Skip to main content
Top
Published in: Breast Cancer Research 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

Localized mammographic density is associated with interval cancer and large breast cancer: a nested case-control study

Authors: Fredrik Strand, Edward Azavedo, Roxanna Hellgren, Keith Humphreys, Mikael Eriksson, John Shepherd, Per Hall, Kamila Czene

Published in: Breast Cancer Research | Issue 1/2019

Login to get access

Abstract

Background

High mammographic density is associated with breast cancer and with delayed detection. We have examined whether localized density, at the site of the subsequent cancer, is independently associated with being diagnosed with a large-sized or interval breast cancer.

Methods

Within a prospective cohort of 63,130 women, we examined 891 women who were diagnosed with incident breast cancer. For 386 women, retrospective localized density assessment was possible. The main outcomes were interval cancer vs. screen-detected cancer and large (> 2 cm) vs. small cancer. In negative screening mammograms, overall and localized density were classified reflecting the BI-RADS standard. Density concordance probabilities were estimated through multinomial regression. The associations between localized density and the two outcomes were modeled through logistic regression, adjusted for overall density, age, body mass index, and other characteristics.

Results

The probabilities of concordant localized density were 0.35, 0.60, 0.38, and 0.32 for overall categories “A,” “B,” “C,” and “D.” Overall density was associated with large cancer, comparing density category D to A with OR 4.6 (95%CI 1.8–11.6) and with interval cancer OR 31.5 (95%CI 10.9–92) among all women. Localized density was associated with large cancer at diagnosis with OR 11.8 (95%CI 2.7–51.8) among all women and associated with first-year interval cancer with OR 6.4 (0.7 to 58.7) with a significant linear trend p = 0.027.

Conclusions

Overall density often misrepresents localized density at the site where cancer subsequently arises. High localized density is associated with interval cancer and with large cancer. Our findings support the continued effort to develop and examine computer-based measures of localized density for use in personalized breast cancer screening.
Appendix
Available only for authorised users
Literature
1.
go back to reference Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD. Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol. 2005;6(10):798–808.PubMedCrossRef Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD. Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol. 2005;6(10):798–808.PubMedCrossRef
2.
go back to reference Blanch J, Sala M, Ibanez J, Domingo L, Fernandez B, Otegi A, Barata T, Zubizarreta R, Ferrer J, Castells X, et al. Impact of risk factors on different interval cancer subtypes in a population-based breast cancer screening programme. PLoS One. 2014;9(10):e110207.PubMedPubMedCentralCrossRef Blanch J, Sala M, Ibanez J, Domingo L, Fernandez B, Otegi A, Barata T, Zubizarreta R, Ferrer J, Castells X, et al. Impact of risk factors on different interval cancer subtypes in a population-based breast cancer screening programme. PLoS One. 2014;9(10):e110207.PubMedPubMedCentralCrossRef
3.
go back to reference Kerlikowske K, Zhu W, Tosteson AN, Sprague BL, Tice JA, Lehman CD, Miglioretti DL. Identifying women with dense breasts at high risk for interval cancer: a cohort study. Ann Intern Med. 2015;162(10):673–81.PubMedPubMedCentralCrossRef Kerlikowske K, Zhu W, Tosteson AN, Sprague BL, Tice JA, Lehman CD, Miglioretti DL. Identifying women with dense breasts at high risk for interval cancer: a cohort study. Ann Intern Med. 2015;162(10):673–81.PubMedPubMedCentralCrossRef
4.
go back to reference Lowery JT, Byers T, Hokanson JE, Kittelson J, Lewin J, Risendal B, Singh M, Mouchawar J. Complementary approaches to assessing risk factors for interval breast cancer. Cancer Causes Control. 2011;22(1):23–31.PubMedCrossRef Lowery JT, Byers T, Hokanson JE, Kittelson J, Lewin J, Risendal B, Singh M, Mouchawar J. Complementary approaches to assessing risk factors for interval breast cancer. Cancer Causes Control. 2011;22(1):23–31.PubMedCrossRef
5.
go back to reference Pollán M, Ascunce N, Ederra M, Murillo A, Erdozáin N, Alés-Martínez JE, Pastor-Barriuso R. Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study. Breast Cancer Res. 2013;15(1):R9.PubMedPubMedCentralCrossRef Pollán M, Ascunce N, Ederra M, Murillo A, Erdozáin N, Alés-Martínez JE, Pastor-Barriuso R. Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study. Breast Cancer Res. 2013;15(1):R9.PubMedPubMedCentralCrossRef
6.
go back to reference Roubidoux MA, Bailey JE, Wray LA, Helvie MA. Invasive cancers detected after breast cancer screening yielded a negative result: relationship of mammographic density to tumor prognostic factors. Radiology. 2004;230(1):42–8.PubMedCrossRef Roubidoux MA, Bailey JE, Wray LA, Helvie MA. Invasive cancers detected after breast cancer screening yielded a negative result: relationship of mammographic density to tumor prognostic factors. Radiology. 2004;230(1):42–8.PubMedCrossRef
7.
go back to reference D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA, et al. ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System. Reston, VA: American College of Radiology; 2013. D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA, et al. ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System. Reston, VA: American College of Radiology; 2013.
8.
go back to reference Highnam R, Jeffreys M, McCormack V, Warren R, Davey Smith G, Brady M. Comparing measurements of breast density. Phys Med Biol. 2007;52(19):5881–95.PubMedCrossRef Highnam R, Jeffreys M, McCormack V, Warren R, Davey Smith G, Brady M. Comparing measurements of breast density. Phys Med Biol. 2007;52(19):5881–95.PubMedCrossRef
9.
go back to reference Berg WA. Supplemental breast cancer screening in women with dense breasts should be offered with simultaneous collection of outcomes data. Ann Intern Med. 2016;164(4):299–300.PubMedPubMedCentralCrossRef Berg WA. Supplemental breast cancer screening in women with dense breasts should be offered with simultaneous collection of outcomes data. Ann Intern Med. 2016;164(4):299–300.PubMedPubMedCentralCrossRef
10.
go back to reference Tabar L, Vitak B, Chen HH, Prevost TC, Duffy SW. Update of the Swedish Two-County Trial of breast cancer screening: histologic grade-specific and age-specific results. Swiss Surg. 1999;5(5):199–204.PubMedCrossRef Tabar L, Vitak B, Chen HH, Prevost TC, Duffy SW. Update of the Swedish Two-County Trial of breast cancer screening: histologic grade-specific and age-specific results. Swiss Surg. 1999;5(5):199–204.PubMedCrossRef
11.
go back to reference Screening IUKPoBC. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012;380(9855):1778–86.CrossRef Screening IUKPoBC. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012;380(9855):1778–86.CrossRef
12.
go back to reference van Gils CH, Otten JD, Verbeek AL, Hendriks JH. Mammographic breast density and risk of breast cancer: masking bias or causality? Eur J Epidemiol. 1998;14(4):315–20.PubMedCrossRef van Gils CH, Otten JD, Verbeek AL, Hendriks JH. Mammographic breast density and risk of breast cancer: masking bias or causality? Eur J Epidemiol. 1998;14(4):315–20.PubMedCrossRef
13.
go back to reference Boyd N, Guo H, Martin L, Sun L, Stone J, Fishell E, Jong R, Hislop G, Chiarelli A, Minkin S, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007;356:227–36.PubMedCrossRef Boyd N, Guo H, Martin L, Sun L, Stone J, Fishell E, Jong R, Hislop G, Chiarelli A, Minkin S, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007;356:227–36.PubMedCrossRef
14.
go back to reference Crosier M, Scott D, Wilson RG, Griffiths CD, May FE, Westley BR. Differences in Ki67 and c-erbB2 expression between screen-detected and true interval breast cancers. Clin Cancer Res. 1999;5(10):2682–8.PubMed Crosier M, Scott D, Wilson RG, Griffiths CD, May FE, Westley BR. Differences in Ki67 and c-erbB2 expression between screen-detected and true interval breast cancers. Clin Cancer Res. 1999;5(10):2682–8.PubMed
15.
go back to reference Kalager M, Tamimi RM, Bretthauer M, Adami HO. Prognosis in women with interval breast cancer: population based observational cohort study. Br Med J. 2012;345:10.CrossRef Kalager M, Tamimi RM, Bretthauer M, Adami HO. Prognosis in women with interval breast cancer: population based observational cohort study. Br Med J. 2012;345:10.CrossRef
16.
go back to reference Eriksson L, Czene K, Rosenberg LU, Tornberg S, Humphreys K, Hall P. Mammographic density and survival in interval breast cancers. Breast Cancer Res. 2013;15(3):7.CrossRef Eriksson L, Czene K, Rosenberg LU, Tornberg S, Humphreys K, Hall P. Mammographic density and survival in interval breast cancers. Breast Cancer Res. 2013;15(3):7.CrossRef
17.
go back to reference Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63(1):181–7.PubMedCrossRef Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63(1):181–7.PubMedCrossRef
18.
go back to reference Pinto Pereira SM, et al. Localized fibroglandular tissue as a predictor of future tumor location within the breast. Cancer Epidemiol Biomarkers Prev. 2011;20(8):1718–25. Pinto Pereira SM, et al. Localized fibroglandular tissue as a predictor of future tumor location within the breast. Cancer Epidemiol Biomarkers Prev. 2011;20(8):1718–25.
19.
go back to reference Ursin G, Hovanessian-Larsen L, Parisky YR, Pike MC, Wu AH. Greatly increased occurrence of breast cancers in areas of mammographically dense tissue. Breast Cancer Res. 2005;7(5):R605.PubMedPubMedCentralCrossRef Ursin G, Hovanessian-Larsen L, Parisky YR, Pike MC, Wu AH. Greatly increased occurrence of breast cancers in areas of mammographically dense tissue. Breast Cancer Res. 2005;7(5):R605.PubMedPubMedCentralCrossRef
20.
go back to reference McConnell JC, O’Connell OV, Brennan K, Weiping L, Howe M, Joseph L, Knight D, O'Cualain R, Lim Y, Leek A, et al. Increased peri-ductal collagen micro-organization may contribute to raised mammographic density. Breast Cancer Res. 2016;18(1):5.PubMedPubMedCentralCrossRef McConnell JC, O’Connell OV, Brennan K, Weiping L, Howe M, Joseph L, Knight D, O'Cualain R, Lim Y, Leek A, et al. Increased peri-ductal collagen micro-organization may contribute to raised mammographic density. Breast Cancer Res. 2016;18(1):5.PubMedPubMedCentralCrossRef
21.
go back to reference Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 2006;4(1):38.PubMedPubMedCentralCrossRef Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 2006;4(1):38.PubMedPubMedCentralCrossRef
22.
go back to reference Gabrielson M, Eriksson M, Hammarström M, Borgquist S, Leifland K, Czene K, Hall P. Cohort profile: the Karolinska mammography project for risk prediction of breast cancer (KARMA). Int J Epidemiol. 2017;46(6):1740–1741g.PubMedPubMedCentralCrossRef Gabrielson M, Eriksson M, Hammarström M, Borgquist S, Leifland K, Czene K, Hall P. Cohort profile: the Karolinska mammography project for risk prediction of breast cancer (KARMA). Int J Epidemiol. 2017;46(6):1740–1741g.PubMedPubMedCentralCrossRef
23.
go back to reference Eriksson M, Li J, Leifland K, Czene K, Hall P. A comprehensive tool for measuring mammographic density changes over time. Breast Cancer Res Treat. 2018;169(2):371–9.PubMedPubMedCentralCrossRef Eriksson M, Li J, Leifland K, Czene K, Hall P. A comprehensive tool for measuring mammographic density changes over time. Breast Cancer Res Treat. 2018;169(2):371–9.PubMedPubMedCentralCrossRef
24.
go back to reference Health ECD-Gf, Protection C, Perry N, Puthaar E. European guidelines for quality assurance in breast cancer screening and diagnosis. Luxembourg: Office for Official Publications of the European Communities; 2006. Health ECD-Gf, Protection C, Perry N, Puthaar E. European guidelines for quality assurance in breast cancer screening and diagnosis. Luxembourg: Office for Official Publications of the European Communities; 2006.
25.
go back to reference Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRef Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRef
26.
go back to reference Holland K, van Gils CH, Mann RM, Karssemeijer N. Quantification of masking risk in screening mammography with volumetric breast density maps. Breast Cancer Res Treat. 2017;162(3):541–8.PubMedPubMedCentralCrossRef Holland K, van Gils CH, Mann RM, Karssemeijer N. Quantification of masking risk in screening mammography with volumetric breast density maps. Breast Cancer Res Treat. 2017;162(3):541–8.PubMedPubMedCentralCrossRef
27.
go back to reference Mahmoudzadeh AP, Malkov S, Hinton B, Sprague B, Kerlikowske K, Shepherd J. Do women with low breast density have regionally high breast density? In: International workshop on digital mammography: 2016. Malmö: Springer; 2016. p. 548–53. Mahmoudzadeh AP, Malkov S, Hinton B, Sprague B, Kerlikowske K, Shepherd J. Do women with low breast density have regionally high breast density? In: International workshop on digital mammography: 2016. Malmö: Springer; 2016. p. 548–53.
28.
go back to reference Aiello EJ, Buist DSM, Emily W, Porter PL. Association between mammographic breast density and breast cancer tumor characteristics. Cancer Epidemiol Biomark Prev. 2005;14(3):662–8.CrossRef Aiello EJ, Buist DSM, Emily W, Porter PL. Association between mammographic breast density and breast cancer tumor characteristics. Cancer Epidemiol Biomark Prev. 2005;14(3):662–8.CrossRef
29.
go back to reference Strand F, Humphreys K, Holm J, Eriksson M, Törnberg S, Hall P, Azavedo E, Czene K. Long-term prognostic implications of risk factors associated with tumor size: a case study of women regularly attending screening. Breast Cancer Res. 2018;20(1):31.PubMedPubMedCentralCrossRef Strand F, Humphreys K, Holm J, Eriksson M, Törnberg S, Hall P, Azavedo E, Czene K. Long-term prognostic implications of risk factors associated with tumor size: a case study of women regularly attending screening. Breast Cancer Res. 2018;20(1):31.PubMedPubMedCentralCrossRef
30.
go back to reference Holm J, Humphreys K, Li J, Ploner A, Cheddad A, Eriksson M, Tornberg S, Hall P, Czene K. Risk factors and tumor characteristics of interval cancers by mammographic density. J Clin Oncol. 2015;33(9):1030–7.PubMedCrossRef Holm J, Humphreys K, Li J, Ploner A, Cheddad A, Eriksson M, Tornberg S, Hall P, Czene K. Risk factors and tumor characteristics of interval cancers by mammographic density. J Clin Oncol. 2015;33(9):1030–7.PubMedCrossRef
31.
go back to reference Mandelson MT, Oestreicher N, Porter PL, White D, Finder CA, Taplin SH, White E. Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 2000;92(13):1081–7.PubMedCrossRef Mandelson MT, Oestreicher N, Porter PL, White D, Finder CA, Taplin SH, White E. Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 2000;92(13):1081–7.PubMedCrossRef
32.
go back to reference DeFilippis RA, Chang H, Dumont N, Rabban JT, Chen YY, Fontenay GV, Berman HK, Gauthier ML, Zhao J, Hu D, et al. CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues. Cancer Discov. 2012;2(9):826–39.PubMedPubMedCentralCrossRef DeFilippis RA, Chang H, Dumont N, Rabban JT, Chen YY, Fontenay GV, Berman HK, Gauthier ML, Zhao J, Hu D, et al. CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues. Cancer Discov. 2012;2(9):826–39.PubMedPubMedCentralCrossRef
33.
go back to reference Woolcott CG, et al. Longitudinal changes in IGF-I and IGFBP-3, and mammographic density among postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2013;22(11):2116–20. Woolcott CG, et al. Longitudinal changes in IGF-I and IGFBP-3, and mammographic density among postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2013;22(11):2116–20.
34.
go back to reference Buist DS, Porter PL, Lehman C, Taplin SH, White E. Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst. 2004;96(19):1432–40.PubMedCrossRef Buist DS, Porter PL, Lehman C, Taplin SH, White E. Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst. 2004;96(19):1432–40.PubMedCrossRef
35.
go back to reference Ferguson DJ, Anderson TJ. Morphological evaluation of cell turnover in relation to the menstrual cycle in the “resting” human breast. Br J Cancer. 1981;44(2):177–81.PubMedPubMedCentralCrossRef Ferguson DJ, Anderson TJ. Morphological evaluation of cell turnover in relation to the menstrual cycle in the “resting” human breast. Br J Cancer. 1981;44(2):177–81.PubMedPubMedCentralCrossRef
36.
go back to reference Mainprize JG, Alonzo-Proulx O, Jong RA, Yaffe MJ. Quantifying masking in clinical mammograms via local detectability of simulated lesions. Med Phys. 2016;43(3):1249.PubMedCrossRef Mainprize JG, Alonzo-Proulx O, Jong RA, Yaffe MJ. Quantifying masking in clinical mammograms via local detectability of simulated lesions. Med Phys. 2016;43(3):1249.PubMedCrossRef
37.
go back to reference Hinton B, Malkov S, Avila J, Fan B, Joe B, Kerlikowske K, Ma L, Mahmoudzadeh A, Shepherd J. A measure of regional mammographic masking based on the CDMAM phantom. In: International workshop on digital mammography: 2016. Malmö: Springer; 2016. p. 525–31. Hinton B, Malkov S, Avila J, Fan B, Joe B, Kerlikowske K, Ma L, Mahmoudzadeh A, Shepherd J. A measure of regional mammographic masking based on the CDMAM phantom. In: International workshop on digital mammography: 2016. Malmö: Springer; 2016. p. 525–31.
Metadata
Title
Localized mammographic density is associated with interval cancer and large breast cancer: a nested case-control study
Authors
Fredrik Strand
Edward Azavedo
Roxanna Hellgren
Keith Humphreys
Mikael Eriksson
John Shepherd
Per Hall
Kamila Czene
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2019
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-019-1099-y

Other articles of this Issue 1/2019

Breast Cancer Research 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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