Medical treatment of mammary desmoid-type fibromatosis: which benefit?

BACKGROUND: 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. CASE PRESENTATION: 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 x 25 mm (i.e., a volume of 27.4 cm3). 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 alpha2b, 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. CONCLUSIONS: 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

Relevance of breast MRI in determining the size and focality of invasive breast cancer treated by mastectomy: a prospective study

Abstract Background The aim of this study was the evaluation of breast MRI in determining the size and focality of invasive non-metastatic breast cancers. Methods The prospective, single-centre study conducted in 2015 compared preoperative MRI with histological analysis of mastectomy. Results 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%. Discussion 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

STARD3: A New Biomarker in HER2-Positive Breast Cancer

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. Methods. 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. Results: 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 (p = 0.013) and after adjustment on other known pathological parameters (p = 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. Conclusion: 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

A prospective study to assess the clinical utility of serum HER2 extracellular domain in breast cancer with HER2 overexpression

Purpose: We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression.Methods: We prospectively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during treatments, and along the follow-up. We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis, its prognosis value, and its utility during the monitoring of a neoadjuvant treatment and the follow-up.Results: Elevated HER2/ECD at diagnosis correlated positively with parameters associated with tumor aggressiveness. Disease-free survival of non-metastatic patients was significantly shorter in patients with high HER2/ECD at diagnosis (HR = 13.6, 95 % CI 1.6–113.6, P < 0.0001). Progression-free survival of metastatic patients was better for patients with low HER2/ECD (HR = 2.6, 95 % CI 1.2–5.3, P = 0.033). A multivariate analysis revealed that HER2/ECD level at diagnosis was an independent prognosis factor. During neoadjuvant therapy, a significant decrease in HER2/ECD was reported only for the complete histological response group (P = 0.031). During the follow-up, HER2/ECD helped predict relapse, disease progression, and metastases before imaging in 18.6 % cases of the studied cohort.Conclusions: HER2/ECD is a prognosis factor that is valuable in evaluating the neoadjuvant treatment efficiency. HER2/ECD also appears to be a helpful surveillance biomarker for the early diagnosis of relapses and to predict the fate of metastases. This study brings evidences to support the use of HER2/ECD in the management of HER2-positive breast cance

Reference standard for the evaluation of automatic segmentation algorithms: Quantification of inter observer variability of manual delineation of prostate contour on MRI

International audienceThe purpose of this study was to investigate the relationship between inter-reader variability in manual prostate contour segmentation on magnetic resonance imaging (MRI) examinations and determine the optimal number of readers required to establish a reliable reference standard. Materials and methods: Seven radiologists with various experiences independently performed manual segmentation of the prostate contour (whole-gland [WG] and transition zone [TZ]) on 40 prostate MRI examinations obtained in 40 patients. Inter-reader variability in prostate contour delineations was estimated using standard metrics (Dice similarity coefficient [DSC], Hausdorff distance and volume-based metrics). The impact of the number of readers (from two to seven) on segmentation variability was assessed using pairwise metrics (consistency) and metrics with respect to a reference segmentation (conformity), obtained either with majority voting or simultaneous truth and performance level estimation (STAPLE) algorithm. Results: The average segmentation DSC for two readers in pairwise comparison was 0.919 for WG and 0.876 for TZ. Variability decreased with the number of readers: the interquartile ranges of the DSC were 0.076 (WG) / 0.021 (TZ) for configurations with two readers, 0.005 (WG) / 0.012 (TZ) for configurations with three readers, and 0.002 (WG) / 0.0037 (TZ) for configurations with six readers. The interquartile range decreased slightly faster between two and three readers than between three and six readers. When using consensus methods, variability often reached its minimum with three readers (with STAPLE, DSC = 0.96 [range: 0.945 −0.971] for WG and DSC = 0.94 [range: 0.912−0.957] for TZ, and interquartile range was minimal for configurations with three readers. Conclusion: The number of readers affects the inter-reader variability, in terms of inter-reader consistency and conformity to a reference. Variability is minimal for three readers, or three readers represent a tipping point in the variability evolution, with both pairwise-based metrics or metrics with respect to a reference. Accordingly, three readers may represent an optimal number to determine references for artificial intelligence applications

Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to D-Dimer Levels

Reports of acute pulmonary embolism associated with coronavirus disease 2019 (COVID-19) have emerged in the literature. For example, Chen et al (1) described 25 pulmonary CT angiographic examinations from 1008 patients with COVID-19; 10 were positive for pulmonary embolism, mostly as segmental or subsegmental acute pulmonary embolism. In addition, d-dimer levels have been reported as elevated in patients with COVID-19 (2,3), with the suggestion of an independent association between the severity of the disease and the level of d-dimer (4). The purpose of this report is to describe the rate of pulmonary embolus in patients classified as having COVID-19 infection who underwent chest CT at a tertiary referral center