Background Few data are available outlining outcomes of panitumumab in advanced colorectal cancer patients benefiting from prior cetuximab-based regimens. Patients and methods Thirty patients with KRAS wild type metastatic colorectal cancer with clinical benefit from prior cetuximab-based regimens between May 2004 and October 2011 were reviewed at nine Italian Institutions. Inclusion key criteria included interruption of cetuximab for reasons other than progressive disease. Patients were classified according to prior regimens (0 or ≥1), prior response or stabilization, surgery of metastases, and Köhne prognostic score. At the time of subsequent progression, patients were treated with single agent panitumumab until progressive disease, unacceptable toxicity, or consent withdrawal. Results Panitumumab obtained 67% disease control rate and 30% objective response rate, with median PFS of 4.2 and median OS of 9.6 mo. Patients with BRAF/NRAS/PI3KCA and KRAS (by mutant enriched technique) wild-type tumors had the best chance of response to panitumumab. Conclusions Single agent panitumumab provided significant clinical benefit in heavily pretreated patients without acquired resistance to prior cetuximab-based regimens.

Approximately 15% of breast cancers are classified as HER2-positive, with an amplification of the ERBB2 gene and/or an overexpression of the HER2 protein. Up to 30% of HER2-positive breast cancers shows heterogeneity in HER2 expression and different patterns of spatial distribution, i.e., the variability in the distribution and expression of the HER2 protein within a single tumour. Spatial heterogeneity may potentially affect treatment, response, assessment of HER2 status and consequently, may impact on the best treatment strategy. Understanding this feature can help clinicians to predict response to HER2-targeted therapies and patient outcomes, and to fine tune treatment decisions. This review summarizes the available evidence on HER2 heterogeneity and spatial distribution and how this may affect current available treatment choices, exploring possible opportunities for overcoming this issue, such as novel pharmacological agents, belonging to the group of antibody–drug conjugates.

Background: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a “less intensive” or personalized approach. Patients and methods: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx^®) as adjuvant chemotherapy. Patients who received surgery for pT1–3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m² biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. Results: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33–76), with mostly pre- and peri-menopausal (65%) and stage I–II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5–100%; interquartile range, IQR: 87.5–100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73–92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77–94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3–4.7) two distant events were observed, and all patients were alive at the date of last visit. Conclusions: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated and could be considered for further evaluation as a treatment option for patients with contraindications to standard anthracyclines or requiring a personalized, less intensive approach.

Background: Radiomics is changing clinical practice by providing quantitative information from images to improve diagnosis, prognosis, and treatment planning. This study aims to investigate a radiomics model developed from contrast-enhanced mammography (CEM) images to predict disease-free survival (DFS) and overall survival (OS) in breast cancer (BC) patients. Methods: From January 2013 to December 2015, all consecutive BC patients who underwent CEM before biopsy at a referral center were enrolled. Clinical data included histological results, receptor profiles, and follow-up (DFS and OS). A region of interest (ROI) of the enhancing lesion was selected from recombined CEM images by experienced radiologists, and radiomic features were extracted. A Cox-LASSO model assigned coefficients to the features, generating patient radiomic scores (RSs), which were dichotomized for graphical representation. Model performance was assessed using the C index. Results: The study included 126 BC patients with predominantly “mass”-type lesions (95%) and a median follow-up of 6.88 years (IQR 3.10–8.15). The median age of the patients at the time of examination was 49.2 years (IQR: [42.33–56.98]). Radiomic and clinical–radiomic models showed significant associations between RS, DFS, and OS, with patients with RS below the median showing a better prognosis (p < 0.001). Bootstrap testing confirmed a good model fit for OS prediction, with median C-index values of 0.82 for the clinical model and 0.84 for the clinical–radiomic model. Conclusions: Radiomic analysis of CEM images may predict DFS and OS in BC patients, offering additional prognostic value beyond clinical models alone.

Incomplete response to neoadjuvant chemotherapy (NACT) in triple negative breast cancer (TNBC) patients is correlated to high risk of relapse. This study aimed to evaluate the role of adjuvant chemotherapy in TNBC with residual tumor after NACT. We retrospectively reviewed the outcome of patients with TNBC with residual tumor at surgery after a neoadjuvant treatment, followed by either adjuvant chemotherapy or observation. Primary endpoints were Disease Free Survival (DFS) and Overall Survival (OS). Between January 2000 and December 2016, 223 patients with early TNBC operated at the European Institute of Oncology were eligible. A total of 83.4 % of patients received adjuvant chemotherapy after surgery. 90 patients received standard dose infusional regimens, while 96 patients (51.6 %) received oral metronomic chemotherapy. Adjusting the analysis by surgical stage and Ki67 value there was a benefit for DFS and OS in favor of the group that received postoperative chemotherapy (DFS-HR 0.58 p = 0.04; OS-HR 0.54, p = 0.02). At a subgroup analysis according to the different adjuvant treatments received, a benefit for metronomic chemotherapy versus no chemotherapy both for DFS (HR 0.46, p = 0.008) and OS (HR 0.45, p = 0.009) was reported. Our retrospective analysis in a large cohort of TNBC patients with residual disease after NACT confirms the benefit of adding a postoperative treatment to reduce risk of relapse and death. Based on these results, we suggest that the adjuvant therapy based on metronomic cyclophosphamide and methotrexate deserves further investigation in this patients population.

Up to 20% of premenopausal patients with early breast cancer (eBC) receiving adjuvant endocrine therapy with luteinizing hormone-releasing hormone agonists (LHRHas) plus aromatase inhibitors (AIs) exhibit inadequate ovarian function suppression (iOFS), defined by elevated serum estradiol (E2) levels. In clinical practice, endocrine therapy manipulations (ETMs) are frequently used to manage iOFS, as AIs are ineffective when iOFS occurs. However, the dynamics of serum E2 during LHRHa therapy and their changes after ETMs remain poorly characterized. This is a single-center cohort study including premenopausal women with eBC receiving adjuvant LHRHa plus AI who exhibited iOFS (E2 ≥24 ng/l on immune assays) between 2015 and 2024. The primary endpoint was time to optimal OFS (<24 ng/l). Serum E2 levels were monitored every 6 months during LHRHa therapy, and at least every 3 months following an iOFS episode. A total of 125 patients were included: 72 in the ETM group and 53 in the non-ETM group (median E2 levels at study entry: 47 and 33 ng/l, respectively). Overall, 14% reported concomitant vaginal bleeding or spotting (all in the ETM group), and 78% had their first iOFS within the second year of LHRHa-based therapy. The most common ETMs were shortening the LHRHa dosing interval (71%) and switching to a different LHRHa agent (25%); 38% required a second ETM during the same episode due to persistent E2 ≥24 ng/l. With a median follow-up of 54.9 months, the median time to optimal OFS was 6.1 months [95% confidence interval (CI) 5.0-7.1 months] in the ETM group and 5.5 months (95% CI 4.5-6.6 months) in the non-ETM group. A second episode of iOFS occurred in 37% of patients. This study shows that iOFS is a transient, potentially recurring, and clinically manageable event that may occur at any point during LHRHa therapy. Among patients receiving LHRHa plus an AI, given the pharmacodynamic implications, our findings support continuous E2 monitoring throughout LHRHa-based treatment to guide the timely implementation of ETMs.