Table 4.

Epidemiologic evidence examining CLS-B as a potential driver of female breast cancer incidence and prognosis.

First Author (Year)	N Total	Study Design	Antibody: % CLS-B+	Outcome	N Outcomes	Adjusted Estimate (95%CI) if Reported	Summary of Results Caveats
Breast cancer incidence studies (n = 2)
Shaik (2020) [84]	55 cases/ 47 controls	Nested case–control	CD68: Cases: 67% Controls: 40%	Invasive breast cancer	-	Any CLS-B vs. none: 3.98 (1.40 to 11.3) ≥5 CLS-B/sample vs. none: 4.99 (1.32 to 18.9)	Positive association between CLS-B and breast cancer among BBD patients Wide CI
Carter (2017) [85]	86 cases / 86 controls	Nested case–control	CD68: Cases: 24% Controls: 19%	Invasive or in situ breast cancer	-	Any CLS-B vs. none: NR >5 CLS-B/sample vs. none: 6.8 (1.4 to 32.4)	Positive association between CLS-B and breast cancer among BBD patients Wide CI
Breast cancer prognosis studies (n = 4)
Maliniak (2020) [69]	319	Cohort	CD68: 30%	OS PFS	46 recurrences 52 deaths	OS (Any CLS-B vs. none): 1.02 (0.55 to 1.87) PFS (Any CLS-B vs. none): 0.99 (0.59 to 1.67)	Null association between CLS-B and breast cancer prognosis in a diverse population of breast cancer patients Wide CI Possible misclassification of CLS-B
Cha (2018) [86]	140 a	Cohort	CD68: 18% CD163: 13%	OS DFS	18 recurrences 11 deaths	OS (CLS-B present vs. absent): CD68: univariate p = 0.390 CD163 univariate p = 0.492 DFS (CLS-B present vs. absent): CD68: univariate p = 0.899 CD163: univariate p = 0.883	Not enough breast cancer outcomes to draw conclusions
Koru-Sengul (2016) [87]	150	Cohort	CD163: NR CD40: NR CD206: NR	OS PFS	83 recurrences 88 deaths	OS (density of CLS): CD163: 2.14 (0.46 to 9.96) b CD40: 9.14 (1.00 to 83.60) b CD206: 0.65 (0.03 to 12.58) b PFS (density of CLS): CD163: 2.30 (0.66 to 8.03) b CD40: 4.12 (0.49 to 34.92) b CD206: 1.16 (0.09 to 14.28) b	Positive association between CLS-B and breast cancer prognosis Wide CI Varied by antibody used for detecting CLS-B Assessed CLS-B in tumor tissue
Iyengar (2016) [82]	127	Case-only analysis	CD68: 41%	Average time to distant recurrence	127 recurrences 99 deaths	Any CLS-B vs. none: 1.83 (1.07 to 3.13)	Positive association between CLS-B and breast cancer prognosis Select population of patients that all developed metastatic disease

NOTE: factors adjusted for varied in different analyses. Abbreviations: CI = confidence interval; CLS-B = crown-like structures in the breast adipose tissue; DFS = disease-free survival; NR = not reported; OS = overall survival; PFS = progression-free survival. ^a Cha et al. (2018) [86] only reported OS and DFS associations for Group 3 (see Table 1). ^b 90% CIs reported.