Is staging breast magnetic resonance imaging for invasive lobular carcinoma worthwhile?

BACKGROUND: Invasive lobular carcinoma (ILC) is challenging to stage accurately using mammography (MG) and ultrasound (US) with undiagnosed ipsilateral and contralateral cancer resulting in poor patient outcomes including return to surgery. Our institution employs routine staging breast MRI in ILC for this reason. However, increased time for further imaging/biopsies contributes to patient anxiety and potentially delays definite management. We aimed to quantify the frequency of staging MRI-detected additional lesions requiring biopsy or follow-up, the added cancer detection rate and MRI prompted change in surgical management. METHODS: An observational study on staging breast MRI for newly diagnosed ILC at a tertiary Western Australian hospital from January 2019 to August 2022. Standardized 3T MRI protocol was performed, double read by unblinded fellowship-trained radiologists. Histopathology from biopsy, surgery, or first annual surveillance was the reference standard for additional MRI-detected lesions. RESULTS: One hundred ten MRI studies demonstrated 49 (45%) patients had at least one additional clinically significant MRI-detected lesion. Thirty-one patients had an additional ipsilateral lesion detected, of which 18 (58%) proved malignant; 14 (45%) multifocal and 4 (13%) multicentric ILC. Additional work-up of MRI-detected lesions averaged a 9-day delay to definitive surgery compared to patients with a negative or definitively benign MRI. MRI changed surgical planning in 11 of 110 cases from breast conservation surgery (BCS) to mastectomy and there were two contralateral cancers diagnosed. BCS reoperation rate was 11%. CONCLUSION: Staging MRI for ILC identifies clinically significant lesions in nearly half of patients, predominantly ipsilateral multifocal disease, without significant delay to definitive surgery.

Unusual Soft Tissue Uptake of Tc-99m MDP in Radiation-induced Sarcoma: Diagnostic Conundrum.

Tc-99m methylene diphosphonate (MDP) is a bone imaging agent used for skeletal staging, but it can also be localized in extraosseous calcifying lesions. We report a case of an 84-year-old woman with breast carcinoma who underwent surgery followed by radiotherapy 10 years ago and now presented with a right axillary mass referred for Tc-99m MDP to exclude bone metastasis. Tc-99m MDP shows intense tracer uptake in the right thoracic region corresponding to the site of calcified soft tissue mass in the right lateral chest wall. Subsequent ultrasonography revealed an ill-defined lesion containing coarse calcifications. Biopsy showed radiation-induced sarcoma. Extra osseous Tc-99m MDP uptake may provide important diagnostic information that may alter patient management.

Quality-by-design-based microemulsion of disulfiram for repurposing in melanoma and breast cancer therapy.

Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy. Materials & methods: The ME was formulated using Cinnamon oil & Tween® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Zavg) and polydispersity index (PDI). Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF. Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.

Identifying new medicinal uses of an existing marketed drug can save both money and time in the process of drug development. From many of the recently reported literature, disulfiram (a drug used for alcoholism) has shown its activity against various cancers, including breast and skin cancer. However, it possesses poor water solubility and absorption, leading to low medicinal activity. The current study aims to develop a novel microemulsion dosage form through a statistical design approach to enhance the solubility, dissolution and anticancer activity for repurposing in melanoma and breast cancer treatment. The novel microemulsion was prepared, statistically analyzed and optimized. The optimized microemulsion was found to be stable and showed improved medicinal activity against breast and skin cancer compared with the pure drug. Our research showed the potential of the developed microemulsion of the disulfiram for its new therapeutic use in skin cancer and breast cancer.

Participation in a High-Risk Program Is Associated with a Diagnosis of Earlier-Stage Disease Among Women at Increased Risk for Breast Cancer Development.

BACKGROUND: High-risk programs provide recommendations for surveillance/risk reduction for women at elevated risk for breast cancer development. This study evaluated the impact of high-risk surveillance program participation on clinicopathologic breast cancer features at the time of diagnosis. METHODS: Women followed in the authors' high-risk program (high-risk cohort [HRC]) with a diagnosis of breast cancer from January 2015 to June 2021 were identified and compared with the general population of women undergoing breast cancer surgery at Memorial Sloan Kettering Cancer Center (MSK; general cohort [GC]) during the same period. Patient and tumor factors were collected. Clinicopathologic features were compared between the two cohorts and in a subset of women with a family history of known BRCA mutation. RESULTS: The study compared 255 women in the HRC with 9342 women in the GC. The HRC patients were slightly older and more likely to be white and have family history than the GC patients. The HRC patients also were more likely to present with DCIS (41 % vs 23 %; p < 0.001), to have smaller invasive tumors (pT1: 100 % vs 77 %; p < 0.001), and to be pN0 (95 % vs 81 %; p < 0.001). The HRC patients had more invasive triple-negative tumors (p = 0.01) and underwent less axillary surgery (p < 0.001), systemic therapy (p < 0.001), and radiotherapy (p = 0.002). Among those with a known BRCA mutation, significantly more women in the HRC underwent screening mammography (75 % vs 40 %; p < 0.001) or magnetic resonance imaging (MRI: 82 % vs 9.9 %; p < 0.001) in the 12 months before diagnosis. CONCLUSIONS: Women followed in a high-risk screening program have disease diagnosed at an earlier stage and therefore require less-intensive breast cancer treatment than women presenting to a cancer center at the time of diagnosis. Identification of high-risk women and implementation of increased surveillance protocols are vital to improving outcomes.

Genetic susceptibility to breast cancer increases the risk of neutropenia and agranulocytosis: insights from Mendelian randomization.

PURPOSE: The causal relationship between breast cancer and its estrogen receptor (ER) subtypes and neutropenia and agranulocytosis is unclear. METHODS: In two-sample Mendelian randomization (MR), we used inverse variance weighting (IVW), Bayesian weighted MR (BWMR), MR-Egger, weighted median, simple mode, and weighted mode methods to analyze causality for ER-positive breast cancer, ER-negative breast cancer, overall breast cancer, and drug-induced neutropenia and agranulocytosis. To validate the results, we performed the analysis again using GWAS data on neutropenia from different databases. In multivariable MR (MVMR), we assessed the independent effects of ER-positive and ER-negative breast cancer on causality. RESULTS: Two-sample MR analysis showed a causal relationship between ER-positive breast cancer (IVW odds ratio (OR) = 1.319, P = 7.580 × 10-10), ER-negative breast cancer (OR = 1.285, P = 1.263 × 10-4), overall breast cancer (OR = 1.418, P = 2.123 × 10-13), and drug-induced neutropenia and a causal relationship between ER-positive breast cancer (OR = 1.349, P = 1.402 × 10-7), ER-negative breast cancer (OR = 1.235, P = 7.615 × 10-3), overall breast cancer (OR = 1.429, P = 9.111 × 10-10), and neutropenia. Similarly, ER-positive breast cancer (OR = 1.213, P = 5.350 × 10-8), ER-negative breast cancer (OR = 1.179, P = 1.300 × 10-3), and overall breast cancer (OR = 1.275, P = 8.642 × 10-11) also had a causal relationship with agranulocytosis. MVMR analysis showed that ER-positive breast cancer remained causally associated with drug-induced neutropenia (OR = 1.233, P = 4.188 × 10-4), neutropenia (OR = 1.283, P = 6.363 × 10-4), and agranulocytosis (OR = 1.142, P = 4.549 × 10-3). Heterogeneity analysis and pleiotropy test showed that our results were reliable. CONCLUSION: Our study provides genetic evidence for a causal association between breast cancer and its estrogen receptor subtypes and neutropenia. In clinical practice, in addition to focusing on therapeutic factors, additional attention should be given to breast cancer patients to avoid severe neutropenia.

Inducing Effect of Corylus avellana on Cytotoxic Activity in Lung and Breast Cancer Cells via Apoptosis.

Turkish hazelnut (Corylus avellana L. cv Tombul) is a widely used nut in the chocolate industry and is also rich in polyphenol content, which promises anticancer effects. The anti-cancer and apoptotic effects of hazelnut leaves extracts examined on lung and breast cancer cells. Sulforhodamine B (SRB) and Adenosine 5'- triphosphate (ATP) assays were carried out for cell viability measurement. The mode of cell death was shown morphologically by the double fluorescence staining. Apoptosis was determined by performing caspase-mediated cytokeratin 18 (M30 ELISA) and western blot analysis. PARP, caspase 3, caspase 8, DR4, and GAPHD (Glyceraldehyde-3-phosphate Dehydrogenase) protein bands were visualized as markers of apoptosis. A wound healing test was employed to measure cell migration. Methanol extract of hazelnut leaf exhibited inhibition of cell growth activities in a dose-dependent manner. IC50 values were determined as 32.17 µg/ml in MCF-7, 32.16 µg/ml in MDA-MB-231, 20.40 µg/ml in A549 and 12.04 µg/ml in H1299 cells for ethanol extract while it was determined as 21.08 µg/ml in MCF-7, 40.16 µg/ml in MDA-MB-231, 22.04 µg/ml in A549 and 5.91 µg/ml in H1299 cells in methanol extract. In comparison, methanol leaf extracts were more effective in H1299 cells (IC50 value was 5.91 µg/ml).In comparison, ethanol leaf extracts were more effective in H1299 cells (IC50 value was 9.722 µg/ml). Western blot analysis demonstrated that hazelnut leaf extract treatment of cancer cells led to cell death via apoptosis and inhibited cell migration in lung and breast cancer cell lines. The cytotoxic effects of hazelnut extract on breast and lung cancer cells might be valuable and promising in elucidating cell death mechanisms for the development of new methods in cancer treatment.

In vitro anti-breast cancer study of hybrid cinnamic acid derivatives bearing 2-thiohydantoin moiety.

Aim: To synthesize new hybrid cinnamic acids (10a, 10b and 11) and ester derivatives (7, 8 and 9) and investigate their anti-breast cancer activities. Materials & methods: Compounds 7-11 were evaluated (in vitro) for their cytotoxic activities against the MCF-7 cell line. A flow cytometry examination was performed. Protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), topoisomerase II and caspase-9 were measured by qRT-PCR. Molecular docking studies were conducted. Results: Several components were discovered to be active, mainly component 11, which induced arrest in the cell cycle at phase S, greatly decreased the expression of Nrf2 and topoisomerase II; and upregulated the expression of caspase-9. Conclusion: The newly thiohydantoin-cinnamic acid hybrids can contribute to creating promising candidates for cancer drugs.

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C-Peptide and BMi predict anti-hyperglycemic treatment lines in breast cancer patients treated with Alpelisib.

PURPOSE: Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib. METHODS: Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control. RESULTS: The study population had a median age of 64 years (range:48-69) with a median body mass index (BMI) of 26.6 kg/m2 (range: 22.9-29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman's Rho 0.553, p = 0.040; Spearman's Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m2), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012). CONCLUSION: A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment.

Contrast-enhanced mammography for surveillance in women with a personal history of breast cancer.

PURPOSE: Women with a personal history of breast cancer have an increased risk of subsequent breast malignancy and may benefit from more sensitive surveillance than conventional mammography (MG). We previously reported outcomes for first surveillance episode using contrast-enhanced mammography (CEM), demonstrating higher sensitivity and comparable specificity to MG. We now report CEM performance for subsequent surveillance. METHODS: A retrospective study of 1,190 women in an Australian hospital setting undergoing annual surveillance following initial surveillance CEM between June 2016 and December 2022. Outcome measures were recall rate, cancer detection rate, contribution of contrast to recalls, false positive rate, interval cancer rate and characteristics of surveillance detected and interval cancers. RESULTS: 2,592 incident surveillance episodes were analysed, of which 93% involved contrast-based imaging. Of 116 (4.5%) recall episodes, 40/116 (34%) recalls were malignant (27 invasive; 13 ductal carcinoma in situ), totalling 15.4 cancers per 1000 surveillance episodes. 55/116 (47%) recalls were contrast-directed including 17/40 (43%) true positive recalls. Tumour features were similar for contrast-directed recalls and other diagnoses. 8/9 (89%) of contrast-directed invasive recalls were Grade 2-3, and 5/9 (56%) were triple negative breast cancers. There were two symptomatic interval cancers (0.8 per 1000 surveillance episodes, program sensitivity 96%). CONCLUSION: Routine use of CEM in surveillance of women with PHBC led to an increase in the detection of clinically significant malignant lesions, with a low interval cancer rate compared to previous published series. Compared to mammographic surveillance, contrast-enhanced mammography increases the sensitivity of surveillance programs for women with PHBC.

Long-term outcome of invasive pure micropapillary breast cancer compared with invasive mixed micropapillary and invasive ductal breast cancer: a matched retrospective study.

PURPOSE: Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients. METHODS: This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype. RESULTS: A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07). CONCLUSION: These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment.

Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

PURPOSE: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). METHODS: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. RESULTS: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). CONCLUSION: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Evaluation of Boric Acid Treatment on microRNA-127-5p and Metastasis Genes Orchestration of Breast Cancer Stem Cells.

Coregulation of microRNAs (miRNAs) and cancer stem cells (CSCs) is very important in carcinogenesis. miR-127-5p is known to be downregulated in breast cancer. In this study, we aimed to investigate how boric acid (BA), known for its previously unstudied anti-cancer properties, would affect the expression of miR127-5p and genes responsible for breast cancer stem cells (BC-SCs) metastasis. BC-SCs were isolated from human breast cancer cells (MCF-7) by immunomagnetic cell separation and characterized with flow cytometry and sphere formation. The viability of BC-SCs and the determination of its IC50 value in response to boric acid (BA) were assessed via the MTT assay. Boric acid exhibited dose- and time-dependent inhibition of cell viability in cells. The IC50 doses of boric acid in MCF-7 cells and BC-SCs were 45.69 mM and 41.27 mM, respectively. The impact of BA on the expression of metastatic genes and miR127-5p was elucidated through RT-qPCR analysis. While the expression of the COL1A1 (p < 0.05) and VIM (p < 0.01) was downregulated, the expression of the miR-127-5p, ZEB1 (p < 0.01), CDH1 (p < 0.05), ITGB1 (p < 0.05), ITGA5 (p < 0.05), LAMA5 (p < 0.01), and SNAIL (p < 0.05), was up-regulated in dose-treated BC-SCs (p < 0.001) to the RT-qPCR results. Our findings suggest that boric acid could induce miR-127-5p expression. However, it cannot be said that it improves the metastasis properties of breast cancer stem cells.

Clinical features and treatment outcomes of intraocular and ocular adnexal metastasis.

The aim of this study was to investigate the primary sites, clinical characteristics, and treatment outcomes of patients with metastatic tumors in the eye and ocular adnexa. This retrospective case series consisted of 42 patients diagnosed with intraocular metastasis (IM) or ocular adnexal metastasis (OAM) at a tertiary center between January 2001 and June 2023. The patients comprised 18 men and 24 women; 24 (57%) and 18 (43%) patients were diagnosed with IM and OAM, respectively. In the IM group, the primary tumors originated from the lungs (79%), followed by the breasts (17%). In the OAM group, the primary tumors originated from the breasts (33%). Previously, 57% of the patients had been diagnosed with cancer. In the IM group, 38% exhibited bilateral involvement. Only 6% of the patients with OAM had bilateral diseases. The 1-, 3-, and 5-year overall survival (OS) was 42%, 18%, and 7%, respectively. The median OS since metastasis diagnosis in the lungs and breast was 11.8 and 10.5 months, respectively. Lung cancer remains the predominant primary cancer in IM, whereas breast cancer is the major cancer in OAM. Despite poor OS, early detection will facilitate the prompt treatment of primary cancer and metastatic sites.

Factors influencing psychological distress among breast cancer survivors using machine learning techniques.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Breast cancer patients experience significant distress relating to their diagnosis and treatment. Managing this distress is critical for improving the lifespan and quality of life of breast cancer survivors. This study aimed to assess the level of distress in breast cancer survivors and analyze the variables that significantly affect distress using machine learning techniques. A survey was conducted with 641 adult breast cancer patients using the National Comprehensive Cancer Network Distress Thermometer tool. Participants identified various factors that caused distress. Five machine learning models were used to predict the classification of patients into mild and severe distress groups. The survey results indicated that 57.7% of the participants experienced severe distress. The top-three best-performing models indicated that depression, dealing with a partner, housing, work/school, and fatigue are the primary indicators. Among the emotional problems, depression, fear, worry, loss of interest in regular activities, and nervousness were determined as significant predictive factors. Therefore, machine learning models can be effectively applied to determine various factors influencing distress in breast cancer patients who have completed primary treatment, thereby identifying breast cancer patients who are vulnerable to distress in clinical settings.

Impending role of inflammatory markers and their specificity and sensitivity in breast cancer patients.

Cancer and related disorders are the most common cause of cancer-related mortality with the incidence of 1 in 9 among the pre-menopausal Pakistani females. among the most common ailments worldwide, indicating the importance of developing particular techniques that could help attenuate the effects of breast cancer and related outcomes. The primary aim of the current study was to review the role of inflammatory and stress markers in the development and progression of breast cancer. Four hundred ninety-eight (n = 498) patients with breast cancer and four hundred and ninety-eight (n = 498) age- and sex-matched controls were selected for this case‒control study. Serum samples were obtained, and the levels of stress and inflammatory markers, including Matrix metalloproteases (MMPs), Interleukins (ILs), Heat shock proteins (HSPs), Malondialdehyde (MDA), Nitric Oxide (NO), inducible Nitric Oxide Synthase (iNOS) and Tumour necrosis factor-alpha (TNF-α), were determined. Most (62%) patients had metastatic breast cancer (stage III or IV) with an adverse grade (65% with Grade III and 35% with Grade II). The present study showed that the levels of oxidants such as MDA, ILs, MMPs and HSPs were significantly greater, while the levels of antioxidants such as Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), vitamin A, C and D were significantly lower in breast cancer patients than in controls, suggesting their diagnostic importance and role in the pathophysiology of breast cancer. Oxidants, including IL-1, HSP27 and MMP9, which are highly specific and sensitive, may be used to develop the pathophysiological pathways of metastatic breast cancer in these patients. These pathways include cell invasion, cell migration and epithelial-mesenchymal transition. Therefore, we concluded that an increase in growth factors, e.g., Vascular Endothelial Growth Factor (VEGF), Tumour Growth Factor-beta (TGF-ß) and B-cell lymphoma (Bcl2), under the influence of these variables plays a crucial role in the metastasis of breast cancer.

Caspase-9 suppresses metastatic behavior of MDA-MB-231 cells in an adaptive organoid model.

Caspase-9, a cysteine-aspartate protease traditionally associated with intrinsic apoptosis, has recently emerged as having non-apoptotic roles, including influencing cell migration-an aspect that has received limited attention in existing studies. In our investigation, we aimed to explore the impact of caspase-9 on the migration and invasion behaviors of MDA-MB-231, a triple-negative breast cancer (TNBC) cell line known for its metastatic properties. We established a stable cell line expressing an inducible caspase-9 (iC9) in MDA-MB-231 and assessed their metastatic behavior using both monolayer and the 3D organotypic model in co-culture with human Foreskin fibroblasts (HFF). Our findings revealed that caspase-9 had an inhibitory effect on migration and invasion in both models. In monolayer culture, caspase-9 effectively suppressed the migration and invasion of MDA-MB-231 cells, comparable to the anti-metastatic agent panitumumab (Pan). Notably, the combination of caspase-9 and Pan exhibited a significant additional effect in reducing metastatic behavior. Interestingly, caspase-9 demonstrated superior efficacy compared to Pan in the organotypic model. Molecular analysis showed down regulation of epithelial-mesenchymal transition and migratory markers, in caspase-9 activated cells. Additionally, flow cytometry analysis indicated a cell cycle arrest. Moreover, pre-treatment with activated caspase-9 sensitized cells to the chemotherapy of doxorubicin, thereby enhancing its effectiveness. In conclusion, the anti-metastatic potential of caspase-9 presents avenues for the development of novel therapeutic approaches for TNBC/metastatic breast cancer. Although more studies need to figure out the exact involving mechanisms behind this behavior.

SerpinB2 deficiency is associated with delayed mammary tumor development and decreased pro-tumorigenic macrophage polarization.

The in vivo functions of SerpinB2 in tumor cells and tumor-associated macrophages (TAMs) during breast cancer development and metastasis remain elusive. SerpinB2-deficient MMTV-PyMT mice (PyMTSB2-/-) were previously produced to explore the biological roles of SerpinB2 in breast cancer. Compared with MMTV-PyMT wild-type (PyMTWT) mice, PyMTSB2-/- mice showed delayed tumor progression and reduced CK8 + tumor cell dissemination to lymph nodes. RNA-Seq data revealed significantly enriched genes associated with inflammatory responses, especially upregulated M1 and downregulated M2 macrophage marker genes in PyMTSB2-/- tumors. Decreased CD206+M2 and increased NOS2+M1 markers were detected in the primary tumors and metastatic lymph nodes of PyMTSB2-/- mice. In an in vitro study, SerpinB2 knockdown decreased the sphere formation and migration of MDA-MB-231 cells and suppressed protumorigenic M2 polarization of RAW264.7 cells. The combination of low SerpinB2, high NOS2, and low CD206 expression was favorable for survival in patients with breast cancer, as assessed in the BreastMark dataset. Our study demonstrates that SerpinB2 deficiency delays mammary tumor development and metastasis in PyMTWT mice, along with reduced sphere formation and migration abilities of tumor cells and decreased macrophage protumorigenic polarization.

Breast cancer treatment and its impact on survival in Morocco: a study over a decade.

BACKGROUND: In Morocco, much progress has been made in breast cancer treatment. However, there is limited information on survival outcomes of breast cancer patients according to their therapeutic management. METHODS: A pattern-of-care study was conducted in Morocco's two main oncology centres: Rabat and Casablanca and has shown that major progress has been made in the quality of care with survival rates comparable to those in developed countries. The present study focuses on the different therapeutic strategies used in breast cancer and their impact on prognosis. Patients were classified into two categories: those considered as appropriately managed and those who were not. RESULTS: A total of 1901 women with stage I to III breast cancer were included in this study, the majority (53%) were adequately managed and had better disease-free survival (DFS) rates than those who were not: DFS at 3 years (88% versus 62%) and at 5 years (80% versus 50%). Potential significant determinants of better management were: treatment in Rabat's oncology centre, treatment between 2008 and 2012, being aged younger than 60 years, and early TN stage. CONCLUSION: This study demonstrated the value of proper integrated and coordinated management in a comprehensive cancer centre, to improve breast cancer survival.

Serum miRNA-1 may serve as a promising noninvasive biomarker for predicting treatment response in breast cancer patients receiving neoadjuvant chemotherapy.

BACKGROUND: MicroRNA-1 (miR-1) is a tumour suppressor that can inhibit cell proliferation and invasion in several cancer types. In addition, miR-1 was found to be associated with drug sensitivity. Circulating miRNAs have been proven to be potential biomarkers with predictive and prognostic value. However, studies of miR-1 expression in the serum of breast cancer (BC) patients are relatively scarce, especially in patients receiving neoadjuvant chemotherapy (NAC). METHODS: Serum samples from 80 patients were collected before chemotherapy, and RT-PCR was performed to detect the serum expression of miR-1. The correlation between miR-1 expression in serum and clinicopathological factors, including pathological complete response (pCR), was analyzed by the chi-squared test and logistic regression. KEGG and GSEA analysis were also performed to determine the biological processes and signalling pathways involved. RESULTS: The miR-1 high group included more patients who achieved a pCR than did the miR-1 low group (p < 0.001). Higher serum miR-1 levels showed a strong correlation with decreased ER (R = 0.368, p < 0.001) and PR (R = 0.238, p = 0.033) levels. The univariate model of miR-1 for predicting pCR achieved an AUC of 0.705 according to the ROC curve. According to the interaction analysis, miR-1 interacted with Ki67 to predict the NAC response. According to the Kaplan-Meier plot, a high serum miR-1 level was related to better disease-free survival (DFS) in the NAC cohort. KEGG analysis and GSEA results indicated that miR-1 may be related to the PPAR signalling pathway and glycolysis. CONCLUSIONS: In summary, our data suggested that miR-1 could be a potential biomarker for pCR and survival outcomes in patients with BC treated with NAC.