title: Association of mammographic density with the proliferation marker Ki-67 in a cohort of patients with invasive breast cancer.
abstract: There is growing evidence that certain breast cancer (BC) risk factors specifically increase the risk for specific molecular tumor subtypes. Different molecular subtypes of BC can partly be described by analyzing proliferation in tumors. Very few data are available regarding the association of mammographic density (MD), as a BC risk factor, with proliferation. The aim of this study was to analyze the association between Ki-67 expression in BCs and MD. In this case-only study, data on BC risk factors, hormone receptor expression, and MD were available for 1,975 patients with incident BC. MD was assessed as percentage mammographic density (PMD) using a semiautomated method by two readers for every patient. The association of the Ki-67 proliferation index and PMD was studied using multifactorial analyses of covariance (ANCOVA), with PMD as the target variable and including well-known factors that are also associated with MD such as age, parity, use of hormone replacement therapy (HRT), and body mass index (BMI). There were no significant differences in PMD between women with BC who had low and high Ki-67 values (P = 0.31). However, there were relevant differences in women with low BMI (P = 0.07), and in women using postmenopausal HRT (P = 0.06) as well as in women with low PR values (P = 0.07). In these subgroups, the Ki-67 expression index increased with decreasing PMD. Likewise PMD is correlated with BMI, parity status, and menopausal status stronger in patients with low proliferating tumors, and with progesterone receptor expression in patients with high proliferating tumors. MD correlates inversely with Ki-67 proliferation in BC tumors only in some subgroups of BC patients, defined by commonly known BC risk factors that are usually associated with MD as well.
authors.affiliation: Department of Gynecology and Obstetrics, University Breast Center for Franconia, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Heusinger
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Jud
authors.forename: Lothar
authors.initials: L
authors.lastname: Häberle
authors.forename: Carolin C
authors.initials: CC
authors.lastname: Hack
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Martina
authors.initials: M
authors.lastname: Meier-Meitinger
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lux
authors.forename: Carsten
authors.initials: C
authors.lastname: Hagenbeck
authors.forename: Christian R
authors.initials: CR
authors.lastname: Loehberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Wittenberg
authors.forename: Claudia
authors.initials: C
authors.lastname: Rauh
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Michael
authors.initials: M
authors.lastname: Uder
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Schulz-Wendtland
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: David L
authors.initials: DL
authors.lastname: Wachter
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008327:Mammography; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human