BackgroundAnti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer.Patients and methodsBERENICE (NCT02132949) is a nonrandomized, phase II, open-label, multicenter, multinational study in patients with normal cardiac function. In the neoadjuvant period, cohort A patients received four cycles of dose-dense doxorubicin and cyclophosphamide, then 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles. Cohort B patients received four standard fluorouracil/epirubicin/cyclophosphamide cycles, then four docetaxel cycles with four standard trastuzumab and pertuzumab cycles. The primary end point was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association class III/IV heart failure and of left ventricular ejection fraction declines (≥10 percentage-points from baseline and to a value of <50%). The main efficacy end point was pathologic complete response (pCR, ypT0/is ypN0). Results are descriptive.ResultsSafety populations were 199 and 198 patients in cohorts A and B, respectively. Three patients [1.5%; 95% confidence interval (CI) 0.31% to 4.34%] in cohort A experienced four New York Heart Association class III/IV heart failure events. Thirteen patients (6.5%; 95% CI 3.5% to 10.9%) in cohort A and four (2.0%; 95% CI 0.6% to 5.1%) in cohort B experienced at least one left ventricular ejection fraction decline. No new safety signals were identified. pCR rates were 61.8% and 60.7% in cohorts A and B, respectively. The highest pCR rates were in the HER2-enriched PAM50 subtype (75.0% and 73.7%, respectively).ConclusionTreatment with pertuzumab, trastuzumab, and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior studies with pertuzumab.Clinical Trial InformationNCT02132949

Objective: This study aimed to estimate asthma control at specialist treatment centers in four Latin American countries and assess factors influencing poor asthma control. Methods: Patients aged !12 years with an asthma diagnosis and asthma medication prescription, followed at outpatient specialist centers in Argentina, Chile, Colombia, and Mexico, were included. The study received all applicable ethical approvals. The Asthma Control Test (ACT) was used to classify patients as having controlled (ACT 20-25) or uncontrolled (ACT 19) asthma. Frequency and statistical tests were used to assess the association between hospital admissions/exacerbations/emergency department (ED) visits and uncontrolled asthma; multivariate logistic regression was used to assess the association of uncontrolled asthma with clinical/demographic variables. Results: A total of 594 patients were included. Overall controlled-asthma prevalence was 43.4% (95% confidence interval [CI]: 39.0, 47.4). Patients with uncontrolled asthma were more likely to be women (adjusted odds ratio [aOR]: 1.85; p ¼ 0.003), non-white (aOR: 2.14; p < 0.001), obese (aOR: 1.71; p ¼ 0.036), to have a low monthly family income (aOR: 1.75; p ¼ 0.004), to have severe asthma (aOR:1.59; p ¼ 0.26), and, compared with patients with controlled asthma, to have a higher likelihood of asthma exacerbations (34.5% vs. 15.9%; p < 0.001), hospital admissions (6.9% vs. 3.1%; p ¼ 0.042), and ED visits (34.5% vs. 15.9%; p < 0.001) due to asthma. Conclusions: Even in specialist ambulatory services, fewer than half of patients were classified as having controlled asthma. The proportion of uncontrolled patients varied according to clinical and demographic variables.

Despite the various different candidate genetic polymorphisms of potential clinical relevance, there is not enough understanding of the inter-individual variability in analgesic administration. The cytochrome P450 2D6 (CYP2D6) genotype is thought to be one of the most studied. The aim of the present evidence-based review was to determine if there is now sufficient evidence to make clinical recommendations based on a specific genomic profile. The data sources utilized were as follows: PubMed (NLM) database, Evidence Based Medicine Guidelines and Google. Research on clinical guidance standards, systematic reviews, meta-analyses and clinical trials, published prior to January 2018, were evaluated in English, using the MeSH terms ‘cancer pain’, ‘polymorphism’, ‘genetic’ and ‘gene polymorphism’. To assess the level of evidence, the Strength of Recommendation Taxonomy of the American Family Physician was applied. From the initial search, 12 systematic reviews and/or meta-analyses, 5 clinical trials and 10 guidelines were selected. The results indicated that genetic variation of µ-opioid receptor 1 (OPRM1) may contribute to inter-individual differences in morphine consumption with recommendation grade A for OPRM A118G single nucleotide polymorphism (rs1799971). Polymorphisms associated with the metabolization process of morphine and other opioid drugs are very relevant in opioid titration and ethnic subgroup differences which have to be taken into account (particularly, for the recommendation grade A for the CYP2D6 polymorphism). In human studies, the catechol-O-methyl transferase (COMT) genotype affects the efficacy of opioids in acute and chronic pain under different settings, with recommendation grade B to the COMT single nucleotide polymorphism rs4680 (Val/Met). Finally, polymorphisms of the ATP-binding cassette family of efflux transporters were highlighted. Consistent data on pain polymorphisms is now widely available; however, these results have had very little impact on clinical guidelines and daily oncologist practice. Persisting pain, side effects of grade 3 (NCI-CTCAE v4.0) and breakthrough pain with more than 4 episodes/day should be considered the criteria for pain multidisciplinary team discussions and for polymorphism screening.

The accomplishment of successful pain treatment requires evaluation, characterization and quantification. The present study characterized pain and survival in a cohort of patients with cancer with bone metastasis who were treated with intravenous bisphosphonates. A total of 84 patients self-completed the Brief Pain Inventory (BPI) and 36-Item Short Form Survey (SF-36), between November 2010 and March 2011 with a 5-year survival follow-up as a surrogate marker of cancer burden. The median age was 62 years old (34–85), 64% of patients were female and 58% of these females had breast cancer. In the population, self-reported pain was 91.6%, with 29 patients (34.5%) reporting severe pain (score 7–10). Among these patients, only 13 (44.8%) presented a similar report to that of their clinical files and 5 were undergoing treatment with strong opioids (17.2%). A total of 45 patients (46%) had not been prescribed analgesic drugs, of these patients, 32 were treated with a weak opioid, and 13 with a strong opioid. An association was observed between pain records and the prescribed analgesic (P=0.031). BPI maximum pain and overall survival data were analyzed, and a significant association was identified between male patients presenting severe pain and decreased survival (P=0.004). Male survival was associated with severe pain, which is consistent with other data. The results revealed a skeletal-related events (SRE)-free survival (time elapsed from diagnosis of the first bone metastasis to the first SRE) of 9 months (4.39–13.73, 95% CI) with a statistically significant difference between subgroups of time since diagnosis of bone metastasis (P=0.005). The added value of the present study is the suggestion that complete and accurate pain narratives are mandatory and may contribute to the optimization of analgesia, and may help to increase survival rates. Optimal pain management for patients with cancer remains an urgent requirement.