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Background: The combination of endocrine therapy with the cyclin-dependent kinases 4/6 inhibitor palbociclib was proven to be effective for the treatment of hormone receptor (HR)-positive/HER2-negative metastatic breast cancer (MBC). Although generally well tolerated, treatment delays and dose reductions are frequently observed with palbociclib, mainly due to severe neutropenia. Predictors of palbociclib-related toxicities are still unknown, as well as the clinical relevance of its relative dose intensity (RDI). Henceforth, this study aimed to identify baseline clinicopathological features associated with a RDI Methods: We reviewed data of 150 consecutive patients with HR-positive/HER2-negative MBC patients treated with palbociclib at two Italian cancer centers from 2017 to 2019. Eligible patients must have received at least 3 cycles of treatment. Those who experienced early suspension due to unacceptable toxicities were still eligible. RDI was calculated as the ratio of actual dose intensity (cumulative administered dose/treatment duration) and planned dose intensity (cumulative planned dose/planned treatment duration). The association of both RDI Results: Overall, 142 patients were deemed eligible. Of these patients, 98 (69.0%) were treated with palbociclib plus fulvestrant, 44 (31.0%) with palbociclib plus aromatase inhibitors, and 73 (51.4%) in the first-line setting. The median number of administered palbociclib cycles was 8 (range: 1-24) and 61 patients (43.0%) required at least a first-level dose reduction (29 within 3 months). Furthermore, the median time to first dose reduction was 3.22 months, with neutropenia being responsible for 85.24% of first-level dose reductions. In the whole cohort, median RDI was 90.5% (95.1% for patients without dose reduction and 80% for those who had received a dose reduction). Notably, 28 patients (19.7%) experienced a RDI Conclusions: In our analysis, baseline weight and WBC were statistically associated with a RDI Citation Format: Giacomo Pelizzari, Elisa Bertoli, Marco Giavarra, Carla Corvaja, Lorenzo Gerratana, Debora Basile, Michele Bartoletti, Camilla Lisanti, Lucia Bortot, Silvia Buriolla, Mattia Garutti, Debora Avoledo, Marta Bonotto, Lucia Da Ros, Silvia Bolzonello, Mauro Mansutti, Paola Di Nardo, Gianpiero Fasola, Simon Spazzapan, Alessandro M Minisini, Fabio Puglisi. Predictors of relative dose intensity and early dose reduction in patients with metastatic breast cancer treated with palbociclib and endocrine therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-08.

Background: Over the last years, the management of patients with node positive early breast cancer has gone through important innovations. On the medical side, new targeted therapies such as olaparib and abemaciclib have been introduced, with promising results on the invasive disease-free survival. Moreover, sparing axillary lymph node dissection has proven to be noninferior in terms of overall survival. However, no tools are currently available to predict lymph node involvement before definitive surgical evaluation. The aim of the study was to analyze clinical and pathological characteristics of patients with node positive early breast cancer to explore potential risk profiles associated with a ≥3 nodal involvement. Methods: The study retrospectively analyzed 335 node-positive breast cancer patients treated at the Breast Unit of the CRO Aviano National Cancer Institute, between 2017 and 2021. Data regarding primary tumor biological features, lymph node involvement and surgical approach were collected. Associations between clinico-pathological characteristics and ≥3 lymph node involvement were tested through stepwise logistic regression and the gradient boosting machine learning algorithm (GBM). Results: Among the 335 analyzed patients, 87.0% had a primary tumor < 5 cm, with a single positive lymph node in 73.3% of cases. Hormone receptors were mainly positive (respectively 93.5% and 83.4% for estrogen and progesterone receptors). Tumor grade was most frequently well differentiated (Grade 1 in 60.7%), with a Ki67 < 20% (59.5%). After multivariable logistic regression, a tumor size ≥ 3 cm (OR 3.24, CI95% 1.47-7.17, p = 0.004), the presence of massive lymphovascular stromal invasion (OR 2.50, CI95% 1.02-6.14, p = 0.045) and 2 or more positive sentinel lymph nodes at surgical evaluation (OR 6.08, CI95% 3.34-11.05, p < 0.001) were associated with a higher risk of identifying ≥ 3 positive lymph nodes after subsequent axillary dissection. Similar results were observed in the luminal-like cohort. A GBM machine learning model was then developed with a 0.77 Area Under the Curve. Features with the highest relative importance (RI) were single sentinel node involvement (RI 16.1873), followed by tumor size ≥ 3 cm (RI 10.2024), ≥2 positive sentinel lymph nodes (RI 8.5050) and lymphovascular stromal invasion (4.0217). Consistently, number of positive sentinel lymph nodes and tumor size were the predominant features in all top 20 GBM models. Conclusions: The present study explored the definition of risk profiles linked to 3 or more positive lymph nodes based on clinical and pathological features. It, moreover, tested the feasibility of developing machine learning classifiers to support future clinical decision-making. Due to the growing complexity of the adjuvant setting, finding a balance between minimally invasive surgical and staging approaches and risk definition for treatment personalization will become increasingly critical. Citation Format: Tania Pivetta, Brenno Pastò, Martina Urbani, Elisabetta Benozzi, Nicola De Pascalis, Tiziana Perin, Mario Mileto, Bruno Pasquotti, Erica Piccoli, Lorenzo Vinante, Chiara Bampo, Silvia Bolzonello, Mattia Garutti, Milena Nicoloso, Serena Corsetti, Simona Scalone, Lucia da Ros, Paola di Nardo, Camilla Lisanti, Simon Spazzapan, Barbara Belletti, Michele Bartoletti, Lorenzo Gerratana, Samuele Massarut, Fabio Puglisi. Clinical and biological predictors of lymph node involvement in patients with early breast cancer for adjuvant treatment personalization [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-06.