ROS1 altered breast cancers – a distinctive molecular subtype of PR- metastatic breast cancers: Expanding the scope of targeted therapeutics

Article type: Research Article

Authors: Krishnamurthy, Kritika^a; | Deb, Arunima^a | Alghamdi, Sarah^{a; b} | Schwartz, Michael^c | Cusnir, Mike^c | Sriganeshan, Vathany^{a; b} | Poppiti, Robert^{a; b}

Affiliations: [a] A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA | [b] Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA | [c] Department of Medical Oncology, Mount Sinai Medical Center, Miami Beach, FL, USA

Correspondence: [*] Corresponding author: Kritika Krishnamurthy. Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA. Tel.: +617 667 4344; Fax: +617 667 7120: E-mail: kkrishn2@bidmc.harvard.edu

Abstract: BACKGROUND:Breast cancer, one of the leading causes of cancer-related mortality in women worldwide, exhibits wide-ranging histo-morphologic, clinical and molecular diversity. OBJECTIVE:This study compares the genetic alterations of breast tumors with the histo-morphological, hormone receptor status and metastatic “organotropism”. MATERIALS AND METHODS:Twenty-two cases of primary invasive breast carcinoma with local/distant metastasis were retrieved from the pathology archives. The status of estrogen and progesterone receptors by immunohistochemistry was recorded along with other pertinent case data. Next generation sequencing was performed on formalin-fixed paraffin embedded blocks of tumor. RESULTS:The mean age of the study subjects was 57.9 ± 13.3 years. TP53 mutation was the most common gene alteration in this study and was seen in 40.9% cases. ROS1 gene was mutated in 44.4% PR negative breast cancers while being wild type in the twelve PR positive tumors. (p = 0.021).STRING interaction network constructed with ROS1 and PR revealed a significantly higher number of interactions in this network than expected (p-value 0.000973). CONCLUSION:This study highlights the significantly higher incidence of ROS1 gene alterations in metastatic PR− breast cancers, with STRING network analysis revealing higher nodal interaction in the nodal network comprised of PR and ROS1 exclusive of ER.

Keywords: Metastatic breast cancer, ER⁺PR⁻, TP53, ROS1, STRING network

DOI: 10.3233/BD-220001

Journal: Breast Disease, vol. 41, no. 1, pp. 295-301, 2022