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Review
. 2025 Aug 7:140:103001.
doi: 10.1016/j.ctrv.2025.103001. Online ahead of print.

Invasive lobular carcinoma: Strategies and perspectives from the lobular breast cancer research group

Giovanni Corso  1 , Sherry Shen  2 , Carmen Criscitiello  3 , Rita Mukhtar  4 , Lauren Gamble  5 , Elena Guerini Rocco  6 , Filippo Pesapane  7 , Luca Nicosia  8 , Komal Jhaveri  9 , Beatrice Taurelli Salimbeni  10 , Giulia Massari  11 , Eleonora Meduri  12 , Alessandra Margherita De Scalzi  13 , Alberto Concardi  14 , Francesca Magnoni  15 , Anita Mamtani  16 , Fresia Pareja  17 , Maria Cristina Leonardi  18 , Virgilio Sacchini  19 , Giorgio Bogani  20 , Carlo La Vecchia  21 , Daniele Presti  22 , Marco Angelo Colleoni  23 , Paolo Veronesi  24 , Mark E Robson  25
Affiliations
Free article
Review

Invasive lobular carcinoma: Strategies and perspectives from the lobular breast cancer research group

Giovanni Corso et al. Cancer Treat Rev. .
Free article

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.

Keywords: E-cadherin; Endocrine therapy; Invasive lobular carcinoma (ILC); Neoadjuvant treatment; Precision oncology.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giovanni Corso reports honoraria from Wolters Kluwer. Fresia Pareja reports consulting fees and membership on the advisory board for AstraZeneca, as well as membership on the scientific advisory board of MultiplexDx. Giorgio Bogani reports honoraria from Novartis, Astellas, and Corcept Therapeutics. Elena Guerini Rocco has received advisory fees, honoraria, travel accommodations/expenses, grants, and/or non-financial support from AbbVie, AstraZeneca, Exact Sciences, GSK, Illumina, Lilly, Novartis, MSD, Pfizer, Roche, Sophia Genetics, Stemline (Menarini), and Thermo Fisher Scientific. Sherry Shen reports honoraria from MJH Life Sciences, advisory/consulting fees from AstraZeneca, and research funding (to institution) from Merck and Sermonix Pharmaceuticals. Presti Daniele reports honoraria from Eli Lilly, Novartis, AstraZeneca, Daiichi Sankyo, Pfizer, Istituto Gentili, participation on advisory boards from Eli Lilly, Novartis, Genetic, Gilead, support for attending meetings or travel accommodation expenses from Eli Lilly, Gilead. Carmen Criscitiello declares advisory or consultancy roles and speakers’ bureau engagements for Eli Lilly, Pfizer, Novartis, Roche, AstraZeneca, MSD, Daiichi Sankyo, Gilead, and Menarini Stemline. Rita Mukhtar declares research funding from GE Healthcare. Maria Cristina Leonardi declares speaker fees for Accuray Inc. Mark Robson declares advisory (all non-compensated): Astra-Zeneca, Merck, Foundation Medicine. Advisory (Compensated): Optum Health; Research Grant Support (all institutional): Astra-Zeneca, Merck, Artios Pharmaceutical; Travel: Astra-Zeneca. Beatrice Taurelli Salimbeni declares honoraria from Eli Lilly, AstraZeneca, support for attending meetings or travel accommodation expenses from AstraZeneca and Pfizer. Anna Rotili declares speaker fees, attending meetings and travel accommodation expenses from Mammotome Devicor. All other authors have nothing to declare..

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