Endocrine therapy (ET) is a cornerstone in the management of patients with hormone receptor-positive early breast cancer, which accounts for over 70% of cases worldwide. The efficacy of adjuvant ET for 5 years in reducing the risk of recurrence and improving survival outcomes is well documented. However, the risk for late relapses, occurring >5 years after initial treatment, has prompted exploration of longer treatment durations. Extending ET beyond the traditional 5-year period offers additional benefit in reducing the risk of recurrence and improving long-term outcomes. Nevertheless, determining the optimal duration and identifying suitable candidates for extended therapy is often nuanced. This review aims to comprehensively evaluate the current landscape of extended ET in breast cancer management. It provides an overview of the rationale behind extending endocrine treatment in both premenopausal and postmenopausal women, with a focus on clinical trials and observational studies supporting extended therapy. Furthermore, it emphasizes the significance of considering associated toxicities in patient management. It also explores novel strategies involving the combination of ET with new drugs, leading to an evolution of treatment paradigms that may make the need for extended therapy obsolete.

Background: Real-world safety profiles of immune checkpoint inhibitors (ICIs) in older adults remain insufficiently characterized. Although ICIs are widely used across tumor types, older patients, particularly those with frailty, multimorbidity, or polypharmacy, are consistently under-represented in clinical trials, limiting the external validity of trial-derived toxicity estimates. Robust real-world data are therefore essential to clarify the incidence, seriousness, and age-related patterns of immune-related adverse events (irAEs) in routine practice. Methods: This is a nationwide retrospective study of spontaneous ICI-related ADRs reported in INFARMED’s Portal RAM (2011–2024). We evaluated the frequency, seriousness, fatality, and organ-specific patterns of ICI-related adverse drug reactions (ADRs) reported to the Portuguese National Pharmacovigilance System. The analytic unit was the ADR case. Endpoints included seriousness (primary), fatality, hospitalization, time-to-onset, and System Organ Class. Multivariable logistic regression adjusted for age, sex, regimen, tumor type, polypharmacy, and calendar period; sensitivity analyses using first ADR per patient were concordant. Results: We identified 2300 eligible ICI-related ADRs (corresponding to 925 patients). Median age at the time of ADR was 65 years (IQR not reported); 33.7% occurred in adults aged ≥70 years, and 62.8% of reports involved male patients. PD-1 inhibitors accounted for 77.5% of ADRs, and monotherapy for 72.9%. Overall, 85.8% of ADRs were classified as serious; 17.9% led to hospitalization and 19.1% were fatal. Serious-event reporting was similar in older and younger adults (≥70 vs. <70 years: 84.5% vs. 86.5%, p = 0.22), and the proportion explicitly labeled immune-related did not differ (9.3% vs. 8.7%, p = 0.56). In contrast, fatal outcomes were significantly more common in older adults (25.3% vs. 16.0%; p < 0.001). Age was associated with distinct organ-specific patterns. Adults ≥ 70 years had higher odds of nervous system disorders (aOR 1.75, 95% CI 1.23–2.48) and immune system disorders (aOR 1.42, 95% CI 1.02–1.98), but lower odds of hepatobiliary (aOR 0.52, 95% CI 0.36–0.76; p = 0.001) and blood/lymphatic disorders (aOR 0.50, 95% CI 0.32–0.79). In multivariable models, age ≥ 70 years did not predict seriousness (aOR 0.98, 95% CI 0.76–1.27), whereas combination therapy remained independently associated with increased seriousness (aOR 1.57, 95% CI 1.13–2.18). Conversely, age ≥ 70 years independently predicted fatal outcomes (aOR 1.66, 95% CI 1.31–2.09). Later calendar periods (2017–2024) were associated with substantially lower fatality (aOR 0.16; 95% CI 0.10–0.27). CTLA-4-containing regimens demonstrated a tendency toward higher fatality (aOR 1.50; 95% CI 0.94–2.37). Conclusions: Chronological age does not seem to increase the likelihood of reporting a serious ICI-related ADR, but, once toxicity occurs, older adults experience higher fatality rates. Age-related phenotypic differences and regimen-specific risks highlight the need for early recognition systems and tailored toxicity management in older populations.

Introduction: The treatment landscape of hormone receptor-positive, HER2-negative (HR+/HER2–) metastatic breast cancer (BC) has been transformed with the advent of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). While myelosuppression is the most common adverse effect, interstitial lung disease (ILD) has emerged as a rare but potentially severe complication in real-world settings. Case Presentation: A 76-year-old woman with metastatic HR+/HER2– BC developed ILD after approximately 20 months of palbociclib therapy. Treatment discontinuation and high-dose corticosteroids resulted in symptomatic and radiological improvement. A concomitant pneumomediastinum was considered a secondary manifestation of ILD. Conclusion: ILD is an underrecognized but clinically significant toxicity of CDK4/6i, requiring early diagnosis and prompt intervention to prevent severe respiratory compromise. A high index of clinical suspicion, prompt diagnosis, and rapid treatment strategies are crucial, particularly in elderly patients, to minimize ILD-associated risks and complications. Further research is needed to establish predictive biomarkers and optimize management guidelines for CDK4/6i-induced ILD.

Real-World Effectiveness and Safety of Tucatinib, Trastuzumab, and Capecitabine in HER2-Positive Advanced Breast Cancer: A Multicenter Portuguese Study - European Journal of Breast Health

Background: Extended maintenance intervals up to 12 weeks for totally implanted venous access ports (TIVAPs) appear safe in oncology patients after chemotherapy, but the safety of 24-week flushing schedules is unknown. We evaluated a 24-week maintenance protocol implemented during the COVID-19 pandemic in cancer survivors with indwelling ports. Materials and methods: We performed a single-center retrospective cohort study including adults (⩾18 years) with solid tumors who had completed intravenous anticancer therapy and were transitioned to a 24-week flushing protocol (January 2020-December 2024). Patients with ongoing port use or shorter/irregular intervals were excluded. The primary endpoint was any port-related complication (occlusion, infection, thrombosis, mechanical failure, or other) during the maintenance phase. Incidence rates per 100 port-years, Kaplan-Meier event-free survival and a univariable Cox model for Charlson comorbidity index were calculated. Results: Among 105 patients (70.5% female; median age 60 years), breast and colorectal cancers accounted for 76.2% of tumors and 81.9% had early-stage disease. Median Charlson index was 0 (IQR 0–1). Ports were followed for 257.4 port-years (median 950 days), with a median of 5 maintenance visits and median interval 25.1 weeks; 88% of flushes occurred within ±4 weeks of schedule. Six patients (5.7%) experienced a complication: two occlusions, two mechanical malfunctions, one catheter-related thrombosis, and one pain-related removal; no infections or port-related deaths occurred. Overall incidence was 2.33 events/100 port-years (95% CI 0.86–5.07). Event-free survival was 97.0% at 12 months and 95.7% at 24 and 36 months; median was not reached. Charlson index was not associated with complications (HR 0.96, 95% CI 0.68–1.34; p = 0.79). Discussion: In a low-comorbidity, post-therapy population managed with standardized insertion and nursing protocols, a 24-week flushing interval yielded very low complication rates, comparable to those reported for 4–12-week schedules. The analytic cohort consisted predominantly of long-term, low-comorbidity survivors with ports already in place for several years, which likely reduced baseline complication risk. This selection bias limits generalizability to higher-risk populations. Although no infections were observed across 257 port-years, the confidence intervals remain wide due to the small number of events; therefore, these findings should be interpreted as suggestive rather than definitive evidence of safety. Conclusion: A 24-week TIVAP maintenance interval after completion of intravenous therapy appeared feasible and safe in this real-world cohort, with no infections and excellent port survival. These findings support cautious consideration of ultra-extended intervals in selected cancer survivors but require confirmation in larger prospective comparative studies before broad implementation. Categories: Supportive oncology, vascular access, health services and survivorship care.