Invasive lobular carcinoma: Strategies and perspectives from the lobular breast cancer research group
Giovanni Corso, Sherry Shen, Carmen Criscitiello, Rita A. Mukhtar, Lauren A. Gamble, Elena Guerini‐Rocco, Filippo Pesapane, Luca Nicosia, Komal Jhaveri, Beatrice Taurelli Salimbeni, Giulia Massari, Eleonora Meduri, Alessandra Margherita De Scalzi, Alberto Concardi, Francesca Magnoni, Anita Mamtani, Fresia Pareja, Maria Cristina Leonardi, Virgilio Sacchini, Giorgio Bogani, Carlo La Vecchia, Daniele Presti, Marco Colleoni, Paolo Veronesi, Mark E. Robson
Abstract
Invasive lobular carcinoma (ILC) represents approximately 10-15% of all breast cancers and is defined by a unique discohesive morphology due to loss of E-cadherin. Despite its prevalence, ILC has been historically underrepresented in clinical and translational research, contributing to diagnostic, therapeutic, and prognostic uncertainties. This narrative review, conducted by the Invasive Lobular Carcinoma Research Group, synthesizes current evidence on ILC with expert perspectives to inform future research and clinical strategies. We highlight the distinct biology of ILC, including characteristic genomic alterations (e.g., CDH1, PIK3CA, ERBB2 mutations) and its relationship with endocrine sensitivity and limited immune infiltration. Diagnostic challenges are underscored by ILC's subtle imaging presentation and underestimation of tumor extent on mammography and ultrasound, with MRI and contrast-enhanced mammography offering improved accuracy. The review discusses evolving surgical approaches, axillary staging considerations, and radiotherapy strategies, with an emphasis on adapting techniques to ILC's infiltrative growth. Endocrine therapy remains central for hormone receptor-positive ILC, with emerging evidence supporting CDK4/6 inhibitors and extended endocrine therapy in high-risk cases. Investigational therapies targeting ILC-enriched mutations and synthetic lethality mechanisms (e.g., ROS1 inhibition in CDH1-deficient tumors) hold promise for personalized treatment. This comprehensive review identifies knowledge gaps and advocates for histology-specific clinical trials, biomarker-driven treatment strategies, and tailored imaging and surgical techniques to improve outcomes for patients with ILC.