Matrix metalloproteinases (MMPs) are a family of zinc-activated peptidases that can be classified into six major classes, including gelatinases, collagenases, stromelysins, matrilysins, membrane type ...metalloproteinases, and other unclassified MMPs. The activity of MMPs is regulated by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). MMPs are involved in a wide range of biological processes, both in normal physiological conditions and pathological states. While some of these functions occur during development, others occur in postnatal life. Although the roles of several MMPs have been extensively studied in cancer and inflammation, their function in metabolism and metabolic diseases have only recently begun to be uncovered, particularly over the last two decades. This review aims to summarize the current knowledge regarding the metabolic roles of metalloproteinases in physiology, with a strong emphasis on adipose tissue homeostasis, and to highlight the consequences of impaired or exacerbated MMP actions in the development of metabolic disorders such as obesity, fatty liver disease, and type 2 diabetes.
Early hormone-positive breast cancers typically have favorable outcomes, yet long-term surveillance is crucial due to the risk of late recurrences. While many studies associate MMP-11 expression with ...poor prognosis in breast cancer, few focus on early-stage cases. This study explores MMP-11 as an early prognostic marker in hormone-positive breast cancers.
In this retrospective study, 228 women with early hormone-positive invasive ductal carcinoma, treated surgically between 2011 and 2016, were included. MMP-11 expression was measured by immunohistochemistry, and its association with clinical and MRI data was analyzed.
Among the patients (aged 31-89, median 60, with average tumor size of 15.7 mm), MMP-11 staining was observed in half of the cases. This positivity correlated with higher uPA levels and tumor grade but not with nodal status or size. Furthermore, MMP-11 positivity showed specific associations with MRI features. Over a follow-up period of 6.5 years, only 12 oncological events occurred. Disease-free survival was linked to Ki67 and MMP-11.
MMP-11, primarily present in tumor-surrounding stromal cells, correlates with tumor grade and uPA levels. MMP-11 immunohistochemical score demonstrates a suggestive trend in association with disease-free survival, independent of Ki67 and other traditional prognostic factors. This highlights the potential of MMP-11 as a valuable marker in managing early hormone-positive breast cancer.
Breast cancer is the most common female cancer in the world. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess ...whether the regular practice of formal breast self-examination (BSE) as opposed to breast awareness has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality.
The Commission of Senology (CS) of the Collège National de Gynécologie et Obstétrique Français (CNGOF) respected and followed the Grading of Recommendations Assessment, Development and Evaluation method to assess the quality of the evidence on which the recommendations were based.
The CS studied 16 questions individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE versus abstention from this examination led to detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival.
BSE should not be recommended for women in the general population, who otherwise benefit from clinical breast examination by practitioners from the age of 25, and from organized screening from 50 to 74 (strong recommendation). In the absence of data on the benefits of BSE in patients aged over 75, for those at high risk and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these categories wish to undergo BSE, information on the benefits and risks observed in the general population must be given, notably that BSE is associated with a higher number of referrals, biopsies, and a reduced quality of life.
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•Impact of breast self-examination (BSE) on breast cancer (BC) early diagnosis and mortality in 4 groups: general population, women over the age of 75, at high-risk, and BC survivors.•In the absence of impact on BC mortality and early diagnosis, BSE is not recommended for general population.•BSE can lead to unnecessary biopsies, false reassurance, and finally decrease quality of life.•the absence of conclusive BSE data for the 3 other groups, no recommendations have been proposed.
Pathological complete response (pCR) after neoadjuvant systemic treatment (NST) is an important prognostic factor in HER2-positive breast cancer. The majority of HER2-positive breast cancers are ...amplified at the HER2 gene locus, several genes are co-amplified with HER2, and a subset of them are co-expressed. The STARD3 gene belongs to the HER2 amplicon, and its role as a predictive marker was never addressed. The objective of this study was to investigate the predictive value of STARD3 protein expression on NST pathological response in HER2-positive breast cancer. In addition, we studied the prognostic value of this marker.
We conducted a retrospective study between 2007 and 2020 on 112 patients with non-metastatic HER2-positive breast cancer treated by NST and then by surgery. We developed an immunohistochemistry assay for STARD3 expression and subcellular localization and determined a score for STARD3-positivity. As STARD3 is an endosomal protein, its expression was considered positive if the intracellular signal pattern was granular.
In this series, pCR was achieved in half of the patients. STARD3 was positive in 86.6% of cases and was significantly associated with pCR in univariate analysis (
= 0.013) and after adjustment on other known pathological parameters (
= 0.044). Performances on pCR prediction showed high sensitivity (96%) and negative predictive value (87%), while specificity was 23% and positive predictive value was 56%. Overall, specific, relapse-free, and distant metastasis-free survivals were similar among STARD3 positive and negative groups, independently of other prognosis factors.
NST is an opportunity for HER2-positive cancers. In this series of over a hundred HER2-positive and non-metastatic patients, a STARD3-negative score was associated with the absence of pathological complete response. This study suggests that determining STARD3 overexpression status on initial biopsies of HER2-positive tumors is an added value for the management of a subset of patients with high probability of no pathological response.
This systematic review aimed at comparing performances of ultrasonography (US), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (PET) for axillary staging, with ...a focus on micro- or micrometastases.
A search for relevant studies published between January 2002 and March 2018 was conducted in MEDLINE database. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies checklist. Sensitivity and specificity were meta-analyzed using a bivariate random effects approach; Results: Across 62 studies (
= 10,374 patients), sensitivity and specificity to detect metastatic ALN were, respectively, 51% (95% CI: 43-59%) and 100% (95% CI: 99-100%) for US, 83% (95% CI: 72-91%) and 85% (95% CI: 72-92%) for MRI, and 49% (95% CI: 39-59%) and 94% (95% CI: 91-96%) for PET. Interestingly, US detects a significant proportion of macrometastases (false negative rate was 0.28 (0.22, 0.34) for more than 2 metastatic ALN and 0.96 (0.86, 0.99) for micrometastases). In contrast, PET tends to detect a significant proportion of micrometastases (true positive rate = 0.41 (0.29, 0.54)). Data are not available for MRI.
In comparison with MRI and PET Fluorodeoxyglucose (FDG), US is an effective technique for axillary triage, especially to detect high metastatic burden without upstaging majority of micrometastases.
Breast fibromatosis is a rare disease characterized by monoclonal fibroblast proliferation. It has no ability to metastasize but has a high local recurrence rate and often infiltrates surrounding ...tissues. Surgical treatment is the reference, but recently, new targeted therapies have emerged. We report an original case of a patient with breast fibromatosis who received exclusive medical treatment. Our aim was to analyze these treatments based on the clinical and radiological outcome, iatrogenic effects, and pharmacological action.
We report the case of a 19-year-old woman who developed a desmoid-type fibromatosis of the lower inner quadrant of the right breast, measuring 50 × 25 mm (i.e., a volume of 27.4 cm
). Initial surgery was not possible because of potential esthetic and functional prejudice. Thus, she had an exclusive medical treatment including several lines: NSAIDs with tamoxifen and triptorelin, followed by sorafenib, then interferon α2b, and finally sunitinib. With tyrosine-kinase inhibitors (TKIs) (sunitinib), a significant partial response was observed (57% reduction of the maximal tumoral volume). For each treatment, we provided the clinical and radiological outcome in association with known pharmacological action.
TKI had been an interesting alternative option to initial surgery, providing at least a partial response and potentially allowing less mutilating surgery. However, no pharmacological mechanism can unequivocally explain TKI efficacy. In general, breast fibromatosis should be treated along with oncologist and interventional radiologists in a trans-disciplinary modality, thus offering an adapted treatment for this particular desmoid-type fibromatosis localization.
The aim of this study was the evaluation of breast MRI in determining the size and focality of invasive non-metastatic breast cancers.
The prospective, single-centre study conducted in 2015 compared ...preoperative MRI with histological analysis of mastectomy.
One hundred one mastectomies from 98 patients were extensively analysed. The rates of false-positive and false-negative MRI were 2 and 4% respectively. The sensitivity of breast MRI was 84.7% for the detection of all invasive foci, 69% for single foci and 65.7% for multiple foci. In the evaluation of tumour size, the Spearman rank correlation coefficient r between the sizes obtained by MRI and histology was 0.62. The MRI-based prediction of a complete response to neoadjuvant chemotherapy was 75%.
MRI exhibits high sensitivity in the detection of invasive breast cancers. False positives were linked to the inflammatory nature of the tumour bed. False negatives were associated with small or low-grade tumours and their retro-areolar location. The size of T1 tumours was overestimated by an average of 7%, but MRI was the most efficient procedure. The sensitivity of MRI for the diagnosis of unifocal tumours was higher than that for multifocal sites. Our study confirmed the positive contribution of preoperative MRI for invasive lobular carcinomas and complete response predictions after neoadjuvant chemotherapy.
While breast hematomas are common, their imaging features are often underrecognized or mistaken for other conditions.Diagnosis of acute hematomas is generally easy when associated with a recent ...history of breast trauma, surgery, or percutaneous biopsy. However, minor trauma might not always be remembered, and breast hematoma might have longlasting imaging manifestations when associated with fat necrosis. Also, because of the increasing use of breast MRI and FDG-PET/CT, breast hematomas are increasingly detected as incidentalomas and may mimic malignancies.Conversely, breast hematomas may also be associated with authentic malignant processes.In this pictorial review, we present the natural history of breast hematomas, their various imaging features, as well as their differential diagnoses, highlighting the situations requiring histopathological correlation.
History An otherwise healthy 18-year-old man was admitted to the emergency department with a closed displaced fracture of the left femoral shaft ( Fig 1 ) after a high-velocity motorbike accident. At ...admission, other physical examination findings were unremarkable. Initial unenhanced and contrast material-enhanced (120 mL of Iomeron 400; Bracco Imaging, Milan, Italy) computed tomography (CT) was performed in the arterial and venous phases from the head to the knees. No abnormalities were noted in the brain or chest at initial CT. Figure: see text Within a few hours, the patient developed sudden mental confusion and severe hypoxemia, with rapidly worsening tachypnea and perturbed arterial blood gas with low partial pressure of oxygen (61 mmHg 8.1 kPa; normal range, 75-100 mmHg 10.0-13.3 kPa) and low partial pressure of carbon dioxide (32 mmHg 4.3 kPa; normal range, 38-42 mmHg 5.1-5.6 kPa). A second contrast-enhanced chest CT examination and initial brain magnetic resonance (MR) imaging were performed. Femoral fracture was stabilized with external fixation, and the patient was admitted to the intensive care unit, with progressive neurologic recovery at day 3 and respiratory improvement at day 4. Treatment included intubation with mechanical ventilation and intravenous administration of steroids and noradrenaline. Afterward, the femoral fracture was stabilized with an intramedullary nail. The patient made a full neurologic recovery 1 month after the accident.
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