The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes. The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively. Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs. -2.1 for capecitabine (95% confidence interval [CI], 1.4-8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale. Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated. NCT02028507 (ClinTrials.gov). 2013-003170-27.

Hormone receptor–positive (HR ⁺ ) breast cancers (BCs) are typically “immune-cold,” poorly immune-infiltrated tumors that do not respond to immune-checkpoint blockade (ICB) therapies. Using clinical data, we report that estrogen receptor α (ERα) signaling was associated with immunosuppressive pathways and a lack of response to ICB in patients with HR ⁺ BC. In this study, we validated ER-mediated immunosuppression by engineering and modulating the ER in preclinical models in vitro, in vivo, and ex vivo. Mechanistically, we found that ERα hijacked LCOR, a nuclear receptor corepressor, thereby preventing LCOR’s function in the induction of tumor immunogenicity and immune infiltration, which is normally observed in the absence of ERα, such as in ER ^– BC. In HR ⁺ BC, we demonstrate that the molecular disruption of LCOR and ERα interaction using anti-ER therapies or using a mutant of the LCOR nuclear receptor–binding domain (LSKLL into LSKAA) that does not interact with ERα, restored the immunogenic functions of LCOR. Remarkably, the LCOR-ERα disruption converted HR ⁺ BC immune-cold tumors into immune-hot tumors responsive to ICB by increased antigen presentation machinery expression, immune infiltration, T cell recognition, and T cell–mediated killing. In conclusion, ERα inhibition and the disruption of LCOR-ERα interaction represent a therapeutic strategy and an opportunity to elicit immunotherapeutic benefit in patients with HR ⁺ BC.

Purpose: The aim of this study was to compare estimates of adherence to oral endocrine therapy (OET) based on real-world data (RWD) and on clinical evaluation in people diagnosed with breast cancer in the public healthcare system in Catalonia (Spain). Methods: We conducted two retrospective cohort studies. Cohort 1 (RWD) consisted of women diagnosed with breast cancer in 2021 in the public healthcare system of Catalonia (Spain). Sources of RWD were the pharmacy billing register, hospital discharge records, and the Catalan health division’s central insurance registry. Nonadherence was defined as below 80% adherence in the first year of treatment. Data for cohort 2 came from two population-based cancer registries in Girona and Tarragona (Catalonia), with diagnoses from 2007 to 2011. We evaluated the impact of variables missing from RWD, such as stage and hormonal status. Analyses were performed using a chi-square test and logistic regression, with results stratified by age group and drug type. Results: Nonadherence at one year was 10.9% in cohort 1 and 11.3% in cohort 2. When we reviewed the medical records of a selection of nonadherent women from cohort 1, we found only 59.4% had documented treatment interruptions. Reasons for interruptions in the patients from RWD cohort included adverse effects (48.8%), patient decision (40.0%), medical reasons (29.4%), and other clinical causes (14.7%). Women aged under 50 years and those receiving tamoxifen or a sequential regimen had lower adherence. Determinants associated with nonadherence were similar in both approaches used. Conclusions: This study confirms the validity of estimating adherence with RWD from the Spanish national health system, although when combined with reviewing medical records, this may provide more reliable and higher-quality data. The RWD method provides valuable evidence to help oncologists discuss adherence with their patients.

Human epidermal growth factor receptor 2 (HER2) is a treatment target in breast cancer (BC), driving therapeutic strategies. Changes over time in HER2 expression have been described and understanding of these fluctuations is crucial for personalized medicine. We aimed to assess HER2 expression dynamics using real-world data and natural language processing (NLP) from electronic health records (EHRs). RosHER is a retrospective, observational, longitudinal, population-based, multicenter study (NCT05217381). An NLP tool extracted HER2 information from EHRs of adult patients with early, locally advanced, or de novo metastatic BC, who were initially diagnosed between 2005 and 2021. The primary endpoint was to evaluate HER2 dynamics in HER2 status and expression between initial diagnosis and recurrence or progression using NLP. The secondary endpoints were description of baseline clinicopathological characteristics and treatment patterns. Between January 2022 and November 2023, 18 533 patients were selected from seven Spanish sites. A cut-off of ≥6 months was established between initial determination and relapse or progression. The artificial intelligence (AI)-based tool identified 510 patients with two documented HER2 determinations and 209 with HER2 expression by immunohistochemistry/in situ hybridization. Overall discordances were 10.6% in HER2 status and 34.0% in HER2 expression. HER2-zero expression switched to HER2-low (23.2%), but not HER2-positive (0%); HER2-low expression converted to HER2-zero (32.0%) and HER2-positive (7.0%); finally HER2-positive expression switched to HER2-low (20.8%) and HER2-zero (15.1%). This is the first study using NLP to evaluate HER2 discordances, which need to be further investigated. Improving AI methods and implementing similar EHR structures among hospitals would increase the success in clinical data extraction.

Background: Up to 80% of patients undergoing taxanes or platinum-based chemotherapy (CT) develop a peripheral polyneuropathy (CIPN), that affects treatment compliance and quality of life (QoL). CIPN is characterized by a remarkable sensitization of peripheral nociceptive endings. We performed a proof-of-concept, double-blind, randomized, two-arms, multicenter clinical study to evaluate if protecting epidermal nociceptive endings with a topical nociceutical formulation prevented CIPN and augmented QoL during CT. Material and methods: Participants started a daily topical application of the assigned formulation in hands (moisturizing or nociceutical). Upon appearance of neuropathic symptoms in hands or feet, they applied the creams twice daily. Diagnosis and follow-up of CIPN was performed using the CTC AE v5.0 criteria. Results: A cohort of 142 patients treated with taxanes and/or platinum agents were randomly distributed into the arms. Withdrawals were similar in both arms. A lower CIPN incidence in hands was observed in the nociceutical arm (32% vs 13%, p = 0.03), while a similar number of participants developed CIPN in feet (73% vs 67%, p = 0.1). Interestingly, the nociceutical formulation increased the number of CT cycles CIPN free (6 vs 8 cycle, p = 0.009). The Leonard Scale Questionnaire revealed that 60% of patients using the moisturizing cream reported frequently bothersome neuropathic symptoms, compared with only 39% in the nociceutical group ( p = 0.0017). Conclusion: Protection of nociceptive epidermal terminals with a topical nociceutical formulation reduced the incidence of CIPN in hands and increased the QoL of patients. These findings provide a solid ground for a confirmatory clinical study.