Multiple metachronus proliferative fasciitis occurring in different anatomic regions: a case report and review of the literature.

Proliferative fasciitis is a benign lesion that usually has a self-limited course and rarely recurs after excision. In the literature, the multifocal occurrence of PF in different anatomic sites has not been reported so far. In this report, we describe the clinical case of a 30-year-old woman with two metachronous proliferative fasciitis occurring firstly in the orbit and, after 18 months, in the forearm; we also review the available literature on this topic, outlining guidelines for therapy and the follow-up of these patients

Non-uniform carrier density in Cd3_3As2_2 evidenced by optical spectroscopy

We report the detailed optical properties of Cd$_3$As$_2$ crystals in a wide parameter space: temperature, magnetic field, carrier concentration and crystal orientation. We investigate high-quality crystals synthesized by three different techniques. In all the studied samples, independently of how they were prepared and how they were treated before the optical experiments, our data indicate conspicuous fluctuations in the carrier density (up to 30%). These charge puddles have a characteristic scale of 100 $\mu$m, they become more pronounced at low temperatures, and possibly, they become enhanced by the presence of crystal twinning. The Drude response is characterized by very small scattering rates ($\sim 1$ meV) for as-grown samples. Mechanical treatment, such as cutting or polishing, influences the optical properties of single crystals, by increasing the Drude scattering rate and also modifying the high frequency optical response. Magneto-reflectivity and Kerr rotation are consistent with electron-like charge carriers and a spatially non-uniform carrier density.Comment: Accepted in Physical Review

Epidural blood patch in Trendelenburg position pre-medicated with acetazolamide to treat spontaneous intracranial hypotension

Background: Spontaneous intracranial hypotension (SIH) is characterized by orthostatic headache, diffuse pachymeningeal enhancement on brain magnetic resonance imaging (MRI) and low cerebrospinal fluid (CSF) pressure. Treatment ranges from conservative management, such as bed rest, overhydration and caffeine, to invasive procedures, such as the autologous epidural blood patch (EBP), computed tomography (CT)-guided fibrin glue injection at the site of the leak and open surgical intervention. EBP has emerged as the treatment of choice for SIH when initial conservative measures fail to bring relief. Methods: Forty-two patients with SIH were treated with lumbar autologous EBP in Trendelenburg position preceded by pre-medication with acetazolamide. Results: A complete recovery was obtained in all patients after one (90%), two (5%) or three (5%) EBPs. After EBP, two patients (5%) also performed evacuation of bilateral chronic subdural hematoma with mass effect. Conclusions: Spontaneous intracranial hypotension can be effectively cured by lumbar autologous EBP in Trendelenburg position pre-medicated with acetazolamide

Extended Adjuvant Endocrine Treatment in Luminal Breast Cancers in the Era of Genomic Tests

In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice

EGFR/HER2 inhibitor AEE788 increases ER-mediated transcription in HER2/ER-positive breast cancer cells but functions synergistically with endocrine therapy

BACKGROUND: Cross-talk between receptor tyrosine kinases and the oestrogen receptor (ER) is implicated in resistance to endocrine therapy. We investigated whether AEE788 (a combined inhibitor of EGFR, HER2 and VEGFR) plus tamoxifen or letrozole enhanced the individual anti-tumour effects of these agents. METHODS: Breast cancer cell lines modelling endocrine-resistant and -sensitive disease were engineered to express aromatase (A) and examined using proliferation, western blotting and ER-alpha transcription assays. RESULTS: AEE788 enhanced the anti-proliferative effect of tamoxifen and letrozole in ER+ cell lines (MCF-7 2A, ZR75.1 A3 and BT474 A3). This associated with an elevated G1 arrest and nuclear accumulation of p27. It is noteworthy that AEE788 alone or in combination with endocrine therapy increased the expression of progesterone receptor (PGR) and TFF1 in BT474 A3 cells. This may indicate a mechanism of resistance to AEE788 in ER+/HER2(+) breast cancers. In a ZR75.1 A3 xenograft, AEE788 alone or in combination with tamoxifen provided no further benefit compared with letrozole. However, letrozole plus AEE788 produced a significantly greater inhibition of tumour growth compared with letrozole alone. CONCLUSION: These data suggest that AEE788 plus letrozole in breast cancer overexpressing HER2 may provide superior anti-tumour activity, compared with single agents. British Journal of Cancer (2010) 102, 1235-1243. doi: 10.1038/sj.bjc.6605641 www.bjcancer.com (C) 2010 Cancer Research U

a propensity score analysis exploring the impact of the addition of adjuvant chemotherapy act to hormone therapy aht in a multi center series of resected luminal early stage pure invasive lobular breast carcinoma ilc

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Clinical outcomes after palbociclib with or without endocrine therapy in postmenopausal women with hormone receptor positive and HER2-negative metastatic breast cancer enrolled in the TREnd trial

Currently, there is limited data regarding the effectiveness of standard subsequent line therapies such as endocrine therapy, chemotherapy, or targeted agents after progression on CDK4/6 inhibitor-based regimens. This paper describes time-to-treatment failure beyond progression on palbociclib or palbociclib+endocrine therapy in patients enrolled in the phase II, multicenter TREnd trial. Our results indicate that there is limited benefit from post-palbociclib treatment, regardless of the type of therapy received. A small population of long responders were identified who demonstrated ongoing benefit from a subsequent line of endocrine therapy after progression to palbociclib-based regimens. A translational research program is ongoing on this population of outliers

"Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

BACKGROUND: In a significant proportion of metastatic breast cancer (MBC) patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance), it is generally believed that the chance of achieving clinical benefit (CB) with further endocrine therapy is minimal. METHODS: Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. RESULTS: In oestrogen receptor (ER) positive MBC patients with assessable disease, CB was achieved in 159 (71.3%) (1(st )line) patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2(nd )line), 46.1% (on 3(rd )line) and 20% (on 4(th )line) with a median duration of response (DOR) in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7%) patients had de novo resistance on 1(st )line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2(nd )line) and 22.2% (on 3(rd )line) with a median DOR in those with CB of 22.7 months and 14 months respectively. CONCLUSION: The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4(th )line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1(st )line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances

Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial

Background: Thymidine kinase 1 (TK1) is an enzyme downstream of the CDK4/6 pathway, with a critical role in DNA synthesis; serum TK1 activity (sTKa) is a novel liquid biopsy biomarker of tumour cell proliferation. Methods: The phase IIIb, BioItaLEE trial (NCT03439046) collected sera from postmenopausal patients with hormone receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) treated with first-line ribociclib plus letrozole at baseline, day 15 of cycle 1 (C1D15), day 1 of cycle 2 (C2D1), and at first imaging. Associations between sTKa assessed at different time points or sTKa dynamic patterns, and progression-free survival (PFS) were evaluated using multivariate Cox models. Results: Overall, 287 patients were enroled. Median follow-up was 26.9 months. High sTKa (>median) at baseline was associated with higher risk of progression (hazard ratio [HR], 2.21; 95% confidence interval [95% CI], 1.45, 3.37; P = 0.0002); similar results were observed for patients with high sTKa levels at C1D15 and C2D1. Early sTKa dynamic patterns were strongly predictive of PFS. The pattern with high sTKa levels at C2D1 following initial decrease at C1D15 was associated with higher risk of progression versus the pattern with low sTKa levels at both time points (HR, 2.89; 95% CI, 1.57, 5.31; P = 0.0006), while the pattern with high sTKa levels at C1D15 was associated with the shortest PFS (HR, 5.65; CI: 2.84, 11.2; P < 0.0001). Baseline and dynamic sTKa changes provided independent information. Conclusions: sTKa appears to be a new promising prognostic and pharmacodynamic biomarker in patients with HR+/HER2– ABC treated with ribociclib plus letrozole as first-line therapy