A breast cancer PDX collection enriched in luminal (ER+) tumors and young premenopausal patients to identify new therapeutic strategies for high-risk patients†.

Abstract

Breast cancer includes a group of neoplasms originating from mammary gland epithelial cells caused by a variety of genetic alterations, with different responses to treatments and outcomes. In clinical practice, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression guides the distinction between luminal A (ER⁺, PR⁺, HER2^-), luminal B (ER⁺, PR⁺, HER2^+/-), and triple-negative (ER^-, PR^-, HER2^-), each with a distinct biological behavior and clinical and therapeutic implications. Approximately 11% of breast cancers are diagnosed in young premenopausal women aged 20-49 years. Patient-derived xenografts (PDXs) offer a powerful solution to integrate personalized medicine and novel therapeutic agents. Dr Belletti's group recently developed a PDX biobank composed of 26 PDX lines highly enriched in luminal A and B and young premenopausal breast cancer patients. The bank faithfully recapitulates the characteristics of the original tumors. A major focus of their research was to exploit these PDXs to assess the resistance to CDK4/6 inhibitors (CDK4/6i), which are critical in managing advanced luminal breast cancers. Their effort addresses a significant gap in existing PDX models, which are limited for these patient subgroups, thereby enabling deeper insights into tumor biology and therapeutic responses in these understudied populations. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.