Efficacy and safety of diphereline 11.25 mg, microrelin 11.25 mg, and microrelin 3.75 mg in premenopausal patients with breast cancer: a non-inferiority randomized clinical trial.

BACKGROUND: Diphereline is a Gonadotropin-Releasing Hormone agonist commonly used in patients with breast cancer. This study aimed to compare the efficacy and safety of one-month and three-month Microrelin injections produced by Homa Pharmed Company with three-month Diphereline injections manufactured by IPSEN, France. METHODS: The study was a non-inferiority randomized clinical trial conducted between 2019 and 2023 on premenopausal women candidates for endocrine therapy. The participants were randomly assigned in blocks of six to one of three groups named A (Diphereline 11.25 mg), B (Microrelin 11.25 mg), and C (Microrelin 3.75 mg). The participants' menopausal symptoms, estradiol, and FSH serum levels were recorded in three-month intervals for one year. The efficacy of each medication and its side effects were compared among the three groups by statistical analysis during the one-year follow-up. RESULTS: The study included 133 patients with breast cancer. A decreasing trend in the serum levels of FSH and estradiol and an increasing trend of menopausal symptoms were recorded during the study. No specific side effects leading to drug disruption, hospitalization, or exclusion from the study were observed. Adjusting the effect of study group and time showed no significant changes in estradiol levels between groups B (p = 0.506) and C (p = 0.607) and group A. Also, serum FSH changes between groups B (p = 0.132) and C (p = 0.104) compared to group A were not significant. Moreover, the menopausal symptoms during the one-year follow-up did not significantly increase in group B (p = 0.108) and C (p = 0.113) compared to group A. CONCLUSIONS: It can be concluded that injections of both Microrelin 11.25 mg and 3.75 mg, produced by Homa Pharmed, Iran, are non-inferior in terms of effectiveness and incidence of menopausal symptoms compared to Diphereline, manufactured by IPSEN, France. TRIAL REGISTRATION: IRCT.ir, IRCT20201227049847N1; Registered on 09/01/2021.

The Effects of Synbiotic Supplementation on Serum Anti-Inflammatory Factors in the Survivors of Breast Cancer with Lymphedema following a Low Calorie Diet: A Randomized, Double-Blind, Clinical Trial.

BACKGROUND AND AIM: Breast cancer-related lymphedema (BCRL) is a treatment-related inflammatory complication in breast cancer survivors (BCSs). This study was aimed to evaluate the effect of synbiotic supplementation on serum concentrations of IL-10, TGF-ß, VEGF, adiponectin, and edema volume among overweight or obese BCSs with lymphedema following a low-calorie diet (LCD). METHOD: In a randomized double-blind, controlled clinical trial, 88 obese and overweight BCSs women were randomized to synbiotic supplement (n = 44) or placebo (n = 44) groups and both groups followed an LCD for 10 weeks. Pre- and post-intervention comparisons were made regarding the anti-inflammatory markers which included IL-10, TGF-ß, VEGF, adiponectin, edema volume, and anthropometric measurements. Also, the same factors were analyzed to find inter-group disparities. RESULTS: There were no significant differences among participants in the baseline, except for IL-10 and adiponectin. Post-intervention, no significant differences were observed regarding the anti-inflammatory markers, including IL-10, VEGF, adiponectin, and TGF-ß between the groups. After 10 weeks of intervention edema volume significantly decreased in the synbiotic group; additionally, anthropometric measurements (body weight, BMI, body fat percent, and WC) decreased in both groups significantly (P < 0.001 and P < 0.005; respectively). CONCLUSION: Synbiotic supplementation coupled with an LCD in a 10-week intervention had beneficial effects on increasing the serum TGF-ß, IL-10, and adiponectin levels in women with BCRL. It also reduced arm lymphedema volume. Therefore, synbiotic supplementation can be effective in improving health status in BCRL patients.

Effectiveness of logotherapy and nutrition counseling on psychological status, quality of life, and dietary intake among breast cancer survivors with depressive disorder: a randomized clinical trial.

Breast cancer (BC) can negatively influence multiple facets of survivors' lives including mental health, quality of life (QoL), and dietary behavior. Logotherapy as a psycho-education program may help breast cancer survivors (BCSs) discover their meaning of life throughout distressful events. The present study aimed to determine the effects of logotherapy along with nutrition counseling on psychological status, QoL, and dietary intake among BCSs who were diagnosed with depression.This randomized clinical trial was conducted on 90 BCSs who scored ≥ 14 on Beck's depression test. Participants were randomly assigned into two groups to receive nutrition counseling plus logotherapy (n = 46) or nutrition counseling alone (n = 44) for 8 weeks. Primary outcomes (depression, anxiety, and QoL) and secondary outcomes (anthropometric indices, dietary intake, and eating disorder status) were measured at baseline and after 8 weeks.All dimensions of QoL, anthropometric measurements, and the compulsive eating scale improved significantly in both groups after 8 weeks. A combination of nutrition counseling and logotherapy resulted in a significant reduction in anxiety (P < 0.001) and depression (P < 0.001) scores compared with the nutrition counseling alone. In addition, participants who received logotherapy plus nutrition counseling significantly consumed less energy, carbohydrate, and fat intake after 8 weeks compared with the control group (P < 0.001).It can be concluded that logotherapy along with nutrition education would be an important step in improving anxiety, depression, and QoL of patients with BC who had depressive symptoms.Trial registration number: (IR.ACECR.IBCRC.REC.1396.17).

Long-term outcomes of non-metastatic breast cancer patients by molecular subtypes.

BACKGROUND: Today, with the progress of medical sciences, increasing the cure probability and survival time is an important goal of cancer treatment. This study compared long-term disease-free survival (DFS) of non-metastatic breast cancer patients based on different molecular subtypes. METHODS: This retrospective cohort study consisted of 1287 patients diagnosed with breast cancer and treated at Motamed Cancer Institute from 2000 to 2016 and followed up until 2018. Kaplan-Meier curve was fitted to data based on molecular subtypes. Then the semi-parametric mixture cure model was applied to determine the survival and cure probability of molecular subtypes by adjusting clinical and demographic factors. RESULTS: Among 1287 breast cancer patients, 200 (15.5%) cases died. The mean age of patients was 47.00 ± 10.72 years. Women with the HR+/HER2-subtype had the best 5-year survival rate (84.2%), whereas other subtypes had a lower rate as follows: HR+/HER2+ (77.3%), triple-negative (76.5%), and HR-/HER2+ (62.3%). Kaplan-Meier curve calculated a cure rate of about 60% and patients who survived more than 150 months were intuitively considered cured. After adjustment for clinical and demographic variables, the cure probability of HR-/Her2+ patients was substantially lower than HR+/HER2- patients (OR = 0.22), though there were no significant variations in short-term DFS based on molecular subtypes (HR = 0.91). CONCLUSIONS: Our results confirm that the most prevalent breast cancer was HR+/HER2- tumor type which had the best prognosis. It is also concluded that HR-/HER2+ patients had the worst outcomes, with the highest rates of recurrence and metastasis and the lowest overall and disease-free survival rates.

Prediction of lymphedema occurrence in patients with breast cancer using the optimized combination of ensemble learning algorithm and feature selection.

BACKGROUND: Breast cancer-related lymphedema is one of the most important complications that adversely affect patients' quality of life. Lymphedema can be managed if its risk factors are known and can be modified. This study aimed to select an appropriate model to predict the risk of lymphedema and determine the factors affecting lymphedema. METHOD: This study was conducted on data of 970 breast cancer patients with lymphedema referred to a lymphedema clinic. This study was designed in two phases: developing an appropriate model to predict the risk of lymphedema and identifying the risk factors. The first phase included data preprocessing, optimizing feature selection for each base learner by the Genetic algorithm, optimizing the combined ensemble learning method, and estimating fitness function for evaluating an appropriate model. In the second phase, the influential variables were assessed and introduced based on the average number of variables in the output of the proposed algorithm. RESULT: Once the sensitivity and accuracy of the algorithms were evaluated and compared, the Support Vector Machine algorithm showed the highest sensitivity and was found to be the superior model for predicting lymphedema. Meanwhile, the combined method had an accuracy coefficient of 91%. The extracted significant features in the proposed model were the number of lymph nodes to the number of removed lymph nodes ratio (68%), feeling of heaviness (67%), limited range of motion in the affected limb (65%), the number of the removed lymph nodes ( 64%), receiving radiotherapy (63%), misalignment of the dominant and the involved limb (62%), presence of fibrotic tissue (62%), type of surgery (62%), tingling sensation (62%), the number of the involved lymph nodes (61%), body mass index (61%), the number of chemotherapy sessions (60%), age (58%), limb injury (53%), chemotherapy regimen (53%), and occupation (50%). CONCLUSION: Applying a combination of ensemble learning approach with the selected classification algorithms, feature selection, and optimization by Genetic algorithm, Lymphedema can be predicted with appropriate accuracy. Developing applications by effective variables to determine the risk of lymphedema can help lymphedema clinics choose the proper preventive and therapeutic method.

Status of breast cancer screening strategies and indicators in Iran: A scoping review.

Background: This scoping review aimed to investigate the status of breast cancer (BC) preventive behaviors and screening indicators among Iranian women in the past 15 years. BC, as the most common cancer in women, represents nearly a quarter (23%) of all cancers. Presenting the comprehensive view of preventive modalities of BC in the past 15 years in Iran may provide a useful perspective for future research to establish efficient services for timely diagnosis and control of the disease. Materials and Methods: The English and Persian articles about BC screening modalities and their indicators in Iran were included from 2005 to 2020. English electronic databases of Web of Science, PubMed, and Scopus, and Persian databases of Scientific Information Database (SID) and IranMedex were used. The critical information of articles was extracted and classified into different categories according to the studied outcomes. Results: A total of 246 articles were assessed which 136 of them were excluded, and 110 studies were processed for further evaluation. Performing breast self-examination, clinical breast examination, and mammography in Iranian women reported 0%-79.4%, 4.1%-41.1%, and 1.3%-45%, respectively. All of the educational interventions had increased participants' knowledge, attitude, and practice in performing the screening behaviors. The most essential screening indicators included participation rate (3.8% to 16.8%), detection rate (0.23-8.5/1000), abnormal call rate (28.77% to 33%), and recall rate (24.7%). Conclusion: This study demonstrated heterogeneity in population and design of research about BC early detection in Iran. The necessity of a cost-effective screening program, presenting a proper educational method for increasing women's awareness and estimating screening indices can be the priorities of future researches. Establishing extensive studies at the national level in a standard framework are advised.

Comparing the efficacy and side-effects of PDLASTA® (Pegfilgrastim) with PDGRASTIM® (Filgrastim) in breast cancer patients: a non-inferiority randomized clinical trial.

BACKGROUND: The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. METHODS: In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. RESULTS: Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. CONCLUSION: It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. TRIAL REGISTRATION: IRCT20190504043465N1 , May 2019.

Development and validation of a guideline on sexual and reproductive health of breast cancer survivors in Iran: a mixed methods study protocol.

BACKGROUND: Sexual and reproductive health problems significantly decrease quality of life in survivors of breast cancer. The best approach is to provide services according to evidence-based guidelines developed based on their practical context. Here, we aim to develop and validate a guideline on the sexual and reproductive health of breast cancer survivors in Iran. METHODS: The guideline will be developed and validated using an exploratory sequential mixed methods approach in three phases: (1) describing sexual and reproductive health needs of survivors of breast cancer in Iran and the health services they receive in this regard, (2) performing a systematic review of existing guidelines, resources, and documents on the sexual and reproductive health of breast cancer survivors worldwide, and (3) developing and validating a guideline on the sexual and reproductive health of women who survived breast cancer in Iran based on the results of phases 1 and 2 through multiple steps. DISCUSSION: A comprehensive and practical guideline on the sexual and reproductive health of breast cancer survivors in Iran will be developed which will be compatible with their specific needs and culture, considering the limited resources available. This guideline can significantly improve the quality of life in breast cancer survivors in Iran. In addition, the approach we will use here can be utilized to develop guidelines on sexual and reproductive health of female cancer survivors in general.

The Effects of Synbiotic Supplementation on Antioxidant Capacity and Arm Volumes in Survivors of Breast Cancer-Related Lymphedema.

Background and Aims: Synbiotics found to be beneficial in breast cancer survivors (BCSs) through its antioxidant properties. The aim of this study was to assess the effects of synbiotic supplementation on edema volume and some oxidative markers among obese and overweight patients with BCRL.Method: This randomized double-blind, placebo-controlled trial was conducted on 88 overweight and obese BCSs aged 18-65 years. All the subjects were given a specified low-calorie diet (LCD) and were randomly assigned into two groups to intake 109 CFU/day synbiotic supplement (n = 44) or placebo (n = 44) for 10 wk. Edema volume and serum total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) concentration were measured at baseline and after the 10-wk intervention.Results: Ten-wk supplementation with synbiotics leads to a significant reduction in serum MDA levels (P = 0.001) and an increase in serum SOD concentration (P = 0.007) compared to placebo. No significant changes were observed in serum GPx, TAC, and edema volume between groups.Conclusion: Our findings reveal that 10-wk synbiotic supplementation along with a LCD program-reduced serum MDA levels and elevate the activity of SOD in overweight and obese patients with BCRL. However, its effect on serum GPx, TAC, and edema volume was not significant.

Effect of lymphedema self-management group-based education compared with social network-based education on quality of life and fear of cancer recurrence in women with breast cancer: a randomized controlled clinical trial.

BACKGROUND: Breast cancer-related lymphedema (BCRL) and its associated symptoms harm the quality of life (QoL) of cancer survivors and can stimulate fear of cancer recurrence (FCR). Self-management education for lymphedema has been introduced as an effective method in controlling FCR. This study investigates the effect of lymphedema group-based education compared to the social network-based and control group on QoL and FCR in breast cancer patients. METHODS: This three-arm clinical trial studied 105 patients with breast cancer-related lymphedema referred to Seyed_Khandan rehabilitation center. Sampling was done by random allocation method in blocks of 3 with 35 subjects in each group. All subjects received routine lymphedema treatments. The group-based education (GE) and social network-based education (SNE) groups received self-management education in the clinic and Telegram™ messenger channel, respectively. Impairment in QoL and mean score of FCR were assessed before, immediately after, and three months after the intervention by using the Persian version of Lymphedema Life Impact Scale (LLIS) and Fear of Progression Questionnaire-Short Form (FoPQ-SF), respectively. Mixed-model ANOVA was applied for statistical analysis. RESULTS: There was a significant time effect on total LLIS (P = 0.007), psychosocial (P = 0.038) and functional (P = 0.024) subscale changes in three groups of study. Interaction between the main effect of group and time on psychosocial subscale changes was statistically significant (P = 0.017). The multicomparison results illustrated that the main effect of time, the main effect of group, and interaction of them on the mean score of FCR were P = 0.084, P = 0.380, and P = 0.568, respectively. CONCLUSION: Despite no significant reduction in the FCR score, results showed the improvement of most QoL aspects after three months of intervention. Although the social network-based education method was effective, the group-based education method was more beneficial. Applying these educational methods in lymphedema treatment protocols needs cost-effectiveness studies. TRIAL REGISTRATION: This study was registered at the Iranian Registry of Clinical Trials (IRCT2017052834176N1).

Randomized Study of the Effect of Dietary Counseling During Adjuvant Chemotherapy on Chemotherapy Induced Nausea and Vomiting, and Quality of Life in Patients With Breast Cancer.

Patients with breast cancer (PsBC) usually face with chemotherapy induced nausea and vomiting (CINV). The aim of this study was to assess the impact of nutritional counseling on CINV and quality of life (QoL) of PsBC. 150 PsBC were randomly assigned for receiving a personalized diet, which contained 1.2-1.5 g/kg of protein, 30% of energy from fat and 55-60% of energy from carbohydrate, a face to face nutrition education, and a pamphlet which contained beneficial nutrition information to reduce the severity of CINV before each chemotherapy session for three times (n = 75) or regular care (n = 75). CINV, QoL, and dietary intake were evaluated after each chemotherapy session. Nausea rating index, overall nausea index, and visual analog scale (P < 0.001) were dramatically lower in the intervention group. Global health status/QoL as well as physical functioning, role functioning, emotional functioning, and cognitive functioning (P < 0.001) were significantly better in the intervention group. Patients in the control group experienced more fatigue, nausea and vomiting, pain, dyspnea, loss of appetite, constipation, and diarrhea (P < 0.001). Nutrition counseling during adjuvant chemotherapy among PsBC reduced the occurrence of CINV and led to significant improvements in the QoL.

The Effect of Dietary Intervention Along with Nutritional Education on Reducing the Gastrointestinal Side Effects Caused by Chemotherapy Among Women with Breast Cancer.

Gastrointestinal (GI) side effects caused by chemotherapy in women with breast cancer are common but poorly understood which might be controlled by nutritional intervention. Thus, the major aim of this study was to assess the effect of dietary intervention along with nutritional education on reducing these side effects. The present study is a single-center, single-controlled, and randomized trial. A total of 150 patients with breast cancer undergoing chemotherapy were randomly assigned into intervention group to receive dietary intervention and nutritional education (n = 73) or control group (n = 67) for 10 weeks, after their three sessions of chemotherapy. The primary endpoint was the GI symptoms after each session of chemotherapy that were measured by a designed questionnaire based on ROMIII questionnaire. The severity of GI side effects in the dietary intervention along with nutritional education was decreased significantly in the third session of chemotherapy compared to the first session, which include reflux disorder (P = 0.05), anorexia (P < 0.001), nausea (P = 0.002), constipation (P < 0.001), and diarrhea (P < 0.001). Moreover, significant reductions were observed in the severity of GI side effects in the intervention group compared to control group after the third session (P < 0.001). After adjusting the analysis for baseline values including age, job, education level, weight, and body mass index, significant changes were observed for GI side effects in the intervention group compared to the control group (P < 0.001). This study showed beneficial effects of individualized dietary intervention along with nutritional education on reducing diarrhea, constipation, vomiting, and nausea in women with breast cancer during the chemotherapy.

Psychometric evaluation of the Persian version of the Lymphedema Life Impact Scale (LLIS, version 1) in breast cancer patients.

BACKGROUND: Despite the high prevalence of lymphedema in Iranian breast cancer patients, there is no valid instrument for measuring quality of life in this population. The aim of this study was to assess reliability and validity of the Persian version of Lymphedema Life Impact Scale (LLIS) in breast cancer patients. METHODS: Forward-backward procedure was applied to translate The LLIS from English into Persian. The LLIS is an 18-item measure of physical, psychosocial, and functional impairments caused by lymphedema. Experts and patients assessed content and face validity, respectively. Discriminant validity was evaluated by comparing breast cancer patients with and without lymphedema. Convergent validity was assessed by comparing LLIS score with SF-36 (functional component) and the EORTC-QLQ-C30 (functional component). The construct validity also was evaluated using confirmatory and exploratory factor analyses. Internal consistency was evaluated by Cronbach's alpha coefficient. Stability was assessed by test-retest analysis over a one-week interval in 13 patients. RESULTS: In all 446 breast cancer patients were entered into the study. The content and face validity of Persian version of LLIS were acceptable and minor corrections were applied in final version. The questionnaire differentiated well in patients' with and without lymphedema and not lending support to its discriminant validity. Confirmatory factor analysis showed a good fit for the data. Cronbach's alpha coefficient in physical, psychosocial and functional subscales were 0.873, 0.854 and 0.884 respectively. Intra-class correlation coefficient of total score of the LLIS was 0.96. CONCLUSIONS: The findings of this study suggest a first indication that reliability and validity of the Persian version of LLIS in patients with breast cancer induced lymphedema was good. Application of this instrument for identifying problems of patients with upper extremity lymphedema may be helpful in designing interventions to improve quality of life.

Structural Challenges of Providing Palliative Care for Patients with Breast Cancer.

INTRODUCTION: To establish a palliative care system (PCS) in Iran, it is necessary to identify the potential barriers. AIM: This study aims to highlight the views of stakeholders to know the challenges of providing palliative care for women with breast cancer. MATERIALS AND METHODS: Semi-structured in-depth interviews are used with purposeful sampling conducted in Tehran, Iran; from January to June 2015. Twenty participants were included in the study: nine patients with breast cancer and ten health-care providers. The interviews were analyzed using qualitative directed content analysis based on Donabedian model. Data credibility was examined using the criteria of Lincoln and Guba. RESULTS: Based on the pattern of Avedis Donabedian model, two main categories were identified: (1) palliative care services in the health system still remain undefined and (2) lack of adequate care providers. The subcategories emerged from the main categories are: (1) Inexistent home care, (2) specialized palliative care being in high demand, lack of: (a) Rehabilitation program and guidelines, (b) treatment/training protocols, (c) inefficient insurance and out-of-pocket costs, (d) patient referral system, (e) nontransparency of job description, and (f) weakness of teamwork. DISCUSSION: The findings of the study identify views and perceptions of patients as well as the health professionals around the challenges of providing palliative care. To establish a structured PCS, we need to meet the challenges and remove perceived barriers to, including but not limited to, building up knowledge and awareness of health professionals, educating professional, and developing updated, well-defined, and standard treatment protocols, tailored to local conditions.

Refractory and Recurrent Idiopathic Granulomatous Mastitis Treatment: Adaptive, Randomized Clinical Trial.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is mostly described as an autoimmune disease with higher prevalence among Middle Eastern childbearing-age women. This study aimed to evaluate the best treatment of choice in patients with resistant or recurrent IGM. STUDY DESIGN: Patients with established recurrent or resistant IGM who were referred to the Breast Cancer Research Center from 2017 to 2020 were randomly assigned to either one of the following treatment groups: A (best supportive care), B (corticosteroids: prednisolone), and C (methotrexate and low-dose corticosteroids). This adaptive clinical trial evaluated radiological and clinical responses, as well as the potential side effects, on a regular basis in each group, with patients followed up for a minimum of 2 years. RESULTS: A total of 318 participants, with a mean age of 33.52 ± 6.77 years, were divided into groups A (10 patients), B (78 patients), and C (230 patients). In group A, no therapeutic response was observed; group B exhibited a mixed response, with 14.1% experiencing complete or partial responses, 7.7% maintaining stability, and 78.2% experiencing disease progression. Accordingly, groups A and B were terminated due to inadequate response. In group C, 94.3% achieved complete response, 3% showed partial remission, and 2.7% had no response to therapy. Among the entire patient cohort, 11.6% tested positive for antinuclear antibodies, 3.5% for angiotensin-converting enzyme, and 12.3% for erythema nodosum. Notably, hypothyroidism was a prevalent condition among the patients, affecting 7.2% of the cohort. The incidence of common side effects was consistent across all groups. CONCLUSIONS: The most effective treatment option for patients with recurrent or resistant IGM is a combination therapy involving steroids and disease-modifying antirheumatic drugs such as methotrexate.

Evaluation Factors Affecting on Recurrence, Metastasis, and Survival of Breast Cancer in Iranian Women by Multi-State Model Approach.

Background: We used the multistate model to investigate how prognostic factors of breast cancer are seen to affect the disease process. Methods: This cohort study was conducted at Motamed Cancer Institute of Tehran, Iran on 2363 breast cancer patients admitted from 1978 to 2017, and they were followed up until 2018. We applied the multistate models, including four states: diagnosis, recurrence, metastasis, and final absorbing mortality state. Results: Age over 50 years, positive lymph nodes and tumor size intensified the hazard of transition from diagnosis to metastasis (P=0.002, P<0.001 and P=0.001 respectively) and they also intensified the hazard of transition from diagnosis to mortality (P=0.010, P<0.001 and P<0.001 respectively). At the same time, the educational level decreased the hazard of mentioned transitions (P<0.001). Positive estrogen receptors reduced the hazard of transition from diagnosis to metastasis (P=0.007) and positive lymph nodes also intensified the hazard of transition from metastasis to mortality (P=0.040). Tumor size had an increasing role in the transitions from diagnosis to recurrence, recurrence to metastasis, and metastasis to mortality (P=0.014, P=0.018 and P=0.002 respectively). Conclusion: Multistate model presented the detailed effects of prognostic factors on progression of breast cancer. Implementing early diagnosis strategies and providing informational programs, especially in younger ages and lower educational level patients may be helpful in reducing the hazard of transition to higher states of breast cancer and increasing the survival of Iranian women with breast cancer by controlling tumor size growth, lymph nodes involvements and estrogen receptor status.

Effectiveness of home-based exercise in breast cancer survivors: a randomized clinical trial.

BACKGROUND: Breast cancer patients are recommended to engage in regular exercise. In developing countries, where there is a lack of facilities to offer specialized, supervised exercise for this population, regularly exercising might be a challenge. We aimed to evaluate the effectiveness of a home-based intervention in this population. METHODS: Breast cancer survivors were randomly assigned to either the home-based exercise program or the usual care group. Exercise intervention included walking, balance, and stretch exercises, along with weekly follow-up telephone calls. Quality of life (QOL) was evaluated using EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires and the predicted VO2 peak was measured using the Ebbeling submaximal treadmill test. RESULTS: Eighty-nine patients were enrolled in the study. Reported minutes of exercise gradually increased from 40.7 min per week in week 1 to 116.9 min per week in week 12. This intervention improved global QOL (P = 0.001), social functioning (P = 0.04), and the predicted VO2 peak (P = 0.01). CONCLUSION: This home-based exercise regime effectively increased quality of life and physical activity levels. TRIAL REGISTRY: Iranian Registry of Clinical Trials identifier: IRCT20140810018746N1, prospectively registered 08/01/2018, https://en.irct.ir/trial/27959 .

Application of Frailty Quantile Regression Model to Investigate of Factors Survival Time in Breast Cancer: A Multi-Center Study.

Background: The prognostic factors of survival can be accurately identified using data from different health centers, but the structure of multi-center data is heterogeneous due to the treatment of patients in different centers or similar reasons. In survival analysis, the shared frailty model is a common way to analyze multi-center data that assumes all covariates have homogenous effects. We used a censored quantile regression model for clustered survival data to study the impact of prognostic factors on survival time. Methods: This multi-center historical cohort study included 1785 participants with breast cancer from four different medical centers. A censored quantile regression model with a gamma distribution for the frailty term was used, and p-value less than 0.05 considered significant. Results: The 10th and 50th percentiles (95% confidence interval) of survival time were 26.22 (23-28.77) and 235.07 (130-236.55) months, respectively. The effect of metastasis on the 10th and 50th percentiles of survival time was 20.67 and 69.73 months, respectively (all p-value < 0.05). In the examination of the tumor grade, the effect of grades 2 and 3 tumors compare with the grade 1 tumor on the 50th percentile of survival time were 22.84 and 35.89 months, respectively (all p-value < 0.05). The frailty variance was significant, which confirmed that, there was significant variability between the centers. Conclusions: This study confirmed the usefulness of a censored quantile regression model for cluster data in studying the impact of prognostic factors on survival time and the control effect of heterogeneity due to the treatment of patients in different centers.

Anti-cancer effect of COVID-19 vaccines in mice models.

AIMS: Without any doubt, vaccination was the best choice for Coronavirus disease 2019 (COVID-19) pandemic control. According to the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO), people with cancer or a history of cancer have a higher risk of dying from Covid-19 than ordinary people; hence, they should be considered a high-priority group for vaccination. On the other hand, the effect of the Covid-19 vaccination on cancer is not transparent enough. This study is one of the first in vivo studies that try to show the impact of Sinopharm (S) and AstraZeneca (A) vaccines on breast cancer, the most common cancer among women worldwide. MATERIALS AND METHODS: Vaccination was performed with one and two doses of Sinopharm (S1/S2) or AstraZeneca (A1/A2) on the 4T1 triple-negative breast cancer (TNBC) mice model. The tumor size and body weight of mice were monitored every two days. After one month, mice were euthanized, and the existence of Tumor-infiltrating lymphocytes (TILs) and expression of the important markers in the tumor site was assessed. Metastasis in the vital organs was also investigated. KEY FINDINGS: Strikingly, all of the vaccinated mice showed a decrease in tumor size and this decrease was highest after two vaccinations. Moreover, we observed more TILs in the tumor after vaccination. Vaccinated mice demonstrated a decrease in the expression of tumor markers (VEGF, Ki-67, MMP-2/9), CD4/CD8 ratio, and metastasis to the vital organs. SIGNIFICANCE: Our results strongly suggest that COVID-19 vaccinations decrease tumor growth and metastasis.

Determining Prognostic Factors of Disease-Free Survival in Breast Cancer Using Censored Quantile Regression.

Background: The analysis of disease-free survival and related factors leads to a better understanding of the patient's condition and recurrence-related characteristics and provides a basis for more appropriate treatment guidance. In this study, we aimed to investigate the role of prognostic factors on disease-free survival in breast cancer with a quantile regression model. Methods: This retrospective study was conducted by reviewing data obtained from 2056 breast cancer patients. Age at diagnosis and education status, tumor size, lymph node ratio, tumor grade, estrogen receptor and progesterone receptor, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were the prognosis factors considered in this study. A quantile regression model was used to investigate prognostic factors of disease-free survival in breast cancer. Results: Disease recurrence was verified in 251 (13.9%) women, and 39 (0.02%) women died before experience recurrence. The 10th percentile of disease-free survival for patients with the hormone therapy was 23.85 months greater than patients who did not receive this treatment (P value < .001). In the examination of the tumor size, the 10th and 20th percentiles of disease-free survival for patients with tumor size > 5 cm were 31.06 and 27 months less than patients with the tumor size < 2 cm, respectively (P value = .006 and .021, respectively). Compared with grade 1 tumors, the 10th and 20th percentiles of disease-free survival for patients with grade 3 tumors decreased 30.11 and 38.32 months, respectively (P value < .001 and .038, respectively). The 10th and 20th percentiles of disease-free survival decreased 28.16 and 45.32 months with a 1 unit increase in lymph node ratio, respectively (P value = .032 and .032, respectively). Conclusions: Among the prognostic factors, tumor size, grade, and lymph node ratio showed a close relationship with disease-free survival in breast cancer. The findings indicated that developing public screening and educational programs through the health care system with more emphasis on low-educated women is needed among Iranian women.