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Endocrine-resistant, hormone receptor-positive, and HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) is largely governed by acquired mutations in the estrogen receptor, which promote ligand-independent activation, and by truncal alterations in the PI3K signaling pathway, with a broader range of gene alterations occurring with less prevalence. Circulating tumor DNA (ctDNA)-based technologies are progressively permeating the clinical setting. However, their utility for serial monitoring has been hindered by their significant costs, inter-technique variability, and real-world patient heterogeneity. We interrogated a longitudinal collection of 180 plasma samples from 75 HR+/HER2- mBC patients who progressed or relapsed after exposure to aromatase inhibitors and were subsequently treated with endocrine therapy (ET) by means of highly sensitive and affordable digital PCR and SafeSEQ sequencing. Baseline PIK3CA and TP53 mutations were prognostic of a shorter progression-free survival in our population. Mutant PIK3CA was prognostic in the subset of patients receiving fulvestrant monotherapy after progression to a CDK4/6 inhibitor (CDK4/6i)-containing regimen, and its suppression was predictive in a case of long-term benefit with alpelisib. Mutant ESR1 was prognostic in patients who did not receive concurrent CDK4/6i, an impact influenced by the variant allele frequency, and its early suppression was strongly predictive of efficacy and associated with long-term benefit in the whole cohort. Mutations in ESR1, TP53, and KRAS emerged as putative drivers of acquired resistance. These findings collectively contribute to the characterization of longitudinal ctDNA in real-world cases of HR+/HER2- mBC previously exposed to aromatase inhibitors and support ongoing studies either targeting actionable alterations or leveraging the ultra-sensitive tracking of ctDNA. Full article

Positive framing has been proposed as an intervention to increase COVID-19 vaccination intentions. However, available research has examined fictitious or unfamiliar treatments. This pre-registered study (aspredicted#78369) compared the effect of standard negatively framed EU patient information leaflets (PILs), with new positively framed PILs, on booster intentions (measured pre- and post-intervention) for AstraZeneca, Pfizer, and Moderna COVID-19 vaccines. A representative sample of 1222 UK-based adults was randomised to one of six groups in a factorial design with framing (Positive vs. Negative) and vaccine familiarity (same (as previous), familiar, unfamiliar) as factors. The benefit of positive framing was hypothesised to be strongest for the least familiar vaccine (Moderna). Framing was moderated by familiarity, where only the unfamiliar vaccine showed a benefit of positive relative to negative Framing. Framing and familiarity also interacted with baseline Intention with the effect of framing on the unfamiliar vaccine especially pronounced at low baseline Intent. Conversely, standard negative framing appeared to increase intentions for familiar vaccines at low baseline intent. Findings provide important evidence that positive framing could improve vaccine uptake globally when switches or new developments require individuals to receive less familiar vaccines. Positive framing of familiar vaccines, however, should be treated with caution until better understood. Full article

Writing (prosaic, non-fictional and (auto)biographical) and photography (as aesthetics and technology, language, material object and practice) can communicate and interrelate in the narration and depiction of physical disorders. The five articles in this Special Issue explore how the body and its pain and disorders can be accessed in projects that either interlace words and images within themselves or that communicate and interrelate with other written or visual texts produced by others. In these photo-textual encounters (or clashes), wounded, tormented, weakened bodies are narrated and mediated, as well as marked, modified and exposed by personal and emotional choices or by ideological and socio-historical circumstances. The articles invite us to reflect on the ideological discourses, issues of power, practice, ethics and agency that any illness implicates, as well as the flexible boundaries of the written and visual language narrating such an overpowering experience. Full article