Health-related quality of life and clinical complexity of a real-life cohort of patients with advanced HR+/HER2- breast cancer treated with CDK4/6 inhibitors and endocrine therapy.

Background: Advanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR+/HER2- ABC treated with CDK4/6 inhibitors. Methods: We evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs). Results: From January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort (p=0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline (p=0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities (p<0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation (p<0.05). No change in QLQ-C30 final score from T0 to T1 was observed (p>0.05). Conclusion: Multimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special_issues/tackling-clinical-complexity-in-breast-cancer/.

The prognostic role of variations in tumour markers (CEA, CA15.3) in patients with metastatic breast cancer treated with CDK4/6 inhibitors.

Tumour markers have no established role in the monitoring of the course of metastatic breast cancer during antineoplastic therapy, yet cancer antigen 15.3 (CA15.3) and carcinoembryonic antigen (CEA) are commonly used in clinical practice to aid in the early detection of progression of disease (PD). In our multicentre, prospective, real-life study, we enrolled 142 consecutive patients with advanced breast cancer receiving endocrine therapy in combination with a CDK4/6 inhibitor from January 2017 to October 2020; 75 patients had PD at the time of database closure. We measured serum marker concentrations at regular 4-month intervals together with radiological tumour response assessments and in cases of clinical suspicion of PD. Appropriate descriptive and inferential statistical methods were used to analyse serum marker level trends amongst prespecified subgroups and at specific time points (baseline, best radiologically documented tumour response and first detection of PD) in the subpopulation of patients with PD at the time of database closure. Notably, the median time from treatment initiation to best tumour response was 4.4 months. We evaluated the presence of an association between baseline CA15.3 and CEA levels and prespecified clinical characteristics but found no clinically meaningful correlation. We assessed marker level variations at the time of best radiologically documented disease response and PD: in the subgroup of patients who responded to treatment before progressing, we detected a statistically significant correlation with tumour marker variation between the time of best response and progression; this finding was not confirmed in the subgroup of patients that did not benefit from treatment. In conclusion, serum tumour marker flares can be useful in the early diagnosis of PD but should not be used as the sole factor prompting a change in treatment strategy without radiological confirmation.

Leptomeningeal carcinomatosis and breast cancer: a systematic review of current evidence on diagnosis, treatment and prognosis.

Leptomeningeal carcinomatosis (LC) is a rare but challenging manifestation of advanced breast cancer with a severe impact on morbidity and mortality. We performed a systematic review of the evidence published over the last two decades, focusing on recent advances in the diagnostic and therapeutic options of LC. Lobular histology and a triple-negative intrinsic subtype are well-known risk factors for LC. Clinical manifestations are diverse and often aspecific. There is no gold standard for LC diagnosis: MRI and cerebrospinal fluid cytology are the most frequently used modalities despite the low accuracy. Current standard of care involves a multimodal strategy including systemic and intrathecal chemotherapy in combination with brain radiotherapy. Intrathecal chemotherapy has been widely used through the years despite the lack of data from randomized controlled trials and conflicting evidence on patient outcomes. No specific chemotherapeutic agent has shown superiority over others for both intrathecal and systemic treatment. Although endocrine therapy was heuristically considered unable to exert significant control on central nervous system metastatic disease, retrospective data suggest a favourable toxicity profile and even a possible positive impact on survival. In recent years, encouraging data on the use of targeted agents has emerged but further research in this field is required. Palliative treatment in the form of whole brain or stereotactic radiotherapy is associated with improvement in clinical manifestations and quality of life, with no proven impact on survival. The most investigated prognostic factors include performance status, non-triple-negative disease and multimodal treatment. Validation of prognostic scores is necessary to aid clinicians in the identification of patient subgroups that are most likely to benefit from an intensive therapeutic approach.