Association between genome-wide epigenetic and genetic alterations in breast cancer tissue and response to HER2-targeted therapies in HER2- positive breast cancer patients: new findings and a systematic review

Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigenetic alterations with the response to anti-HER2 agents in HER2-positive breast cancer patients.PubMed was screened for articles published until March 2021 on observational studies investigating the association of genome-wide genetic and epigenetic alterations,measured in breast cancer tissues or blood,with the response to targeted treatment in HER2-positive breast cancer patients.Sixteen studies were included in the review along with ours,in which we compared the genome-wide DNA methylation pattern in breast tumor tissues of patients who acquired resistance to treatment (case group, n = 6) to that of patients who did not develop resistance (control group, n =6). Among genes identified as differentially methylated between the breast cancer tissue of cases and controls, oneof them, PRKACA, was also reported as differentially expressed in two studies included in the review. Althoughincluded studies were heterogeneous in terms of methodology and study population, our review suggests thatgenes of the PI3K pathway may play an important role in developing resistance to anti-HER2 agents in breastcancer patients. Genome-wide genetic and epigenetic alterations measured in breast cancer tissue or blood mightbe promising markers of resistance to anti-HER2 agents in HER2-positive breast cancer patients. Further studiesare needed to confirm these data.

Using data from‘visible’populations to estimate the size and importance of‘hidden’populations in an epidemic:A modelling technique

We used reported behavioural data from cisgender men who have sex with men and transgender women(MSM/TGW)in Bangalore,mainly collected from‘hot-spot’locations that attract MSM/TGW,to illustrate a technique to deal with potential issues with the representativeness of this sample.A deterministic dynamic model of HIV transmission was developed,incorporating three subgroups of MSM/TGW,grouped according to their reported predominant sexual role(insertive,receptive or versatile).Using mathematical modelling and data triangulation for‘balancing’numbers of partners and role preferences,we compared three different approaches to determine if our technique could be useful for inferring characteristics of a more‘hidden’insertive MSM subpopulation,and explored their potential importance for the HIV epidemic.Projections for 2009 across all three approaches suggest that HIV prevalence among insertive MSM was likely to be less than half that recorded in the surveys(4.5e6.5%versus 13.1%),but that the relative size of this subgroup was over four times larger(61e69%of all MSM/TGW versus 15%).We infer that the insertive MSM accounted for 10e20%of all prevalent HIV infections among urban males aged 15e49.Mathematical modelling can be used with data on‘visible’MSM/TGW to provide insights into the characteristics of‘hidden’MSM.A greater understanding of the sexual behaviour of all MSM/TGW is important for effective HIV programming.More broadly,a hidden subgroup with a lower infectious disease prevalence than more visible subgroups,has the potential to contain more infections,if the hidden subgroup is considerably larger in size.