Evaluation of Intraoperative End-Tidal Carbon Dioxide Change Relates to Length Hospitalisation in Peridiaphragmatic Surgery: A Pilot Study.

Intraoperative evaluation is deeply changed using many new tools, both invasive and non-invasive. Peripheral oxygen saturation percentage (SpO2) is the more reliable method for a non-invasive monitoring of patient's blood oxygen concentration. Capnography (using end-tidal CO2 (EtCO2)) evaluation is an immediate and continuous non-invasive monitoring of carbon dioxide (CO2) in the breathing that provides important information on circulatory status and ventilation.Aim of this study is to perform a preliminary analysis of oxygen change during surgery exploring its possible influence on post-operative evolution. METHODS AND RESULTS: Intraoperative evaluation of SpO2 and EtCO2 was performed. Change in each parameter was categorised as 1 point for each five-point variation from baseline value (∆SpO2 as 1 point for each 5%, ∆EtCO2 as 1 point for each 5 mmHg). For each patient, the length of stay (LOS) in the intensive care unit (ICU), total hospitalisation, duration of intervention, surgical risk and complications were recorded. RESULTS: We analysed 93 consecutive patients (43 males and 40 females, aged 66.35 ± 9.79 years) that underwent peridiaphragmatic surgery. Forty patients (48.19%) presented complications after surgery. There was no statistically significant difference in age, duration of intervention and length of stay in ICU between complicated and non-complicated patients. As expected, patients with complications present an increased hospitalisation time compared to uncomplicated cases (14.69 ± 11.41 days vs 10.70 ± 6.28 days; p < 0.05). ∆EtCO2 was significantly increased (p < 0.05) in complicated compared to non-complicated. No differences were found in ∆SpO2 between the two groups. Considering the whole population, ∆EtCO2 presents a significant direct correlation to surgical risk, hospitalisation and duration of intervention. CONCLUSION: ∆EtCO2 may be related to possible complications after surgery and hospitalisation. An important comparison between SpO2 and EtCO2 and strict monitoring with an intraoperative arterial blood gas (ABG) sample during the main steps of surgery could bring some essential information to understand oxygen changes in intra- and post-operative evolution. However, a further validation analysis is needed before the approach can be used extensively in daily clinical settings.

BRCA germline mutation test for all woman with ovarian cancer?

BACKGROUND: Delivering widespread BRCA testing to patients with ovarian cancer has been suggested by several scientists, recommended by professional societies and solicited by patients organizations. However, based on the lack of studies clearly demonstrating the cost-effectiveness of such approach compared to standard practice, we evaluated the possibility to better select subgroups of ovarian cancer (OC) patients with higher probability to be a BRCA mutation carrier'. METHODS: We analyzed the database of 2222 germline BRCA analyses from OC patients recently published by Song et al. (Song 2014) by applying multivariate and conditional inference regression tree-analyses. RESULTS: Overall, 178/2192 (8.1%) evaluable OC women showed pathogenic germline mutations in BRCA genes (84 BRCA1;94 BRCA2). BRCA mutations resulted significantly more frequent in Epithelial tumors (10.7%), less differentiated tumours (11.0%) and younger subjects (13.4%). Regression tree analysis permitted to individualize a subset of 66% OC patients with particularly low risk (3.5%) to carry a BRCA mutation vs a subgroup (24% of the series), with a probability higher than 17% to carry a pathogenic mutation. Younger age, OC and Breast Cancer family history were confirmed powerful factors in selecting subgroups of patients with significantly different BRCA mutation probability. CONCLUSIONS: Our regression tree-analysis can represent an innovative approach taking into consideration all main clinical pathological information to select OC patients to be candidated for BRCA test.

Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue.

Background: Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods: Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens. Results: In silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO + TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology. Conclusions: Our study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients' survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME.

u-PAR expression in cancer associated fibroblast: new acquisitions in multiple myeloma progression.

BACKGROUND: Multiple Myeloma (MM) is a B-cell malignancy in which clonal plasma cells progressively expand within the bone marrow (BM) as effect of complex interactions with extracellular matrix and a number of microenvironmental cells. Among these, cancer-associated fibroblasts (CAF) mediate crucial reciprocal signals with MM cells and are associated to aggressive disease and poor prognosis. A large body of evidence emphasizes the role of the urokinase plasminogen activator (u-PA) and its receptor u-PAR in potentiating the invasion capacity of tumor plasma cells, but little is known about their role in the biology of MM CAF. In this study, we investigated the u-PA/u-PAR axis in MM-associated fibroblasts and explore additional mechanisms of tumor/stroma interplay in MM progression. METHODS: CAF were purified from total BM stromal fraction of 64 patients including monoclonal gammopathy of undetermined significance, asymptomatic and symptomatic MM, as well as MM in post-treatment remission. Flow cytometry, Real Time PCR and immunofluorescence were performed to investigate the u-PA/u-PAR system in relation to the level of activation of CAF at different stages of the disease. Moreover, proliferation and invasion assays coupled with silencing experiments were used to prove, at functional level, the function of u-PAR in CAF. RESULTS: We found higher activation level, along with increased expression of pro-invasive molecules, including u-PA, u-PAR and metalloproteinases, in CAF from patients with symptomatic MM compared to the others stages of the disease. Consistently, CAF from active MM as well as U266 cell line under the influence of medium conditioned by active MM CAF, display higher proliferative rate and invasion potential, which were significantly restrained by u-PAR gene expression inhibition. CONCLUSIONS: Our data suggest that the stimulation of u-PA/u-PAR system contributes to the activated phenotype and function of CAF during MM progression, providing a biological rationale for future targeted therapies against MM.

miRNA profiling in serum and tissue samples to assess noninvasive biomarkers for NSCLC clinical outcome.

In NSCLC, the altered expression of some miRNAs in primary tumor tissues has been correlated with diagnosis and prognosis, while the role of circulating miRNAs as cancer biomarkers is currently emerging. MiRNA expression profile through miRNA Affymetrix array was evaluated on a training set formed by the tumor component (n = 30 NSCLC serum, n = 11/30 tumor tissues) and the control component (n = 10 healthy serum and n = 11/30 noncancerous counterparts). Statistical analyses highlighted the following: a = 55 miRNAs deregulated in tumor serum, b = 27 miRNAs deregulated in tumor tissues, and c = 2 miRNAs deregulated both in tumor serum and in tumor tissues. MiRwalk tool and enrichment pathway analyses selected some miRNAs whose target genes are correlated with the main pathways involved in NSCLC tumorigenesis. The altered expression of the selected miR-486-5p (a), miR-29c* (b), and miR-133a (c) was confirmed in the validation set (n = 40). MiR-486-5p had a higher expression in tumor serum than in tumor tissues (P = 0.004), and miR-29c* showed a lower expression in tumor tissues than in tumor serum (P < 0.001). MiR-133a had a not different expression in both tumor serum and tumor tissues (P = 0.07). The low level of miR-486-5p expression in the serum of affected patients was associated with a worse time to progression of disease (P = 0.010), and serum level of miR-486-5p was a significant prognostic indicator of NSCLC (adjusted hazard ratio = 0.179, P = 0.019). These data suggest the possibility to monitor affected patients through serum and/or tissue samples, analyzing the altered expression of specific miRNAs, in order to detect prognostic biomarkers in the NSCLC.

MicroRNA expression profiling in male and female familial breast cancer.

BACKGROUND: Gender-associated epigenetic alterations are poorly investigated in male and female familial breast cancer (fBC). MicroRNAs may contribute to the different biology in men and women particularly related to RASSF1A pathways. METHODS: Microarray technology was used to evaluate miRNA profile in 24 male and 43 female fBC. Key results were validated using RT-qPCR in an external samples set. In vitro studies were carried out to verify microRNA-target gene interaction. RESULTS: Pathway enrichment analysis with the 287 differentially expressed microRNAs revealed several signalling pathways differently regulated in male and female cases. Because we previously hypothesised a peculiar involvement of RASSF1A in male fBC pathogenesis, we focussed on the MAPK and the Hippo signalling pathways that are regulated by RASSF1A. Male miR-152 and miR-497 upregulation and RASSF1A and NORE1A interacting gene downregulation were observed, confirming a possible indirect interaction between miRNAs and the two genes. CONCLUSIONS: For the first time, a different microRNA expression pattern in male and female fBC has been shown. Moreover, the importance of RASSF1A pathway in male fBC carcinogenesis has been confirmed, highlighting a possible role for miR-152 and miR-497 in controlling MAPK and Hippo signalling pathways, regulated by RASSF1A.

MRI assessment of temporomandibular disorders: an approach to diagnostic and therapeutic setting.

AIMS: The aim of this study was to evaluate the relationship between the clinical and the radiological data obtained by magnetic resonance imaging (MRI) in patients with temporomandibular disorder (TMD). METHODOLOGY: The study group included 17 patients with symptoms of TMDs. The radiological assessments before and after therapy was evaluated by MRI; in the clinical analysis, signs and associated symptoms have been assessed. RESULTS: With MRI before therapy, we were able to distinguish the specific type of TMD that each patient had. At the end of the treatment, a general improvement of the clinical status was noticed; MRI, however, showed the permanence of several degrees of condyle-disc incoordination in some patients. CONCLUSIONS: Certainly TMDs can be diagnosed without MRI; nevertheless, MRI gives us the possibility to obtain objective data of the patients concerned. Symptoms recorded during a clinical evaluation cannot be the only terms of diagnosis; MRI provides objective data in the diagnostic and post-therapy phases.

BRCAness: a deeper insight into basal-like breast tumors.

The molecular scenario of breast cancer has become more complex in the last few years. Distinguishing between BRCA-associated, sporadic, HER2-enriched and triple-negative tumors is not sufficient to allow effective clinical management. Basal-like breast cancer, a subtype of triple-negative breast cancer, differs from others grouped under this heading. Commonalities between BRCA-related tumors and basal-like breast cancers (BRCAness phenotype) are highly relevant to ongoing clinical trials, in particular those investigating targeted therapies (e.g. PARP inhibitors) in sporadic breast tumors. The 'gold standard' to identify basal-like phenotype is DNA microarray, but integrated results could provide a panel of biomarkers helpful in identifying 'BRCAness' tumors (e.g. copy number aberrations, abnormal protein localization and altered transcriptional levels) and other molecular targets, such as APE1,the inhibition of which is emerging as an attractive breast cancer treatment in certain therapeutic settings.

Three novel human sporadic melanoma cell lines: signaling pathways controlled by MC1R, BRAF and ß-catenins.

We studied the behaviour of three novel human sporadic melanoma cell lines (hmel1, hmel9, hmel11) extracted from tumors with different degrees of malignancy, concerning the cell signalling pathways controlled by MC1R, BRAF, NRAS and ß-catenins. The novel cell lines were compared to metastatic cell lines (HBL, LND1), wild type (wt) for MC1R and BRAF genes, that have been extensively characterised and were used as control. All the novel cell lines have silent or no MC1R mutations even though MC1R signalling is severely impaired. Conversely, they harbour BRAF mutations at the V600 residue. These mutations determine a constitutive ERK phosphorylation in all the three cell lines. Our new melanoma cell lines were BRAF mutated in hetero- and homozygosis, even with a wild type MC1R, and unresponsive to NDP-MSH treatment. Quantity and subcellular localization of ß-catenin were analyzed in both novel and control cell lines. In HBL and LND1 there were high levels of beta-catenin distributed in the cytoplasm/nucleus, while in the novel melanoma cell lines ß-catenins were less abundant and seemed to be located at the plasma membrane/cytoplasm and absent in the nucleus. We sequenced beta-catenin cDNA for all the melanoma cell lines, and found mutations in HBL, LND1 and hmel1, while hmel9 and hmel11 were wt. We found that beta-catenin levels were not influenced by the RAS/RAF/MAPK pathway because inhibition with PD98059 (a MEK inhibitor) did not produce any effect on beta-catenin stability and/or localization.

Unclassified variants in BRCA genes: guidelines for interpretation.

In the last few years, several studies have focused on the interpretation of unclassified variants (UVs) of BRCA1 and BRCA2 genes. Analysis of UVs through a unique approach is not sufficient to understand their role in the development of tumors. Thus, it is clear that assembling results from different sources (genetic and epidemiological data, histopathological features, and in vitro and in silico analyses) represents a powerful way to classify such variants. Building reliable integrated models for UV classification requires the joining of many working groups to collaborative consortia, allowing data exchange and improvements of methods. This will lead to improvement in the predictivity of gene testing in BRCA1 and BRCA2 and, consequently, to an increase in the number of families that can be correctly classified as linked or unlinked to these genes, allowing more accurate genetic counseling and clinical management.

Innovative technology for cancer risk analysis.

After completion of the Human Genome Project, analysis of genetic and genomic variations in different pathological states became possible. The capillary system based on Sanger methods is still very expensive in terms of time, cost and professionalism required. For this reason, the National Human Genome Institute proposed an 'advanced sequencing technology development' project with the aim of sequencing a genome in 1 day for $1000. Three validated platforms are commercially available and single molecule sequencing methods have been recently introduced, which are not only competitive in time and costs, but display greater accuracy than 'past generation' sequencing. Next generation technology allows, in a single experiment, the identification of copy number variation and large rearrangements, or detection of fusion transcripts analysis thus permitting the evaluation of cancer risk at multiple levels (genomic, transcriptomic, proteomic, epigenetic).

Body Composition Change, Unhealthy Lifestyles and Steroid Treatment as Predictor of Metabolic Risk in Non-Hodgkin's Lymphoma Survivors.

Unhealthy lifestyle, as sedentary, unbalanced diet, smoking, and body composition change are often observed in non-Hodgkin's lymphoma (NHL) survivors, and could be determinant for the onset of cancer treatment-induced metabolic syndrome (CTIMetS), including abdominal obesity, sarcopenia, and insulin resistance. The aim of this study was to assess whether changes in body composition, unhealthy lifestyles and types of anti-cancer treatment could increase the risk of metabolic syndrome (MetSyn) and sarcopenia in long-term NHL survivors. We enrolled 60 consecutive NHL patients in continuous remission for at least 3 years. Nutritional status was assessed by anthropometry-plicometry, and a questionnaire concerning lifestyles and eating habits was administered. More than 60% of survivors exhibited weight gain and a change in body composition, with an increased risk of MetSyn. Univariate analysis showed a significantly higher risk of metabolic disorder in patients treated with steroids, and in patients with unhealthy lifestyles. These data suggest that a nutritional intervention, associated with adequate physical activity and a healthier lifestyle, should be indicated early during the follow-up of lymphoma patients, in order to decrease the risk of MetSyn's onset and correlated diseases in the long term.

Immune checkpoint inhibitor associated vitiligo and its impact on survival in patients with metastatic melanoma: an Italian Melanoma Intergroup study.

BACKGROUND: Checkpoint inhibitors in melanoma can lead to self-immune side-effects such as vitiligo-like depigmentation (VLD). Beyond the reported association with favorable prognosis, there are limited data regarding VLD patient features and their echo on the therapeutic outcomes. METHODS: To assess the association between VLD and a series of clinical and biological features as well as therapeutic outcomes, we built an observational cohort study by recruiting patients who developed VLD during checkpoint inhibitors. RESULTS: A total of 148 patients from 15 centers (101 men, median age 66 years, BRAF mutated 23%, M1c 42%, Eastern Cooperative Oncology Group (ECOG) status 0/1 99%, normal lactate dehydrogenase 74%) were enrolled. VLD was induced by ipilimumab, programmed cell death-1 (PD-1) inhibitors, and their combination in 32%, 56%, and 12%, respectively. The median onset was 26 weeks and it was associated with other skin and nonskin toxicities in 27% and 28%, respectively. After 3 years of VLD onset, 52% (95% confidence interval 39% to 63%) were progression free and 82% (95% confidence interval 70% to 89%) were still alive. The overall response rate was 73% with 26% complete response. Univariable analysis indicated that BRAF V600 mutation was associated with a better overall survival (P = 0.028), while in multivariable analysis a longer progression-free survival was associated with BRAF V600 (P = 0.093), female sex (P = 0.008), and M stage other than 1a (P = 0.024). When VLD occurred, there was a significant decrease of white blood cell (WBC) count (P = 0.05) and derived WBC-to-lymphocytes ratio (dWLR; P = 0.003). A lower monocyte count (P = 0.02) and dWLR (P = 0.01) were also reported in responder patients. CONCLUSIONS: Among VLD population, some features might help to identify patients with an effective response to immunotherapy, allowing clinicians to make more appropriate choices in terms of therapeutic options and duration.

Spatio-temporal parameters of ataxia gait dataset obtained with the Kinect.

Ataxic syndromes include several rare, inherited and acquired conditions. One of the main issues is the absence of specific, and sensitive automatic evaluation tools and digital outcome measures to obtain a continuous monitoring of subjects' motor ability. Gait evaluation was performed by Kinect v2 in a cohort of young participant affected by ataxia syndrome. The dataset is composed of the spatio-temporal parameters calculated by the skeleton acquired by the Kinect sensor, by the diagnosis of each participant, and by the total score of the clinical scale SARA. These parameters have been previously validated and corrected as requested by the Bland-Altman test.

Validation of low-cost system for gait assessment in children with ataxia.

BACKGROUND: Ataxic syndromes include several rare, inherited and acquired conditions. One of the main issues is the absence of specific, and sensitive automatic evaluation tools and digital outcome measures to obtain a continuous monitoring of subjects' motor ability. OBJECTIVES: This study aims to test the usability of the Kinect system for assessing ataxia severity, exploring the potentiality of clustering algorithms and validating this system with a standard motion capture system. METHODS: Gait evaluation was performed by standardized gait analysis and by Kinect v2 during the same day in a cohort of young patient (mean age of 13.8±7.2). We analyzed the gait spatio-temporal parameters and we looked at the differences between the two systems through correlation and agreement tests. As well, we tested for possible correlations with the SARA scale as well. Finally, standard classification algorithm and principal components analysis were used to discern disease severity and groups. RESULTS: We found biases and linear relationships between all the parameters. Significant correlations emerged between the SARA and the Speed, the Stride Length and the Step Length. PCA results, highlighting that a machine learning approach combined with Kinect-based evaluation shows great potential to automatically assess disease severity and diagnosis. CONCLUSIONS: The spatio-temporal parameters measured by Kinect cannot be used interchangeably with those parameters acquired with standard motion capture system in clinical practice but can still provide fundamental information. Specifically, these results might bring to the development of a novel system to perform easy and quick evaluation of gait in young patients with ataxia, useful for patients stratification in terms of clinical severity and diagnosis.

Assessing bradykinesia in Parkinson's disease using gyroscope signals.

Parkinson's disease (PD) is a neurodegenerative brain disorder that slowly brings on the dopaminergic neurons death. The depletion of the dopaminergic signal causes the onset of motor symptoms such as tremor, bradykinesia and rigidity. Usually, neurologists regularly monitor motor symptoms and motor fluctuations using the MDS-UPDRS part III clinical scale. Nevertheless, to have a more objective and quantitative evaluation, it is possible to assess the cardinal motor symptoms of PD using wearable sensors and portable robotic devices. Unfortunately while there are several research papers on the use of these devices on PD patients, their use is not so common in clinical practice. In this work we recorded specific MDS-UPDRS motor tasks using magneto-inertial devices, worn by seven PD subjects and seven age-matched controls, in order to deeply analyze the kinematic and dynamic characteristics of goal-directed movements of upper limb, in addition to extract quantitative indices (peak velocity, smoothness, etc) useful for the assessment of motor symptoms. Using only gyroscope signals we looked at those parameters useful to assess bradykinesia. We observed parameters changes from OFF to ON phase congruent with the MDS-UPDRS changes, especially in the frequency domain. Our results suggest the prono-supination task is the more consistent to describe the bradykinesia symptom with the gyroscopes. Probably because of the amplitude of the movement performed. Moreover the peak power looks appropriate for bradykinesia symptom evaluation. We can conclude that, similar to the studies in which tremor symptom is evaluated, it is possible to monitor the bradykinesia using few wearable sensors and few simple parameters.

Sporadic melanoma in South-Eastern Italy: the impact of melanocortin 1 receptor (MC1R) polymorphism analysis in low-risk people and report of three novel variants.

Environmental and genetic risk factors are involved in the development of melanoma. The role of the melanocortin 1 receptor (MC1R) gene has been investigated and differences according to geographic areas have been described. To evaluate the role of some clinical and genetic risk factors in melanoma development, we performed a case-control study involving 101 melanoma patients and 103 controls coming from South-Eastern Italy (Puglia), after achieving informed consent. We confirmed the role of known clinical risk factors for melanoma. Furthermore, 42 MC1R polymorphisms were observed. Three of these variants (L26V, H232L, D294Y) were not previously reported in the literature. Their predicted impact on receptor function was evaluated using bioinformatic tools. We report an overall frequency of MC1R variants in our population higher than in Northern or Central Italy. The most common polymorphism found was V60L, that has been recently reported to spread among South Mediterranean population. This variant influenced phenotypic characteristics of our population while it did not impinge on melanoma risk. An increased risk of melanoma was associated with two or more MC1R variants, when at least one was RHC, compared to people carrying the MC1R consensus sequence or a single MC1R polymorphism. Interestingly, we observed an increased risk of melanoma in subjects with darker skin and lower nevus count, usually considered at low risk, when carrying MC1R polymorphisms.

A body-machine interface for training selective pelvis movements in stroke survivors: A pilot study.

The body-machine interfaces (BMIs) map the subjects' movements into the low dimensional control space of external devices to reach assistive and/or rehabilitative goals. This work is a first proof of concept of this kind of BMI as tool for rehabilitation after stroke. We designed an exercise to improve the control of selective movements of the pelvis in stroke survivors, increasing the ability to decouple the motion in the sagittal and frontal planes and decreasing compensatory adjustments at the shoulder girdle. A Kinect sensor recorded the movements of the subjects. Subjects played different games by controlling the vertical and horizontal motion of a cursor on a screen with respectively the lateral tilt and the ante/retroversion of their pelvis. We monitored also the degrees of freedom not directly involved in cursor control, thus subjects could complete the task only with a correct posture. Our preliminary results highlight significant improvement not only in cursor control, but also in the Trunk Impairment Scale (TIS) and in the Five Times Sit to Stand Test (5xSST).

DNA methylation and miRNAs regulation in hereditary breast cancer: epigenetic changes, players in transcriptional and post- transcriptional regulation in hereditary breast cancer.

The genetic alterations associated with breast carcinogenesis are well known. On the contrary epigenetic alterations in hereditary breast cancer are a new field. Two epigenetic mechanisms have emerged as the most critical players in transcriptional regulation in breast cancer: the methylation of DNA and microRNA interference. In this review we will focus on recent findings on gene silencing caused by DNA methylation and microRNA to explore the potential role of these epigenetic changes in the understanding of hereditary breast cancer. Moreover we will describe the same alterations in basal-like breast cancer and in triple-negative breast cancer, since their phenotypes have similarities with BRCA1-mutated tumors. To underline the possibility that some epigenetic alterations could also be used as potential epigenetic biomarkers of drug sensitivity or resistance, we will discuss the more common therapies in hereditary breast cancer that could also be applied to breast cancer with basal-like or triple negative phenotypes.