The predominant forms of breast cancer (BC) are hormone receptor-positive (HR+) tumors characterized by the expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). Patients with HR+ tumors can benefit from endocrine therapy (ET). Three types of ET are approved for the treatment of HR+ BCs and include selective ER modulators, aromatase inhibitors, and selective ER downregulators. ET is the mainstay of adjuvant treatment in the early setting and the backbone of the first-line treatment in an advanced setting; however, the emergence of acquired resistance can lead to cancer recurrence or progression. The mechanisms of ET resistance are often related to the occurrence of mutations in the ESR1 gene, which encodes the ER-alpha protein. As ESR1 mutations are hardly detectable at diagnosis but are present in 30% to 40% of advanced BC (ABC) after treatment, the timeline of testing is crucial. To manage this resistance, ESR1 testing has recently been recommended; in ER+ HER2− ABC and circulating cell-free DNA, so-called liquid biopsy appears to be the most convenient way to detect the emergence of ESR1 mutations. Technically, several options exist, including Next Generation Sequencing and ultra-sensitive PCR-based techniques. In this context, personalization of ET through the surveillance of ESR1 mutations in the plasma of HR+ BC patients throughout the disease course represents an innovative way to improve the standard of care.

Based on immunohistochemistry (IHC) and in situ hybridization (ISH), HER2-low breast cancers (BC) subtype—defined as IHC1+ or IHC2+/ISH− tumors—emerged and represent more than half of all BC. We evaluated the performance of NGS for integrated molecular characterization of HER2-low BC, including identification of actionable molecular targets, copy number variation (CNV), and microsatellite instability (MSI) analysis. Thirty-one BC specimens (11 HER2+, 10 HER2−, and 10 HER2-low) were routinely analyzed using IHC and ISH, and were selected and analyzed using NGS for gene mutations including ESR1, PIK3CA, AKT1, ERBB2, TP53, BRCA1, and BRCA2, CNV, and MSI. CNV values for the ERBB2 gene were significantly (p < 0.001) different between HER2+, and either HER2-low or HER2− tumors with mean values of 7.8 (SD = 6.8), 1.9 (SD = 0.3), and 2.0 (SD = 0.3), respectively. Using 3.25 as the cutoff value, 96.8% overall concordance of HER2 status was achieved between IHC and NGS compared to IHC and ISH. Using NGS, gene mutations and amplifications were detected in 68% (21/31) and 19% (6/31) of the cases, respectively. One case of MSI was detected in a HER2-negative and ISH unamplified case. Beside IHC, NGS allows the identification of HER2-low subtype simultaneously, with the detection of multiple actionable gene mutations being helpful for molecular board treatment selection.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved the prognosis of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), but their impact on the efficacy of second-line treatments remains poorly described. This retrospective study included patients from the Epidemiological Strategy and Medical Economics database who initiated endocrine therapy ± CDK4/6i as first-line treatment for HR-positive/HER2-negative MBC between 2008 and 2019 across 18 French cancer centres and subsequently received second-line therapy. Objectives were to describe treatment patterns, time to progression (TTP), and post-progression survival after CDK4/6i, and to compare chemotherapy efficacy between CDK4/6i-exposed and historical CDK4/6i-naive patients, using propensity score adjustments. Among 13 577 HR-positive/HER2-negative MBC patients, 538 received CDK4/6i and 4030 received endocrine therapy alone as first-line treatment. Following CDK4/6i exposure, 47% of patients received chemotherapy as first subsequent treatment {median TTP 5.94 months [95% confidence interval (CI) 5.23-7.10 months]; 5.00 months (95% CI 3.68-6.63 months) for taxanes, 6.43 months (95% CI 3.87-12.29 months) for anthracyclines, 7.62 months (95% CI 6.13-8.30 months) for fluoropyrimidines}, 26% received endocrine therapy alone [6.14 months (95% CI 4.43-10.03 months)], 16% received phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors [5.16 months (95% CI 3.90-6.48 months)], and 9% underwent CDK4/6i rechallenge [9.57 months (95% CI 6.0 months-not applicable)]. In the comparative analysis, chemotherapy appeared slightly less effective in CDK4/6i-exposed patients than in CDK4/6i-naive patients, with a median TTP of 5.77 months (95% CI 5.13-6.67 months) versus 7.77 months (95% CI 7.428.07 months), respectively. This difference remained significant after adjusting for patient characteristics (hazard ratio 1.26, P = 0.003), except for comparison with fluoropyrimidine-based regimens, which showed comparable efficacy across groups. This study highlights the variability in second-line treatment strategies following CDK4/6i and suggests the presence of cross-resistance reducing the efficacy of subsequent chemotherapy.

To evaluate outcomes of first-line ET + CDK4/6i for HR+/HER2 metastatic breast cancer (MBC) based on BRCA/PALB2 mutations status known at treatment initiation. This cohort study included patients from 18 French comprehensive cancer centers treated with first-line ET and CDK4/6i between August 1, 2013, and December 31, 2023. Multivariable models including a Cox proportional hazard with a time-varying approach and landmark analyses at different timepoints (at the initiation of the first-line therapy and at 6 months after the initiation of the first line) assessed the association between germline and/or somatic BRCA and PALB2 genes alteration (categorized as "BRCA/PALB2m" (mutated) "BRCA/PALB2wt" (wild type), and "untested"), with progression-free (PFS) and overall survival (OS). Among 4283 eligible patients, baseline status was categorized as BRCA/PALB2m in 80 patients (1.9%), BRCA/PALB2wt in 467 patients (10.9%), and untested in 3736 patients (87.2%). Median follow-up was 43.7 months [95%CI, 42.6-44.9]. Median PFS was significantly shorter in BRCA/PALB2m patients (9.9 months [7.6-13.0]) compared to BRCA/PALB2wt (15.4 months [13.9-17.3]) and untested patients (18.3 months [17.6-19.3]). In the multivariable analysis ((including age, number of metastatic sites, presence of visceral metastases, de novo status, and tumor grade), BRCA/PALB2m carriers had a shorter PFS compared to BRCA/PALB2wt (adjusted HR [95% CI] 1.61 [1.24-2.09]; p < 0.001). Time-varying approach, landmark analysis at 6-months and propensity score matching analysis showed consistent results. In this cohort, using a careful methodology, BRCA1/2 and PALB2 mutation carriers had reduced PFS with first-line ET + CDK4/6i compared to wild-type patients.

Background: Sarcopenia is a recognized adverse prognostic factor in many cancers and can be reliably assessed using computed tomography (CT) scans. Its prognostic value in bladder cancer patients undergoing neoadjuvant chemotherapy remains underexplored. This study aimed to assess sarcopenia’s impact on survival and compare different measurement thresholds. Methods: We conducted a retrospective multicenter study including patients with invasive urothelial carcinoma treated with neoadjuvant chemotherapy followed by cystectomy between 2015 and 2021. Sarcopenia was assessed by measuring the Skeletal Muscle Index on CT scans before chemotherapy (BC) and prior to surgery (BS). The primary endpoint was overall survival. Secondary endpoints included progression-free survival (PFS), pathological complete response (pCR), and treatment-related complications. Results: Seventy-four patients were included, the majority receiving the MVAC regimen (71.7%). Forty percent of patients achieved a pCR, 35% experienced disease recurrence, and the median PFS was 25 months. Sarcopenia was observed in 27% of patients BC and in 39% BS. Sarcopenia was associated with an increased risk of all-cause mortality: BC according to the definition by Martin et al. (HR 3.38; 95% CI [1.25–9.12]; p = 0.016) and Fearon et al. (HR 4.03; 95% CI [1.13–14.3]; p = 0.031); and BS according to Martin et al. (HR 3.7; 95% CI [1.12–12.2]; p = 0.032) and Fearon et al. (HR 6.08; 95% CI [1.48–24.9]; p = 0.012). Sarcopenia was an independent risk factor of shorter PFS. Conclusions: Sarcopenia represent an independent and reproducible prognostic factor for mortality in patients with bladder cancer. The study is the first study to compare threshold values at different time points.

Background: The transition from traditional handwritten prescriptions to electronic prescribing systems represents a significant advancement, with the potential to enhance treatment efficacy, patient safety, and professional communication. Objective: This study aimed to examine the impact of this transition within a medical oncology service, assessing the compliance of electronic prescriptions with established good practice standards and exploring the associated risks. Methods: In this retrospective analysis, we compared handwritten prescriptions from the pre-electronic era (January to May 2018) with electronic prescriptions (January to May 2021) following the implementation of the electronic prescribing system PandaLab Pro (PandaLab SAS). The inclusion criteria focused on outpatient oncology treatments, with a clear set of exclusion parameters to ensure a focused study scope. We defined good compliance as the written mention of the evaluated terms. The compliance rates were then compared using a chi-square test. Results: Our findings, based on a sample size of 260 prescriptions (randomized among 30,526 archived prescriptions), indicate a substantial improvement in electronic prescriptions’ compliance with prescribers and patient details, treatment accuracy, and overall adherence to regulatory standards. Notably, electronic formats achieved a remarkable 80.8% accuracy rate in compliance with safety criteria compared with 8.5% for handwritten prescriptions (P<.001). The use of prefilled prescriptions significantly increased compliance from a safety perspective (56% vs 96.2%; P<.001) compared with electronic prescriptions from scratch. Conclusions: The analysis further underscores the advantages of prefilled electronic prescription templates, which significantly improved compliance rates compared with manually filled electronic and handwritten prescriptions. Furthermore, the study revealed a marked shift in prescribing behaviors, with electronic prescriptions tending to be more concise yet more numerous, suggesting an impact on medication management and patient adherence, which warrants further investigation. The study supports the transition to electronic prescribing systems in oncology, highlighting enhanced traceability, compliance with health authority standards, and patient safety. The implementation of prefilled templates supported by pharmacists has emerged as a pivotal factor in this improved process. While acknowledging certain limitations, such as the nonquantitative assessment of time savings and acceptability, this research advocates for the widespread adoption of electronic prescriptions and serves as a benchmark for future e-prescription initiatives in France.