Neuroendocrine carcinomas of the breast

INTRODUCTION: Neuroendocrine (NE) breast cancers encompass a heterogeneous group of tumours showing morphological features similar to those of NE neoplasms of the gut and lung and expressing one or more neuroendocrine markers (neuron specific enolase, chromogranins synaptophysin) in at least 50% of tumour cells. They are rare lesions representing about 2-3% of all breast cancers and affecting more frequently elderly patients. AIM: Prospective observational study is to analyse the clinico-pathological aspects of NE carcinomas of the breast undergone surgical resection compared to breast carcinomas with a minor neuroendocrine component and to conventional invasive ductal or lobular cancers. MATERIAL AND METHOD: Thirty-five consecutive breast carcinomas showing morphological features suggestive of an endocrine differentiation were selected among breast cancers undergone surgical treatment during the period of January 1979-December 2004. RESULTS: The 35 patients were divided into two categories: 13 neuroendocrine carcinomas (NECs) and 22 ductal carcinomas with a minor neuroendocrine component (DC-NE). The average follow-up was 60 months. The patients with CNE developed breast cancer in an advanced age compared to the patients with infiltrating ductal carcinoma NAS or infiltrating lobular carcinoma. We did not find recurrent disease in the NEC group, while it was observed in 2 patients (9%) with DC-NE, in 6 cases (17%) with infiltrating ductal carcinoma NAS and in 7 cases (20%) with infiltrating lobular carcinoma. DISCUSSION: The CNE compared with the infiltrating ductal and lobular carcinoma are statistically different in relation to the expression of the receptor of c-erb-B2, p53, progesterone, for the lymph node state at diagnosis and the risk of reappearance of breast tumour. Our study confirms the choice to consider the neuroendocrine carcinoma of the breast as a separate histological group and seems to suggest a less aggressiveness of this type of tumou

Optical frequency measurement of the 1S-3S two-photon transition in hydrogen

This article reports the first optical frequency measurement of the $1\mathrm{S}-3\mathrm{S}$ transition in hydrogen. The excitation of this transition occurs at a wavelength of 205 nm which is obtained with two frequency doubling stages of a titanium sapphire laser at 820 nm. Its frequency is measured with an optical frequency comb. The second-order Doppler effect is evaluated from the observation of the motional Stark effect due to a transverse magnetic field perpendicular to the atomic beam. The measured value of the $1\mathrm{S}_{1/2}(F=1)-3\mathrm{S}_{1/2}(F=1)$ frequency splitting is $2 922 742 936.729 (13) \mathrm{MHz}$ with a relative uncertainty of $4.5\times10^{-12}$. After the measurement of the $1\mathrm{S}-2\mathrm{S}$ frequency, this result is the most precise of the optical frequencies in hydrogen

Osteoimmunology of Spondyloarthritis

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA

High-resolution microwave frequency dissemination on an 86-km urban optical link

We report the first demonstration of a long-distance ultra stable frequency dissemination in the microwave range. A 9.15 GHz signal is transferred through a 86-km urban optical link with a fractional frequency stability of 1.3x10-15 at 1 s integration time and below 10-18 at one day. The optical link phase noise compensation is performed with a round-trip method. To achieve such a result we implement light polarisation scrambling and dispersion compensation. This link outperforms all the previous radiofrequency links and compares well with recently demonstrated full optical links.Comment: 11 pages, 5 figure

An Optical Lattice Clock with Spin-polarized 87Sr Atoms

We present a new evaluation of an 87Sr optical lattice clock using spin polarized atoms. The frequency of the 1S0-3P0 clock transition is found to be 429 228 004 229 873.6 Hz with a fractional accuracy of 2.6 10^{-15}, a value that is comparable to the frequency difference between the various primary standards throughout the world. This measurement is in excellent agreement with a previous one of similar accuracy

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients

Background: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. Patients and methods: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). Results: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75\u20130.80). After external validation the accuracy of the nomogram was confirmed. Conclusion: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients

Low neutrophil-to-lymphocyte ratio and pan-immune-inflammation-value predict nodal pathologic complete response in 1274 breast cancer patients treated with neoadjuvant chemotherapy: a multicenter analysis

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51–0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44–0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)−/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12–0.83; p = 0.02) and ER−/HER2− (OR = 0.41; 95% CI, 0.17–0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806