Transcription factor STAT4 counteracts radiotherapy resistance in breast carcinoma cells by activating the MALAT1/miR-21-5p/THRB regulatory network.

Considering the limited research and the prevailing evidence of STAT4's tumor-suppressing role in breast carcinoma (BC) or in breast radiotherapy (RT) sensitivity requires more in-depth exploration. Our study delves into how STAT4, a transcription factor, affects BC cell resistance to radiotherapy by regulating the MALAT1/miR-21-5p/THRB axis. Bioinformatics analysis was performed to predict the regulatory mechanisms associated with STAT4 in BC. Subsequently, we identified the expression profiles of STAT4, MALAT1, miR-21-5p, and THRB in various tissues and cell lines, exploring their interactions and impact on RT resistance in BC cells. Moreover, animal models were established with X-ray irradiation for further validation. We discovered that STAT4, which is found to be minimally expressed in breast carcinoma (BC) tissues and cell lines, has been associated with a poorer prognosis. In vitro cellular assays indicated that STAT4 could mitigate radiotherapy resistance in BC cells by transcriptional activation of MALAT1. Additionally, MALAT1 up-regulated THRB expression by adsorbing miR-21-5p. As demonstrated in vitro and in vivo, overexpressing STAT4 inhibited miR-21-5p and enhanced THRB levels through transcriptional activation of MALAT1, which ultimately contributes to the reversal of radiotherapy resistance in BC cells and the suppression of tumor formation in nude mice. Collectively, STAT4 could inhibit miR-21-5p and up-regulate THRB expression through transcriptional activation of MALAT1, thereby mitigating BC cell resistance to radiotherapy and ultimately preventing BC development and progression.

Circ_0072088 promotes breast carcinoma progression via modulating miR-607/RNF2 axis.

OBJECTIVES: To explore how the circular non-coding RNA circ_0072088 influences the progression of breast carcinoma (BC) by affecting cell behavior. METHODS: We measured the levels of circ_0072088, microRNA-607 (miR-607), and ring finger protein 2 (RNF2) mRNA levels in BC tissues and cell lines using quantitative real-time PCR. We also conducted cell counting kit-8 (CCK-8), BrdU incorporation, and flow cytometry assays to assess cell viability, cell cycle, and apoptosis, respectively. RESULTS: We observed increased levels of circ_0072088 and RNF2, and decreased levels of miR-607 in BC tissues. Overexpressing circ_0072088 promoted BC cell proliferation and cell cycle progression while inhibiting apoptosis. Conversely, silencing circ_0072088 had the opposite effects. Our data suggest that circ_0072088 directly targets and downregulates miR-607, which in turn upregulates RNF2, a target of miR-607. Moreover, miR-607 overexpression could mitigate the pro-proliferative and anti-apoptotic effects of circ_0072088 on BC cells. CONCLUSION: Circ_0072088 drives BC progression by downregulating miR-607 and upregulating RNF2, thereby promoting cell proliferation and cycle progression while reducing apoptosis.

Expression of p16 protein in breast cancer.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

Diagnostic utility and sensitivities of matrix Gla protein (MGP), TRPS1 and GATA3 in breast cancer: focusing on metastatic breast cancer, invasive breast carcinoma with special features, and salivary gland-type tumours.

Matrix Gla protein (MGP) and trichorhinophalangeal syndrome type 1 (TRPS1) have recently emerged as novel breast-specific immunohistochemical (IHC) markers, particularly for triple-negative breast cancer (TNBC) and metaplastic carcinoma. The present study aimed to validate and compare the expression of MGP, TRPS1 and GATA binding protein 3 (GATA3) in metastatic breast carcinoma (MBC), invasive breast carcinoma (IBC) with special features, including special types of invasive breast carcinoma (IBC-STs) and invasive breast carcinoma of no special type with unique features, and mammary and non-mammary salivary gland-type tumours (SGTs). Among all enrolled cases, MGP, TRPS1 and GATA3 had comparable high positivity for ER/PR-positive (p=0.148) and HER2-positive (p=0.310) breast carcinoma (BC), while GATA3 positivity was significantly lower in TNBC (p<0.001). Similarly, the positive rates of MGP and TRPS1 in MBCs (99.4%), were higher than in GATA3 (90.9%, p<0.001). Among the IBC-STs, 98.4% of invasive lobular carcinomas (ILCs) were positive for all three markers. Among neuroendocrine tumours (NTs), all cases were positive for TRPS1 and GATA3, while MGP positivity was relatively low (81.8%, p=0.313). In the neuroendocrine carcinoma (NC) subgroup, all cases were positive for GATA3 and MGP, while one case was negative for TRPS1. All carcinomas with apocrine differentiation (APOs) were positive for GATA3 and MGP, while only 60% of the cases demonstrated moderate staining for TRPS1. Among mammary SGTs, MGP demonstrated the highest positivity (100%), followed by TRPS1 (96.0%) and GATA3 (72.0%). Positive staining for these markers was also frequently observed in non-mammary SGTs. Our findings further validate the high sensitivity of MGP and TRPS1 in MBCs, IBC-STs, and breast SGTs. However, none of these markers are capable of distinguishing between mammary and non-mammary SGTs.

Integration of Pathological Criteria and Immunohistochemical Evaluation for Invasive Lobular Carcinoma Diagnosis: Recommendations From the European Lobular Breast Cancer Consortium.

Invasive lobular carcinoma (ILC) is the second most frequent type of breast cancer (BC) and its peculiar morphology is mainly driven by inactivation of CDH1, the gene coding for E-cadherin cell adhesion protein. ILC-specific therapeutic and disease-monitoring approaches are gaining momentum in the clinic, increasing the importance of accurate ILC diagnosis. Several essential and desirable morphologic diagnostic criteria are currently defined by the World Health Organization, the routine use of immunohistochemistry (IHC) for E-cadherin is not recommended. Disagreement in the diagnosis of ILC has been repeatedly reported, but interpathologist agreement increases with the use of E-cadherin IHC. In this study, we aimed to harmonize the pathological diagnosis of ILC by comparing 5 commonly used E-cadherin antibody clones (NCH-38, EP700Y, Clone 36, NCL-L-E-cad [Clone 36B5], and ECH-6). We determined their biochemical specificity for the E-cadherin protein and IHC staining performance according to type and location of mutation on the CDH1 gene. Western blot analysis on mouse cell lines with conditional E-cadherin expression revealed a reduced specificity of EP700Y and NCL-L-E-cad for E-cadherin, with cross-reactivity of Clone 36 to P-cadherin. The use of IHC improved interpathologist agreement for ILC, lobular carcinoma in situ, and atypical lobular hyperplasia. The E-cadherin IHC staining pattern was associated with variant allele frequency and likelihood of nonsense-mediated RNA decay but not with the type or position of CDH1 mutations. Based on these results, we recommend the indication for E-cadherin staining, choice of antibodies, and their interpretation to standardize ILC diagnosis in current pathology practice.

Translational Aspects in Metaplastic Breast Carcinoma.

Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are classified as predominantly triple-negative breast carcinomas (TNBCs; HR-negative/HER2-negative). Histologically, MpBC is classified into six subtypes. Two of these are considered low-grade and the others are high-grade. MpBCs seem to be more aggressive, less responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than other TNBCs. MpBCs have a lower survival rate than expected for TNBCs. MpBC treatment represents a challenge, leading to a thorough exploration of the tumor immune microenvironment, which has recently opened the possibility of new therapeutic strategies. The epithelial-mesenchymal transition in MpBC is characterized by the loss of intercellular adhesion, downregulation of epithelial markers, underexpression of genes with biological epithelial functions, upregulation of mesenchymal markers, overexpression of genes with biological mesenchymal functions, acquisition of fibroblast-like (spindle) morphology, cytoskeleton reorganization, increased motility, invasiveness, and metastatic capabilities. This article reviews and summarizes the current knowledge and translational aspects of MpBC.

A Rare and Intriguing Case Report of Metaplastic Breast Carcinoma.

Metaplastic breast carcinoma (MBC) is a rare and aggressive subtype of breast cancer characterized by the presence of both epithelial and mesenchymal components within the tumor. Its clinical and radiological appearance is comparable to other types of breast cancer, but it grows rapidly. The diagnosis of metaplastic carcinoma is largely based on the epithelial origin of the cells confirmed by immunohistochemistry (IHC). Compared to invasive ductal carcinoma, metaplastic carcinoma has a worse overall survival rate. Any patient with a rapidly growing breast mass should be assessed with suspicion of sarcomatoid or metaplastic malignant neoplasm. We report this case due to its rarity and the complex nature of the disease.

Efficacy of Peripheral Nerve Stimulator Guided Pectoral Nerve Block-1 and Serratus Anterior Plane Block for Post-operative Analgesia in Modified Radical Mastectomy: A Randomized Controlled Study.

BACKGROUND: Breast carcinoma is one of the most common cancers in present-day women worldwide, hence surgical intervention for the same is inevitable. General anesthesia being the preferred technique, the selection of appropriate postoperative pain management is a major concern in which superficial fascial plane chest wall blocks play a pivotal role. We aimed to prove the efficacy of peripheral nerve stimulator-guided pectoral nerve-1 (PEC 1) block and serratus anterior plane (SAP) block for postoperative analgesia in modified radical mastectomy. METHODS: This prospective randomized controlled clinical study comprised 60 females undergoing modified radical mastectomy and was randomly allocated to two groups. Group A patients received general anesthesia while, in addition to general anesthesia, group B patients received PEC 1 and SAP blocks. Postoperatively the active and passive visual analog score (VAS), duration of analgesia, cumulative requirement of rescue analgesics in the first 24 hours and associated perioperative complications were noted. All quantitative data were analyzed by student t-test and qualitative data by chi-square test using MedCalc software 12.5. RESULTS: VAS score for first 24 hours in group B was lower at rest, on pressure over the surgical site as well as on movements compared with the patients in group A with the p-value being < 0.0001 at all time intervals. Time for receiving first rescue analgesia was shorter (1.25±0.56hour vs 20.05±7.78hour, p<0.001) with the significantly higher requirement of cumulative doses of tramadol in the first 24 hours in patients belonging to group A (233.33±47.95mg vs 110±31.62 mg, p<0.001). CONCLUSION: PEC 1 and SAP blocks given under peripheral nerve stimulator guidance have a high success rate and are reliable in providing adequate postoperative analgesia for patients undergoing modified radical mastectomy.

Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma.

BACKGROUND: Some studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1-2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC). MATERIALS METHODS: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis. RESULTS: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p = 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78-66.7%) compared to IDC (207/460 - 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs. CONCLUSIONS: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1-2 positive SLNs still requires further investigation.

Reducing the effective dose of cisplatin using cobalt modified silver nano-hybrid as a carriers on MCF7 and HCT cell models.

Cancer is a deadly illness with a convoluted pathogenesis. The most prevalent restrictions that frequently result in treatment failure for cancer chemotherapy include lack of selectivity, cytotoxicity, and multidrug resistance. Thus, considerable efforts have been focused in recent years on the establishment of a modernistic sector termed nano-oncology, which offers the option of employing nanoparticles (NPs) with the objective of detecting, targeting, and treating malignant disorders. NPs offer a focused approach compared to conventional anticancer methods, preventing negative side effects. In the present work, a successful synthetic process was used to create magnetic cobalt cores with an AgNPs shell to form bimetallic nanocomposites CoAg, then functionalized with Cis forming novel CoAg@Cis nanohybrid. The morphology and optical properties were determined by TEM, DLS, FTIRs and UV-vis spectroscopy, furthermore, anticancer effect of CoAg and CoAg@Cis nanohybrids were estimated using MTT assay on MCF7 and HCT cell lines. Our results showed that Co@Ag core shell is about 15 nm were formed with dark CoNPs core and AgNPs shell with less darkness than the core, moreover, CoAg@Cis has diameter about 25 nm which are bigger in size than Co@Ag core shell demonstrating the loading of Cis. It was observed that Cis, CoAg and CoAg@Cis induced a decline in cell survival and peaked at around 65%, 73%and 66% on MCF7 and 80%, 76%and 78% on HCT at 100 µg/ml respectively. Compared to Cis alone, CoAg and CoAg@Cis caused a significant decrease in cell viability. These findings suggest that the synthesized CoAg can be used as a powerful anticancer drug carrier.

A Unique Surgical Case of Mixed Metaplastic Breast Carcinoma With Heterologous Mesenchymal Differentiation and Conventional Adenocarcinomatous Elements.

Metaplastic breast carcinoma (MBC) is very rare among all invasive breast carcinomas, accounting for less than 1.0% of them. MBCs are classified into five subtypes, including mixed MBC - where the mix might be multiple metaplastic elements or a mixture of epithelial and mesenchymal elements. Overall survival for mixed MBC tends to correlate with a significantly worse outcome. Therefore, an early accurate diagnosis and surgical treatment for mixed MBCs must allow for an improved quality of life and better prognosis. However, there have not been many recently published papers describing the detailed cytological features of mixed MBCs on fine-needle aspiration (FNA) specimens. A 60-year-old female presented with a history of a hard breast mass on the left lateral side, showing an ill-defined and marginally enhanced tumor nodule on magnetic resonance imaging. The cytologic specimens of FNA contained a large number of three-dimensional, cohesive and sheet-like clusters, or non-cohesive single cells, of highly atypical spindled sarcomatoid to oval epithelioid cells having hyperchromatic pleomorphic nuclei and mitotic figures, in a necrotic and hemorrhagic background. A small amount of osteoid matrix-like substance was rarely seen, associated with a very small number of osteoclast-like giant cells. We first interpreted it as an invasive breast carcinoma of high grade. A mastectomy was performed, and a gross examination of the neoplasm revealed a hemorrhagic solid tumor lesion with a gray-whitish cut surface, measuring approximately 35 × 24 × 21 mm in diameter. On a microscopic examination, the tumor was predominantly composed of the proliferation of highly atypical oval to spindled cells predominantly in a sarcomatous growth fashion with focal production of chondroid and osteoid matrix, peripherally coexisted with a smaller volume of conventional invasive breast carcinoma. Immunohistochemistry showed that the sarcomatous tumor cells were specifically positive for vimentin, α-smooth muscle actin, or epithelial membrane antigen. Therefore, we finally made a diagnosis of invasive mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements. To the best of our knowledge, this would most recently be the first case report of mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements, with a focus on its FNA cytomorphologic findings. We should be aware that owing to its characteristic cytological features, cytopathologists might be able to make a correct diagnosis of MBC, based on multiple and adequate samplings.

Immunohistochemical and molecular profiles of heterogeneous components of metaplastic breast cancer: a squamous cell carcinomatous component was distinct from a spindle cell carcinomatous component.

Metaplastic breast carcinoma (MBC), a category of breast cancer, includes different histological types, which are occasionally mixed and heterogeneous. Considering the heterogeneity of cancer cells in a tumour mass has become highly significant, not only from a biological aspect but also for clinical management of recurrence. This study aimed to analyse the immunohistochemical and molecular profiles of each MBC component of a tumour mass. Twenty-five MBC tumours were histologically evaluated, and the most frequent MBC component (c) was squamous cell carcinoma (SCC), followed by spindle cell carcinoma (SpCC). A total of 69 components of MBC and non-MBC in formalin-fixed paraffin-embedded sections were examined for 7 markers by immunohistochemistry. SCC(c) were significantly PTEN negative and CK14 positive, and SpCC(c) were significantly E-cadherin negative and vimentin positive. Multivariate analyses revealed that immunohistochemical profiles of normal/intraductal (IC)(c), no special type (NST)(c), and MBC(c) differed; moreover, SCC(c) and SpCC(c) were distinctly grouped. PTEN gene mutation was detected only in SCC(c) (2/7), but not in SpCC(c). Next-generation sequence analyses for 2 cases with tumours containing SCC(c) demonstrated that PTEN gene mutation increased progressively from IC(c) to NST(c) to SCC(c). In conclusion, the immunohistochemical and molecular profiles of the SCC(c) of MBC are distinct from those of the SpCC(c).

Need for Staging Investigations in Newly Diagnosed Breast Cancer: Establishing Local Guidelines for Radiological Staging in Bahrain.

Objective: Staging workup and detection of distant metastases is important in newly diagnosed breast cancer in order to make treatment decisions and establish the prognosis. There is wide variation in current recommendations for staging investigations in breast cancer. Routine staging is performed for all patients in Bahrain because of lack of consistent guidelines. Optimization of the criteria for staging is important for identification of metastases, while minimizing harm and costs. The aim of this study was to evaluate factors associated with distant metastases in newly diagnosed patients with breast cancer, in order to establish local guidelines for proper selection of patients for systemic staging. Materials and Methods: Patients with newly diagnosed breast cancer at Salmaniya Medical Complex in Bahrain who underwent staging investigations between January 2016 and December 2022 were identified from a pathology database. Patients with previous history of cancer, synchronous tumors, bilateral breast cancer and ductal carcinoma in situ were excluded. Clinical, radiological and pathological data were retrospectively analyzed. Results: A total of 593 patients underwent staging computed tomography and bone scans or a PET scan. Distant metastases were identified in 20.7% of cases. M1 disease was significantly associated with multifocality/multicentricity, high grade tumors, hormone receptor-negative cancers, high Ki67 index, advanced tumor stage, node-positive disease, triple-negative breast cancer, use of PET scans and those who underwent neoadjuvant chemotherapy. Age was not associated with identification of distant metastases. Conclusion: The prevalence of distant metastases in this population of newly diagnosed patients with breast cancer was higher than previously reported. Routine staging of all patients at presentation was not indicated, especially for asymptomatic patients with early breast cancer. This study identified certain groups of patients with a higher risk of distant metastasis, in whom metastatic workup should be performed. These findings may allow for the development of a local guideline that addresses the question of which breast cancer patients need staging investigations for distant metastases.

The Relationship Between Breast Density and Breast Cancer Surgical Outcomes: A Systematic Review.

This study aims to investigate the relationship between mammographic breast density and the surgical outcomes of breast cancer. PubMed, SCOPUS, Web of Science, Science Direct, and the Wiley Library were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Our results included ten studies with a total of 5017 women diagnosed with breast cancer. The follow-up duration ranged from 1 year to 15.1 years. Eight out of the twelve included studies reported that low mammographic breast density was significantly associated with no local recurrence, metachronous contralateral breast cancer, and fewer challenges in the preoperative and intraoperative phases. On the other hand, four studies reported that mammographic breast density is not linked to disease recurrence, survival, re-excision, or an incomplete clinical and pathological response. There is a significant association between low mammographic breast density and reduced challenges in the preoperative and intraoperative phases, as well as no local recurrence and fewer mastectomy cases. However, the link between mammographic breast density and disease recurrence, survival, re-excision, and incomplete clinical and pathological response is less clear, with some studies reporting no significant association. The findings suggest that mammographic breast density may play a role in certain aspects of breast cancer outcomes, but further research is needed to fully understand its impact.

Correlation Analysis of Digital Mammography, Ultrasonography, and Pathologic Features in Pure Invasive Micropapillary Carcinoma of the Breast (PIMPC).

Purpose: This study determined the digital mammography and ultrasonography imaging features of pure invasive micropapillary carcinoma of the breast (PIMPC) and the correlation with pathologic features. Patients Methods: Nineteen patients diagnosed with PIMPC at Yantaishan Hospital from October 2015 to February 2022 were included in the study group. Forty patients with breast masses diagnosed as nonspecific invasive ductal carcinoma of the breast (NIDC) from July to December 2021 were included in the control group. Digital mammography and ultrasonography features were compared between the two groups. Results: Patients with PIMPC had a younger age profile compared to patients with NIDC (P=0.017). Moreover, PIMPC masses were smaller than NIDC masses (P=0.040). Imaging features analysis revealed significant differences in age groups (<45 years: χ²=5.971, P=0.044) and the presence of spiculations or the crab claw sign (χ²=8.583, P=0.004) between patients with PIMPC and NIDC. However, there were no statistically significant differences in the presence of calcifications, blood flow grading, pathologic molecular subtypes between the study and control groups. The Ki-67 proliferative index (χ²=1.052, P=0.389), vascular invasion (χ²=2.263, P=0.197), and lymph node metastasis (χ²=1.968, P=0.386) showed no significant differences between PIMPC and NIDC patients. Conclusion: PIMPC imaging features show specificity, such as tiny breast masses, spiculated edges, or crab claw-like patterns, and malignant signs appeared when the lesion was <2 cm in diameter. PIMPC mainly occurs in middle-aged women 45-59 y of age. Patients with PIMPC and NIDC of the breast are frequently associated with lymph node metastases and greater than one-half of the cases (74%) were shown to have a Ki-67 index >30%, suggesting a significant risk of recurrence and metastasis. Early therapeutic care for these patients is crucial. These results warrant further validation with additional samples from several centers due to the limited single-center sample size in the current study.

Effect of Ambrosia arborescens Mill. ethanolic extract on breast cancer induced in rats.

Background and Aims: Ambrosia arborescens Mill. (A. arborescens) is an aromatic plant used in traditional medicine as an anti-inflammatory, anti-tussive, anti-rheumatic, and anti-diarrheal agent. This study aimed to evaluate the effect of A. arborescens Mill. on a Rattus norvegicus var. albinus-induced breast cancer model. Materials and Methods: We collected A. arborescens from the province of Julcán, La Libertad Region, Per, and prepared an ethanolic extract using pulverized leaves macerated in 96° ethanol for 72 h with magnetic stirring. In the evaluation of anticancer activity, four experimental groups with 10 female rats each were formed: Group I (Control-7,12-dimethylbenz[a]anthracene [DMBA]), which received DMBA (single dose) and physiological saline solution for 4 months, and Groups II, III, and IV, which received DMBA (single dose) and 200, 400, and 600 mg/kg/day of the ethanolic extract of A. arborescens, respectively, for 4 months. Results: The DMBA control group presented histological characteristics of ductal carcinoma in situ with necrotic and inflammatory areas, whereas the A. arborescens extract group showed a decrease in tumor volume and recovery of the ductal duct. Conclusion: Ethanol extract of A. arborescens leaves decreases tumor development in rats with induced breast cancer, and this effect is dose-dependent.

ESHO 1-85. Hyperthermia as an adjuvant to radiation therapy in the treatment of locally advanced breast carcinoma. A randomized multicenter study by the European Society for Hyperthermic Oncology.

BACKGROUND: The ESHO protocol 1-85 is a multicenter randomized trial initiated by the European Society for Hyperthermic Oncology with the aim to investigate the value of hyperthermia (HT) as an adjuvant to radiotherapy (RT) in treatment of locally advanced breast carcinoma. The trial is one of the largest studies of hyperthermia in radiotherapy but has not been previously published. PATIENTS AND METHODS: Between February 1987 and November 1993, 155 tumors in 151 patients were included. Tumors were stratified according to institution and size (T2-3/T4) and randomly assigned to receive radiotherapy alone (2 Gy/fx, 5 fx/wk) to a total dose of 65-70 Gy, incl. boost, or the same radiotherapy followed once weekly by hyperthermia (aimed for 43 °C for 60 min). Radiation was given with high voltage photons or electrons. The primary endpoint was persistent complete response (local control) in the treated area. RESULTS: A total of 146 tumors in 142 patients were evaluable, with a median observation time of 19 (range 1-134) months. Seventy tumors were randomized to RT alone and 76 to RT + HT. Size was T4 in 92, and T2-3 in 54 tumors, respectively. The compliance to RT was good with all but 4 patients fulfilling the planned RT treatment. The tolerance to HT was fair, but associated with moderate to severe pain and discomfort in 15 % of the treatments. In 84 % of the heated patients a least one heat treatment achieved the target temperature, but the temperature variation was large. Addition of heat did not significantly increase the acute nor late radiation reactions. Overall, the 5-year actuarial local failure rate was 57 %. Univariate analysis showed a significant influence of hyperthermia (RT alone 68 % versus RT + HT 50 %, p = 0.04, and T-size (T4 75 % versus T2-3 36 %, p < 0.01). A Cox multivariate analysis showed the same factors to be the only significant prognostic parameters: hyperthermia (HR: 0.61 [0.38-0.98], and small tumor strata (HR: 0.46 [0.26-0.92]. Consequentially, more patients given RT + HT (36 %) survived without disease (DFS), than after RT alone (19 %), p = 0.021) CONCLUSION: A randomized multicenter trial investigating the addition of a weekly hyperthermia treatment to radiotherapy of patients with locally advanced breast cancer significantly enhanced the 5-year tumor control and yielded more patients surviving free from cancer. The results substantiate the potential clinical benefit of hyperthermic oncology.

Breast Metastasis: An Unusual Cause of Malignant Breast Lesion.

Teaching point: Although rare, an intra-mammary metastasis from extramammary cancer should be considered in a patient with an oncological history.

Paclitaxel combined with trastuzumab chemotherapy-related posterior reversible encephalopathy syndrome: A case report and literature review.

Posterior reversible encephalopathy syndrome (PRES) in breast carcinoma is a rare disease in clinical practice that is often misdiagnosed and ignored. This study reported a case of a patient admitted to our hospital and discussed the clinical, imaging, and pathogenesis properties of the disease. We retrospectively analyzed the clinical data of this patient and reviewed the relevant literature. Imaging was used to diagnose PRES based on clinical findings, and clinical symptoms improved after discontinuation of the relevant drugs.

Predictors of re-attendance at biennial screening mammography following a false positive referral: A study among women in the south of the Netherlands.

AIM: A false positive (FP) referral after screening mammography may influence a woman's likelihood to re-attend the screening program. The impact of having a FP result in the first or subsequent screening round on re-attendance after a FP result was investigated. In addition, we aimed to study differences in re-attendance rates between women who underwent non-invasive and invasive additional examinations as part of the diagnostic work-up following a FP referral. METHODS: A consecutive series of 13,597 women with a FP referral following biennial screening mammography in the south of the Netherlands between 2009 and 2019 was included. RESULTS: The screening re-attendance rate was 81.2% after a FP referral, and 91.3% when also including women who had clinical mammographic follow-up. Women who received a FP referral in the first screening round were less likely to re-attend the screening programme in the following three years, compared to those with a FP test in any subsequent round (odds ratio (OR): 0.59, 95%-confidence interval (CI): 0.51-0.69). Women with a FP referral who underwent invasive examinations after referral were less likely to re-attend the screening programme than those who only received additional imaging (OR, 0.48; 95% CI 0.36-0.64). CONCLUSION: Women with a FP referral are less likely to re-attend the screening programme if this referral occurs at their first screening round or when they undergo invasive diagnostic workup. Hospitals and screening organizations should prioritize informing women about the importance of re-attending the programme following a FP referral.