title: Expression of melatonin receptors in triple negative breast cancer (TNBC) in African American and Caucasian women: relation to survival.
abstract: In the normal rodent breast, the pineal hormone melatonin controls the development of ductal and alveolar tissue. Melatonin counteracts tumor occurrence and tumor cell progression in vivo and in vitro in animal and human breast cancer cell cultures. It acts predominantly through its melatonin MT1 receptor. Our aim was to investigate the presence or absence of the MT1 melatonin receptor in the aggressive triple negative group of human breast carcinoma (TNBC) and its possible relationship to the course of the disease. A total of 167 patients with a ER-, PR-, Her-2/neu- phenotype in which tissue for receptor studies was available were examined. The MT1 receptor immunostain was evaluated semiquantitatively as staining intensity (0, 1, 2, 3), percentage of stained cells and the weighted index (WI) (staining intensity times percentage of stained cells). A score of WI < 60 was regarded as "negative". There was a striking difference in incidence of MT1 positivity and staining intensity between carcinomas in African American (AA) and Caucasian (C) women. The AA showed a higher incidence of MT1 negative tumors (41/84 = 48.8 % in AA, 6/51 = 11.8 % in C) and a lower average WI. MT1 positivity in TNBC was associated with a lower stage and a smaller tumor size at time of diagnosis. In multivariable survival analysis, MT1 negative TNBC in all cases regardless of race showed a significantly higher hazard ratio for disease progression, shorter progression free survival, and disease-related death, and shorter OS. This was especially pronounced in the AA group but did not reach statistical significance in the smaller group of C alone. These results suggest that melatonin or a melatonin receptor agonist may be useful biologic additions in the treatment of some forms of TNBC, especially in AA who generally show a more aggressive course of their disease.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Emory University and Winship Cancer Institute, 1364 Clinton Road NE, Atlanta, GA 30322, USA. goprea@emory.edu
authors.forename: Gabriela
authors.initials: G
authors.lastname: Oprea-Ilies
authors.forename: Erhard
authors.initials: E
authors.lastname: Haus
authors.forename: Linda
authors.initials: L
authors.lastname: Sackett-Lundeen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lauren
authors.initials: L
authors.lastname: McLendon
authors.forename: Robert
authors.initials: R
authors.lastname: Busch
authors.forename: Amy
authors.initials: A
authors.lastname: Adams
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D044094:Receptors, Melatonin / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D047368:Tumor Burden; D044465:White People
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D044122:Receptor, Melatonin, MT1; D011960:Receptors, Estrogen; D044094:Receptors, Melatonin; D011980:Receptors, Progesterone