Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Causes & Control
Published in: Cancer Causes & Control 10/2019

01-10-2019 | Breast Cancer | Original Paper

Associations of mammographic breast density with breast stem cell marker-defined breast cancer subtypes

Authors: Lusine Yaghjyan, Ashwini K. Esnakula, Christopher G. Scott, Akemi T. Wijayabahu, Matthew R. Jensen, Celine M. Vachon

Published in: Cancer Causes & Control | Issue 10/2019

Login to get access

Abstract

Purpose

High mammographic breast density is a strong, well-established breast cancer risk factor. Whether stem cells may explain high breast cancer risk in dense breasts is unknown. We investigated the association between breast density and breast cancer risk by the status of stem cell markers CD44, CD24, and ALDH1A1 in the tumor.

Methods

We included 223 women with primary invasive or in situ breast cancer and 399 age-matched controls from Mayo Clinic Mammography Study. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were assessed using computer-assisted thresholding technique. Immunohistochemical analysis of the markers was performed on tumor tissue microarrays according to a standard protocol. We used polytomous logistic regression to quantify the associations of breast density measures with breast cancer risk across marker-defined tumor subtypes.

Results

Of the 223 cancers in the study, 182 were positive for CD44, 83 for CD24 and 52 for ALDH1A1. Associations of PD were not significantly different across t marker-defined subtypes (51% + vs. 11–25%: OR 2.83, 95% CI 1.49–5.37 for CD44+ vs. OR 1.87, 95% CI 0.47–7.51 for CD44−, p-heterogeneity = 0.66; OR 2.80, 95% CI 1.27–6.18 for CD24+ vs. OR 2.44, 95% CI 1.14–5.22 for CD24−, p-heterogeneity = 0.61; OR 3.04, 95% CI 1.14–8.10 for ALDH1A1+ vs. OR 2.57. 95% CI 1.30–5.08 for ALDH1A1−, p-heterogeneity = 0.94). Positive associations of DA and inverse associations of NDA with breast cancer risk were similar across marker-defined subtypes.

Conclusions

We found no evidence of differential associations of breast density with breast cancer risk by the status of stem cell markers. Further studies in larger study populations are warranted to confirm these associations.
Appendix
Available only for authorised users
Literature
1.
McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 15:1159–1169CrossRef
2.
Vachon CM, Kuni CC, Anderson K, Anderson VE, Sellers TA (2000) Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States). Cancer Causes Control 11:653–662CrossRefPubMed
3.
Vachon CM, Sellers TA, Vierkant RA, Wu FF, Brandt KR (2002) Case–control study of increased mammographic breast density response to hormone replacement therapy. Cancer Epidemiol Biomark Prev 11:1382–1388
4.
Titus-Ernstoff L, Tosteson AN, Kasales C, Weiss J, Goodrich M, Hatch EE, Carney PA (2006) Breast cancer risk factors in relation to breast density (United States). Cancer Causes Control 17:1281–1290CrossRefPubMedPubMedCentral
5.
Tamimi RM, Hankinson SE, Colditz GA, Byrne C (2005) Endogenous sex hormone levels and mammographic density among postmenopausal women. Cancer Epidemiol Biomark Prev 14:2641–2647CrossRef
6.
Yaghjyan L, Colditz GA, Rosner B, Bertrand KA, Tamimi RM (2016) Reproductive factors related to childbearing and mammographic breast density. Breast Cancer Res Treat 158:351–359CrossRefPubMedPubMedCentral
7.
Cobaleda C, Cruz JJ, Gonzalez-Sarmiento R, Sanchez-Garcia I, Perez-Losada J (2008) The emerging picture of human breast cancer as a stem cell-based disease. Stem Cell Rev 4:67–79CrossRefPubMed
8.
Smalley M, Ashworth A (2003) Stem cells and breast cancer: a field in transit. Nat Rev Cancer 3:832–844CrossRefPubMed
9.
Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439:993–997CrossRefPubMed
10.
Trichopoulos D, Adami HO, Ekbom A, Hsieh CC, Lagiou P (2008) Early life events and conditions and breast cancer risk: from epidemiology to etiology. Int J Cancer 122:481–485CrossRefPubMed
11.
Savarese TM, Low HP, Baik I, Strohsnitter WC, Hsieh CC (2006) Normal breast stem cells, malignant breast stem cells, and the perinatal origin of breast cancer. Stem Cell Rev 2:103–110CrossRefPubMed
12.
Giatromanolaki A, Sivridis E, Fiska A, Koukourakis M (2011) The CD44+/CD24− phenotype relates to ‘triple-negative’ state and unfavorable prognosis in breast cancer patients. Med Oncolgy 28(3):745–752CrossRef
13.
Abraham BK, Fritz P, Van der Kuip H, Buck M, Szabo Z, Athelogou M, and Brauch H (2005) Evaluation of CD44+/CD24−/low cells in breast cancer and relevance for distant metastasis. AACR Meeting Abstracts, p 481
14.
Neumeister V, Agarwal S, Bordeaux J, Camp RL, Rimm DL (2010) In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosis. Am J Pathol 176:2131–2138CrossRefPubMedPubMedCentral
15.
Eden JA (2010) Human breast cancer stem cells and sex hormones–a narrative review. Menopause 17:801–810PubMed
16.
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567CrossRefPubMedPubMedCentral
17.
Liu Y, Lv DL, Duan JJ, Xu SL, Zhang JF, Yang XJ, Zhang X, Cui YH, Bian XW, Yu SC (2014) ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: a systematic review and meta-analysis. BMC Cancer 14:444CrossRefPubMedPubMedCentral
18.
Yaghjyan L, Stoll E, Ghosh K, Scott CG, Jensen MR, Brandt KR, Visscher D, Vachon CM (2017) Tissue-based associations of mammographic breast density with breast stem cell markers. Breast Cancer Res 19:100CrossRefPubMedPubMedCentral
19.
Vachon CM, Brandt KR, Ghosh K, Scott CG, Maloney SD, Carston MJ, Pankratz VS, Sellers TA (2007) Mammographic breast density as a general marker of breast cancer risk. Cancer Epidemiol Biomark Prev 16:43–49CrossRef
20.
Bertrand KA, Tamimi RM, Scott CG, Jensen MR, Pankratz VS, Visscher D, Norman A, Couch F, Shepherd J, Fan B, Chen Y-Y, Ma L, Beck AH, Cummings SR, Kerlikowske K, Vachon CM (2013) Mammographic density and risk of breast cancer by age and tumor characteristics. Breast Cancer Res 15:R104CrossRefPubMedPubMedCentral
21.
Ursin G, Ma H, Wu AH, Bernstein L, Salane M, Parisky YR, Astrahan M, Siozon CC, Pike MC (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomark Prev 12:332–338
22.
Byng JW, Boyd NF, Fishell E, Jong RA, Yaffe MJ (1994) The quantitative analysis of mammographic densities. Phys Med Biol 39:1629–1638CrossRefPubMed
23.
Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87:670–675CrossRefPubMed
24.
Phipps AI, Buist DS, Malone KE, Barlow WE, Porter PL, Kerlikowske K, O’Meara ES, Li CI (2012) Breast density, body mass index, and risk of tumor marker-defined subtypes of breast cancer. Ann Epidemiol 22:340–348CrossRefPubMedPubMedCentral
25.
Ziv E, Tice J, Smith-Bindman R, Shepherd J, Cummings S, Kerlikowske K (2004) Mammographic density and estrogen receptor status of breast cancer. Cancer Epidemiol Biomark Prev 13:2090–2095
26.
Cerhan JR, Sellers TA, Janney CA, Pankratz VS, Brandt KR, Vachon CM (2005) Prenatal and perinatal correlates of adult mammographic breast density. Cancer Epidemiol Biomark Prev 14:1502–1508CrossRef
27.
28.
Xue F, Michels KB (2007) Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol 8:1088–1100CrossRefPubMed
29.
Rice MS, Tamimi RM, Connolly JL, Collins LC, Shen D, Pollak MN, Rosner B, Hankinson SE, Tworoger SS (2012) Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and lobule type in the nurses’ health study II. Breast Cancer Res 14:1–7CrossRef
30.
31.
Rinaldi S, Peeters PHM, Berrino F, Dossus L, Biessy C, Olsen A, Tjonneland A, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Téhard B, Nagel G, Linseisen J, Boeing H, Lahmann PH, Trichopoulou A, Trichopoulos D, Koliva M, Palli D, Panico S, Tumino R, Sacerdote C, van Gils CH, van Noord P, Grobbee DE, Bueno-de-Mesquita HB, Gonzalez CA, Agudo A, Chirlaque MD, Barricarte A, Larrañaga N, Quiros JR, Bingham S, Khaw KT, Key T, Allen NE, Lukanova A, Slimani N, Saracci R, Riboli E, Kaaks R (2006) IGF-I, IGFBP-3 and breast cancer risk in women: the European prospective investigation into cancer and nutrition (EPIC). Endocr Relat Cancer 13:593–605CrossRefPubMed
32.
Baer HJ, Colditz GA, Willett WC, Dorgan JF (2007) Adiposity and sex hormones in girls. Cancer Epidemiol Biomark Prev 16:1880–1888CrossRef
33.
Bertrand KA, Baer HJ, Orav EJ, Klifa C, Shepherd JA, Van Horn L, Snetselaar L, Stevens VJ, Hylton NM, Dorgan JF (2015) Body fatness during childhood and adolescence and breast density in young women: a prospective analysis. Breast Cancer Res 17:1–10CrossRef
34.
Poole EM, Tworoger SS, Hankinson SE, Schernhammer ES, Pollak MN, Baer HJ (2011) Body size in early life and adult levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3. Am J Epidemiol 174:642–651CrossRefPubMedPubMedCentral
35.
Warner ET, Eliassen AH, Chen WY, Holmes MD, Willett WC, Tamimi RM (2013) Abstract 130: childhood and adolescent body size and risk of fatal breast cancer. Cancer Res 73:130
36.
Baer HJ, Colditz GA, Rosner B, Michels KB, Rich-Edwards JW, Hunter DJ, Willett WC (2005) Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study. Breast Cancer Res 7:1–12CrossRef
37.
Palmer JR, Adams-Campbell LL, Boggs DA, Wise LA, Rosenberg L (2007) A prospective study of body size and breast cancer in black women. Cancer Epidemiol Biomark Prev 16:1795–1802CrossRef
38.
39.
Warner ET, Hu R, Collins LC, Beck AH, Schnitt S, Rosner B, Eliassen AH, Michels KB, Willett WC, Tamimi RM (2016) Height and body size in childhood, adolescence, and young adulthood and breast cancer risk according to molecular Subtype in the nurses’ health studies. Cancer Prev Res 9:732–738CrossRef
40.
Woolcott CG, Koga K, Conroy SM, Byrne C, Nagata C, Ursin G, Vachon CM, Yaffe MJ, Pagano I, Maskarinec G (2012) Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case–control studies. Breast Cancer Res Treat 132:1163–1171CrossRefPubMedPubMedCentral
41.
Yaghjyan L, Mahoney MC, Succop P, Wones R, Buckholz J, Pinney SM (2012) Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort. Br J Cancer 106(5):996–1003CrossRefPubMedPubMedCentral
42.
Anwar T, Kleer CG (2013) Tissue-based identification of stem cells and epithelial-to-mesenchymal transition in breast cancer. Hum Pathol 44:1457–1464CrossRefPubMedPubMedCentral
43.
Collins LC, Marotti J, Baer HJ, Deitz AC, Colditz GA, Tamimi RM (2008) Comparison of estrogen receptor assay results from pathology reports with results from central laboratory testing: implications for population-based studies of breast cancer. J Natl Cancer Inst 100:218–221CrossRefPubMed
44.
Ma H, Wang Y, Sullivan-Halley J, Weiss L, Burkman RT, Simon MS, Malone KE, Strom BL, Ursin G, Marchbanks PA, McDonald JA, Spirtas R, Press MF, Bernstein L (2009) Breast cancer receptor status: do results from a centralized pathology laboratory agree with SEER registry reports? Cancer Epidemiol Biomark Prev 18:2214–2220CrossRef
45.
Ahern TP, Beck AH, Rosner BA, Glass B, Frieling G, Collins LC, Tamimi RM (2017) Continuous measurement of breast tumour hormone receptor expression: a comparison of two computational pathology platforms. J Clin Pathol 70(5):428–434CrossRefPubMed
Metadata
Title
Associations of mammographic breast density with breast stem cell marker-defined breast cancer subtypes
Authors
Lusine Yaghjyan
Ashwini K. Esnakula
Christopher G. Scott
Akemi T. Wijayabahu
Matthew R. Jensen
Celine M. Vachon
Publication date
01-10-2019
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 10/2019
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-019-01207-w

Other articles of this Issue 10/2019

Cancer Causes & Control 10/2019 Go to the issue

Original Paper

US urban–rural disparities in breast cancer-screening practices at the national, regional, and state level, 2012–2016

Original Paper

Type 2 diabetes and obesity in midlife and breast cancer risk in the Reykjavik cohort

Original Paper

Leveraging the strength of comprehensive cancer control coalitions to support policy, systems, and environmental change

Original Paper

Care experiences among dually enrolled older adults with cancer: SEER-CAHPS, 2005–2013

Original Paper

Improving the diagnostic accuracy of a stratified screening strategy by identifying the optimal risk cutoff

Original Paper

Inflammation and breast density among female Chinese immigrants: exploring variations across neighborhoods
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits