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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Mammographic microcalcifications and breast cancer tumorigenesis: a radiologic-pathologic analysis

Authors: Madiha Naseem, Joshua Murray, John F Hilton, Jason Karamchandani, Derek Muradali, Hala Faragalla, Chanele Polenz, Dolly Han, David C Bell, Christine Brezden-Masley

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their significance in breast tumorigenesis is controversial. This study had two objectives: (1) to find associations between mammographic MCs and tumor pathology, and (2) to compare the diagnostic value of mammograms and breast biopsies in identifying malignant MCs.

Methods

A retrospective chart review was performed for 937 women treated for breast cancer during 2000–2012 at St. Michael’s Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 over-expression and presence of MCs were collected. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All p-values less than 0.05 were considered statistically significant.

Results

A total of 937 patient charts were included. About 38.3% of the patients presented with mammographic MCs on routine mammographic screening. Patients were more likely to have MCs if they were HER-2 positive (52.9%; p < 0.001). There was a significant association between MCs and peri-menopausal status with a mean age of 50 (64%; p = 0.012). Patients with invasive ductal carcinomas (40.9%; p = 0.001) were more likely to present with MCs than were patients with other tumor histologies. Patients with a heterogeneous breast density (p = 0.031) and multifocal breast disease (p = 0.044) were more likely to have MCs on mammograms. There was a positive correlation between MCs and tumor grade (p = 0.057), with grade III tumors presenting with the most MCs (41.3%). A total of 52.2% of MCs were missed on mammograms which were visible on pathology (p < 0.001).

Conclusion

This is the largest study suggesting the appearance of MCs on mammograms is strongly associated with HER-2 over-expression, invasive ductal carcinomas, peri-menopausal status, heterogeneous breast density and multifocal disease.
Literature
2.
go back to reference Tabar L, Duffy SW, Vitak B, Chen HH, Prevost TC. The natural history of breast carcinoma: what have we learned from screening? Cancer. 1999;86(3):449–62.CrossRefPubMed Tabar L, Duffy SW, Vitak B, Chen HH, Prevost TC. The natural history of breast carcinoma: what have we learned from screening? Cancer. 1999;86(3):449–62.CrossRefPubMed
3.
go back to reference Bellahcene A, Castronovo V. Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer. Am J Pathol. 1995;146(1):95–100.PubMedPubMedCentral Bellahcene A, Castronovo V. Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer. Am J Pathol. 1995;146(1):95–100.PubMedPubMedCentral
5.
go back to reference Bansal GJ, Thomas KG. Screen-detected breast cancer: does presence of minimal signs on prior mammograms predict staging or grading of cancer? Clin Radiol. 2011;66(7):605–8.CrossRefPubMed Bansal GJ, Thomas KG. Screen-detected breast cancer: does presence of minimal signs on prior mammograms predict staging or grading of cancer? Clin Radiol. 2011;66(7):605–8.CrossRefPubMed
6.
go back to reference Castronovo V, Bellahcene A. Evidence that breast cancer associated microcalcifications are mineralized malignant cells. Int J Oncol. 1998;12(2):305–8.PubMed Castronovo V, Bellahcene A. Evidence that breast cancer associated microcalcifications are mineralized malignant cells. Int J Oncol. 1998;12(2):305–8.PubMed
7.
go back to reference Morgan MP, Cooke MM, McCarthy GM. Microcalcifications associated with breast cancer: an epiphenomenon or biologically significant feature of selected tumors? J Mammary Gland Biol Neoplasia. 2005;10(2):181–7.CrossRefPubMed Morgan MP, Cooke MM, McCarthy GM. Microcalcifications associated with breast cancer: an epiphenomenon or biologically significant feature of selected tumors? J Mammary Gland Biol Neoplasia. 2005;10(2):181–7.CrossRefPubMed
8.
go back to reference Zunzunegui RG, Chung MA, Oruwari J, Golding D, Marchant DJ, Cady B. Casting-type calcifications with invasion and high-grade ductal carcinoma in situ: a more aggressive disease? Arch Surg. 2003;138(5):537–40.CrossRefPubMed Zunzunegui RG, Chung MA, Oruwari J, Golding D, Marchant DJ, Cady B. Casting-type calcifications with invasion and high-grade ductal carcinoma in situ: a more aggressive disease? Arch Surg. 2003;138(5):537–40.CrossRefPubMed
9.
go back to reference Palka I, Ormandi K, Gaal S, Boda K, Kahan Z. Casting-type calcifications on the mammogram suggest a higher probability of early relapse and death among high-risk breast cancer patients. Acta Oncol. 2007;46(8):1178–83.CrossRefPubMed Palka I, Ormandi K, Gaal S, Boda K, Kahan Z. Casting-type calcifications on the mammogram suggest a higher probability of early relapse and death among high-risk breast cancer patients. Acta Oncol. 2007;46(8):1178–83.CrossRefPubMed
10.
go back to reference Wang Y, Ikeda DM, Narasimhan B, Longacre TA, Bleicher RJ, Pal S, et al. Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression. Radiology. 2008;246(2):367–75.CrossRefPubMed Wang Y, Ikeda DM, Narasimhan B, Longacre TA, Bleicher RJ, Pal S, et al. Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression. Radiology. 2008;246(2):367–75.CrossRefPubMed
11.
12.
go back to reference Hynes NE, Stern DF. The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994;1198(2–3):165–84.PubMed Hynes NE, Stern DF. The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994;1198(2–3):165–84.PubMed
13.
go back to reference Seo BK, Pisano ED, Kuzimak CM, Koomen M, Pavic D, Lee Y, et al. Correlation of HER-2/neu overexpression with mammography and age distribution in primary breast carcinomas. Acad Radiol. 2006;13(10):1211–8.CrossRefPubMed Seo BK, Pisano ED, Kuzimak CM, Koomen M, Pavic D, Lee Y, et al. Correlation of HER-2/neu overexpression with mammography and age distribution in primary breast carcinomas. Acad Radiol. 2006;13(10):1211–8.CrossRefPubMed
14.
go back to reference Griniatsos J, Vassilopoulos PP, Kelessis N, Agelatou R, Apostolikas N. The prognostic significance of breast tumour microcalcifications. Eur J Surg Oncol. 1995;21(6):601–3.CrossRefPubMed Griniatsos J, Vassilopoulos PP, Kelessis N, Agelatou R, Apostolikas N. The prognostic significance of breast tumour microcalcifications. Eur J Surg Oncol. 1995;21(6):601–3.CrossRefPubMed
15.
go back to reference Karamouzis MV, Likaki-Karatza E, Ravazoula P, Badra FA, Koukouras D, Tzorakoleftherakis E, et al. Non-palpable breast carcinomas: correlation of mammographically detected malignant-appearing microcalcifications and molecular prognostic factors. Int J Cancer. 2002;102(1):86–90.CrossRefPubMed Karamouzis MV, Likaki-Karatza E, Ravazoula P, Badra FA, Koukouras D, Tzorakoleftherakis E, et al. Non-palpable breast carcinomas: correlation of mammographically detected malignant-appearing microcalcifications and molecular prognostic factors. Int J Cancer. 2002;102(1):86–90.CrossRefPubMed
16.
go back to reference Ferranti C, Coopmans DYG, Biganzoli E, Bergonzi S, Mariani L, Scaperrotta G, et al. Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer. Br J Radiol. 2000;73(871):698–705.CrossRefPubMed Ferranti C, Coopmans DYG, Biganzoli E, Bergonzi S, Mariani L, Scaperrotta G, et al. Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer. Br J Radiol. 2000;73(871):698–705.CrossRefPubMed
17.
go back to reference Hayes DF. Disease related indicators for a proper choice of adjuvant treatments. Breast. 2011;20 Suppl 3:162–4.CrossRef Hayes DF. Disease related indicators for a proper choice of adjuvant treatments. Breast. 2011;20 Suppl 3:162–4.CrossRef
18.
go back to reference Gajdos C, Tartter PI, Bleiweiss IJ, Hermann G, Csepel J, Estabrook A, et al. Mammographic appearance of nonpalpable breast cancer reflects pathologic characteristics. Ann Surg. 2002;235(2):246–51.CrossRefPubMedPubMedCentral Gajdos C, Tartter PI, Bleiweiss IJ, Hermann G, Csepel J, Estabrook A, et al. Mammographic appearance of nonpalpable breast cancer reflects pathologic characteristics. Ann Surg. 2002;235(2):246–51.CrossRefPubMedPubMedCentral
19.
go back to reference Dinkel HP, Gassel AM, Tschammler A. Is the appearance of microcalcifications on mammography useful in predicting histological grade of malignancy in ductal cancer in situ? Br J Radiol. 2000;73(873):938–44.CrossRefPubMed Dinkel HP, Gassel AM, Tschammler A. Is the appearance of microcalcifications on mammography useful in predicting histological grade of malignancy in ductal cancer in situ? Br J Radiol. 2000;73(873):938–44.CrossRefPubMed
20.
go back to reference Skandalis SS, Labropoulou VT, Ravazoula P, Likaki-Karatza E, Dobra K, Kalofonos HP, et al. Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas. BMC Cancer. 2011;11:314.CrossRefPubMedPubMedCentral Skandalis SS, Labropoulou VT, Ravazoula P, Likaki-Karatza E, Dobra K, Kalofonos HP, et al. Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas. BMC Cancer. 2011;11:314.CrossRefPubMedPubMedCentral
21.
go back to reference Tabar L, Dean PB. Thirty years of experience with mammography screening: a new approach to the diagnosis and treatment of breast cancer. Breast Cancer Res. 2008;10 Suppl 4:3.CrossRef Tabar L, Dean PB. Thirty years of experience with mammography screening: a new approach to the diagnosis and treatment of breast cancer. Breast Cancer Res. 2008;10 Suppl 4:3.CrossRef
22.
go back to reference Tot T, Gere M, Pekar G, Tarian M, Hofmever S, Hellberg D, et al. Breast cancer multifocality, disease extent, and survival. Hum Pathol. 2011;42(11):1761–9.CrossRefPubMed Tot T, Gere M, Pekar G, Tarian M, Hofmever S, Hellberg D, et al. Breast cancer multifocality, disease extent, and survival. Hum Pathol. 2011;42(11):1761–9.CrossRefPubMed
23.
go back to reference Bick U, Diekmann F. Digital mammography: what do we and what don’t we know? Eur Radiol. 2007;17(8):1931–42.CrossRefPubMed Bick U, Diekmann F. Digital mammography: what do we and what don’t we know? Eur Radiol. 2007;17(8):1931–42.CrossRefPubMed
Metadata
Title
Mammographic microcalcifications and breast cancer tumorigenesis: a radiologic-pathologic analysis
Authors
Madiha Naseem
Joshua Murray
John F Hilton
Jason Karamchandani
Derek Muradali
Hala Faragalla
Chanele Polenz
Dolly Han
David C Bell
Christine Brezden-Masley
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1312-z

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