Biomarkers in Breast Cancer

Breast cancer is the most common cancer in women and its incidence experienced an important increase, thanks to the introduction of a systematic screening. The increased incidence of early breast cancer has led to debates on its over-treatment, which may cause unnecessary harm to patients with favorable prognosis. Therefore, modern research is in the quest of finding the perfect prognostic marker to avoid overtreatment in patients with a favorable prognosis. In this perspective, many molecular markers have been studied in the last decades in order to provide both a useful prognostic tool, able to determine whether the cancer is likely to be indolent or aggressive, and a possible therapeutic target. In this chapter, we review the current knowledge about the principal biomarkers, which are usually immunohistochemically tested on breast surgical specimens, including ER and PR, Mib1/Ki-67 and HER2/neu expression. Furthermore, we will analyze other possible prognostic markers which may have in the future a key role in breast cancer management, such as several multigene panels (OncotypeDX, Mammaprint, NanoString Prosigma). Finally, we will discuss the role of genetic tests for some know genetic mutations associated with higher breast cancer susceptibility (BRCA1 and 2 genes)

Breast and Axilla Treatment in Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS) represents a challenge for the breast unit team, beginning from its difficult radiological detection and continuing with its controversial multimodal treatment and management. With the introduction of the mammographic screening, DCIS has become a common diagnosis. In fact, today DCIS is mostly identified by mammography or magnetic resonance imaging (MRI). The increased prevalence of DCIS diagnosis, in the past, raised the problem of the therapeutic management. In this chapter, the breast and axillary surgery in case of DCIS and the most controversial aspects regarding DCIS management are reviewed based on international guidelines and on the current literature

Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review

This narrative review aims to clarify the role of breast and gynecological risk-reduction surgery in BRCA mutation carriers. We examine the indications, contraindications, complications, technical aspects, timing, economic impact, ethical issues, and prognostic benefits of the most common prophylactic surgical options from the perspectives of a breast surgeon and a gynecologist. A comprehensive literature review was conducted using the PubMed/Medline, Scopus, and EMBASE databases. The databases were explored from their inceptions to August 2022. Three independent reviewers screened the items and selected those most relevant to this review’s scope. BRCA1/2 mutation carriers are significantly more likely to develop breast, ovarian, and serous endometrial cancer. Because of the Angelina effect, there has been a significant increase in bilateral risk-reducing mastectomy (BRRM) since 2013. BRRM and risk-reducing salpingo-oophorectomy (RRSO) significantly reduce the risk of developing breast and ovarian cancer. RRSO has significant side effects, including an impact on fertility and early menopause (i.e., vasomotor symptoms, cardiovascular disease, osteoporosis, cognitive impairment, and sexual dysfunction). Hormonal therapy can help with these symptoms. Because of the lower risk of developing breast cancer in the residual mammary gland tissue after BRRM, estrogen-only treatments have an advantage over an estrogen/progesterone combined treatment. Risk-reducing hysterectomy allows for estrogen-only treatments and lowers the risk of endometrial cancer. Although prophylactic surgery reduces the cancer risk, it has disadvantages associated with early menopause. A multidisciplinary team must carefully inform the woman who chooses this path of the broad spectrum of implications, from cancer risk reduction to hormonal therapies

Molecular and clinical characterization of a series of patients with childhood-onset lysosomal acid lipase deficiency. Retrospective investigations, follow-up and detection of two novel LIPA pathogenic variants

Background and aims Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system. The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D. Methods Data collected included clinical and laboratory investigations, liver imaging, liver biopsy and LIPA gene analysis. The response to lipid-lowering medications, liver transplantation and enzyme replacement therapy (ERT) was reported for some patients. Results LAL-D was suspected at 4.4 \uc2\ub1 3.3 years of age for the presence of hepatomegaly, elevated serum transaminases and hypercholesterolemia, and was confirmed by liver biopsy/imaging and LAL assay. The follow up period ranged from 3 to 40 years (mean 7.8 \uc2\ub1 4.0 years in 13 cases). Patients treated with statins with or without ezetimibe showed 28% reduction of plasma LDL-cholesterol without a tangible effect on liver enzymes; some patients receiving ERT showed normalized lipoprotein profile and transaminase levels. The common c.894G > A variant was observed in homozygosity or compound heterozygosity in 10 patients. We found seven previously reported variants: p.(Trp140*), p.(Arg218*), p.(Gly266*), p.(Thr288Ile), p.(Leu294Ser), p.(His295Tyr) and p.(Gly342Arg) and two novel variants: p.(Asp345Asn), affecting the LAL catalytic triad, and c.229+3A > C, affecting splicing. Homozygosity for p.(Thr288Ile) or c.229+3A > C was associated with a severe phenotype. Conclusions This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene

Search for physics beyond the standard model in multilepton final states in proton-proton collisions at root s=13 TeV

A search for physics beyond the standard model in events with at least three charged leptons (electrons or muons) is presented. The data sample corresponds to an integrated luminosity of 137 fb(-1) of proton-proton collisions at root s = 13 TeV, collected with the CMS detector at the LHC in 2016-2018. The two targeted signal processes are pair production of type-III seesaw heavy fermions and production of a light scalar or pseudoscalar boson in association with a pair of top quarks. The heavy fermions may be manifested as an excess of events with large values of leptonic transverse momenta or missing transverse momentum. The light scalars or pseudoscalars may create a localized excess in the dilepton mass spectra. The results exclude heavy fermions of the type-III seesaw model for masses below 880 GeV at 95% confidence level in the scenario of equal branching fractions to each lepton flavor. This is the most restrictive limit on the flavor-democratic scenario of the type-III seesaw model to date. Assuming a Yukawa coupling of unit strength to top quarks, branching fractions of new scalar (pseudoscalar) bosons to dielectrons or dimuons above 0.004 (0.03) and 0.04 (0.03) are excluded at 95% confidence level for masses in the range 15-75 and 108-340 GeV, respectively. These are the first limits in these channels on an extension of the standard model with scalar or pseudoscalar particles.Peer reviewe

Multiplicity and transverse momentum dependence of charge-balance functions in pPb and PbPb collisions at LHC energies

International audienceMeasurements of the charge-dependent two-particle angular correlation function in proton-lead (pPb) collisions at a nucleon-nucleon center-of-mass energy of $\sqrt{s_\mathrm{NN}}$ = 8.16 TeV and lead-lead (PbPb) collisions at$\sqrt{s_\mathrm{NN}}$ = 5.02 TeV are reported. The pPb and PbPb datasets correspond to integrated luminosities of 186\nbinv and 0.607 nb$^{-1}$, respectively, and were collected using the CMS detector at the CERN LHC. The charge-dependent correlations are characterized by balance functions of same- and opposite-sign particle pairs. The balance functions, which contain information about the creation time of charged particle pairs and the development of collectivity, are studied as functions of relative pseudorapidity ($\Delta \eta$) and relative azimuthal angle ($\Delta \phi$), for various multiplicity and transverse momentum ($p_\mathrm{T}$) intervals. A multiplicity dependence of the balance function is observed in $\Delta \eta$ and $\Delta \phi$ for both systems. The width of the balance functions decreases towards high-multiplicity collisions in the momentum region $\lt$2 GeV, for pPb and PbPb results. No multiplicity dependence is observed at higher transverse momentum. The data are compared with HYDJET, HIJING and AMPT generator predictions, none of which capture completely the multiplicity dependence seen in the data

Performance of the local reconstruction algorithms for the CMS hadron calorimeter with Run 2 data

International audienceA description is presented of the algorithms used to reconstruct energy deposited in the CMS hadron calorimeter during Run 2 (2015-2018) of the LHC. During Run 2, the characteristic bunch-crossing spacing for proton-proton collisions was 25 ns, which resulted in overlapping signals from adjacent crossings. The energy corresponding to a particular bunch crossing of interest is estimated using the known pulse shapes of energy depositions in the calorimeter, which are measured as functions of both energy and time. A variety of algorithms were developed to mitigate the effects of adjacent bunch crossings on local energy reconstruction in the hadron calorimeter in Run 2, and their performance is compared

Study of charm hadronization with prompt Λc+\Lambda^+_\mathrm{c} baryons in proton-proton and lead-lead collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

The production of prompt $\Lambda^+_\mathrm{c}$ baryons is measured via the exclusive decay channel $\Lambda^+_\mathrm{c}\to$ pK$^-\pi^+$ at a center-of-mass energy per nucleon pair of 5.02 TeV, using proton-proton (pp) and lead-lead (PbPb) collision data collected by the CMS experiment at the CERN LHC. The pp and PbPb data were obtained in 2017 and 2018 with integrated luminosities of 252 and 0.607 nb$^{-1}$, respectively. The measurements are performed within the $\Lambda^+_\mathrm{c}$ rapidity interval $\vert y\vert \lt$ 1 with transverse momentum ($p_\mathrm{T}$) ranges of 3-30 and 6-40 GeV/$c$ for pp and PbPb collisions, respectively. Compared to the yields in pp collisions scaled by the expected number of nucleon-nucleon interactions, the observed yields of $\Lambda^+_\mathrm{c}$ with $p_\mathrm{T}\gt$ 10 GeV/$c$ are strongly suppressed in PbPb collisions. The level of suppression depends significantly on the collision centrality. The $\Lambda^+_\mathrm{c}$/D$^0$ production ratio is similar in PbPb and pp collisions at $p_\mathrm{T}\gt$ 10 GeV/$c$, suggesting that the coalescence process does not play a dominant role in prompt $\Lambda^+_\mathrm{c}$ baryon production at higher $p_\mathrm{T}$

First measurement of the top quark pair production cross section in proton-proton collisions at s\sqrt{s} = 13.6 TeV

The first measurement of the top quark pair ($\mathrm{t\bar{t}}$) production cross section in proton-proton collisions at $\sqrt{s}$ = 13.6 TeV is presented. Data recorded with the CMS detector at the CERN LHC in Summer 2022, corresponding to an integrated luminosity of 1.21 fb$^{-1}$, are analyzed. Events are selected with one or two charged leptons (electrons or muons) and additional jets. A maximum likelihood fit is performed in event categories defined by the number and flavors of the leptons, the number of jets, and the number of jets identified as originating from b quarks. An inclusive $\mathrm{t\bar{t}}$ production cross section of 882 $\pm$ 23 (stat+syst) $\pm$ 20 (lumi) pb is measured, in agreement with the standard model prediction of 921$^{+29}_{-37}$ pb