Crown-Like Structures in Breast Adipose Tissue: Early Evidence and Current Issues in Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Complex Relationship between Obesity and Breast Cancer
2.1. Obesity-Induced Changes in Adipose Tissue
2.2. Breast Adipose Tissue Microenvironment
3. Crown-Like Structures of the Breast (CLS-B): Histologic Marker of Local Inflammation
4. Potential Etiologic Drivers of CLS-B
4.1. Obesity and CLS-B
4.2. Other Factors and CLS-B
5. CLS-B and Incident Breast Cancer
6. CLS-B as a Potential Driver of Prognosis
7. Future Directions
7.1. Methodology in CLS-B Assessment
7.2. The Role of CLS-B in the Incidence of Breast Cancer
7.3. The Role of CLS-B in Predicting Therapeutic Effectiveness and Breast Cancer Prognosis
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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First Author (Year) | Study Design | Institutions/ Affiliations | Country, Race/ Ethnicity Distribution | Study Population | Study Years | CLS-B Analyses Conducted |
---|---|---|---|---|---|---|
Breast cancer incidence studies (n = 2) | ||||||
Shaik (2020) [84] | Nested case–control + cross-sectional analysis | Detroit BBD cohort and KTB | USA 100% AA | n = 84 BBD cases n = 47 BBD controls n = 50 KTB volunteers without BBD or breast cancer | BBD diagnosis: 1997–2010 Follow up for breast cancer through 2016 |
|
Carter (2017) [85] | Nested case–control + cross-sectional analysis | Mayo BBD cohort and KTB | USA Unknown | n = 86 BBD cases n = 86 BBD controls n = 86 KTB volunteers without clinical breast abnormalities | BBD diagnosis: 1967–2001 Follow up for breast cancer: Unknown |
|
Breast cancer prognosis studies (n = 4) | ||||||
Maliniak (2020) [69] | Cohort + cross-sectional analysis | Emory University-affiliated tumor registries | USA 51% AA 49% White | n = 342 breast cancer patients
| Breast cancer diagnosis: 2007–2012 Follow up for breast cancer outcomes: 2018 |
|
Cha (2018) [86] | Cohort + cross-sectional analysis | Yonsei University | South Korea | Group 1: n = 56 non-breast cancer patients
| Unknown |
|
Koru-Sengul (2016) [87] | Cohort + cross-sectional analysis | University of Miami/Jackson Memorial Hospital tumor registry | USA 33% Black 33% non-Black Latina 33% Caucasian | n = 150 breast cancer patients
| Cases obtained: 1978–1997 Followed for at least 5 years |
|
Iyengar (2016) [82] | Cohort + cross-sectional analysis | MSKCC | USA 83% White 13% Black 3% Asian | Cohort 1: n = 100 patients (mostly breast cancer)
| Mastectomy: 2011–2013 (Cohort 1); 2001–2006 (Cohort 2) Cohort 2: Follow up for breast cancer outcomes: 2014 | Cohort 1:
|
Cross-sectional studies of CLS-B (n = 8) | ||||||
Greenlee (2018) [70] | Cross-sectional | Columbia University Medical Center | USA 100% Hispanic a | n = 91 breast cancer patients
| Mastectomy: 2007–2012 |
|
Iyengar (2018) [81] | Cross-sectional | National Taiwan University Hospital and MSKCC | Taiwan USA 100% Caucasian | n = 72 Taiwanese breast cancer patients
| Mastectomy: 2011–2016 (Taiwanese); 2011–2013 (US Caucasian) |
|
Iyengar (2017) [71] | Cross-sectional | MSKCC | USA 76% Caucasian 9% Black, Asian, or Other 14% Unknown | n = 72 patients (mostly breast cancer)
| Mastectomy: 2011–2013 |
|
Mullooly (2017) [80] | Cross-sectional | PBCS | Poland | n = 83 breast cancer patients
| Study recruitment: 2000–2003 |
|
Vaysse (2017) [83] | Cross-sectional | Energy Balance and Breast Cancer Aspects-II | Norway | n = 107 breast cancer patients
| Unknown |
|
Brown (2017) [72] | Cross-sectional | MSKCC | USA | n = 161 patients (mostly breast cancer)
| Unknown |
|
Iyengar (2015) [73] | Cross-sectional | MSKCC | USA 86% White 7% Black 6% Asian | n = 237 patients (mostly breast cancer)
| Mastectomy: 2011–2013 |
|
Morris (2011) [67] | Cross-sectional (pilot study) | MSKCC | USA | n = 30 patients (mostly breast cancer)
| Enrolled: 2010 |
|
First Author (Year) | Patient Study Population | % CLS-B+ by BMI (kg/m2) Group | Association between BMI and CLS-B aOR (95%CI) if Presented | Association with Other Adiposity Measures | Direction of Association: -/Null/+ | |
---|---|---|---|---|---|---|
Shaik (2020) [84] | BBD + Komen Normal Tissue Bank | NR | Not associated (p > 0.1) | Null | ||
Carter (2017) [85] | BBD + Komen Normal Tissue Bank | BMI < 25: BMI 25–< 30: BMI ≥ 30: | 7% 13% 29% | + | ||
Maliniak (2020) [69] | Breast cancer | BMI < 25: BMI 25–< 30: BMI ≥ 30: | 16% 29% 45% | Reference 2.34 (1.17 to 4.70) 4.73 (2.48 to 9.01) | + | |
Cha (2018) a [86] | Breast cancer | BMI < 25: BMI ≥ 25: | 15% 27% | + | ||
Greenlee (2018) [70] | Breast cancer | BMI 18.5–< 25: BMI 25–< 30: BMI 30–< 35: BMI ≥ 35: | 24% 34% 57% 65% | + | ||
Iyengar (2018) b [81] | Breast cancer | BMI < 23: BMI 23–< 27.5: BMI ≥ 27.5: | 24% 48% 76% | Body fat, VAT, and SAT (all p < 0.01) | + | |
Iyengar (2017) [71] | Mostly breast cancer | All BMI < 25: | 39% | CLS-B- vs. CLS-B + median BMI: 21.8 vs. 23.0, p = 0.04 | + | |
Mullooly (2017) [80] | Breast cancer | BMI < 25: BMI 25–< 30: BMI ≥ 30: | 17% 36% 54% | Reference 1.93 (0.50 to 7.40) 4.63 (1.08 to 19.83) | + | |
Vaysse (2017) [83] | Breast cancer | BMI < 25: BMI 25–< 30: BMI ≥30: | NR | Reference 3.2 (1.28 to 8.15) 6.9 (1.35 to 35.0) | WHR and % truncal fat (all p < 0.05) | + |
Iyengar (2016) c [82] | Breast cancer | BMI < 25: BMI 25–< 30: BMI ≥ 30: | 23% 33% 67% | + | ||
Iyengar (2015) [73] | Mostly breast cancer | BMI < 25 BMI 25–< 30: BMI ≥ 30: | 34% 53% 90% | CLS concordance between breast and abdominal SAT (p = 0.12) | + |
First Author (Year) | N Studies | Summary of Evidence |
---|---|---|
Patient characteristics | ||
Obesity | 11 studies [69,70,71,73,80,81,82,83,84,85,86] | Strong positive association in studies of breast cancer patients (see Table 2); inconclusive evidence for BBD patients and women without BBD or breast cancer |
Age | 8 studies [69,70,71,73,80,81,85,86] | Positive trend with age in studies of breast cancer patients although majority of associations were not statistically significant; no association observed between age and CLS-B among BBD patients [85] |
Menopausal status | 6 studies [69,70,71,72,73,81] | Positive trend with postmenopausal status among breast cancer patients although majority of associations were not statistically significant |
Race/ethnicity | 4 studies [69,70,81,87] | Evidence of greater CLS-B density among Black breast cancer patients in n = 2 studies [69,83] (no association when adjusting for BMI in the one study [69] with this information); No strong evidence of differences in CLS-B detection by country of origin among Hispanic/Latina patients [70] or when comparing Taiwanese to US Caucasian patients [80] |
Smoking status | 2 studies [69,70] | Positive trend with current smoking status in breast cancer patients but inconclusive (very few current smokers in both studies) |
Age at menopause | 2 studies [69,80] | Inconclusive evidence |
Reproductive factors | 2 studies [69,80] | Inconclusive evidence |
Family history of breast cancer | 2 studies [69,80] | Inconclusive evidence |
Tumor characteristics | ||
Molecular subtype | 6 studies [69,70,71,73,80,86] | No/little evidence for differences by ER status, PR status, or other tumor subtypes observed |
Nodal status | 4 studies [69,80,82,86] | Some evidence suggesting association with lymph node-negative disease but all together inconclusive |
Grade | 4 studies [69,80,82,86] | Inconclusive evidence |
Stage | 3 studies [69,70,86] | Inconclusive evidence |
First Author (Year) | N Total | Study Design | Antibody: % CLS-B+ | Outcome | N Outcomes | Adjusted Estimate (95%CI) if Reported | Summary of Results
|
---|---|---|---|---|---|---|---|
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
|
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
|
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
|
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
|
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
|
First Author (Year) | Tissue Specimen | Tissue Specimens per Subject | Antibody | % CLS-B+ |
---|---|---|---|---|
Breast cancer incidence studies (n = 2) | ||||
Shaik (2020) [84] | BBD: FFPE BBD biopsy tissue KTB donors: FFPE percutaneous needle biopsy tissue | 1 | CD68 | BBD Cases: 67% BBD Controls: 40% KTB donors: 18% |
Carter (2017) [85] | BBD: FFPE BBD biopsy tissue KTB donors: FFPE normal breast tissue | 1 | CD68 | BBD Cases: 24% BBD Controls: 19% KTB donors: 3% |
Breast cancer prognosis studies (n = 4) | ||||
Maliniak (2020) [69] | FFPE non-tumor tissue | 1 | CD68 | Overall: 30% AA: 32% White: 29% |
Cha (2018) [86] | Group 1: FFPE reduction mammoplasty Group 2: FFPE non-tumor tissue Group 3: FFPE tumor tissue | Unknown | CD68 CD163 | CD68, CD163 Group 1: 2%, 2% Group 2: 0%, 0% Group 3: 18%, 13% |
Koru-Sengul (2016) [87] | FFPE tumor tissue | 1 | CD163 CD206 CD40 | Density of CLS: CD163, CD206, CD40 Mean (SD) All: 0.06 (0.14); 0.03 (0.07); 0.01 (0.07) Black: 0.11 (0.22); 0.04 (0.09); 0.02 (0.11) NBLA: 0.05 (0.08); 0.03 (0.05); 0 (0) CA: 0.03 (0.07); 0.02 (0.06); 0 (0.02) |
Iyengar (2016) [82] | FFPE non-tumor tissue | 5 | CD68 | 41% |
Cross-sectional studies of CLS-B (n = 8) | ||||
Greenlee (2018) [70] | FFPE non-tumor tissue | 5 | CD68 | 45% |
Iyengar (2018) [81] | FFPE non-tumor tissue | 5 | CD68 | Taiwanese: 43% US Caucasian: 55% |
Iyengar (2017) [71] | FFPE non-tumor tissue | 5 | CD68 | 39% |
Mullooly (2017) [80] | FFPE non-tumor tissue | 1 | CD68 | 36% |
Vaysse (2017) [83] | FFPE tumor tissue | Unknown | CD68 | 54% |
Brown (2017) [72] | FFPE non-tumor tissue | 5 | CD68 | 57% |
Iyengar (2015) [73] | FFPE non-tumor tissue | 5 | CD68 | 51% |
Morris (2011) [67] | FFPE non-tumor tissue | 4–5 | CD68 | 47% |
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Maliniak, M.L.; Miller-Kleinhenz, J.; Cronin-Fenton, D.P.; Lash, T.L.; Gogineni, K.; Janssen, E.A.M.; McCullough, L.E. Crown-Like Structures in Breast Adipose Tissue: Early Evidence and Current Issues in Breast Cancer. Cancers 2021, 13, 2222. https://doi.org/10.3390/cancers13092222
Maliniak ML, Miller-Kleinhenz J, Cronin-Fenton DP, Lash TL, Gogineni K, Janssen EAM, McCullough LE. Crown-Like Structures in Breast Adipose Tissue: Early Evidence and Current Issues in Breast Cancer. Cancers. 2021; 13(9):2222. https://doi.org/10.3390/cancers13092222
Chicago/Turabian StyleMaliniak, Maret L., Jasmine Miller-Kleinhenz, Deirdre P. Cronin-Fenton, Timothy L. Lash, Keerthi Gogineni, Emiel A. M. Janssen, and Lauren E. McCullough. 2021. "Crown-Like Structures in Breast Adipose Tissue: Early Evidence and Current Issues in Breast Cancer" Cancers 13, no. 9: 2222. https://doi.org/10.3390/cancers13092222