Use and Applicability of the Gail Model to Calculate Breast Cancer Risk: A Scoping Review

Objective: To perform a scoping review of the applicability of the Gail model in different countries for different ethnicities. Methods: The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and search strategies based on the PICOS approach. The reviewed articles were included if they were published between 2013 and 2018 in English, Portuguese, or Spanish; were original articles available in full online; and described the use of the Gail model. The PubMed, Embase, and Web of Science data bases were searched. Results: A total of 38 articles eligible for analysis were identified, of which 16 used the Gail model to assess breast cancer risk in women, eight analyzed the applicability of this tool in their population, seven compared the tool and/or modified it according to the specific risk factors of their population, and seven cited the model in determining eligibility for chemoprevention. Conclusion: The Gail model has different applicabilities Greater effectiveness and breast cancer risk are found in developed countries.     

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal,non-small cell lung,and pancreatic cancer

KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated.     

Trends in Cervical Cancer Mortality in Brazilian Women who are Screened and Not Screened

Objective: This study aimed to analyze the trend in cervical cancer (ICD C53) mortality in Brazilian regions in women who are who are screened and not screened from 1996 to 2015. Methods: An epidemiological study, of time series of mortality from cervical cancer performed in 90,856 women under 24 years old (343 women), between 25 and 64 years old (32,703 women), and over 65 years old (10,909 women). The data from this research were collected from the DATASUS, from the SIM Health Surveillance Secretariat files, captured through TABNET selecting the resident population by gender and age group and ICD 10 C53 from 1996 to 2015. Results: Among women, 43.8% were white, and 76% had less than eight years of formal education. Polynomial regression showed an increasing trend in cervical cancer mortality in Brazil for women aged 15 - 24 years (p=0.01). Between 25 - 64 and 65 years or older it remained constant, but high (p=0.07; 0.99). The Northeast region pointed a growing trend in women aged 15 to 24 (p=0.01), 25 to 64 years (p=0.01) and 65 or older (p=0.001). The Northeast presented the highest average growth per year. In the Southeast, South and Midwest regions, decreasing trends were observed despite the high rates. The Joinpoint regression showed a 95% confidence interval, and that mortality from cervical cancer in the North region increased throughout the period analyzed. an increasing trend was observed from 1996 to 1998, whereas in the Midwest region, the trend remained stable throughout the period analyzed. The Federal District presented an upward trend from 1996 to 2015. In Brazil, an upward trend was observed throughout the whole period analyzed. Conclusions: Cervical cancer mortality in younger women is becoming more predominant, in addition to the high rate observed for women aged 65 or older.     

A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Theory of mind,mental state talk and social relationships in aging: The case of friendship

Objectives: Previous research has shown a decline in Theory of mind (ToM) associated with normal aging. However, very few studies have investigated older people’s ToM using an ecological approach. The present study was designed to fill this gap and examine older people’s frequency of mental state talk (MST) in describing their best friend, together with their performance on a traditional ToM task. In addition, the study examined the association between these two ToM indices and relationships with friends and family members.

Method: Seventy-two healthy older adults (age range 60–79) participated in the study. We measured ToM ability with a classic measure, the Faux Pas task, and selected the Describe-a-friend task to measure MST frequency; social relationships were investigated with the Lubben Social Network Scale. Correlation and regression analyses were performed.

Results: No significant association between MST and scores on the Faux Pas task emerged. In addition, MST (but not Faux Pas scores) significantly predicted friendships (but not family relationships) over and above general cognitive functioning.

Conclusion: These findings show the crucial distinction between possessing an ability and using it in daily life and suggest the need to move toward more ecological measures of older adults’ abilities. In addition, the present results indicate that the spontaneous use of ToM ability, not the ability per se, impacts on older adults’ social relationships.     

Measuring female intrasexual competition by the scale for intrasexual competition: a validation of the German version

Competitive behaviour amongst members of the same sex is termed intrasexual competition. The tendency to engage in such competition appears to be strongly related to stable individual characteristics such as personality traits. Additionally, recent studies have revealed transient fluctuations in competitiveness according to the female menstrual cycle. To date, no German questionnaire exists to measure intrasexual competition. Our first study aimed to translate and validate the Intrasexual Competition Scale (ICS) by Buunk and Fisher (J Evol Psychol 7:37–48, 2009) in a population of healthy Swiss females (n = 241). Our second study applied the validated German ICS in a group of healthy, regularly cycling females (n = 49) in order to examine possible associations between the menstrual cycle phase and ICS scores. The psychometric properties suggest that the German ICS is a reliable and valid tool to assess individual differences in female intrasexual competition. Furthermore, our second study demonstrated that on average, women showed higher intrasexual competition scores when tested in the late follicular phase (M = 35.77 ± SD = 12.03) compared to the mid-luteal phase (M = 30.93 ± SD = 10.20). Our studies support previous findings of an association between ICS scores and relatively stable individual characteristics such as personality traits. Furthermore, our research endorses the assumption of cycle-dependent fluctuations in intrasexual competition. Future research should clarify the precise mechanisms underlying these findings and include biomarkers such as oestrogen and testosterone.

     

Mutational landscape of patients with acute promyelocytic leukemia at diagnosis and relapse

Despite the high probability of cure of patients with acute promyelocytic leukemia (APL), mechanisms of relapse are still largely unclear. Mutational profiling at diagnosis and/or relapse may help to identify APL patients needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene-panel, we tested BM samples of 44 APLs at the time of diagnosis, and of 31 at relapse. Mutations in PML and RARA genes were studied using a customized-NGS-RNA panel. Patients relapsing after ATRA-chemotherapy rarely had additional mutations (P = .009). In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. We then evaluated the predictive value of mutations at APL diagnosis. A median of two mutations was detectable in 9/11 patients who later relapsed, vs one mutation in 21/33 patients who remained in CCR (P = .0032). This corresponded to a significantly lower risk of relapse in patients with one or less mutations (HR 0.046; 95% CI 0.011-0.197; P < .0001). NGS-analysis at the time of APL diagnosis may inform treatment decisions, including alternative treatments for cases with an unfavorable mutation profile.