceived benefit from adjuvant endocrine therapy. We hypothesis that patients do not understand this benefit and sought to develop the questions needed to test this hypothesis and obtain initial patient estimates. From 8/2022 to 3/2023, qualitative interviews focused on assessing and modifying 9 initial varied question types asking about the overall survival (OS) benefit from adjuvant endocrine therapy. Subsequent focus groups modified and selected the optimal questions. Patients’ self-assessment of their OS benefit was compared to their individualized PREDICT model results. Fifty-three patients completed the survey; 42% Hispanic, 30% rural, and 47% with income < $39,999 per year. Patients reported adequate health care literacy (61.5%) and average confidence about treatment and medication decisions 49.4 (95% CI 24.4–59.5). From the original 9 questions, 3 modified questions were ultimately found to capture patients’ perception of this OS benefit, focusing on graphical and prose styles. Patients estimated an OS benefit of 42% compared to 4.4% calculated from the PREDICT model (p < 0.001). In this group with considerable representation from ethnic minority, rural and low-income patients, qualitative data showed that more than one modality of question type was needed to clearly capture patients’ understanding of treatment benefit. Women with breast cancer significantly overestimated their 10-year OS benefit from adjuvant endocrine therapy compared to the PREDICT model.

Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy–Related Cardiac Dysfunction

BackgroundThe impact of recent consensus definitions of cancer therapy–related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed. ObjectivesThe aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria. MethodsThe cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation. ResultsThe cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization. ConclusionsMild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134)

The role of Shenqi Fuzheng injection as adjuvant therapy for breast cancer: an overview of systematic reviews and meta-analyses

BackgroundBreast cancer (BC) is the most frequent malignancy in the world. Chemotherapy (CT) is a common treatment for BC but is accompanied by toxicity and side effects. Shenqi Fuzheng Injection (SFI) is an adjuvant therapy with promising results in improving efficacy and reducing toxicity in clinical studies. This overview of systematic reviews and meta-analysis (SRs/MAs) aimed to summarize the benefits and evaluate the quality of evidence supporting SFI adjuvant as CT for BC.MethodsA systematic search for SRs/MAs of randomized controlled trials (RCTs) on SFI treatment for BC was performed by searching PubMed, Web of Science, EMbase, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases from inception to October 1, 2022. The quality of SRs/MAs was evaluated using AMSTAR-2, PRISMA 2020, ROBIS, and GRADE by two reviewers. The corrected covered area (CCA) was used to quantify the degree of duplication of the original SRs/MAs. Finally, quantitative analysis of RCTs was conducted using RevMan 5.4 software. This study was registered with PROSPERO, CRD42022377290.ResultsSix SRs/MAs including 61 RCTs with 5593 patients were included in this study. Studies were published between 2015 and 2019, the original RCTs ranged from 7–49, with sample sizes ranging from 336–1989. The quantitative meta-analysis found that adjuvant CT of SFI improved the clinical response rate (RR=1.37, 95% CI=1.28, 1.46; P<0.00001) and the KPS score (RR=1.66, 95% CI 1.54, 1.79, P<0.00001) of patients with BC. In terms of immune function, CD3+ (SMD=1.51, 95% CI 0.91, 2.10; P<0.00001), CD4+ (SMD=1.87, 95% CI 1.18, 2.56; P<0.00001), CD4+/CD8+ (SMD=0.86, 95% CI 0.48, 1.23; P<0.00001), and NK cell levels (SMD=0.94, 95% CI 0.63, 1.24; P<0.00001) in the adjuvant CT group SFI were better than those with CT alone. Adverse reactions following SFI adjuvant CT showed reduced incidence of leukopenia (RR=0.53, 95% CI 0.46, 0.62; P<0.00001) and gastrointestinal reactions (RR=0.48, 95% CI 0.39, 0.58; P<0.00001). However, the GRADE results showed ‘very low’ to ‘moderate’ evidence for the 42 outcomes, without high-quality evidence supporting them, limited mainly by deficiencies in the design of RCTs (42/42, 100.00%), inconsistency (19/42, 45.24%), publication bias (41/42, 97.62%), and inaccuracy (3/42, 7.14%). The unsatisfactory results of AMSTAR-2, PRISMA 2020, and ROBIS were limited to lack of registration of study protocols, explanation of inclusion basis of RCTs, description of funding sources for the included studies, incomplete search strategy and screening process, addressing heterogeneity and sensitivity, and reporting potential conflicts of interest.ConclusionAdjuvant CT with SFI for BC had better benefits and a lower risk of adverse events. The methodology and quality of the evidence are generally low, highlighting a need of greater attention during study implementation. More objective and high-quality studies are needed to verify the efficacy of adjuvant CT with SFI in clinical decision-making for BC.

Effects of Reishimmune-S, a Fungal Immunomodulatory Peptide Supplement, on the Quality of Life and Circulating Natural Killer Cell Profiles of Patients With Early Breast Cancer Receiving Adjuvant Endocrine Therapy.

To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC). Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models. Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19+ lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A+ and NKp30+ NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30+ NK cells (β ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model). Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.

Epiretinal membrane formation associated with letrozole therapy – Two case reports

Letrozole, an aromatase inhibitor, is being increasingly used for adjuvant endocrine therapy in hormone-positive postmenopausal breast cancer. Although aromatase inhibitors are thought to increase vitreoretinal traction by causing estrogen reduction, posterior segment complications of letrozole are sparsely reported. We report two cases of presumed epiretinal membrane formation in postmenopausal, hormone receptor–positive breast cancer patients on adjuvant letrozole therapy.

A narrative review: research progress of adjuvant intensive endocrine therapy for early breast cancer.

Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) is the most prevalent subtype of all BCs. The primary treatment modality is endocrine therapy (ET). Traditional adjuvant ET for early-stage breast cancer (EBC) has undergone extensive exploration and is relatively well-established. However, patients at high risk of recurrence may still experience early relapse, necessitating consideration of intensified adjuvant ET to reduce recurrence risk. The objective of this narrative review is to examine various strategies for intensifying adjuvant ET in EBC, thoroughly analyze key clinical studies, and summarize the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation. As of March 2024, a comprehensive literature search, compilation, and analysis were conducted across PubMed, Baidu Scholar, ClinicalTrials.gov, and relevant academic conferences. There are numerous methods to intensify adjuvant ET: (I) combining ovarian function suppression (OFS) to reduce estrogen levels in the body and induce a state of artificial menopause to enhance the efficacy of ET; (II) individual extension of the duration of ET based on patients' varying risks of recurrence, with high-risk patients covering two peak recurrence periods; (III) the addition of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) can significantly extend invasive disease-free survival and reduce the risk of recurrence, serving as the main intensive treatment for high-risk patients; (IV) combination with bone-modifying drugs (BMD) can significantly reduce rates of bone metastasis and slightly enhance prognosis but is not commonly used in adjuvant settings; (V) combined with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, current studies only show a trend towards benefit in HR+ patients with germline BRCA1/2 mutations; more data are still needed to support its clinical benefit. This narrative review examines various strategies for intensifying adjuvant ET in EBC, critically evaluates key clinical studies, and summarizes the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation. In the context where traditional adjuvant ET is relatively well-established, the emergence of novel ET has notably addressed issues of endocrine resistance more effectively. Various intensified adjuvant ET has shown potential in further reducing recurrence risk among high-risk patients. However, additional research and time are essential to determine the optimal approaches for intensified adjuvant ET.

Comparative metabolomics of MCF-7 and MCF-7/TAMR identifies potential metabolic pathways in tamoxifen resistant breast cancer cells.

Breast cancer is the most common cancer and the leading cause of cancer-related death among women. An Estrogen Receptor (ER) antagonist called tamoxifen is used as an adjuvant therapy for ER-positive breast cancers. Approximately 40% of patients develop tamoxifen resistance (TAMR) while receiving treatment. Cancer cells can rewire their metabolism to develop resistant phenotypes, and their metabolic state determines how receptive they are to chemotherapy. Metabolite extraction from human MCF-7 and MCF-7/TAMR cells was done using the methanol-methanol-water extraction method. After treating the dried samples with methoxamine hydrochloride in pyridine, the samples were derivatized with 2,2,2-Trifluoro-N-methyl-N-(trimethylsilyl)-acetamide, and Chlorotrimethylsilane (MSTFA + 1% TMCS). The Gas chromatography/mass spectrometry (GC-MS) raw data were processed using MSdial and Metaboanalyst for analysis. Univariate analysis revealed that 35 metabolites were elevated in TAMR cells whereas 25 metabolites were downregulated. N-acetyl-D-glucosamine, lysine, uracil, tyrosine, alanine, and o-phosphoserine were upregulated in TAMR cells, while hydroxyproline, glutamine, N-acetyl-L-aspartic acid, threonic acid, pyroglutamic acid, glutamine, o-phosphoethanolamine, oxoglutaric acid, and myoinositol were found to be downregulated. Multivariate analysis revealed a distinct separation between the two cell lines, as evidenced by their metabolite levels. The enriched pathways of deregulated metabolites included valine, leucine, and isoleucine degradation, Citric Acid Cycle, Warburg effect, Malate-Aspartate shuttle, glucose-alanine cycle, propanoate metabolism, and Phospholipid biosynthesis. This study revealed dysregulation of various metabolic processes in TAMR cells, which may be crucial in elucidating the molecular basis of the mechanisms underlying acquired tamoxifen resistance.

Роль ингибиторов циклинзависимых киназ в адьювантной терапии рака молочной железы

Роль ингибиторов циклинзависимых киназ в адьювантной терапии рака молочной железы

Validation of CTS5 Model in Large-scale Breast Cancer Population and Combination of CTS5 and Ki-67 Status to Develop a Novel Nomogram for Prognosis Prediction.

More than half of patients with early-stage estrogen receptor-positive (ER+) breast cancer relapse after completing 5 years of adjuvant endocrine therapy, so it is important to determine which patients are candidates for extended endocrine therapy. The clinical treatment score after 5 years (CTS5) is a prognostic tool developed based on postmenopausal ER+ breast cancer to assess the risk of late distant recurrence (LDR) after 5 years of adjuvant endocrine therapy for breast cancer. We aimed to externally validate the prognostic value of CTS5 in premenopausal and postmenopausal patients and combined with Ki-67 to develop a new model to improve the ability of prognosis prediction. We included a total of 516 patients with early-stage ER+ breast cancer who had received 5 years of adjuvant endocrine therapy and were recurrence-free for 5 years after surgery. According to menopausal status, we divided the study population into 2 groups: premenopausal and postmenopausal women. The CTS5 of each patient was calculated using a previously published formula, and the patients were divided into low, intermediate, and high CTS5 risk groups according to their CTS5 values. Based on the results of the univariate analysis ( P <0.01), a multivariate COX proportional hazards regression analysis was conducted to establish a nomogram with significant variables ( P <0.05). The discriminative power and accuracy of the nomograms were assessed using the concordance index (C-index), calibration curve, and area under the time-dependent receiver operating characteristic curve. Discrimination and calibration were evaluated by bootstrapping 1000 times. Finally, we utilized decision curve analysis to assess the performance of our novel predictive model in comparison to the CTS5 scoring system with regard to their respective benefits and advantages. The median follow-up time was 7 years (6 to 9 years). The 516 women were categorized by CTS5 as follows: 246(47.7%) low risk, 179(34.7%) intermediate risk, and 91(17.6%) high risk. Using the CTS5 score as a continuous variable, patients' risk score was significantly positively associated with recurrence risk in both premenopausal and postmenopausal subgroups. For HER2- premenopausal patients and HER2+ postmenopausal patients, the CTS5 score was positively correlated with LDR risk. Patients with a Ki-67≥20% had a higher risk of LDR regardless of menopausal status. Using the CTS5 score as a categorical variable, the high-risk group of HER2- premenopausal patients had a higher risk of LDR. However, the CTS5 model could not distinguish the risk of LDR in different risk groups for HER2+ postmenopausal patients. In the high-risk group, patients with Ki-67≥20% had a higher risk of LDR, regardless of menopausal status. We developed a new nomogram model by combining the CTS5 model with Ki-67 levels. The C-indexes premenopausal and postmenopausal cohorts were 0.731 and 0.713, respectively. The nomogram model was well calibrated, and the time-dependent ROC curves indicated good specificity and sensitivity. Furthermore, decision curve analysis demonstrated that the new model had a wider and practical range of threshold probabilities, resulting in an increased net benefit compared with the CTS5 model. Our study demonstrated that the CTS5 model can effectively predict the risk of LDR in early-stage ER+ breast cancer patients in both premenopausal and postmenopausal patients. Extended endocrine therapy is recommended for patients with Ki-67≥20% in the CTS5 high-risk group, as well as premenopausal patients with HER2-. Compared with CTS5, the new nomogram model has better identification and calibration capabilities, and further research is required to validate its efficacy in large-scale, multicenter, and prospective studies.

Predictors of information needs among women with breast cancer receiving adjuvant therapy at Tikur Anbessa specialized hospital, Addis Ababa Ethiopia: a cross-sectional study

BackgroundWomen undergoing adjuvant therapy for breast cancer have diverse information needs that remain unfulfilled. Extensive research has shown that access to relevant information about their condition can significantly enhance the quality of life for these women, making it an essential part of cancer care. However, various clinical and socioeconomic factors influence the information needs of these women. Hence, the primary aim of this study is to identify predictors of the information needs of women undergoing adjuvant therapy for breast cancer. In addition, this study will also describe the preferred sources of information and the optimal timing for its acquisition.MethodsA facility-based cross-sectional study was undertaken at Tikur Anbessa Specialty Hospital, enlisting a cohort comprising 121 women undergoing adjuvant therapy for breast cancer. Trained interviewers administered an Amharic-translated Toronto information needs questionnaire specifically designed for breast cancer to assess the information needs of the study participants Statistical analysis was executed using the sophisticated software SPSS (version 25). Descriptive statistics were employed to summarize the variables of the study. A linear regression analyses was then carried out to identify notable predictors that significantly influenced the information needs of the women.ResultsThe total mean score for overall information needs in the current study was 194.30 (± 28.01), with a range scale of 142–260 and a standardized mean score of 3.74 (± 0.54). The disease and treatment domains had the highest information needs, with standardized mean scores (standard deviation) of 4.00 (± 0.54) and 3.77 (± 0.59), respectively. 95% of the participants sought information from healthcare professionals, and 67.7% of the women needed the information before beginning the treatments. Predictors of information needs were following a single treatment option (β = 12.68; 95% CI (0.68, 24.68); P = 0.039) and joining higher education and above (β = 17.1; 95% CI (1.47, 34.14); P = 0.033).ConclusionThe women exhibited a substantial demand for information. Healthcare professionals need to consider the women’s educational background and treatment status while delivering the needed information.

Role of ovarian suppression in adjuvant treatment of breast cancer

Adjuvant endocrine therapy is an integral component of treatment for resectable luminal breast cancer. Tamoxifen or aromatase inhibitors monotherapy has been the standard of practice for many years. However, recent studies have shown that the addition of ovarian suppression statistically significantly increases survival rates in patients at high risk for recurrence and with poor prognosis factors. In this literature review, we summarized recent data regarding the role of ovarian suppression in adjuvant therapy for hormone-positive breast cancer. Suppression of ovarian function was most effective in young patients (&lt; 35 years) in the premenopausal stage when adverse prognostic factors were present (indications for (neo)adjuvant CT, G3, etc.) The authors noted that using of aromatase inhibitors instead of tamoxifen in this subgroup significantly reduced the risk of breast cancer recurrence. Ovarian suppression, especially in combination with aromatase inhibitors, was accompanied by an increase in the incidence of adverse side effects, particularly osteoporosis and bone fractures, which can be reduced by prescribing adequate accompanying therapy with OMA. The optimal duration of ovarian function suppression has also not been determined, but a two-year course seems optimal, given the results of large clinical trials. In the protocols performed, there was no significant effect of temporary ovarian suppression on the likelihood of subsequent pregnancy.

Abstract LB_B07: Probability of negative impact on adherence caused by the most frequent side effects of adjuvant endocrine therapy for premenopausal breast cancer in SOFT and TEXT Trials

Abstract Background: Regardless of adjuvant chemotherapy, the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy tamoxifen or exemestane in pre-menopausal women with estrogen receptor (ER)-positive breast cancer cause adverse events may affect adherence. Among the 22 targeted adverse events systematically reported in SOFT and TEXT trials, adverse events commonly experienced in exemestane–OFS group (32.3%) and tamoxifen–OFS group (31.0%), compared with tamoxifen alone group (24.6%). Side effects associated with endocrine therapy cause negative impact on adherence. Early discontinuation of endocrine therapy in 22.5%, 19.3%, and 23.7% of the tamoxifen, tamoxifen–OFS, and exemestane–OFS groups, respectively, in SOFT and TEXT trials. This report is intended to evaluate the possible contribution of the 8 most frequently studied side effects that have negative impact on adherence to hormone therapy in breast cancer. Methods: Calculating the probability of negative impact of most frequent endocrine therapy`s side effects (per SOFT-TEXT trials) on adherence per Leanne Fleming et al quantitative systematic review “The impact of medication side effects on adherence and persistence to hormone therapy in breast cancer survivors” Results: Musculoskeletal/joint pain had the most negative impact on the adherence in tamoxifen, tamoxifen–OFS, and exemestane–OFS groups (56%, 63% and 73%, respectively). Average of negative impact of tamoxifen, tamoxifen–OFS, and exemestane–OFS on adherence is 22%, 25% and 27%) Conclusions: The probability of adherence of using tamoxifen alone seems better than tamoxifen–OFS and exemestane–OFS. Citation Format: Tariq Hassan AL Qurayshah. Probability of negative impact on adherence caused by the most frequent side effects of adjuvant endocrine therapy for premenopausal breast cancer in SOFT and TEXT Trials [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B07.

EE210 Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy as Neoadjuvant Therapy and Continued as a Single Agent as Adjuvant Therapy for High-Risk Early-Stage Triple-Negative Breast Cancer in Greece

EE210 Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy as Neoadjuvant Therapy and Continued as a Single Agent as Adjuvant Therapy for High-Risk Early-Stage Triple-Negative Breast Cancer in Greece

Hormone Treatment for Breast Cancer

Hormone receptor-positive breast cancer accounts for 60-70% of all breast cancers and has a better prognosis than human epidermal growth factor receptor-2 (HER2)-positive or triple-negative breast cancer. Hormone treatment for breast cancer is an important treatment method that is effective and has few side effects for hormone receptor-positive breast cancer. Hormone therapy is performed as adjuvant therapy in early breast cancer and as palliative therapy in metastatic breast cancer. In the past decade, molecularly targeted agents against intracellular targets such as mammalian target of rapamycin (everolimus), cyclin-dependent kinase 4 and 6 (palbociclib, ribociclib, abemaciclib), and phosphatidylinositol 3-kinase (alpelisib) has offered patients effective therapeutic options, and combination of hormone treatment with the molecular agents have continued to improve the outcome of breast cancer.

Curcumin and quercetin loaded nanocochleates gel formulation for localized application in breast cancer therapy

After surgical excision of breast cancer, chemotherapy is recommended to eradicate any undiagnosed cancer cells and lower the likelihood of the cancer recurring. Curcumin and quercetin are two old flavonoid medicines used to treat breast cancer. Besides ambient popularity, they possess poor water solubility and poor bioavailability, limiting their usefulness. Hence to overcome these limitations, the present research aims to formulate curcumin and quercetin-loaded nanocochleates and convert them into a gel for localized application to enhance the breast cancer treatment. In this research article, we have developed curcumin and quercetin-loaded nanocochleates gel for breast cancer adjuvant therapy. The particle size, zeta potential encapsulation efficiency, and drug release of quercetin nanocochleates were 327 nm, −16.8 mV, 83.28 %, and 80.23 %, respectively, and that of curcumin nanocochleates were 328.6 nm, −15.0 mV, 82.30 %, and 77.19 %, respectively. The quercetin and curcumin-loaded nanocochleates gel was further characterized for pH, spreadability, and viscosity. The in vitro drug release behaviour of gel is controlled compared to plain quercetin and quercetin nanocochleates. The release of quercetin and curcumin from nanocochleates gel was 78.19 %, and 77.19 %, respectively. The MTT assay results showed quercetin and curcumin-loaded nanocochleates have maximum inhibition compared to control, quercetin alone, quercetin liposomes, and quercetin nanocochleates. Thus the quercetin and curcumin combination nanocochleates gel formulation can be a better option for the localized application in the breast cancer treatment.

Load-velocity Relationship of the Bench Press Exercise is not Affected by Breast Cancer Surgery and Adjuvant Therapy.

We examined the effect of breast cancer surgery and adjuvant therapy on the relationship between bar velocity and relative intensity (load-velocity [L-V] relationship) of the bench press (BP) exercise. Twenty-two breast cancer survivors (age: 48.0±8.2 yr., relative strength: 0.40±0.08) completed a loading test up to the one-repetition maximum (1RM) in the BP using a lightweight carbon bar. General and individual relationships between relative intensity (%1RM) and mean propulsive velocity (MPV) were studied. Furthermore, the mean test velocity (MPVTest) and velocity attained to the 1RM (MPV1RM) were analyzed. These procedures and analyses were also conducted in 22 healthy women (age: 47.8±7.1 yr., relative strength: 0.41±0.09) to examine the differences in velocity parameters derived from these L-V relationships. Polynomial regressions showed very close relationships (R2≥0.965) and reduced estimation errors (≤4.9% 1RM) for both groups. Between-group differences in MPV attained to each %1RM were small (≤0.01 m·s-1) and not significant (p≥0.685). Similarly, the MPVTest (0.59±0.06 m·s-1) and MPV1RM (0.17±0.03 m·s-1) were identical for breast cancer survivors and healthy women. These results suggest that practitioners could use the same velocity parameters derived from the BP L-V relationship to prescribe this exercise in middle-aged women, regardless of whether they have suffered from breast cancer.

Interplay of Oncoplastic Reconstruction and Adjuvant Radiation Therapy in Breast Cancer

PurposeOncoplastic breast surgery (OBS) combines breast cancer tumor removal with the cosmetic benefits of plastic surgery at the time of breast conserving surgery. Potential advantages of OBS include wider surgical margins around the tumor bed, while the natural shape and appearance of the breast are maintained more than standard lumpectomy procedures. However, limited information is available regarding the potential impact on adjuvant radiation treatment planning. Materials and MethodsWomen with localized breast cancer undergoing lumpectomy with immediate OBS and adjuvant radiation therapy between 2014 and 2019 were reviewed. OBS was performed utilizing volume displacement techniques and patients received whole breast irradiation with three-dimensional conformal radiation therapy. ResultsVolume of additional ipsilateral breast tissue removed during OBS ranged from 21-2,086 cm3 (median 304 cm3), 29% of patients had >500 cm3 of tissue removed. Surgical margins were positive in 12.5% and were not affected by volume of breast tissue removed (445 vs 439 cm3). Patients with surgical clips more often received a lumpectomy bed boost (75.9% versus 50.0%), boost volumes were on average 157 cm3 with clips versus 205 cm3 without clips. Mean V105 was comparable in patients with >500 cm3 tissue removed and irradiated breast volume >1,000 cm3, while higher absolute volumes were found in patients with >26 cm posterior separation (58.0 cm3 vs 102.7 cm3, p=0.07). No meaningful difference was observed in Dmax or radiation coverage (95% of the volume receiving 95% of the prescription dose) for patients with >26 cm posterior separation, >500 cm3 of breast tissue removed, or irradiated breast volume >1,000 cm3. ConclusionRadiation dosimetry plans for patients undergoing oncoplastic surgery were acceptable and no significant radiation or surgical advantage was gained in patients with more tissue removed. Our study stresses the importance of clear communication between surgeons and radiation oncologists about sufficient marking of the lumpectomy cavity, utilizing practices that minimize the need for re-excisions, and minimizing lumpectomy cavity disruption during rearrangement.