Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Twitter is an indicator of “real-world performance”, thus is an appropriate arena to assess the social consideration and attitudes toward psychosis. Objective: To perform a mixed-methods study of the content and key metrics of tweets referring to psychosis in comparison to tweets referring to control diseases (Breast Cancer, Diabetes, Alzheimer’s and HIV). Methods: Each tweet’s content was rated as nonmedical (NM: testimonies, health care products, solidarity/awareness and misuse) or medical (M: included a reference to the illness’s diagnosis, treatment, prognosis or prevention). NM tweets were classified as positive or pejorative. We assessed the appropriateness of the medical content. The number of retweets generated and the potential reach and impact of the hashtags analyzed was also investigated. Results: We analyzed a total of 15,443 tweets: 8,055 classified as NM and 7,287 as M. Psychosis-related tweets (PRT) had a significantly higher frequency of misuse (33.38% vs 1.15%, p<0.001) and pejorative content (36.22% vs 11.33%, p<0.001). The medical content of the PRT showed the highest scientific appropriateness (100% vs 93.66%, p<0,001) and had a higher frequency of content about disease prevention. The potential reach and impact of the tweets related to psychosis were low, but they had a high retweet-to-tweet ratio. Conclusions: We show a reduced number and a different pattern of contents in tweets about psychosis compared to control diseases. Psychosis-related tweets showed a predominance of non-medical content with increased frequencies of misuse and pejorative tone. However, the medical content of psychosis-related tweets showed high scientific appropriateness aimed toward prevention.

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

Pharmacogenomics, the study of how genetic variations influence drug response, has become integral to cancer treatment as personalized medicine evolves. This review aims to explore key pharmacogenomic biomarkers relevant to cancer therapy and their clinical implications, providing an updated and comprehensive perspective on how genetic variations impact drug metabolism, efficacy, and toxicity in oncology. Genetic heterogeneity among oncology patients significantly impacts drug efficacy and toxicity, emphasizing the importance of incorporating pharmacogenomic testing into clinical practice. Genes such as CYP2D6, DPYD, UGT1A1, TPMT, EGFR, KRAS, and BRCA1/2 play pivotal roles in influencing the metabolism, efficacy, and adverse effects of various chemotherapeutic agents, targeted therapies, and immunotherapies. For example, CYP2D6 polymorphisms affect tamoxifen metabolism in breast cancer, while DPYD variants can result in severe toxicities in patients receiving fluoropyrimidines. Mutations in EGFR and KRAS have significant implications for the use of targeted therapies in lung and colorectal cancers, respectively. Additionally, BRCA1/2 mutations predict the efficacy of PARP inhibitors in breast and ovarian cancer. Ongoing research in polygenic risk scores, liquid biopsies, gene–drug interaction networks, and immunogenomics promises to further refine pharmacogenomic applications, improving patient outcomes and reducing treatment-related adverse events. This review also discusses the challenges and future directions in pharmacogenomics, including the integration of computational models and CRISPR-based gene editing to better understand gene–drug interactions and resistance mechanisms. The clinical implementation of pharmacogenomics has the potential to optimize cancer treatment by tailoring therapies to an individual’s genetic profile, ultimately enhancing therapeutic efficacy and minimizing toxicity.

In advanced HER2-positive breast cancer, the standard taxane-trastuzumab-pertuzumab (THP) regimen faces competition from new therapies, emphasizing the need for biomarkers to guide treatment. This study evaluates the HER2DX ERBB2 mRNA score as a prognostic predictor, aiming to tailor treatment strategies. We retrospectively analyzed 94 patients treated with the THP regimen between 2010 and 2024. The HER2DX ERBB2 mRNA score was categorized as low (n = 14), medium (n = 20), or high (n = 60), and its correlation with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models. The median follow-up was 31.5 months. Patients with ERBB2-high scores had significantly better median PFS (33.9 vs. 10.6 months, hazard ratio [HR] = 0.40, 95% CI: 0.24–0.69, p < 0.001) and OS (not reached vs. 30.8 months, HR = 0.26, 95% CI: 0.13–0.49, p < 0.001) compared to ERBB2-low patients. Based on these findings, further validation of this biomarker in tumor samples from the CLEOPATRA phase III trial is ongoing, which could help optimize treatment strategies in this population.

Purpose: Elacestrant has shown significantly prolonged progression-free survival compared with standard-of-care endocrine therapy in estrogen receptor–positive (ER-positive), HER2-negative metastatic breast cancer, whereas potential benefit in early-stage disease requires further exploration. The SOLTI-ELIPSE window-of-opportunity trial investigated the biological changes induced by a short course of preoperative elacestrant in postmenopausal women with early breast cancer. Patients and Methods: Eligible patients with untreated T1c (≥1.5 cm)-T3, N0, ER-positive/HER2-negative breast cancer with locally assessed Ki67 ≥10% received elacestrant at a daily dose of 345 mg for 4 weeks. The primary efficacy endpoint was complete cell cycle arrest, defined as Ki67 ≤2.7%, on day 28. Results: Overall, 22 patients were evaluable for the primary endpoint. Elacestrant was associated with a complete cell cycle arrest rate of 27.3% and a statistically significant Ki67 geometric mean change of −52.9% (P = 0.007; 95% confidence interval, −67.4 to −32.1). Notably, the treatment with elacestrant led to a shift toward a more endocrine-sensitive and less proliferative tumor phenotype based on PAM50-based gene signatures. Elacestrant increased the expression of immune-response genes (GZMB, CD4, and CD8A) and suppressed proliferation and estrogen-signaling genes (MKI67, ESR1, and AR). These biological changes were independent of the levels of Ki67 suppression on day 28. The most common adverse events were grade 1 anemia (21.7%), hot flushes (8.7%), constipation (8.7%), and abdominal pain (8.7%). One patient experienced a grade 3 cutaneous rash, leading to treatment discontinuation. No other serious adverse events were reported. Conclusions: Preoperative treatment with elacestrant in early breast cancer demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting.

Dairy products might influence breast cancer (BC) risk. However, evidence is inconsistent. We sought to examine the association between dairy product consumption—and their subtypes—and incident BC in a Mediterranean cohort. The SUN (“Seguimiento Universidad de Navarra”) Project is a Spanish dynamic ongoing cohort of university graduates. Dairy product consumption was estimated through a previously validated 136-item food frequency questionnaire (FFQ). Incident BC was reported in biennial follow-up questionnaires and confirmed with revision of medical records and consultation of the National Death Index. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with Cox regression models. Among 123,297 women-years of follow-up (10,930 women, median follow-up 12.1 years), we confirmed 119 incident BC cases. We found a nonlinear association between total dairy product consumption and BC incidence (p_nonlinear = 0.048) and a significant inverse association for women with moderate total dairy product consumption (HR_Q2vs.Q1 = 0.49 (95% CI 0.28–0.84); HR_Q3vs.Q1 = 0.49 (95% CI 0.29–0.84) p_trend = 0.623) and with moderate low-fat dairy product consumption (HR_Q2vs.Q1 = 0.58 (95% CI 0.35–0.97); HR_Q3vs.Q1 = 0.55 (95% CI 0.32–0.92), p_trend = 0.136). In stratified analyses, we found a significant inverse association between intermediate low-fat dairy product consumption and premenopausal BC and between medium total dairy product consumption and postmenopausal BC. Thus, dairy products, especially low-fat dairy products, may be considered within overall prudent dietary patterns.