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.

Design: 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.

Conclusion: 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.

Figure 1. Classification of BBD lesions

BBD (benign breast disease) SBBD (simple or homogeneous benign breast disease): Only one BBD lesion is present HBBD (heterogeneous benign breast disease): Multiple BBD lesions of different pathologic diagnoses SL-HBBD (Single-level HBBD): Multiple BBD lesions within a single risk level ML-HBBD (Multi-level HBBD): Multiple BBD lesions with different risk levels NPL: Non-proliferative lesions PLWA: Proliferative lesions without atypia PLA: Proliferative lesions with atypia

Figure 2. Cumulative frequency of lesion risk level with lesion number

Risk 1: Black circles Risk 2: Gray circles Risk 3: White circles

Figure 3. Cumulative frequency of single- and multi-level HBBD with lesion number

SL-HBBD: Filled circles ML-HBBD: Open circles