Prognostic significance of prolactin receptor on overall survival of patients with early breast cancer: a long-term retrospective analysis

Abstract The value of prolactin receptor (PRLR) determination in predicting overall survival has been retrospectively evaluated in a group of 170 women bearing primary breast cancer stage I, II and IIIA. All patients underwent surgery (radical or modified mastectomy or quadrantectomy and axillary dissection followed by radiotherapy according to TNM stage) between January 1977 and December 1986. In all patients, oestrogen and progesterone receptors concentrations were also determined. Overall actuarial survival was higher in patients having PRLR positive tumours when compared to patients having PRLR negative tumours (p = 0.0126). No difference in survival was observed between oestrogen or progesterone receptor positive or negative patients. Using Cox's multivariate analysis on 164 patients, stage and PRLR status were the only significant prognostic factors affecting survival (

Dairy Intake and Risk of Cognitive Decline and Dementia:A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies

Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with &gt;300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.</p

Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients

Background: Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods: We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results: Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that "RANK-negative" and "RANK-positive" patients had a SDFS of 105.7 months (95% CI: 73.9-124.4) and 58.9 months (95% CI: 34.7-68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions: This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients

Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival

BACKGROUND Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting.PATIENTS AND METHODS We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least one week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics.RESULTS We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥ 50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median progression free survival (PFS) was 5,5 months (4,6-6,5) and the median overall survival (OS) was 17,1 months (8,8-25,2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p=0.003, and OS, HR 0.21 95% CI 0.06-0.72, p=0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days.CONCLUSION A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥ 50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS

Third-line sorafenib after sequential therapy with sunitinib and mTOR inhibitors in metastatic renal cell carcinoma

Background: Sunitinib and everolimus have been approved for first- and second-line treatment, respectively, in metastatic renal cell carcinoma (mRCC). The role of sorafenib, which is approved for second-line treatment after cytokines failure, is presently to be defined. Objective: To determine whether third-line sorafenib after sequential use of sunitinib and mammalian target of rapamycin inhibitors (everolimus or temsirolimus) is feasible and effective. Design, setting, and participants: One hundred fifty medical records of patients with mRCC treated with first-line sunitinib between January 2006 and January 2010 were reviewed at four participating centers. Data regarding patients treated with the sequence sunitinib-everolimus or temsirolimus-sorafenib were extracted. Central analysis of radiographic images was performed using RECIST criteria to determine progression-free survival (PFS) and overall response rate (oRR) to sorafenib treatment. Measurements: PFS and oRR to sorafenib were the primary end points. Secondary outcomes were safety and overall survival (OS). Results and limitations: Thirty-four patients were eligible for the study. A median PFS of 4 mo (range: 3-6 mo) and a median OS of 7 mo since sorafenib treatment (range: 6-10 mo) were reported. Of the patients, 23.5% showed response to sorafenib, with an overall disease control rate (complete responses plus partial responses plus stable disease) of 44%. Selection bias, data incompleteness, and absence of study design are inevitable limitations of the study, although central review can strengthen the quality of presented data. Conclusions: Third-line sorafenib appears to be active and well tolerated in mRCC after first-line sunitinib and second-line everolimus or temsirolimus, with no patients interrupting sorafenib because of toxicity or lack of compliance. Prospective, placebo-controlled trials are completely lacking and are required in this setting

Determinacions del perfil genètic del càncer pediàtric

Oncologia; Perfil genètic; Càncer pediàtric; PrecisióOncología; Perfil genético; Cáncer pediátrico; PrecisiónOncology; Genetic profile; Pediatric cancer; AccuracyL'àmbit d'aquest grup de treball és la implementació de panels NGS per a diagnòstic / pronòstic / tractament de càncer en pacients menors de 18 anys (oncologia i hematologia). Els casos de predisposició genètica en pacients pediàtrics es tractaran en el grup de predisposició genètica. El càncer infantil comprèn més de 40 entitats entre leucèmies, limfomes, tumors cerebrals i sòlids extracranials; per la qual cosa no és possible tècnicament o operativament fer panels específics per a cada un d'aquests càncers. Serà necessari utilitzar panels comercials o acadèmics dissenyats específicament per a càncer infantil

Determinacions del perfil genètic del càncer pediàtric

Oncologia; Perfil genètic; Càncer pediàtric; PrecisióOncología; Perfil genético; Cáncer pediátrico; PrecisiónOncology; Genetic profile; Pediatric cancer; AccuracyL'àmbit d'aquest grup de treball és la implementació de panels NGS per a diagnòstic / pronòstic / tractament de càncer en pacients menors de 18 anys (oncologia i hematologia). Els casos de predisposició genètica en pacients pediàtrics es tractaran en el grup de predisposició genètica. El càncer infantil comprèn més de 40 entitats entre leucèmies, limfomes, tumors cerebrals i sòlids extracranials; per la qual cosa no és possible tècnicament o operativament fer panels específics per a cada un d'aquests càncers. Serà necessari utilitzar panels comercials o acadèmics dissenyats específicament per a càncer infantil