title: Positive Association of Fibroadenomatoid Change with HER2-Negative Invasive Breast Cancer: A Co-Occurrence Study.
abstract: BACKGROUND
  Risk assessment of a benign breast disease/lesion (BBD) for invasive breast cancer (IBC) is typically done through a longitudinal study. For an infrequently-reported BBD, the shortage of occurrence data alone is a limiting factor to conducting such a study. Here we present an approach based on co-occurrence analysis, to help address this issue. We focus on fibroadenomatoid change (FAC), an under-studied BBD, as our preliminary analysis has suggested its previously unknown significant co-occurrence with IBC.
  
  
  METHODS
  A cohort of 1667 female patients enrolled in the Clinical Breast Care Project was identified. A single experienced breast pathologist reviewed all pathology slides for each case and recorded all observed lesions, including FAC. Fibroadenoma (FA) was studied for comparison since FAC had been speculated to be an immature FA. FA and Fibrocystic Changes (FCC) were used for method validation since they have been comprehensively studied. Six common IBC and BBD risk/protective factors were also studied. Co-occurrence analyses were performed using logistic regression models.
  
  
  RESULTS
  Common risk/protective factors were associated with FA, FCC, and IBC in ways consistent with the literature in general, and they were associated with FAC, FA, and FCC in distinct patterns. Age was associated with FAC in a bell-shape curve so that middle-aged women were more likely to have FAC. We report for the first time that FAC is positively associated with IBC with odds ratio (OR) depending on BMI (OR = 6.78, 95%CI = 3.43-13.42 at BMI<25 kg/m2; OR = 2.13, 95%CI = 1.20-3.80 at BMI>25 kg/m2). This association is only significant with HER2-negative IBC subtypes.
  
  
  CONCLUSIONS
  We conclude that FAC is a candidate risk factor for HER2-negative IBCs, and it is a distinct disease from FA. Co-occurrence analysis can be used for initial assessment of the risk for IBC from a BBD, which is vital to the study of infrequently-reported BBDs.
authors.affiliation: Biomedical Informatics, Windber Research Institute, Windber, Pennsylvania, United States of America.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Biomedical Informatics, Windber Research Institute, Windber, Pennsylvania, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bekhash
authors.affiliation: Clinical Breast Care Project, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, United States of America.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Kovatich
authors.affiliation: Clinical Breast Care Project, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, United States of America.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hooke
authors.affiliation: Biomedical Informatics, Windber Research Institute, Windber, Pennsylvania, United States of America.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Biomedical Informatics, Windber Research Institute, Windber, Pennsylvania, United States of America.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kvecher
authors.affiliation: Clinical Breast Care Project, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, United States of America.
authors.forename: J Leigh
authors.initials: JL
authors.lastname: Fantacone-Campbell
authors.affiliation: Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Edith P
authors.initials: EP
authors.lastname: Mitchell
authors.affiliation: Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hallgeir
authors.initials: H
authors.lastname: Rui
authors.affiliation: Biomedical Informatics, Windber Research Institute, Windber, Pennsylvania, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Mural
authors.affiliation: Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shriver
authors.affiliation: Biomedical Informatics, Windber Research Institute, Windber, Pennsylvania, United States of America.
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D005260:Female; D018226:Fibroadenoma / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human