Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer.

INTRODUCTION: Ado-trastuzumab emtansine (T-DM1) is employed in the treatment of patients with HER2-positive breast cancer. The most common side effects are fatigue, diarrhoea, anaemia, transaminase elevation and drug-induced thrombocytopenia. This report describes a patient with metastatic breast cancer who developed drug-induced lupus due to T-DM1. CASE REPORT: A 54-year-old woman was diagnosed with breast cancer in March 2018. She underwent modified radical mastectomy and axillary lymph node dissection (pT2N1aM0). Following supraclavicular lymph node metastasis in May 2018, she received 8 cycles of docetaxel, trastuzumab, and pertuzumab. In December 2020, the patient presented with axillary and intra-abdominal lymph node metastases, along with bone metastases observed on PET/CT scan. Treatment with T-DM1 and zoledronic acid was initiated. After 18 months on T-DM1, she developed drug-induced lupus. Her symptoms resolved with hydroxychloroquine treatment and discontinuation of T-DM1. DISCUSSION: Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.

STAT3 Regulates the Redox Profile in MDA-MB-231 Breast Cancer Cells.

Unbalanced redox status and constitutive STAT3 activation are related to several aspects of tumor biology and poor prognosis, including metastasis and drug resistance. The triple-negative breast cancer (TNBC) is listed as the most aggressive and exhibits the worst prognosis among the breast cancer subtypes. Although the mechanism of reactive oxygen species (ROS) generation led to STAT3 activation is described, there is no data concerning the STAT3 influence on redox homeostasis in TNBC. To address the role of STAT3 signaling in redox balance, we inhibited STAT3 in TNBC cells and investigated its impact on total ROS levels, contents of hydroperoxides, nitric oxide (NO), and total glutathione (GSH), as well as the expression levels of 3-nitrotyrosine (3NT), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nuclear factor kappa B (NF-κB)/p65. Our results indicate that ROS levels depend on the STAT3 activation, while the hydroperoxide level remained unchanged, and NO and 3NT expression increased. Furthermore, GSH levels, Nrf2, and NF-κB/p65 protein levels are decreased in the STAT3-inhibited cells. Accordingly, TNBC patients' data from TCGA demonstrated that both STAT3 mRNA levels and STAT3 signature are correlated to NF-κB/p65 and Nrf2 signatures. Our findings implicate STAT3 in controlling redox balance and regulating redox-related genes' expression in triple-negative breast cancer.

Non-Contrast-Enhanced Multiparametric MRI of the Hypoxic Tumor Microenvironment Allows Molecular Subtyping of Breast Cancer: A Pilot Study.

Tumor neoangiogenesis is an important hallmark of cancer progression, triggered by alternating selective pressures from the hypoxic tumor microenvironment. Non-invasive, non-contrast-enhanced multiparametric MRI combining blood-oxygen-level-dependent (BOLD) MRI, which depicts blood oxygen saturation, and intravoxel-incoherent-motion (IVIM) MRI, which captures intravascular and extravascular diffusion, can provide insights into tumor oxygenation and neovascularization simultaneously. Our objective was to identify imaging markers that can predict hypoxia-induced angiogenesis and to validate our findings using multiplexed immunohistochemical analyses. We present an in vivo study involving 36 female athymic nude mice inoculated with luminal A, Her2+, and triple-negative breast cancer cells. We used a high-field 9.4-tesla MRI system for imaging and subsequently analyzed the tumors using multiplex immunohistochemistry for CD-31, PDGFR-ß, and Hif1-α. We found that the hyperoxic-BOLD-MRI-derived parameter ΔR2* discriminated luminal A from Her2+ and triple-negative breast cancers, while the IVIM-derived parameter fIVIM discriminated luminal A and Her2+ from triple-negative breast cancers. A comprehensive analysis using principal-component analysis of both multiparametric MRI- and mpIHC-derived data highlighted the differences between triple-negative and luminal A breast cancers. We conclude that multiparametric MRI combining hyperoxic BOLD MRI and IVIM MRI, without the need for contrast agents, offers promising non-invasive markers for evaluating hypoxia-induced angiogenesis.

Navigating norms and expectations: the influence of culture on Latino couples and their interpersonal communication and coping post-breast cancer diagnosis.

OBJECTIVES: Cultural norms shape expectations, care, and communication. Effective interpersonal communication is a prominent predictor of patient-partner cancer management, improving the overall quality of life for the dyad by increasing their ability to cope with cancer. However, couples-based cancer interventions often do not consider cultural factors. Additionally, although Latinas have a high incidence of breast cancer, few studies focus on Latino couples and the influence of culture in cancer care interventions. This study focuses on understanding how Latino culture's norms and expectations influence how couples communicate and cope post-breast cancer diagnosis. DESIGN: This study conducted interviews and focus groups with a purposive sample of Spanish-speaking Latina breast cancer survivors (N = 21) and intimate partners (N = 5). In the focus group and interviews, participants were asked about the influence cancer had on their relationship, with specific questions focusing on communication within the dyad. The study team used CARV: Community-Engaged Adaptation with Rapid Analysis and Visualization framework to identify cultural considerations and recurring themes. RESULTS: The cross-cutting cultural considerations and themes found were: the negative influence of gendered and social norms on managing emotions and coping; the silent struggle with physical intimacy; and the inability to discuss the topic - or even say the word 'cancer.' CONCLUSION: Understanding the role of Latino culture in how couples cope with and communicate about cancer post-diagnosis is essential. This understanding will help strengthen the dyad by assisting with positive interpersonal support, which contributes to a better quality of life. These findings will also help providers assist dyads in navigating the cancer diagnosis and journey, helping to lessen the interpersonal stress and tensions that can occur after diagnosis.

Breast Cancer Prognosis: A Study on Mortality Indicators.

Background: The prognosis of breast cancer patients is critical for tailored treatment options. While previous observational studies have identified various prognostic markers, a consensus in their clinical application is lacking. This single-center retrospective study aimed to validate the most frequent risk factors associated with increased mortality in breast cancer patients. Methods: Our study spanned an 8-year interval (2014-2020) and included 213 female patients with stage IIA-IIIB breast cancer. Key variables such as age, disease stage, and type of treatment were analyzed in relation to one-year survival as the primary outcome measure. Results: Elevated preoperative levels of tumor markers ACE and CA 15-3, larger tumor size, and advanced lymph nodal invasion were significantly associated with increased mortality. Immunohistochemistry indicated that the presence of Estrogen and Progesterone Receptors (ER and PR) were protective factors, whereas Human Epidermal Growth Factor Receptor 2 (HER2) was a negative prognostic indicator. Among molecular subtypes, Luminal A demonstrated protective effects, whereas HER2-positive and Triple-negative subtypes were identified as risk factors. Conclusion: This study confirms the significant role of tumor size, lymph node stage, and specific molecular markers in predicting breast cancer mortality. These findings contribute to a nuanced understanding of disease prognosis and offer crucial insights for clinicians in managing treatment plans.

Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma Using Image-Guided Clip Placement.

Background The present study aims to evaluate the response of locally advanced breast carcinoma (LABC) to neoadjuvant chemotherapy (NACT) using image-guided clip placement based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Methods Thirty-four patients with LABC were included in the study. Consent for three-dimensional titanium clip placement (400/300/200 mm Liga clips) under local anesthesia with USG guidance was obtained. Serial sonographic/X-ray evaluations of tumor bed size were conducted before every cycle of NACT. All data were recorded in millimeters of concentric tumor regression/non-regression. Tumor regression in a concentric or Swiss cheese pattern and non-responders were evaluated. Assessment of the response to NACT was performed using RECIST criteria, dividing it into four categories. Tumor response was confirmed with computerized tomography (CT) conducted before and after the completion of NACT. Patients underwent surgical management, mostly modified radical mastectomy (MRM), as they had locally advanced breast carcinoma. Following MRM, the clips in the specimen guided the original site of the tumor for histopathological evaluation and response to chemotherapy. Results Tumor response was classified into four types: complete response (CR), partial response (PR), progressive disease (PD), and stable disease. RECIST 1.1 criteria were elaborated and defined. Data for all patients were entered into an Excel sheet (Microsoft Corporation, Redmond, Washington) to prepare a master chart, and the following observations were made and analyzed using SPSS software. The duration of chemotherapy for the study population ranged from 32 to 206 days, with a mean (±SD) of 111.82 (± 52.64) days and a median (IQR) of 81 (63, 158) days. The mean period between clip insertion and completion of NACT was 111.82 days. The baseline sum diameters and post-NACT diameters of the tumors were 70.50 (±13.60) mm before NACT and 17.75 (±17.20) mm after NACT. Hence, the mean size of the lump was statistically significantly lower after NACT, with a mean difference of 52.75 (p<0.05). The mean rate of reduction in tumor diameter was found to be 74.32% (±23.44%) based on RECIST 1.1 criteria. Pathological response was observed in all patients except for 8.8% of the patients. Clinical complete response was seen in 35.29% of patients, and partial response was observed in 52.92% of the patients based on RECIST 1.1 criteria. The study thus demonstrates the effectiveness of NACT in LABC, with a mean reduction in tumor diameter of 74.32%, assessed with the help of RECIST 1.1 criteria. Conclusion NACT for patients with LABC has shown a significant reduction in tumor size. NACT should be the initial mode of management for patients with LABC. RECIST 1.1 criteria are effective and can be used to assess tumor response to NACT. This has aided in the stratification of the response of NACT for further management through systemic therapy (adjuvant chemotherapy) after the surgical excision of the tumor.

The Effect of Education on Knowledge Regarding Breast Cancer Related Lymphedema Risk Reduction and Prevention Among Nursing Personnel.

Aim The development of lymphedema post-breast-cancer surgery has been identified as a significant burden worldwide, with nurses at the forefront of prevention and risk reduction practices. Prevention is of crucial importance to avoid lymphedema formation and its complications. This study aims to assess the knowledge gained through an educational session regarding risk reduction and prevention of breast cancer-related lymphedema (BCRL) among nursing professionals and compare the pre-test and post-test knowledge. Methods and material The research approach was quantitative in nature, and the design adopted was a pre-experimental, one-group pre-test post-test design. The study was conducted in a 400-bed multispecialty teaching hospital in Bangalore, Karnataka. After obtaining formal permission from the authorities, the participants were approached and informed about the purpose of the study. Eighty-four staff nurses working with breast cancer-related lymphedema (BCRL) patients participated in the study. The data for the study was collected using a validated questionnaire based on the National Lymphedema Network's (NLN) breast cancer-related lymphedema (BCRL) risk reduction and preventive guidelines. The questionnaire consisted of two sections. Section A consisted of the staff nurses' demographic data, and Section B consisted of questions on risk reduction and prevention of lymphedema. The pre-test was conducted, followed by a structured teaching session on risk reduction and prevention of lymphedema among 84 staff nurses working with BCRL patients. After the teaching session, the post-test was conducted. Results Descriptive and inferential statistics were used for analysis in this study. The t-test determined the statistical significance using the software SPSS (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). The result showed that the mean knowledge score was 4.286 with SD 0.97 in the pre-test, which increased to 4.452 with SD 1.511 with a significant p-value (<0.001).  Conclusion According to the study's findings, nurses must get standardized lymphedema training in order to prevent lymphedema from developing in patients having breast cancer surgery. The study's outcome has implications on the focus areas for nurses in the context of the team's adoption and dissemination of breast cancer-related lymphedema preventive measures. Key messages of this study are - 1) BCRL is an irreversible, progressive complication with no cure if not diagnosed early. 2) Poor knowledge of lymphedema prevention among nurses leads to frustration for BCRL patients. 3) Risk reduction and prevention education enable the patient to reduce BCRL complications, minimize the severity of the condition, and improve the quality of life. 4) Pre-habilitation - patient education on early diagnosis and risk reduction/prevention of BCRL reduces the cost, time, and energy for the patient and health care delivery system.

The mutual determination of self-efficacy to cope with cancer and cancer-related coping over time: a prospective study in women with breast cancer.

OBJECTIVE: The aim of this study was to examine the longitudinal impact of self-efficacy to cope with cancer on the cancer-related coping reactions of breast cancer patients and vice versa. DESIGN AND MAIN OUTCOMES MEASURES: Data from the BOUNCE Project (https://www.bounce-project.eu/) were used to address the hypotheses. Participants (N = 403) were enrolled in the study a few weeks after surgery or biopsy. Coping self-efficacy was assessed at baseline and six months later (M6). Cancer-related coping was assessed three (M3) and nine months (M9) after baseline. The analyses were performed using structural equation modeling with Mplus 8.6. RESULTS: Baseline coping self-efficacy predicted all M3 coping reactions, while M6 coping self-efficacy also predicted changes in all but one M9 coping reaction. Moreover, one of the M3 coping reactions, that is, hopelessness/helplessness, predicted the changes in M6 coping self-efficacy. The relation between coping self-efficacy and one coping reaction (i.e. cognitive avoidance) was rather weak. Stability paths from M3 to M9 coping reactions were moderate to high. CONCLUSION: The relationship between self-efficacy to cope with cancer and cancer-related coping is complex. New theoretical models are needed to more accurately describe the diverse aspects of this association.

Response to a novel, weight self-awareness plan used in a multi-component lifestyle intervention programme to reduce breast cancer risk factors in older women-Secondary analysis from the ActWELL trial.

BACKGROUND: The ActWELL randomised controlled trial assessed the effectiveness of a weight management programme delivered by volunteer lifestyle coaches (LCs) in women attending breast clinics. The intervention focused on caloric intake and physical activity, utilising behavioural change techniques including a weight awareness plan (WAP). The current work is a secondary analysis of the ActWELL data and aims to examine the response to the weight self-awareness plan (used as part of the intervention programme). METHODS: The LCs invited participants (n = 279) to undertake an implementation intention discussion to formulate a self-weighing (SW) plan. Bodyweight scales were offered, and recording books provided. The physical activity component of the intervention focused on a walking plan assessed by accelerometers. The LCs contacted participants by telephone monthly and provided personalised feedback. Mann-Whitney tests and chi-squared analysis were used to examine the effect of SW on weight change. A qualitative evaluation utilising semi-structured interviews was also undertaken. RESULTS: Most participants (96.4%) agreed to set a weekly SW goal and 76 (27%) requested scales. At 12 months, 226 (81%) returned for follow up. The median (interquartile range) weight change for those who self- reported at least one weight (n = 211) was -2.3 kg (-5.0 to 0.0) compared to -1.2 kg (-5.0 to 0.03) in those who did not (n = 14). Participants who reported weights on more than eight occasions (39%) were significantly more likely (p = 0.012) to achieve 5% weight loss compared to those who weighed less often. Low numbers of accelerometers were returned that did not allow for significance testing. Qualitative data (n = 24) indicated that many participants found the WAP helpful and motivating. CONCLUSIONS: Greater adherence to the WAP initiated by volunteer coaches is associated with achieving 5% weight loss.

The Impact of Screening and Surgery on Life Expectancy in Breast Cancer - A Mathematical Model Case Study in the European Union.

Background: In the last 20 years in European Union states, the life expectancy did not change much. In the period 2012-2021 the average life expectancy remained almost constant at 82 years. Breast cancer represents the main cause of death by cancer in women The purpose of this research is to identify o identify and measure the influence of some medical interventions and procedures related to breast cancer on life expectancy. In our article, the target group is the feminine population from 27 EU countries. Methodology: For the analysis several indicators provided by Eurostat were considered: life expectancy for female population as a dependent variable and breast cancer screenings, surgical operations and procedures performed in hospitals (partial and total excision) were used as independent variables. The research used a mathematical model (regression panel) for 27 EU countries, for a 10 year period, to evaluate the impact of each independent variable on the life expectancy in EU as a whole. Results: From a statistical point of view, screening has a significant effect on life expectancy. On the other hand, surgical interventions have a role in the overall medical process and positively influence life expectancy. The panel model has shown that partial interventions contribute less than screening procedures to increase life expectancy. Conclusion: The development of mathematical models in health care is useful in the process of improving health care quality. In our days, the measurement and quantification of some medical methods is particularly difficult due to so many variables and observations. In these difficult circumstances, the mathematical models could bring some clarifications and structure.

Charcoal Localization for Surgical Resection of Non-Palpable Suspicious Breast Lesions.

Background: Breast cancer is more frequently detected as radiographic non-palpable lesions with the increased utilization of national screening programs. Moreover, the sizes of tumors detected have decreased in recent years, increasing the need for accurate image-directed localization for surgical excision in a significant portion of cases. Although Wire guided localization has been the most commonly used method for many years, inherent problems remain and limit its practice. Radio-guided occult lesion localization (ROLL) is currently the standard method of localization, however, it is unavailable in most low resource communities. This encourages us to use charcoal localization which is a simple and cheap method of surgical localization of non-palpable suspicious breast lesions. Methods: This prospective study included 34 patients who presented with non-palpable suspicious breast lesions (BIRADS 4 or 5). All patients were injected 1-3 ml of sterilized 3% aqueous suspension of charcoal granules under the guidance of ultrasound at the superficial border of the suspicious lesion and the track between the lesion and the needle entry point in the skin which will occur at the future incision. This method was carried out in most patients one day before the operation, however, two patients underwent surgical excision after 6 days of localization without any interruption. Results: Thirty-four patients had 36 Lesions. The median age was 43 years. The mean diameter of lesions was 10.9 mm. Of 36 lesions; the BIRADS as follow10 (4a), 12 (4b), 8 (4c), and 6 (5). Postoperative investigations revealed 16 malignant lesions and 20 benign lesions. All 20 benign lesions were managed by wide local excision; All 14 BIRADS 4a lesions were proved to be benign. Sixteen malignant lesions were managed as the following; nine patients had breast-conserving surgery, five patients had modified radical mastectomy (three patients had past history of modified radical mastectomy, one patient had Multicentric IDC and one patient had infiltrated safety margins on conservation), and one patient had Nipple Sparing Mastectomy with immediate breast reconstruction by Latissimus Dorsi Flap. There was no reaction or infection reported in our study. Conclusion: Charcoal localization has many advantages and helps surgical localization.

Sentimag® Technique for Sentinel Lymph Node Biopsy in Breast Cancer Patients: Evaluation of Effectiveness, Feasibility and Challenges.

AIM: The gold standard technique of Sentinel Lymph Node Biopsy (SLNB) is the dual technique of radioactive tracer with blue dye. The aim of this study was to assess the node identification rate and feasibility in terms of ease of use of this technique for SLNB in breast cancer patients. Methods: Retrospectively collected data of 143 breast cancer patients with clinically and radiologically negative axilla were analysed. SLNB procedures were performed using the superparamagnetic iron oxide (SPIO) nanoparticles. Sentinel lymph nodes were identified using the Sentimag magnetometer and visual aid. Results: A total of 146 SLNB procedures were undertaken on 143 patients. Lymph node identification rate (IR) was 97.9%. Thirty seven patients (25.3%) were detected with cancer in their lymph nodes, 19% had at least one macrometastasis, 6% at least one micrometastasis and 1% had ITCs. The mean average lymph node retrieval was 2.2 nodes per procedure. Mild brownish discolouration was noted around the injection site. No allergic reaction or side effect of Sienna+î tracer / Magtraceî was reported. CONCLUSION: The new magnetic detection method of sentinel lymph nodes (Sentimag) is effective, feasible and comparable to the gold standard technique of sentinel lymph node biopsy in patients with breast cancer.

Prospective Evaluation of Response Outcomes of Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

Introduction Breast cancer is a global health problem, with more than 1 million cases of breast cancer diagnosed worldwide each year, and is the most common cancer among Indian women. Locally advanced breast cancer (LABC) accounts for 10-20% in the Western world while in India it accounts for 40-50% of all cases. Locally advanced breast cancer is a very common clinical scenario especially in developing countries possibly due to various factors like lack of education and poor socioeconomic status. Women with the locally advanced disease require multimodality therapy and coordinated treatment planning. This study aimed to prospectively study the clinical profile of the LABC patients presenting to our institute and also to evaluate the role of neoadjuvant chemotherapy in downstaging the tumor. Materials and Methods Seventy patients diagnosed with locally advanced breast cancer were enrolled in this prospective study. After thorough preoperative workup, patients were either taken up for upfront surgery or neoadjuvant chemotherapy followed by surgery. Post chemotherapy clinical response of the tumor and postoperative histopathological evaluation of the specimen was performed. Results The mean age of the patients in our study was 45 years. Out of 70 patients, 18 underwent upfront surgery, and 52 received neoadjuvant chemotherapy followed by surgery. A total of 44 cases had a clinical response to chemotherapy with 9% having a complete response. The incidence of margin positivity in the postoperative specimen was significantly lower in patients who received neoadjuvant chemotherapy. Conclusion  Locally advanced breast cancer accounted for the predominant number of breast cancer patients mostly females in their middle age. Neoadjuvant chemotherapy was effective in downstaging the tumor in the majority of cases, although complete clinical response was lower in our study. The rate of margin positivity in mastectomy specimens can also be reduced if chemotherapy is considered prior to mastectomy.

Never-smokers and the fraction of breast cancer attributable to second-hand smoke from parents during childhood: the Norwegian Women and Cancer Study 1991-2018.

BACKGROUND: Second-hand smoke (SHS) is not an established risk factor for breast cancer. We examined exposure to SHS from parents during childhood and breast-cancer risk overall and by oestrogen- and progesterone-receptor status in the Norwegian Women and Cancer Study. Furthermore, we utilized our nationally representative prospective cohort study to estimate the fraction of breast cancer attributable to parental SHS during childhood. METHODS: We followed 45 923 never-smoking women, aged 34-70 years, who completed a baseline questionnaire between 1991 and 2007 through linkages to national registries through December 2018. We used Cox proportional-hazards models to estimate age-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). We estimated the attributable and the population attributable fraction of breast cancer with 95% CIs. RESULTS: During a mean follow-up of 19.8 (6.8) years, 2185 women developed invasive breast cancer, confirmed by histology. Women exposed to SHS from parents during childhood had an 11% higher (95% CI: 1.02-1.22) risk of breast cancer compared with those who were not. No difference was found for oestrogen (Pheterogeneity = 0.31) and progesterone (Pheterogeneity = 0.95) receptor status. For women exposed, the attributable fraction was 10.3% (95% CI: 1.8-18.0), whereas the population attributable fraction of breast cancer was 7.0% (95% CI: 1.0-13.0). CONCLUSIONS: Our results suggest that 1 in 14 breast-cancer cases could have been avoided in the absence of SHS exposure from parents during childhood in a population of never-smoking women. The cancer burden attributable to SHS may be underestimated.

The Implication of microRNAs as non-invasive biomarkers in 179 Egyptian breast cancer female patients.

Background: MicroRNAs (miRs) are small (19-25 nucleotides), non-protein coding RNAs that regulate gene expression, and thus play essential roles in cell cycle progression. The evidence has demonstrated that the expression of several miRs is dysregulated in human cancer. Methods: The study includes 179 female patients and 58 healthy women Patients were identified as luminal A, B, Her-2/neu, and basal-like, as well as classified into I, II, and III stages. Analysis of the expression fold change of miR-21 and miR-34a with molecular markers, including the oncogene Bcl-2 (B-cell lymphoma 2) and the tumor suppressor genes BRCA1 (breast cancer susceptibility gene 1), BRCA2 (breast cancer susceptibility gene 2), and the tumor suppressor protein p53, was carried out for all patients, pre- and post-chemotherapy, and for all healthy women. Results: At diagnosis (pre-chemotherapy), miR-21 was up-regulated (p < 0.001), while miR-34a was down-regulated (p < 0.001). Post-chemotherapy, the expression of miR-21 decreased significantly (p < 0.001), while the expression of miR-34a increased significantly (p < 0.001). Conclusion: miR-21 and miR-34a may be helpful to non-invasive biomarkers to evaluate the response of breast cancer to chemotherapy.

Autologous fat grafting for breast reconstruction after breast cancer: a 12-year experience.

PURPOSE: The aim of our study was to examine the surgical outcome and complications (efficiency) as well as the incidence of locoregional recurrence and distant metastases (oncological safety) in patients who underwent autologous fat grafting (AFG) of the breast following breast cancer surgery. METHODS: In our monocentric cohort study, retrospective and prospective data were collected from all consecutive patients who underwent AFG after breast cancer between 2008 and 2020; a total of 93 patients met the inclusion criteria. RESULTS: Our long-term results showed no increase in tumor recurrence and distant metastases in the studied collective when compared to the available literature. We observed 1 local recurrence (1.1%), 2 distant metastases (2.2%), and 1 tumor-related death (1.1%). There was a high degree of patient satisfaction; 67.12% of patients reported adequate satisfaction with autologous fat grafting. CONCLUSION: Currently, to our knowledge, this is the study with the longest follow-up time (mean 6.7 years after AFG and 11.5 years after tumor resection). The results of our clinical study will contribute to improve evidence in the broad field of AFG, adipose stem cell and tumor research. Consistent with our study, the literature review shows a clear tendency of clinical trial results with a low incidence rate of tumor recurrence and metastasis following the use of AFG. AFG seems to be a safe procedure also after breast cancer treatment.

Reverse Abdominoplasty: A Novel Practical Approach Using Oncoplastic Reconstruction in Managing Major Chest Wall Defects for Patients With Loco-Regional Recurrence Following Breast Cancer Surgery.

Background Loco-regional recurrence of breast cancer in patients with large chest wall defects following mastectomy poses significant oncoplastic challenges. Reverse abdominoplasty is most commonly used to treat patients with excess upper abdominal soft tissue and laxity following massive weight loss. Widely employed as a technique for aesthetic contouring of the upper anterior trunk, as well as in augmentation mammoplasty, its use to date for reconstructive purposes is mainly limited to burns and large site surgical tumour ablation. Method Here we review our experience of using reverse abdominoplasty as a novel approach to filling major anterior chest wall defects in patients with cutaneous manifestations of loco-regional or distant recurrence of breast cancer. Results Seven patients with metastatic breast cancer underwent reverse abdominoplasty for disease recurrence following mastectomy, with good patient-reported outcomes, and minimal surgical complications. Moreover, follow-up data in the patients surveyed also showed minimal to no limitations on their activities of daily living following the procedure. Conclusion Here we demonstrate the successful employment of reverse abdominoplasty - a technique not usually reserved in breast oncoplastic surgery - to treat fungating breast lesions and/or other manifestations of loco-regional recurrence in metastatic breast cancer. This may herald a paradigm shift in the way surgeons approach breast cancer recurrence in patients with pre-existing major chest wall defects.

The oncogenic kinase NEK2 regulates an RBFOX2-dependent pro-mesenchymal splicing program in triple-negative breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most heterogeneous and malignant subtype of breast cancer (BC). TNBC is defined by the absence of expression of estrogen, progesterone and HER2 receptors and lacks efficacious targeted therapies. NEK2 is an oncogenic kinase that is significantly upregulated in TNBC, thereby representing a promising therapeutic target. NEK2 localizes in the nucleus and promotes oncogenic splice variants in different cancer cells. Notably, alternative splicing (AS) dysregulation has recently emerged as a featuring trait of TNBC that contributes to its aggressive phenotype. METHODS: To investigate whether NEK2 modulates TNBC transcriptome we performed RNA-sequencing analyses in a representative TNBC cell line (MDA-MB-231) and results were validated in multiple TNBC cell lines. Bioinformatics and functional analyses were carried out to elucidate the mechanism of splicing regulation by NEK2. Data from The Cancer Genome Atlas were mined to evaluate the potential of NEK2-sensitive exons as markers to identify the TNBC subtype and to assess their prognostic value. RESULTS: Transcriptome analysis revealed a widespread impact of NEK2 on the transcriptome of TNBC cells, with 1830 AS events that are susceptible to its expression. NEK2 regulates the inclusion of cassette exons in splice variants that discriminate TNBC from other BC and that correlate with poor prognosis, suggesting that this kinase contributes to the TNBC-specific splicing program. NEK2 elicits its effects by modulating the expression of the splicing factor RBFOX2, a well-known regulator of epithelial to mesenchymal transition (EMT). Accordingly, NEK2 splicing-regulated genes are enriched in functional terms related to cell adhesion and contractile cytoskeleton and NEK2 depletion in mesenchymal TNBC cells induces phenotypic and molecular traits typical of epithelial cells. Remarkably, depletion of select NEK2-sensitive splice-variants that are prognostic in TNBC patients is sufficient to interfere with TNBC cell morphology and motility, suggesting that NEK2 orchestrates a pro-mesenchymal splicing program that modulates migratory and invasive properties of TNBC cells. CONCLUSIONS: Our study uncovers an extensive splicing program modulated by NEK2 involving splice variants that confer an invasive phenotype to TNBCs and that might represent, together with NEK2 itself, valuable therapeutic targets for this disease.

The Natural History of Ductal Carcinoma In Situ of the Breast - An Overview.

Ductal carcinoma in situ (DCIS) of the breast is a heterogenous disease and its natural history cannot be directly observed as surgical removal is part of the current standard of care. Studies of incompletely excised breast lesions that were considered benign after biopsy, but at review years later were recognized as DCIS, offers some insight to the natural history of DCIS. Summarizing these retrospective data; 14-53 % of the cases retrospectively diagnosed as DCIS progressed to invasive breast cancer (IBC) during follow-up. While observations from retrospective re-evaluation of biopsies and autopsies adds epidemiological input for understanding the natural history of DCIS, the most important results are still awaited from the ongoing prospective studies on active surveillance of DCIS. These studies with collected data on patient characteristics, life-style and environmental factors, as well as tumor and stromal metabolomics and genomics, will probably further elucidate the natural history of DCIS and how the disease should be treated in the future.

Misinformation About Breast Cancer Screening and the Possible Unanticipated Importance of Detecting Ductal Carcinoma In Situ.

For decades there has been an unrelenting effort to limit access to breast cancer screening based on scientifically unsupportable arguments. As each argument has been raised against screening it has been refuted by science. These issues are summarized below. Within the larger debate have been legitimate concerns about the importance and treatment of a range of lesions classified as Ductal Carcinoma In Situ (DCIS). These are almost certainly precursor lesions to invasive breast cancer. What has been lost in the discussions is the fact that, in the U.S., the incidence of invasive breast cancer had been increasing steadily since 1940, at 1-1.3% per year. However, since the start of screening the incidence of invasive breast cancer is lower than the extrapolated expectation. It is likely that the removal of DCIS, due to mammographic screening, has resulted in fewer subsequent invasive cancers.