Constantine Dimitrakakis

Background/objectives: Metaplastic breast carcinoma (MpBC) is a rare, poorly differentiated breast cancer defined by the presence of ductal carcinoma along with areas of matrix-producing, spindle-cell, sarcomatous, or squamous differentiation. It does not express hormone receptors and has a poor overall prognosis. The Hippo molecular pathway was recently related to cancer progression and adjuvant therapy resistance. The objective of this study was to evaluate the expression of Hippo pathway transducers, YAP/TAZ, CCND1, and CTGF, in MpBC and their relation to the clinicopathological characteristics of the disease. Methods: Specimens from patients with MpBC treated at our department from 2003 to 2021 were analyzed utilizing immunohistochemistry and real-time PCR. Results: Forty-four female patients (62.6 ± 14.7 years old) met inclusion criteria and were included in this study. Strong nuclear YAP/TAZ expression was found in 61.4% of patients, while the expressions of CCND1 and CTGF were 3.9% and 12.5%, respectively. Patients presenting at an advanced stage had a statistically worse prognosis compared to the ones diagnosed with stage IA disease. Adjuvant chemotherapy was associated with better overall survival, while disease recurrence was significantly associated with a worse prognosis. Conclusions: Advanced stage at diagnosis and disease recurrence were significantly associated with worse prognosis in MpBC. However, adjuvant chemotherapy significantly led to better overall survival. The Hippo pathway is frequently deregulated (nuclear YAP/TAZ in 61.4% of patients), suggesting it is a compelling novel therapeutic target for this aggressive disease.

Background: Preoperative breast MRI is widely used in surgical planning because of its high sensitivity. However, discrepancies with histopathology remain common and can affect tumor size assessment and treatment decisions. In addition, recent comparative studies have highlighted the growing role of contrast-enhanced mammography (CEM) and multiparametric MRI (mpMRI), both of which may improve specificity and accessibility compared to conventional MRI. Methods: A structured literature review was conducted in PubMed (2000–2025) according to PRISMA guidelines. Studies included if they evaluated preoperative breast MRI with histopathological correlation and reported sensitivity, specificity, or concordance outcomes. Data extraction focused on study design, patient and tumor characteristics, imaging methods, and clinical impact. Results: MRI demonstrates high sensitivity, particularly in detecting IDC and ILC. However, overestimation of tumor size remains a concern, particularly in ILC and high-grade DCIS, while underestimation is frequently observed after neoadjuvant therapy, especially in Luminal A tumors. Tumor size and stage significantly affect concordance, with advanced-stage tumors (T2–T3) showing better MRI-histopathology concordance than early-stage lesions (T0–T1). Specificity remains limited, particularly in DCIS and multifocal disease. Emerging evidence suggests that contrast-enhanced mammography (CEM) achieves comparable sensitivity with higher specificity, while multiparametric MRI (mpMRI) incorporating diffusion-weighted imaging (DWI) improves lesion characterization and prediction of treatment response. Conclusions: While MRI remains a valuable diagnostic tool for breast cancer, histopathological validation is essential to guide treatment decisions. Future research should focus on AI-enhanced imaging techniques, CEM and multiparametric MRI to improve concordance rates, reduce overdiagnosis and translate imaging advances into meaningful clinical outcomes.

Background/Objectives: Autologous fat grafting (AFT) has become a widely used technique in breast reconstruction, offering natural aesthetics, tissue integration, and patient satisfaction. However, its clinical outcomes require comparison with implant-based reconstruction (IBR), the most common method in clinical practice. While AFT provides a more natural appearance and avoids foreign body-related complications, issues such as fat resorption, procedural variability, and oncological concerns necessitate further investigation. Additionally, artificial intelligence (AI) has been increasingly integrated into breast imaging and reconstructive planning, improving diagnostic accuracy, procedural optimization, and complication prevention. This study aims to compare AFT and IBR while exploring AI’s role in enhancing breast reconstruction outcomes. Methods: A comprehensive review of clinical studies was conducted to evaluate the advantages, limitations, and oncological implications of AFT versus IBR. AI-driven applications in breast imaging and reconstructive planning were examined for their potential in predicting fat graft retention and optimizing implant selection. Data from systematic reviews and meta-analyses were incorporated to refine reconstruction strategies. Results: AFT offers superior aesthetic outcomes with better tissue integration but presents variability in fat resorption. IBR remains the preferred approach due to its predictability but carries risks of implant-related complications. AI technologies contribute to improved reconstruction planning, enhancing surgical precision and long-term patient outcomes. Conclusions: Optimized patient selection and long-term follow-up are essential for improving breast reconstruction techniques. AI-driven approaches provide valuable tools for enhancing procedural predictability and personalized treatment strategies. Future research should focus on refining AI algorithms and establishing standardized protocols for reconstructive decision-making.

Breast cancer and cardiovascular diseases (CVD) represent significant global health challenges, with CVD being the leading cause of mortality and breast cancer, showing a complex pattern of incidence and mortality. We explore the intricate interplay between these two seemingly distinct medical conditions, shedding light on their shared risk factors and potential pathophysiological connections. A specific connection between hypertension (HTN), atrial fibrillation (AF), myocardial infarction (MI), and breast cancer was evaluated. HTN is explored in detail, emphasizing the role of aging, menopause, insulin resistance, and obesity as common factors linking HTN and breast cancer. Moreover, an attempt is made to identify the potential impact of antihypertensive medications and highlight the increased risk of breast cancer among those women, with a focus on potential mechanisms. A summary of key findings underscores the need for a multisystem approach to understanding the relationship between CVD and breast cancer is also explored with a highlight for all the gaps in current research, such as the lack of clinical observational data on MI and breast cancer in humans and the need for studies specifically designed for breast cancer. This paper concludes that there should be a focus on potential clinical applications of further investigation in this field, including personalized prevention and screening strategies for women at risk. Overall, the authors attempt to provide a comprehensive overview of the intricate connections between breast cancer and cardiovascular diseases, emphasizing the importance of further research in this evolving field of cardio-oncology.

Introduction: Breast cancer affects almost 1.5 million women worldwide below the age of 45 years each year. Many of these women will be advised to undergo adjuvant chemotherapy to minimize the risk of death or recurrence of the tumor. For these patients, chemotherapy is a known cause of infertility, as it can damage primordial follicles, which can lead to early menopause or premature ovarian insufficiency. This systematic review aims to synthesize the current evidence of the most suitable treatments for fertility preservation. Methodology: This review was performed following the PRISMA guidelines. The authors conducted an extensive search from the last 15 years. Relevant studies were pursued in PubMed, Embase, and the Cochrane Library up until 31 July 2023. A total of seven eligible studies were identified. Results: From the reviewed literature, ovarian suppression with gonadotropin-releasing hormone agonists showed promising results in preserving fertility for breast cancer patients undergoing chemotherapy. Additionally, oocyte and embryo cryopreservation demonstrated successful outcomes, with embryo cryopreservation being the most effective option. Notably, the slow-freezing and vitrification methods were both effective in preserving embryos, with vitrification showing superior results in clinical-assisted reproductive technologies. Ovarian tissue cryopreservation emerged as a viable option for prepubertal girls and those unable to undergo conventional ovarian stimulation. The potential of in vitro maturation (IVM) as an alternative method presents a promising avenue for future fertility preservation research. Discussion: The most suitable treatments for fertility preservation in young patients is the temporary suppression with luteinizing hormone-releasing analogs, while the patient undergoes chemotherapy and cryopreservation. For cryopreservation, the physicians might deem it necessary to either cryopreserve ovarian tissue taken from the patient before any treatment or cryopreserve embryos/oocytes. Cryopreservation of oocytes and/or embryos is the most effective solution for fertility preservation in women of reproductive age, who have a sufficient ovarian reserve and are diagnosed with breast cancer, regardless of the histological type of the tumor. Because approximately 50% of young breast cancer patients are interested in becoming pregnant right after completion of therapy, the evolution and development of fertility preservation techniques promise to be very exciting.

Breast cancer and cardiovascular diseases (CVD) represent significant global health challenges, with CVD being the leading cause of mortality and breast cancer showing a complex pattern of incidence and mortality. We explore the intricate interplay between these two seemingly distinct medical conditions, shedding light on their shared risk factors and potential pathophysiological connections. A specific connection between hypertension (HTN), atrial fibrillation (AF), myocardial infarction (MI), and breast cancer was evaluated. HTN is explored in detail, emphasizing the role of aging, menopause, insulin resistance, and obesity as common factors linking HTN and breast cancer. Moreover, an attempt is made to identify the potential impact of antihypertensive medications and highlight the increased risk of breast cancer among those women, with a focus on potential mechanisms. A summary of key findings underscores the need for a multisystemic approach to understanding the relationship between CVD and breast cancer is also explored with a highlight for all the gaps in current research, such as the lack of clinical observational data on MI and breast cancer in humans and the need for studies specifically designed for breast cancer. This paper concludes that there should be a focus on potential clinical applications of further investigation in this field, including personalized prevention and screening strategies for women at risk. Overall, the authors attempt to provide a comprehensive overview of the intricate connections between breast cancer and cardiovascular diseases, emphasizing the importance of further research in this evolving field of cardio-oncology.

Introduction: Breast cancer affects worldwide almost 1.5 million women below the age of 45 years each year. Many of these women will be advised to undergo adjuvant chemotherapy to minimize the risk of death or recurrence of the tumor. For these patients, chemotherapy is a known cause of infertility, as it can damage primordial follicles which can lead to early menopause or premature ovarian insufficiency. This systematic review aims to synthesize the current evidence of the most suitable treatments for fertility preservation. Methodology: This review is performed following the PRISMA guidelines. The authors conducted an extensive search from the last 15 years. Relevant studies were pursued in PubMed, Embase and the Cochrane Library up until the July 31, 2023. A total of 7 eligible studies were identified. Discussion: The most suitable treatments for fertility preservation in young patients, is the temporary suppression with luteinizing hormone-releasing analogs, while the patient undergoes chemotherapy and cryopreservation. For cryopreservation, the physicians might deem it necessary to either cryopreserve ovarian tissue taken from the patient before any treatment or cryopreserve embryos/oocytes. Cryopreservation of oocytes and/or embryos is the most effective solution for fertility preservation in women of reproductive age, who have sufficient ovarian reserve and are diagnosed with breast cancer, regardless of the histological type of the tumor. Since approximately 50% of young breast cancer patients are interested in becoming pregnant right after completion of therapy, the evolution and development of fertility preservation techniques promise to be very exciting.

Metaplastic carcinoma of the breast (MpBC) is a very rare and aggressive type of breast cancer. Data focusing on MpBC are limited. The aim of this study was to describe the clinicopathological features of MpBC and evaluate the prognosis of patients with MpBC. Eligible articles about MpBC were identified by searching CASES SERIES gov and the MEDLINE bibliographic database for the period of 1 January 2010 to 1 June 2021 with the keywords metaplastic breast cancer, mammary gland cancer, neoplasm, tumor, and metaplastic carcinoma. In this study, we also report 46 cases of MpBC stemming from our hospital. Survival rates, clinical behavior, and pathological characteristics were analyzed. Data from 205 patients were included for analysis. The mean age at diagnosis was 55 (14.7) years. The TNM stage at diagnosis was mostly stage II (58.5%) and most tumors were triple negative. The median overall survival was 66 (12–118) months, and the median disease-free survival was 56.8 (11–102) months. Multivariate Cox regression analysis revealed that surgical treatment was associated with decreased risk of death (hazard ratio 0.11, 95% confidence interval 0.02–0.54, p = 0.01) while advanced TNM stage was associated with increased risk of death (hazard ratio 1.5, 95% confidence interval 1.04–2.28, p = 0.03). Our results revealed that surgical treatment and TNM stage were the only independent risk factors related to patients’ overall survival.

Background: Testosterone implants have been used for over eighty years to treat symptoms of hormone deficiency in pre and postmenopausal women. Evidence supports that androgens are breast protective. However, there is a lack of data on the long-term effect of testosterone therapy on the incidence of invasive breast cancer (IBC). This study was specifically designed to investigate the incidence of IBC in pre and postmenopausal women (presenting with symptoms of androgen deficiency) treated with subcutaneous testosterone implants or testosterone implants combined with anastrozole.Methods: The 10-year prospective cohort study was approved in March 2008 at which time recruitment was initiated. Recruitment was closed March 2013. Pre and postmenopausal women receiving at least two pellet insertions were eligible for analysis (N = 1267). Breast cancer incidence rates were reported as an unadjusted, un-weighted value of newly diagnosed cases divided by the sum of ‘person-time of observation’ for the at-risk population. Incidence rates on testosterone therapy were compared to age-specific Surveillance Epidemiology and End Results (SEER) incidence rates and historical controls. Bootstrap sampling distributions were constructed to verify comparisons and tests of significance that existed between our results and SEER data.Results: As of March 2018, a total of 11 (versus 18 expected) cases of IBC were diagnosed in patients within 240-days following their last testosterone insertion equating to an incidence rate of 165/100000 p-y, which is significantly less than the age-matched SEER expected incidence rate of 271/100000 p-y (p < 0.001) and historical controls.Conclusion: Long term therapy with subcutaneous testosterone, or testosterone combined with anastrozole, did not increase the incidence of IBC. Testosterone should be further investigated for hormone therapy and breast cancer prevention.

Introduction: Lobular breast carcinoma includes lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC). The association of LCIS with total metastatic lobular breast cancer is very rare. Presentation of case: We present a case of a totally metastatic lobular breast cancer in an asymptomatic 64-year-old postmenopausal woman, with no suspicious microcalcifications in mammography. A total hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, infracolic omentectomy and appendectomy was performed along with a quadrantectomy of the upper outer quadrant of left breast, and systematic isolateral lymphadenectomy of the left axilla. Discussion: LCIS is usually undetectable because it isn't associated with clinical abnormalities in clinical examination and is presented in mammography as microcalcifications or focal asymmetric densities. ILC histopathologic features are responsible for the high false-negative rates on mammography, leading to moderate detection sensitivity. Conclusion: Our case is a very rare condition. No 'similar' case have been described in the literature so far. Highlights: