Detection of crown-like structures in breast adipose tissue and clinical outcomes among African-American and White women with breast cancer

Abstract

Background: Crown-like structures in breast adipose tissue (CLS-B), composed of necrotic adipocytes encircled by macrophages, are associated with obesity and hypothesized to worsen breast cancer prognosis; however, data are sparse, particularly in multi-racial populations. Methods:We assessed specimens for CLS-B from 174 African-American and 168 White women with stage I-III breast cancer treated by mastectomy. Benign breast tissue from an uninvolved quadrant was immunohistochemically stained for CD68 to determine CLS-B presence and density (per cm 2 of adipose tissue). Demographic and lifestyle factors, collected via medical record review, were analyzed for associations with CLS-B using logistic regression. Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CLS-B and overall (OS) or progression-free (PFS) survival.Results: Detection of any CLS-B was similar between African-American (32%) and White (29%) patients with no evidence of an association between race and CLS-B in multivariable models (OR = 0.82, 95% CI = 0.49-1.36). Detection of CLS-B was associated with obesity (OR = 4.73, 95% CI = 2.48-9.01) and age ≥ 60 years at diagnosis (OR = 1.78, 95% CI = 0.99-3.21). There was some evidence of associations with parity and current smoking status. Detection of CLS-B was not associated with OS (HR = 1.02, 95% CI = 0.55-1.87) or PFS (HR = 0.99, 95% CI = 0.59-1.67). Conclusions: Our results show a strong, positive association between BMI and CLS-B in non-tumor tissue similar to previous findings. Detection of CLS-B did not vary by race and was not associated with worse OS or PFS.

Crown-Like Structures in Breast Adipose Tissue: Early Evidence and Current Issues in Breast Cancer

“…At the tissue level, several studies have demonstrated that CLS-B are positively correlated with breast adipocyte diameter, as would be expected given their association with obesity [ 67 , 69 , 70 , 71 , 73 , 81 , 83 , 84 ]. Even among ideal-weight women, a positive, linear association was found between CLS-B density and adipocyte diameter (ρ = 0.36; p < 0.01) [ 71 ].…”

“…No minimum amount of encirclement has been proposed for defining CLS-B. One study used ≥50% encirclement for primary analyses and made comparisons using higher cut points (≥75% and ≥90%) with few differences in conclusions by cut point used [ 69 ]. Based on the study’s definition of CLS-B, a breast pathologist then enumerates CLS-B typically by visual assessment.…”

“…Patient breast adipose tissue samples are often classified according to the presence or absence of CLS-B and can be further quantified using the density of CLS-B per total area of breast WAT (e.g., CLS-B/cm 2 of WAT). Previous studies have used CLS-B density for assessing the severity of WAT inflammation in the breast [ 69 , 70 , 71 , 72 , 73 ]. These studies used the median density value among those with CLS-B to categorize the severity of WAT inflammation with those below the median considered as having mild WAT inflammation and those above the median as having severe WAT inflammation [ 69 , 70 , 71 , 72 , 73 ].…”

“…Few clinical and lifestyle factors beyond BMI have been identified as associated with CLS-B ( Table 3 ). In several investigations, older age and postmenopausal status have been linked to higher prevalence of CLS-B detection [ 69 , 70 , 73 , 80 , 86 ]. This relation could be due to increased breast fat percentage [ 88 ] and/or alterations to adipose tissue [ 89 ] that occur with age and menopausal transition.…”

“…Race/ethnicity has also been explored as a possible driver of CLS-B due to the known differences in the prevalence of obesity, obesity-related comorbidities, and visceral fat accumulation by race/ethnicity [ 90 ]. Evidence of greater CLS-B density among Black breast cancer patients was observed in two studies [ 69 , 87 ]; however, the association attenuated after BMI adjustment in one investigation [ 69 ]. The other study did not obtain patient-level BMI data.…”