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.

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.

Cancer Is Associated with the Emergence of Placenta-Reactive Autoantibodies.

Placenta-specific antigens are minimally expressed or unexpressed in normal adult tissues, while they are widely expressed in cancer. In the course of carcinogenesis, a vast array of autoantibodies (AAbs) is produced. Here, we used a quantitative approach to determine the reactivity of AAbs in the sera of patients with breast (BrC: N = 100, 100% female, median age: 51 years), gastric (GC: N = 30, 46.6% female, median age: 57 years), bladder (BC: N = 29, 34.4% female, median age: 57 years), and colorectal (CRC: N = 34, 41.1% female, median age: 51 years) cancers against first-trimester (FTP) and full-term placental proteome (TP) in comparison with age- and sex-matched non-cancer individuals. Human-on-human immunohistochemistry was used to determine reactive target cells in FTP. The effect of pregnancy on the emergence of placenta-reactive autoantibodies was tested using sera from pregnant women at different trimesters of pregnancy. Except for BC, patients with BrC (p < 0.0284), GC (p < 0.0002), and CRC (p < 0.0007) had significantly higher levels of placenta-reactive AAbs. BrC (p < 0.0001) and BC (p < 0.0409) in the early stages triggered higher autoantibody reactivity against FTP. The reactivities of BrC sera with FTP did not show an association with ER, PR, or HER2 expression. Pregnancy in the third trimester was associated with the induction of TP- and not FTP-reactive autoantibodies (=0.018). The reactivity of BrC sera with placental proteins was found to be independent of gravidity or abortion. BrC sera showed a very strong and specific pattern of reactivity with scattered cells beneath the syncytiotrophoblast layer. Our results reinforce the concept of the coevolution of placentation and cancer and shed light on the future clinical application of the placental proteome for the non-invasive early detection and treatment of cancer.

Ultrasound features of pregnancy-associated breast cancer: A retrospective observational analysis.

Pregnancy-associated breast cancer (PABC) is a poor prognosis in women, and the mortality rate is higher in this subgroup of patients than in non-PABC. This study aims to assess clinicopathological and ultrasound features of patients with PABC. Of 75 patients with breast cancer, 31 cases were in lactating, or pregnancy phase and 44 patients had no recent history of pregnancy/lactation at the time of cancer detection. The available pathological characteristics and ultrasound findings of the PABC and non-PABC groups were compared. The analysis of ultrasound findings demonstrated that the percentages of antiparallel orientation (p = 0.04) and heterogeneous internal echo pattern (p = 0.002) were higher in the PABC group. The final Breast Imaging Reporting and Data System (BI-RADS) assessment in the two groups was significantly different (p = 0.008). In this study, most PABCs were BI-RADS 4c or 5; compared with age-matched non-PABC cases. There were significant differences in ER (p = 0.03), receptor groups (p = 0.007), and tumor grade (p = 0.02) in PABC compared to non-PABC group. To conclude, radiologists should be careful about ultrasound findings of PABC and recommend core needle biopsy in suspected cases.

A micropillar array-based microfluidic chip for label-free separation of circulating tumor cells: The best micropillar geometry?

INTRODUCTION: The information derived from the number and characteristics of circulating tumor cells (CTCs), is crucial to ensure appropriate cancer treatment monitoring. Currently, diverse microfluidic platforms have been developed for isolating CTCs from blood, but it remains a challenge to develop a low-cost, practical, and efficient strategy. OBJECTIVES: This study aimed to isolate CTCs from the blood of cancer patients via introducing a new and efficient micropillar array-based microfluidic chip (MPA-Chip), as well as providing prognostic information and monitoring the treatment efficacy in cancer patients. METHODS: We fabricated a microfluidic chip (MPA-Chip) containing arrays of micropillars with different geometries (lozenge, rectangle, circle, and triangle). We conducted numerical simulations to compare velocity and pressure profiles inside the micropillar arrays. Also, we experimentally evaluated the capture efficiency and purity of the geometries using breast and prostate cancer cell lines as well as a blood sample. Moreover, the device's performance was validated on 12 patients with breast cancer (BC) in different states. RESULTS: The lozenge geometry was selected as the most effective and optimized micropillar design for CTCs isolation, providing high capture efficiency (>85 %), purity (>90 %), and viability (97 %). Furthermore, the lozenge MPA-chip was successfully validated by the detection of CTCs from 12 breast cancer (BC) patients, with non-metastatic (median number of 6 CTCs) and metastatic (median number of 25 CTCs) diseases, showing different prognoses. Also, increasing the chemotherapy period resulted in a decrease in the number of captured CTCs from 23 to 7 for the metastatic patient. The MPA-Chip size was only 0.25 cm2 and the throughput of a single chip was 0.5 ml/h, which can be increased by multiple MPA-Chips in parallel. CONCLUSION: The lozenge MPA-Chip presented a novel micropillar geometry for on-chip CTC isolation, detection, and staining, and in the future, the possibilities can be extended to the culture of the CTCs.

Long-term Survival and Prognostic Factors of Breast Cancer.

BACKGROUND: Breast cancer survival rate is an important index for assessment of treatment effect in reducing the mortality. Weaimed to determine the fifteen-year survival rate for breast cancer at a referral center in Iran and its correlated factors. METHODS: This survival study enrolled patients with breast cancer who referred to Motamed Cancer Institute (MCI) from 1998 to2016. The survival rate was calculated using the Kaplan-Meier method. The relationship of demographic, clinical and therapeuticfactors with overall survival (OS) was studied using Cox's proportional hazard model. RESULTS: Totally, 3443 patients were studied. Their mean age and follow-up period were 47.7 (±11.43) years and 61.66 (±52.1)months, respectively. The median follow-up time was 48.4 months (range: 1-413 months), 49.7% of the patients had high schoolor higher education, and 71.3% presented in the early stage of the disease. Death occurred in 505 (14.7%) of the patients. Theoverall 2-, 5-, 7-, 10- and 15-year survival rates were 93%, 82%, 78%, 74%, and 66%, respectively. Lymph node involvement(HR=2.07; 95% CI: 1.38-3.09), tumor size≥5 cm (HR=2.83; 95% CI: 1.59-2.04), being single/divorced/widowed (HR=1.65;95% CI: 1.13-2.4), and education level

Practical Recommendations for the Preoperative Screening and Protective Protocols in Cancer Surgeries During COVID-19: A Systematic Review.

Introduction: The new coronavirus (COVID-19) has posed many new challenges to the health care and the timing of surgical care. At the beginning of the pandemic many guidelines recommended postponing elective surgical procedures to reallocate resources. As regards, delay in cancer treatment could be effective on cancer progression. The aim of this systematic review was to outline a guideline for preoperative screening before cancer surgeries and protecting health care workers during the pandemic. Materials and Methods: This study was conducted through a search in electronic databases up to August 2020. PubMed, EMBASE, Web of Science, Scopus, Science Direct, and Google Scholar databases were searched without time limitation. The keywords were a combination of preoperative, cancer surgery, COVID-19, and their synonyms. Results: The most commonly used ways to triage preoperatively were telephone pre-assessment for suspicious symptoms and history of contact or travel, 14-day self-isolation, in- hospital queries at admission, temperature monitoring, and isolation in a single room COVID-free ward or physical distancing. Reverse transcription-polymerase chain reaction (RT-PCR) test 24-72 h before operation was recommended commonly, except in inaccessible centers, but non-contrast chest-CT scan is not routinely advised for elective surgeries to salvage medical resources. Recommended personal protective equipment (PPE) for staffs were wearing N95 mask in addition to gown, gloves, eye protection in aerosol-generating procedures (AGPs), and wearing gloves, hats, and disposable surgical masks, practice distancing, and hand hygiene for all staffs. Meanwhile team separation of hospital staffs caring for COVID-19 patients, segregated areas for COVID-19 clean and contact, restriction of visitors and family members, and personal distancing are mostly recommended. Conclusion: We hope this review would be a guidance for triage, preoperative testing, and summarizing safety principles during COVID-19 pandemic alongside with surgical reintegration.

Assessment of Ultrasound Features and BI-RADS Categories of Malignant Breast Masses in Women ≤40.

BACKGROUND: To evaluate ultrasound (US) characteristics and BI-RADS (Breast imaging-reporting and data system) of malignant breast masses in women <40 years and to compare with older patients. METHODS: In a retrospective, descriptive-analytical study, we assessed the US images and BI-RADS category of 78 malignant masses with a final pathology of invasive ductal carcinoma (IDC, NOS type). RESULTS: Overall, the most frequent US descriptors of IDC were indistinct margin (45%), irregular shaped (63.5%), posterior shadowing (38.8%), heterogeneous internal echogenicity (56.3%) and non-parallel orientation (76.3%). In this study, most malignant masses of young patients were categorized as BI-RADS 4a while in the older patients (over 40), they were mostly BI-RADS 4b and 5 with P=0.03 and odds ratio (OR) of 2.57 (95% confidence interval (CI), 0.74-8.8). In addition, the mean dimension of the mass in young cases was greater (18.3 mm) compared with older patients (13.2 mm) with P value of 0.04 and OR of 3.8 (95% CI, 1.1-13.4). CONCLUSION: Similar to previous studies, malignant masses were diagnosed in greater dimensions in younger cases which may be due to the delay in diagnosis, the rapid growth of the tumor and the absence of routine screening guidelines. Radiologists should be aware of the possibility of malignancy in palpable slightly suspicious masses (BI-RADS 4A) in young cases.

Informational Needs in Patients With Breast Cancer With Lymphedema: Is It Important?

INTRODUCTION: Lymphedema is one of the complications of breast cancer treatment. It has no cure yet and can affect the quality of life. This study aimed to identify and investigate informational needs, preferred delivery methods, and time of receiving information about lymphedema for these patients. METHODS: One hundred participants were recruited through Lymphedema Clinic in Motamed Cancer Institute in Tehran, Iran, through convenience sampling and were asked to complete a self-administered survey. Data collection took place on all opening days between October 2018 and mid-March 2019. RESULTS: Most of the participants were above 40 years, have a diploma, homemaker, and the average income of most of the participants (57.2%) was low. The importance of having lymphedema information was very high for them. Most of them wanted detailed information at diagnosis of breast cancer. The preferred information of delivery methods were private sessions and social networks. CONCLUSIONS: Patients with breast cancer who have lymphedema have high needs as regards concise lymphedema information. Private sessions with physicians and social networks can provide detailed information for them.

A Systematic Review of Electronic Health (eHealth) interventions to improve physical activity in patients with breast cancer.

BACKGROUND: Electronic Health (eHealth) may have a positive effect on healthcare, such as patient education and decreasing the costs of healthcare services. Evidence suggests that such interventions can also improve physical activity (PA) of patients. This systematic review aimed to investigate the effects of PA interventions provided through eHealth on breast cancer patients. METHODS: This study was conducted through a search in electronic databases up to July 2018. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, Science Direct, and Google Scholar databases were searched without time limitation. RESULTS: In total, 2187 articles were retrieved and finally 16 articles remained. Five were pre/post and 11 were randomized trial studies. Different platforms were used in these studies including web-based, mobile-based, both web-and-mobile-based and email. In total, these articles comprise 2304 breast cancer patients with the mean age of 51 years and 50% were conducted in the USA. Four studies measured PA using wearable devices such as accelerometers and pedometers. All studies reported an increase in PA level at least in one of moderate or vigorous PA, although not all these results were significant. CONCLUSION: The results show that eHealth interventions can improve the level of PA in breast cancer patients. Although there are numerous eHealth interventions focusing on PA in cancer patients, there is still an essential need for eHealth interventions to be tailored for breast cancer patients specifically. Clinical trials with appropriate methodology, enough intervention time and follow-up are needed to make evidence-based results more generalizable. TRIAL REGISTRATION: PROSPERO CRD42018092422; https://www.crd.york.ac.uk/PROSPERO/.

The Expression of Dopamine Receptors Gene and their Potential Role in Targeting Breast Cancer Cells with Selective Agonist and Antagonist Drugs. Could it be the Novel Insight to Therapy?

BACKGROUND: Breast cancer is one of the common causes of mortality for women in Iran and other parts of the world. The substantial increasing rate of breast cancer in both developed and developing countries warns the scientists to provide more preventive steps and therapeutic measures. This study is conducted to investigate the impact of neurotransmitters (e.g., Dopamine) through their receptors and the importance of cancers via damaging immune system. It also evaluates dopamine receptors gene expression in the women with breast cancer at stages II or III and dopamine receptor D2 (DRD2) related agonist and antagonist drug effects on human breast cancer cells, including MCF-7 and SKBR-3. METHODS: The patients were categorized into two groups: 30 native patients who were diagnosed with breast cancer at stages II and III, with the mean age of 44.6 years and they were reported to have the experience of a chronic stress or unpleasant life event. The second group included 30 individuals with the mean age of 39 years as the control group. In order to determine the RNA concentration in all samples, the RNA samples were extracted and cDNA was synthesized. The MCF-7 cells and SKBR-3 cells were treated with dopamine receptors agonists and antagonists. The MTT test was conducted to identify oxidative and reductive enzymes and to specify appropriate dosage at four concentrations of dopamine and Cabergoline on MCF-7 and SKBR-3 cells. Immunofluorescence staining was done by the use of a mixed dye containing acridine orange and ethidiume bromide on account of differentiating between apoptotic and necrotic cells. Flow cytometry assay was an applied method to differentiate necrotic from apoptotic cells. RESULTS: Sixty seven and thirty three percent of the patients were related to stages II and III, respectively. About sixty three percent of the patients expressed ER, while fifty seven percent expressed PR. Thirty seven percent of the patients were identified as HER-2 positive. All types of D2-receptors were expressed in PBMC of patients with breast cancer and healthy individuals. The expression of the whole dopamine receptor subtypes (DRD2-DRD4) was carried out on MCF-7 cell line. The results of RT-PCR confirmed the expression of DRD2 on SKBR-3 cells, whereas the other types of D2- receptors did not have an expression. The remarkable differences in gene expression rates between patients and healthy individuals were revealed in the result of the Real-time PCR analysis. The over expression in DRD2 and DRD4 genes of PBMCs was observed in the patients with breast cancer at stages II and III. The great amount of apoptosis and necrosis occurred after the treatment of MCF-7 cells by Cabergoline from 25 to 100 µmolL-1 concentrations. CONCLUSION: This study revealed the features of dopamine receptors associated with apoptosis induction in breast cancer cells. Moreover, the use of D2-agonist based on dopamine receptors expression in various breast tumoral cells could be promising as a new insight of complementary therapy in breast cancer.

Application of Canonical Correlation Analysis for Detecting Risk Factors Leading to Recurrence of Breast Cancer.

BACKGROUND: Advances in treatment options of breast cancer and development of cancer research centers have necessitated the collection of many variables about breast cancer patients. Detection of important variables as predictors and outcomes among them, without applying an appropriate statistical method is a very challenging task. Because of recurrent nature of breast cancer occurring in different time intervals, there are usually more than one variable in the outcome set. For the prevention of this problem that causes multicollinearity, a statistical method named canonical correlation analysis (CCA) is a good solution. OBJECTIVES: The purpose of this study was to analyze the data related to breast cancer recurrence of Iranian females using the CCA method to determine important risk factors. PATIENTS AND METHODS: In this cross-sectional study, data of 584 female patients (mean age of 45.9 years) referred to Breast Cancer Research Center (Tehran, Iran) were analyzed anonymously. SPSS and NORM softwares (2.03) were used for data transformation, running and interpretation of CCA and replacing missing values, respectively. Data were obtained from Breast Cancer Research Center, Tehran, Iran. RESULTS: Analysis showed seven important predictors resulting in breast cancer recurrence in different time periods. Family history and loco-regional recurrence more than 5 years after diagnosis were the most important variables among predictors and outcomes sets, respectively. CONCLUSIONS: Canonical correlation analysis can be used as a useful tool for management and preparing of medical data for discovering of knowledge hidden in them.

Evaluation of factors impacting cosmetic outcome of breast conservative surgery--a study in Iran.

BACKGROUND: Breast conservative surgery (BCS) followed by radiotherapy is the standard approach in management of stage I-II breast cancer. Several factors can affect cosmetic outcomes. The aim of this study was to evaluate the cosmetic results of BCS and influencing factors in the Iranian Breast Cancer Research Center. MATERIALS AND METHODS: Patients who had undergone BCS were included. Photographs were taken of both breasts of the patients in three aspects and were evaluated by three specialists. The cosmetic scores were calculated based on a standard questionnaire. The data were analyzed using univariate and multivariate regression for relationships between cosmetic scores and clinical data. RESULTS: A total number of 103 patients were included in the study. Mean age and BMI of the patients were 46.8±8.9 and 28.1±3.9, respectively. Breast cup sizes C and D accounted for 74.7% of the study group. The mean cosmetic score obtained from three referees was 5.72+2.06, consisting of 35.9% excellent-good, 35% moderate, and 29.1% unsatisfactory results. Patient BMI, volume of the resected tissue and breast cup size (D) showed significant correlation with the cosmetic score. On multivariate regression analysis, cosmetic score and BMI (p=0.022,) as well as breast cup size (p=0.040), remained significant. CONCLUSIONS: Immediate or delayed symmetrization of the breasts is suggested during breast conservative surgery, meanwhile performing oncoplastic techniques to improve the results significantly. Also it is suggested to discuss anticipation of less satisfactory results with patients having higher BMI and large breast cup size.

Granulomatous mastitis, erythema nodosum, and oligoarthritis in a pregnant woman.

Granulomatous mastitis (GM) is an uncommon chronic inflammation of the breast and erythema nodosum (EN), is a rare extramammary manifestation of this entity. We describe a case of GM with EN and arthritis in a young pregnant woman. Review of literature showed rare similar cases.