title: Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009).
abstract: OBJECTIVE
  Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER), which are the oldest, extend back only to the 1970s.
  
  
  METHODS
  To extend scant knowledge about the feasibility of obtaining long-term data on tumor biomarkers, we randomly selected 60 breast cancer cases (10 per decade) diagnosed between 1947-2009 among women members of the Kaiser Permanente Northern California health plan to obtain and analyze their formalin-fixed paraffin-embedded (FFPE) tumor specimens. For each tumor specimen, we created duplicate tissue microarrays for analysis.
  
  
  RESULTS
  We located tumor blocks and pathology reports for 50 of the 60 cases (83%), from which we randomly sampled 5 cases per decade for biomarker analysis (n= 30). All 30 cases displayed excellent morphology and exhibited biomarkers compatible with histologic type and grade. Test-retest reliability was also excellent: 100% for ER; 97% for human epidermal growth factor receptor 2 and epidermal growth factor receptor; 93% for progesterone receptor and cytokeratin 5/6; and 90% for Ki67 and molecular phenotype; the kappa statistic was excellent (>0.9) for 4 of the 7 biomarkers, strong (0.6-0.8) for 2, and fair for only 1 (owing to low prevalence).
  
  
  CONCLUSIONS
  These results indicate immunostaining for biomarkers commonly used to evaluate breast cancer biology and assign surrogate molecular phenotypes can reliably be employed on archival FFPE specimens up to 60 years old.
authors.affiliation: Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Krieger
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, USA.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.affiliation: Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Pamela D
authors.initials: PD
authors.lastname: Waterman
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Melina
authors.initials: M
authors.lastname: Shabani
authors.affiliation: Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: Lis
authors.initials: L
authors.lastname: Ellison-Loschmann
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, USA.
authors.forename: Ninah S
authors.initials: NS
authors.lastname: Achacoso
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Acton
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt