Authors' Reply To the Letters to the Editor by Puklin et al and by Iyengar and Ligibel

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

The role of dose-dense (DD) adjuvant chemotherapy (CT) in HER2-positive (HER2+) early breast cancer (BC) patients (pts) before and after the introduction of trastuzumab (T): Exploratory analysis of the GIM2 trial

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Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

Background: The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety. Material and methods: A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy). Results: Nine RCTs (N \ubc 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46\u20132.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N \ubc 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37\u20134.66, P \ubc 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51\u20132.67, P \ubc 0.711). Two RCTs (N \ubc 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49\u20131.06, P \ubc 0.094) and OS (HR 0.86, 95% CI 0.46\u20131.63, P \ubc 0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy. Conclusion: In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients

Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines

Cardiovascular (CV) toxicity is a potential short- or long-term complication of various anticancer therapies. Some drugs, such as anthracyclines or other biological agents, have been implicated in causing potentially irreversible clinically important cardiac dysfunction. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy agents, rare but serious complications have been described, and longer follow-up is needed to determine the exact profile and outcomes of related cardiac side-effects. Some of these side-effects are irreversible, leading to progressive CV disease, and some others induce reversible dysfunction with no long-term cardiac damage to the patient. Assessment of the prevalence, type and severity of cardiac toxicity caused by various cancer treatments is a breakthrough topic for patient management. Guidelines for preventing, monitoring and treating cardiac side-effects are a major medical need. Efforts are needed to promote strategies for cardiac risk prevention, detection and management, avoiding unintended consequences that can impede development, regulatory approval and patient access to novel therapy. These new ESMO Clinical Practice Guidelines are the result of a multidisciplinary cardio-oncology review of current evidence with the ultimate goal of providing strict criteria-based recommendations on CV risk prevention, assessment, monitoring and management during anticancer treatmen

Inhibitory activity of red and yellow araçá genotypes towards carbohydrate-hydrolyzing enzymes: putative role of ellagitannins.

Abstract: Psidium cattleianum Sabine (araçá) is a species native to Southeast Brazil that grows under abiotic stress conditions conferring high content of bioactive compounds to its fruits. The presence of these compounds is thought to be responsible for the many health-promoting effects including antioxidant, anti-inflammatory, anti-aging and antidiabetic activities. In this study, we evaluated the inhibitory potential of 10 (red and yellow) araçá genotypes towards carbohydrate-hydrolyzing enzymes (CHEs) using cell-free (α-glucosidase, α-amylase) and cell-based assays (sucrase). Araçá extracts displayed stronger inhibition towards α-glucosidase than α-amylase, and only 3 inhibited sucrase activity. The high variability towards the in vitro inhibitory CHEs activity was reflected in the total phenolics content with values ranging between 38.9 and 117 mg/100 g. Of the thirty compounds identified by High-Performance Liquid Chromatography-Diode Array Detection-Electrospray Ionization-Tandem Mass Spectrometry (HPLC-DAD-ESIMS/MS), including caffeic acids (9), organic acids (3) ellagitannins (15) and flavonoids (3), ellagitannins were the most abundant class. Statistical analysis showed ellagitannins were the main discriminators to the CHEs inhibitory activity. In summary, by expanding the panel of red and yellow araçá varieties studied, our results show that not all araçá genotypes inhibit CHE as only YA-23, RA-29, and RA-87 inhibited all 3 CHE which were related to the presence of ellagitannins. Information on the araçá genotypes with greater CHE inhibitory activity allied with the health-promoting effects of ellagitannin-rich foods, can be used to scale-up commercially exploitable genotypes with the aim to develop araçá-containing food formulations targeted to the pre-diabetic population

Reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients

Background: Preclinical evidence suggests a possible negative impact of deleterious BRCA mutations on female fertility. However, limited and rather conflicting clinical data are available. This study assessed the reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients. Patients and methods: This was a retrospective analysis of two prospective studies investigating oocyte cryopreservation and ovarian tissue cryopreservation in newly diagnosed early breast cancer patients. In the current analysis, baseline anti-Mullerian hormone (AMH) and performance of cryopreservation strategies were compared between patients with or without germline deleterious BRCA mutations. Results: Out of 156 patients included, 101 had known BRCA status of whom 29 (18.6%) were BRCA-mutated and 72 (46.1%) had no mutation. Median age in the entire cohort was 31 years [interquartile range (IQR) 28-33). Median AMH levels were 1.8 lg/l (IQR 1.0-2.7) and 2.6 \u3bcg/l (IQR 1.5-4.1) in the BRCA-positive and BRCA-negative cohorts, respectively (P=0.109). Among patients who underwent oocyte cryopreservation (N=29), women in the BRCA-positive cohort tended to retrieve (6.5 versus 9; P=0.145) and to cryopreserve (3.5 versus 6; P=0.121) less oocytes than those in the BRCA-negative cohort. Poor response rate (i.e. retrieval of 644 oocytes) was 40.0% and 11.1% in the BRCA-positive and BRCA-negative cohorts, respectively (P=0.147). Among patients who underwent ovarian tissue cryopreservation (N=72), women in the BRCA-positive cohort tended to have a numerically lower number of oocytes per fragment (0.08 versus 0.14; P=0.193) and per square millimeter (0.33 versus 0.78; P=0.153) than those in the BRCA-negative cohort. Two BRCA-mutated patients were transplanted after chemotherapy and one delivered at term a healthy baby. No difference between BRCA1- and BRCA2-mutated patients was observed in any of the above-mentioned outcomes. Conclusion: A consistent trend for reduced reproductive potential and performance of cryopreservation strategies was observed in BRCA-mutated breast cancer patients. Independent validation of these results is needed

O psiquiatra forense frente às demandas dos tribunais de família

Nas sociedades contemporâneas, a união entre as pessoas ocorre, de forma mais frequente, a partir das escolhas afetivas. No Brasil da última década, observou-se o aumento de 20% nas dissoluções de uniões conjugais. Alguns cônjuges não conseguem superar as dificuldades que emergem quando do término da relação, passando os filhos a serem alvo da conduta dos pais, configurando, em alguns casos, a Síndrome da Alienação Parental, observada em certos litígios que chegam às Varas de Família. O presente artigo enfoca o papel do psiquiatra forense frente às demandas oriundas das separações conjugais, à Síndrome de Alienação Parental e às legislações relacionadas a esta síndrome, em especial à lei brasileira nº 12.318, de 26 de agosto de 2010.In modern societies, people decide to marry, more frequently, based on affective choices. In Brazil, during the last decade, there was a 20% increase in marital unions dissolutions. Some spouses fail to overcome the problems and difficulties that arise at the end of a relationship, with their children being the ones affected by their parents' actions and behavior, thus giving place, in some cases, to the Parental Alienation Syndrome, which is observed in certain disputes that reach Family Courts. This article focuses on the Forensic Psychiatry role regarding the claims and demands that arise from marital dissolution, the Parental Alienation Syndrome and the legislation related to this syndrome, in particular the Brazilian Law 12.318, issued on August 26th, 2010