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With the exception of endocrine therapy, no other systemic treatment of patients with breast cancer has reached such a magnitude of beneficial effect as trastuzumab. This targeted agent (monoclonal antibody) is associated with a significant improvement in both disease-free (DFS) and overall survival (OS) in women with HER-2 positive breast cancer when given in combination with or in sequence to adjuvant chemotherapy. This has been confirmed in a recent Cochrane meta-analysis of randomized controlled trials (RCTs), including 6 adjuvant and 2 neoadjuvant studies (NSABP B-31, NCCTG N9831, BCIRG 006, HERA, FinHer, PACS-04, Buzdar and NOAH), with data collection until February 2010. Overall, mortality is reduced by one-third and the risk of relapse by 40%. Concerns regarding cardiac dysfunction are declining, with reports indicating its reversibility in most instances, however truly long term cardiac evaluation is still lacking. Hence, the benefit of trastuzumab could be challenged by cardiac toxicity, in lower-risk patients [T1a,b node-negative (N0) tumors] or those with increased cardiovascular risk (older women and patients with previous significant heart disease/suboptimal left ventricular ejection fraction [LVEF (<55%)], all of whom were largely excluded from the aforementioned adjuvant RCTs. These patient subgroups might warrant a specific approach, such as anti-HER2 treatment combined with just a taxane (avoiding anthracyclines) or with endocrine therapy. Reasonably large phase II trials aimed at exploring these more individualized regimens are underway in the US. The optimal duration of trastuzumab therapy remains unknown since the selection of the one year duration in the pivotal trials was arbitrary. The HERA trial showed that prolonging trastuzumab administration to two years does not confer additional advantage over one year. The PHARE trial compared 6 versus 12 months of trastuzumab and failed to show non-inferiority of the shorter treatment administration. At the present time, one year of adjuvant trastuzumab remains the standard-of-care until results from SOLD, Short-HER and PERSEPHONE consolidate or negate this finding. The route of trastuzumab administration has also been recently challenged. A subcutaneous formulation is being evaluated in several studies. The HannaH phase III trial compared the subcutaneous (SC) to the intravenous (IV) formulation of trastuzumab. The former was proven non-inferior to the latter, although the incidence of serious adverse events was slightly higher in the SC arm. The authors concluded that SC trastuzumab, administered at a fixed dose of 600mg over 5min, is a valid alternative option, with the potential for human and economic savings in clinical practice.

Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines can cause permanent damage, anti-HER2 agents may cause transitory and reversible cardiac dysfunction and others, such as those used in endocrine therapy, primarily disturb lipid metabolism. Considering the seriousness of these complications, trials are now being conducted to address cardiotoxicity associated with new drugs; however, to fully understand their toxicity profiles, longer follow-up is needed. In this review, we compile the information available about cardiac toxicity related to well-established systemic breast cancer treatments, as well as newer drugs, including antiangiogenics, mTOR inhibitors and novel anti-HER2 agents. We also describe current and next generation cardiac biomarkers and functional tests that can optimize treatment and reduce and prevent the incidence of treatment-related cardiotoxicity.

The growth and reproductive biology of the limpet Patella aspera were studied in the north-eastern Atlantic, Madeira archipelago, to enhance the knowledge concerning biological parameters and population dynamics of this species. This study comprised the estimation of growth rates, sexual maturity, reproduction, recruitment patterns, mortality coefficients and the exploitation rate, and yield-per-recruit (Y/R) based on monthly shell-length frequency data. A total of 16,941 specimens were sampled from January to December 2015. The relative growth pattern exhibited a negative allometric nature of growth for both sexes. The estimated von Bertalanffy growth parameters showed an asymptotic length of 84.15 mm for females and 80.51 mm for males with a growth coefficient of 0.36 and 0.32 year −1 respectively. P. aspera in this geographical area is a moderately long-lived limpet with a predominance of specimens younger than 3 years old. This species is a winter breeder with a reproductive cycle encompassing three main periods namely development, spawning and resting with a synchronous gametogenesis for both sexes. Gonadal development lasts from October to December, spawning likely occurs from January until April and resting occurs from May to September. The mean size at sexual maturity was determined as 41.78 mm for females and 38.29 mm for males and the length at first capture as 42.62 mm. The recruitment pattern was continuous throughout the year with a major peak identified in March. The natural, fishing and total mortalities were similar between sexes, with fishing mortality exerting greatest pressure on this resource. However, yield-per-recruit analysis showed that the stock of P. aspera, in the study area, is exploited at levels below the fishing mortality that returns maximum sustainable yield. This study revealed that currently the stock of P. aspera is under-exploited, nonetheless due to it's slow growth and long life, continuous monitoring and the enforcement of the existing harvest regulations must be accomplished if future overexploitation is to be avoided. Further genetic studies are necessary to establish connectivity of the populations and improve present conservation strategies.

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Background:Limited data are available on the prognostic performance of Adjuvant! Online (AOL) and Nottingham Prognostic Index (NPI) in young breast cancer patients.Methods:This multicentre hospital-based retrospective cohort study included young (⩽40 years) and older (55–60 years) breast cancer patients treated from January 2000 to December 2004 at four large Belgian and Italian institutions. Predicted 10-year overall survival (OS) and disease-free survival (DFS) using AOL and 10-year OS using NPI were calculated for every patient. Tools ability to predict outcomes (i.e., calibration) and their discriminatory accuracy was assessed.Results:The study included 1283 patients, 376 young and 907 older women. Adjuvant! Online accurately predicted 10-year OS (absolute difference: 0.7% P=0.37) in young cohort, but overestimated 10-year DFS by 7.7% (P=0.003). In older cohort, AOL significantly underestimated both 10-year OS and DFS by 7.2% (P<0.001) and 3.2% (P=0.04), respectively. Nottingham Prognostic Index significantly underestimated 10-year OS in both young (8.5% P<0.001) and older (4.0% P<0.001) cohorts. Adjuvant! Online and NPI had comparable discriminatory accuracy.Conclusions:In young breast cancer patients, AOL is a reliable tool in predicting OS at 10 years but not DFS, whereas the performance of NPI is sub-optimal.

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case–control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P = 7.3E–9) and Italian (OR, 1.84; P = 6.0E–5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.