Breast cancer is the most frequent cancer in women: in 2018, almost two million cases have been diagnosed all over the world and it represents the principal cause of death from a neoplastic disease in women. In the past years, breast cancer prognosis has significantly improved over time: currently 5-year survival rates are in the range of 90%, and 10-year survival is about 80%. This improvement has been mostly observed in western countries, due to high coverage and compliance with screening programs, leading to early diagnosis, i.e., when the disease is at a subclinical level, and to an improvement in tumor molecular characterization and innovative systemic treatments. Yet the identification of different biological breast cancer subtypes prompted the development of innovative targeted agents and improved treatment personalization. On the other hand, longer survival rates and increasing proportions of cured patients require dedicated strategies to manage long-term sequelae of breast cancer treatments, with particular attention to quality of life. This review analyzes the most important issues, potentially occurring with cancer treatments, concerning long-term sequelae and quality of life, to define a global approach to breast cancer survivorship.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, despite several advances has been achieved in last decades. Few prognostic and predictive biomarkers guide therapeutic choice in metastatic CRC (mCRC), among which DNA mismatch repair deficiency and/or microsatellite instability (dMMR/MSI) holds a crucial role. Tumors characterized by dMMR/MSI benefit from immune checkpoint inhibitors. However, most of the mCRC patients (around 95%) are microsatellite stable (MSS), thereby intrinsically resistant to immunotherapy. This represents a clear unmet need for more effective treatments in this population of patients. In this review, we aim to analyze immune-resistance mechanisms and therapeutic strategies to overcome them, such as combinations of immunotherapy and chemotherapy, radiotherapy or target therapies specifically in MSS mCRC. We also explored both available and potential biomarkers that may better select MSS mCRC patients for immunotherapy. Lastly, we provide a brief overview on future perspectives in this field, such as the gut microbiome and its potential role as immunomodulator.

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Objectives To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death. Methods One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected. Results 98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period of time. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support. Conclusions Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients did access to Psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home-centered in Italy.

e15263 Background: The introduction of immune check-point inhibitors (ICIs) in the treatment of a broad range of tumor types has led to a significant and clinically meaningful improvement in overall survival (OS) in advanced disease stages. However, the efficacy of these agents is not consistent across trials and in routine practice. The role of PD-L1 expression as a tumour-agnostic predictive correlate of response to ICIs remains unclear. We performed a pooled analysis of the efficacy of PD-1/PD-L1-targeted ICI regimens as compared to standard of care (SoC) therapy according to PD-L1 expression, based on landmark clinical studies. Methods: We searched literature databases to identify phase III randomized controlled trials that compared anti-PD-1/PD-L1 antibodies alone or in combination with chemotherapy or targeted agents against SoC therapy in the treatment of different tumor types. We reported efficacy data, in terms of OS, according to PD-L1 status. Log hazard ratios (HRs) were pooled across the studies overall and by PD-L1 status by inverse variance weighting. All statistical tests were two-sided. Results: Twenty-four studies including 17687 randomised patients with advanced lung, renal, urothelial, liver, breast, head and neck cancers and melanoma, were eligible for analysis. Efficacy according to PD-L1 immunohistochemical expression, with a 1% cutoff ( < 1% versus > 1%), was reported in 11 studies (7126 patients). Overall, ICI-containing regimes were significantly superior in terms of OS to SoC regimens (pooled HR = 0.64; 95% CI 0.60 to 0.68). When OS data were pooled according to PD-L1 expression, HR was 0.66; 95% CI 0.61 to 0.71 in PD-L1 < 1%, versus 0.62; 95% CI 0.56 to 0.68 in PD-L1 >1% (p = 0.7). Conclusions: The significant improvement in OS favoring the use of ICIs over SoC does not seem to be confined to patients with PD-L1-overexpressing tumours. The difference in efficacy according to PD-L1 status appears to be, at best, marginal.

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1024 Background: Estrogen receptors (ER) are considered predictive biomarkers to identify ER+ MBC patients who would likely benefit from endocrine therapies (ET). However, 30 to 40% of ER+ MBC patients fail to achieve a durable response. 18F-FES PET/CT has been shown to represent a valuable and accurate diagnostic tool to determine ER status at the level of metastatic sites and can be proposed as a valid alternative to biopsy of metastatic lesions. In this trial, we evaluated 18F-FES PET/CT as a predictive tool for endocrine responsiveness in ER+ MBC. Methods: ET-FES is an international, multicenter, academic clinical trial, conducted within the JTC-2011 ERA-NET TRANSCAN programme. Patients with ER+/HER2- MBC and first evidence of relapse were eligible for the study. All patients underwent a baseline 18F-FES PET/CT in addition to conventional staging procedures. Tumors were classified as endocrine sensitive if overall Standardized Uptake Value (SUV) ≥ 2; SUVmax was measured in the 3 largest lesions to quantify ER expression and a cutoff value of 2 was used to dichotomize results (endocrine sensitive vs resistant). In the ET-FES trial, patients with SUV ≥ 2 received single agent ET until PD; patients with SUV < 2 were randomized to receive single agent ET or chemotherapy (CT). The predictive role of 18F-FES PET/CT results was assessed for PFS and OS by univariate and multivariate analyses. Results: Overall, 147 patients (142 for ITT analysis) were enrolled from 04/2015 to 12/2020; 113 presented with 18F-FES SUV ≥ 2 and received ET; 29 pts, with SUV < 2 were randomly assigned to ET or first line chemotherapy (CT), following local clinical practice. After a median follow up of 4.6 years, 51 deaths had occurred (54.2%). Median PFS was 18,0 months (95%CI 11,2- 22,9) in the overall population and in 18F-FES SUV ≥ 2 versus 12,4 months (95%CI 3,1 – NR) in patients with SUV <2 treated with ET and 23.0 months (95%CI 7,7 – 30,0) if treated with CT. Median OS was not reached in the overall patient population and in patients with SUV ≥2, treated with single agent ET. Median OS was 28.1 months (95%CI 14,2 – NR) in patients with SUV <2 treated with ET versus 52,8 months (95%CI 16,1 – NR) if treated with CT. The Kaplan–Meier estimate of OS at 48 months was 64.4% (SE +/-5%) in all patients and 66% in 18F-FES SUV ≥ 2; at 60 months was 54.4% (SE +/-6%) and 57% (SE +/-5%), respectively. Among the 113 pts with SUV ≥ 2 treated with ET, the Kaplan–Meier estimate of OS at 60 months was 73.0% if treated with aromatase inhibitors versus 35% in case of fulvestrant or tamoxifen (p< 0.0005). Conclusions: ET-FES is the first prospective trial to assess the efficacy of ET alone in patients selected for endocrine responsiveness on the basis of whole body molecular ER imaging by 18F-FES PET/CT. These results suggest that the efficacy of ET may be maximized by using the appropriate assessment of endocrine responsiveness at the different metastatic sites. Clinical trial information: EUDRACT 2013-000-287-29 .