Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

Plain language summary

Breast cancer is the most common cancer among women worldwide. Breast cancer is not a unique disease, but rather a heterogeneous disease, with different subtypes. Lobular breast cancer is the second most common histologic subtype of breast cancer after ductal breast cancer. Lobular breast cancer has some peculiar characteristics that make it a distinct entity in the context of breast cancer. Nevertheless, few clinical studies so far have focused specifically on this subtype. ROSALINE is a clinical study aimed to test entrectinib, a new drug that showed promising activity in preliminary research studies, in combination with endocrine therapy in women with lobular breast cancer before surgery.

Trial Registration Number: NCT04551495 ( ClinicalTrials.gov).

Keywords:

Papers of special note have been highlighted as: •• of considerable interest

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Vol. 18, No. 22

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Received 7 April 2022

Accepted 26 May 2022

Published online 13 June 2022

Published in print July 2022

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Acknowledgments

The abstract of the present work was presented at the ESMO Breast Annual Meeting 2021. The authors thank the Clinical Trials Supporting Unit (CTSU) team of the Institut Jules Bordet.

Financial & competing interests disclosure

This study is supported by F. Hoffmann-La Roche Ltd. E Agostinetto: consultancy fees/honoraria from Eli Lilly and Sandoz; support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics and Istituto Gentili (all outside the submitted work). G Nader-Marta: travel grants from Roche and Bayer (all outside the submitted work). L Buisseret: postdoctoral clinical mandate (2020–2025) from the not-for-profit organization Foundation contre le Cancer (Brussels, Belgium); clinical research grant to the Institute: Astra Zeneca; institutional travel expenses: Roche; consultant: iTEOS therapeutics; speaker fee: BMS. D Taylor: consulting: Roche, Novartis, Daiichi Sankyo and Lilly; travel grants: Pfizer, Roche and AstraZeneca. C Fontaine: travel grants from Eli Lilly, Roche, Gilead, PharmaMar and Merck; advisory board paid by Eli Lilly and GSK to the oncology department. FP Duhoux: received a postdoctoral clinical mandate (2017–034) from the not-for-profit organization Foundation Against Cancer (Brussels, Belgium); advisory/consultancy roles for Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Novartis, Pfizer, Pierre Fabre, Roche and Teva (paid to institution, outside the submitted work); speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer and Roche (paid to institution, outside the submitted work); travel support from Amgen, Pfizer, Roche and Teva. H Denys: consulting (paid to institution): Pfizer, Roche, AstraZeneca, Eli Lilly, Novartis, Amgen, Tesaro and GSK; travel support: Pfizer, Roche, PharmaMar, Teva and AstraZeneca. F Coussy: travel grants: Roche, Lilly and Novartis; research funding to institution: Novartis. C Chakiba: travel grants from Gilead and Pfizer. M Piccart: board member (scientific board): Oncolytics, Radius; consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Oncolytics, Periphagen, Pfizer, Roche, Seattle Genetics; Research grants to her Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon. M Ignatiadis: Consultant or advisory role (honoraria): Celgene, Novartis, Pfizer, Seattle Genetics and Tesaro; research grants to institute: Roche, Natera Inc and Pfizer. P Aftimos: consulting: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius and Deloitte; honoraria: Synthon, Amgen, Novartis and Gilead; travel grants: Amgen, MSD, Pfizer and Roche; research funding to institution: Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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