title: Benign breast disease heterogeneity: association with histopathology, age, and ethnicity.
abstract: BACKGROUND
  Benign breast biopsies with concurrent multiple benign lesions with different histopathologic diagnoses were termed heterogeneous benign breast disease (HBBD). Multiplicity of benign breast disease (BBD) lesions in a biopsy is a risk factor for progression to breast cancer (BC). Elucidation of the biological characteristics and clinical implications of HBBD may also be relevant to the refinement of risks for BC in women with a BBD diagnosis.
  
  
  METHODS
  In this study, we investigated the association of HBBD with histopathology, age, and ethnicity. A cohort of 4,341 women, 1,208 African Americans and 3,133 Caucasians, diagnosed with BBD, was identified after examination of an excisional breast biopsy. BBD biopsies were categorized as nonproliferative (NP, low risk or risk 1 lesions), proliferative without atypia (P, intermediate risk or risk 2 lesions), and proliferative with atypia (AH, high risk or risk 3 lesions). A BBD biopsy with only a single BBD lesion was termed simple BBD (SBBD). BBD biopsies with multiple lesions were further classified as single level HBBD (SL-HBBD) if the concurrent lesions were within the same risk level, or as multiple level HBBD (ML-HBBD) if lesions fell into more than one risk group.
  
  
  RESULTS
  In this cohort, 69% of women with a BBD diagnosis fit the HBBD criteria. Among women with HBBD, ML-HBBD was almost three times more prevalent than SL-HBBD and was significantly more likely to be composed of risk 2 and risk 3 lesions. The likelihood of HBBD was 57% higher in Caucasian American women than in African American women with BBD (OR 1.57; 95% CI: 1.37, 1.81). The average lesion number in HBBD was directly proportional to increasing lesion risk (P < 0.001). Compared to women with risk 1 lesions, the likelihood of HBBD was 5.59 (95% CI: 4.85-6.44) and 17.0 (95% CI: 10.2-28.5) times higher when risk 2 and risk 3 lesions, respectively, were present. Women in the age range of 46-55 years and >55 years had a 3.12 (95% CI: 2.59, 3.75) and a 2.28 (95% CI: 1.94, 2.68) fold higher likelihood of HBBD compared to those < or =45 years. Significant interaction was found between concurrent lesion levels and age (P < 0.01). The likelihood of HBBD was considerably higher across all age groups for risk 3 lesions. Compared to the reference (risk 1, age < or =45), the likelihood of HBBD for risk 2 lesions was 4.4 times greater (95% CI: 3.70, 5.33) in women < or =45 YEARS, BUT THAT LIKELIHOOD INCREASED TO 17.6 (95% CI: 12.8, 24.2) AND 13.4 (95% CI: 10.1, 17.9) TIMES IN WOMEN OF 46-55 AND >55 YEARS, RESPECTIVELY.
  
  
  CONCLUSIONS
  HBBD is more prevalent in Caucasian American women than in African American women. Women with higher risk BBD lesions are more likely to have HBBD. Lesion number and higher risk BBD lesions are significantly correlated with ML-HBBD. Additionally, the associations of HBBD and lesion risk level are modified by age.
authors.affiliation: Department of Otolaryngolog, Head and Neck Surgery, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Cheng
authors.forename: Shijing
authors.initials: S
authors.lastname: Qiu
authors.forename: Usha
authors.initials: U
authors.lastname: Raju
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Wolman
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Worsham
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D044383:Black People; D001941:Breast Diseases / Q000208:ethnology* / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008875:Middle Aged; D044465:White People; D001741:Black or African American