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Retinoblastoma protein expression and its predictors in triple-negative breast cancer

Authors
  • Patel, Jaymin M.1, 2
  • Goss, Andrew1
  • Garber, Judy E.2, 3
  • Torous, Vanda2, 4
  • Richardson, Edward T.2, 5
  • Haviland, Miriam J.6, 7
  • Hacker, Michele R.1, 6, 7
  • Freeman, Gordon J.2, 3
  • Nalven, Tessa1
  • Alexander, Brian2, 8
  • Lee, Larissa2, 8
  • Collins, Laura C.2, 6
  • Schnitt, Stuart J.2, 5
  • Tung, Nadine1, 2
  • 1 Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA , Boston (United States)
  • 2 Harvard Medical School, Boston, MA, USA , Boston (United States)
  • 3 Division of Medical Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA , Boston (United States)
  • 4 Massachusetts General Hospital, Boston, MA, USA , Boston (United States)
  • 5 Brigham and Women’s Hospital, Boston, MA, USA , Boston (United States)
  • 6 Beth Israel Deaconess Medical Center, Boston, MA, USA , Boston (United States)
  • 7 Harvard T.H. Chan School of Public Health, Boston, MA, USA , Boston (United States)
  • 8 Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA , Boston (United States)
Type
Published Article
Journal
npj Breast Cancer
Publisher
Nature Publishing Group UK
Publication Date
Jun 05, 2020
Volume
6
Issue
1
Identifiers
DOI: 10.1038/s41523-020-0160-4
Source
Springer Nature
License
Green

Abstract

Retinoblastoma protein (Rb) is a product of the RB tumor suppressor gene. Its expression is highly prevalent in luminal breast cancers and is critical to the success of cyclin-dependent kinase (CDK) 4/6 inhibitor therapy. Expression of Rb in triple-negative breast cancer (TNBC), tumors generally associated with basal biology, is not well known. However, heterogeneity among TNBC and presence of subtypes with luminal features are well described. The purpose of this study was to determine prevalence and predictors of Rb protein expression in BRCA1-associated and sporadic TNBCs. We studied 180 TNBC patients (70 BRCA1-associated and 110 sporadic). The clinical and pathologic features of these cases were previously assessed and reported. For this study, immunohistochemical stains for Rb were performed on tissue microarray sections. Details of treatment and outcome were abstracted from medical records. Fifty-one percent of TNBC were Rb positive (≥10% nuclei staining), and 85% of these cases had ≥50% nuclei staining. Rb expression was significantly associated with sporadic TNBC (71.4% vs 49.4%; p < 0.001), androgen receptor (AR) expression (16.5% vs 3.4%; p = 0.007), histologic grade 1 or 2 (9.9% vs 2.2%; p = 0.04), and first recurrence in bone (8.8% vs 1.1%; p = 0.03). Expression of p53 was not associated with Rb expression. Expression of Rb in TNBC was significantly associated with sporadic TNBC, AR expression, lower histologic grade, and metastasis to bone. These observations characterize a TNBC subtype with features suggestive of luminal-like biology and the potential to benefit from CDK 4/6 inhibition.

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