Abstract PS2-06-14: Breast Cancer (BC) in Younger Women: A Multicentre Cohort Study of Clinical and Pathological Features

Abstract Background Younger women with BC have more aggressive disease and poorer survival than older women.1 Incidence is rising faster in this group (1.4% in <50y vs 1% overall), yet they remain underrepresented in trials, limiting insights into their distinct tumour biology and risk profiles.2˒3 Aim To examine risk factors, clinicopathological features, age-related trends, and treatment responses in women <50y with BC. Methods We conducted a multicentre retrospective study of women <50y (n=337) diagnosed with invasive BC. All cases were discussed at the University College London Hospital (UCLH) and Whittington Health (WH) Breast Multidisciplinary Team meetings (May 2019-February 2025). Patients were stratified into five age groups: ≤30, 31-35, 36-40, 41-45, 46-49y. Variables included age at diagnosis, risk factors, tumour characteristics, recurrence, and treatment data. Categorical variables were compared with Chi-squared/Fisher’s exact tests; continuous variables with Mann-Whitney/Kruskal-Wallis tests. Logistic regressions were performed to assess associations. Results Patients aged ≤30 had more node-positive disease at diagnosis than patients aged 41-49 (OR 3.085; p=0.022). Younger age was associated with a higher-grade (≤30y: 73.7% G3; p=0.002) and a higher Ki-67 (p=0.028). The youngest women had lower BMI (p=0.026). A higher BMI was associated with increased odds of G3 tumours (p=0.024) and TNBC (p=0.007). The full <50 cohort showed higher rates of G3 (42.7%) and node-positive tumours (44.8%) than general BC population datasets.4,5 Most BC diagnoses in parous women occurred within 10 years postpartum (57.5%), supporting a postpartum risk window. Genetic mutations were more frequent in younger women (p=0.020). 47.2% of mutation carriers had no family history of BC. Neoadjuvant systemic therapy was administered to 26.1% of patients, achieving a pathological complete response in 64.7% of TNBC and 61.1% of HER2-positive cases. At the time of analysis, 15 patients (4.5%) had documented recurrence and 6 (1.8%) had died. Conclusions BC in women <50y, particularly those ≤30y, is characterised by higher grade, elevated Ki-67, and more frequent nodal positivity. Clinicians must maintain a high index of suspicion when evaluating breast symptoms in young women, and perform careful nodal assessment. Our findings also challenge the reliance on family history for genetic testing, indicating that the current UK testing criteria should be expanded to a wider patient cohort to avoid missing pathogenic mutations. Future work must prioritise survivorship, addressing impacts on fertility, premature menopause, and psychological wellbeing in this population. A key limitation of this study is its small retrospective design. To strengthen the evidence base, a prospective registry capturing clinical, pathological, and survivorship data in young women with BC should be considered. Citation Format: R. Boopathy, R. Javed, B. Gwyther, B. Kirresh, J. Islam, A. Hallam, E. Papadimitraki, D. Betal, K. Desouza. Breast Cancer (BC) in Younger Women: A Multicentre Cohort Study of Clinical and Pathological Features [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-06-14.