ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast

Future Oncol. 2022 Jul;18(22):2383-2392. doi: 10.2217/fon-2022-0358. Epub 2022 Jun 13.


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.

Keywords: ROS1; breast cancer; entrectinib; lobular; neoadjuvant.

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 (

Publication types

  • Review

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Cadherins
  • Carcinoma, Ductal, Breast* / pathology
  • Carcinoma, Lobular* / drug therapy
  • Carcinoma, Lobular* / pathology
  • Clinical Trials, Phase II as Topic
  • Female
  • Humans
  • Neoadjuvant Therapy
  • Protein-Tyrosine Kinases / therapeutic use
  • Proto-Oncogene Proteins
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism


  • Cadherins
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor, ErbB-2

Associated data