European Journal of Cardiovascular Medicine

Breast carcinoma is a major cancer in both developed and developing countries is a real threat challenging all efforts to screening, prevention and treatment aspects to reduce this cancer. The incidence of breast cancer is rising in India and is now the second most common cancer diagnosed in women after cervical cancer. It is estimated that by 2030 the number of new cases of breast cancer in India will reach just under 200,000 per year. It is fast becoming the number one cancer among urban women (1).

X-ray mammography is still the gold standard of investigational procedures for breast lesions. Digital mammography has improved diagnostics, especially in younger women and in denser breasts, and CAD (computer aided detection) can be of some help. However, every effort is necessary to raise the early cancer detection rate and thereby reduce the mortality rate. (2) The earliest sign of breast cancer is an abnormality depicted on a mammogram, before it can be felt by the woman or her physician. (3)

The sensitivity of mammography alone decreases with increasing parenchymal density. Numbers of missed cancers in very dense breasts have been reported to be as high as 52% - 76% (4); in analogue screening programs, up to 30% of detectable cancers were not detected.   There are numerous reasons for this, the most important being the structured or anatomical noise produced by the overlapping tissue structures in the 2D imaging of a 3D object. Misinterpretation of architectural distortion and asymmetrical density, fibroglandular tissue overlapping the cancer and obscuring the margins of the cancer leads to false negative results. False positive findings which may mimic cancer can also be a result of these summation artefacts. The diffuse growth pattern of some tumors with ill-defined borders present a special problem. Digital Breast Tomosynthesis (D.B.T.) is a three-dimensional imaging technique which provides an arbitrary set of reconstruction planes in the breast from a limited angle series of projection images acquired while the X-ray tube moves through an arc above the stationary detector (4).  The result is a 3D data set of the entire breast volume. The individual planes of interest‖ of a chosen slice, usually 1 mm, can be viewed separately from the rest of the image, thereby reducing the impact of anatomical noise.  The individual slice shows enhancement of a lesion, while there is a blurring of the out-of- focus information of the breast tissue. (2).

Digital breast tomosynthesis (DBT) is one technology being developed to improve detection and characterization of breast lesions especially in women with non-fatty breasts. DBT may be useful in both the screening and diagnostic evaluation. (5). Hence this study was undertaken to compare and evaluate the impact of Digital Breast Tomosynthesis (DBT) combined with Full Field Digital Mammography (FFDM) versus FFDM alone in the diagnosis and interpretation of benign and malignant breast lesions utilizing the BIRADS score and to correlate the findings with histo-pathological diagnosis and to assess the accuracy of breast lesion characterization particularly, architectural distortion using BIRADS criteria with FFDM combined with DBT versus FFD.

This was a prospective, longitudinal study conducted in the department of Radiodiagnosis in a tertiary hospital in Western India from January 2018 to December 2019. Ethical clearance was obtained for the study for the time period mentioned. 

Informed consent was taken from all patients for participation in the study. All patients presenting to the department with breast lesion or lump with suspicion of breast malignancy were evaluated with full field digital mammography (FFDM) and digital breast tomosynthesis (DBT). All cases with BIRADS of 4 or above based on FFDM and DBT were further advised to undergo biopsy which will be sent for histopathological investigation. The remaining patients (BIRADS less than 4) will be either subjected to follow up (by ultrasonography or mammography) for a period of 6 months to exclude breast malignancy.

Inclusion criteria:

1. Patients coming for routine mammography screening for breast malignancy.
2. Patients presenting with a breast lump or lesion with clinical suspicion of malignancy.

Exclusion criteria:

1. Pregnant and lactating women
2. Patients who have undergone any surgeries on the breast in the past.
3. Patients not giving consent.

The continuous variables were analysed by Unpaired t test. Categorical data was analysed using Chi square test.  p values < 0.05 will be accepted as indicative of statistically significant.

All patients included had already undergone routine mammography in CC & MLO Views followed by complete digital tomosynthesis in CC & MLO Views. All examinations were performed on ― MAMMOMAT INSPIRATION WITH PRIME TECHNOLOGY by SIEMENS mammography & tomosynthesis machine. Mammomat Inspiration with PRIME Technology results in up to 30% less dose, without compromising image quality. The widest tomo angle with 50° and 25 projections in this machine provides the perspective required for optimal depth resolution, and cannot be achieved with smaller angles. (https://www.siemens-healthineers.com/en-in/mammography/digital-mammography/mammomat-inspiration-prime).

Legends Of Figures:

Figure 1: Mammomat Inspiration with Prime Technology by Siemens Mammography & Tomosynthesis Machine.

After acquisition, the data from the projection images was used to reconstruct between 50 to 90 or 60- 120 (depending on the tissue bulk) parallel 2 to 3 mm-thick slices depending on the thickness of breast. Re-reporting was done as per ACR guidelines. First only mammography films were reported without looking into tomosynthesis, findings were recorded & BIRADS categorization was done. Then for the same patient mammography films were read with the help of tomosynthesis, combined findings were recorded & BIRADS categorization was done. Results obtained by reporting digital mammography without tomosynthesis were compared with the Digital mammography + tomosynthesis reports. Finally, these results were correlated with    pathological findings. The agreement between the diagnostic modalities is compared by calculating the kappa statistic with 95% confidence interval and by percentage agreement with 95% confidence interval. The sensitivity and specificity of the imaging modalities is calculated with 95% confidence intervals.  The confidence intervals for percentage agreement and sensitivity and specificity is calculated using Wilson efficient-score method, corrected for continuity. Sensitivities and specificities are compared using McNemar test. p values < 0.05 are accepted as indicative of statistical significance

The study included 141 participants with breast lesion or lump with suspicion of breast malignancy and also the patients undergoing routine screening.

In our study 141 patients were included, who were in range of 29 to 91 yrs. Majority were in the age group of 51-60 years.

The breast masses were characterized according to the ACR BI-RADS Atlas® 5th Edition. Majority of the breast mass with irregular shape turned out to be malignant on HPE correlation.

Out of 141 patients 40 showed calcification on mammography which were seen equally well on tomosynthesis.

Younger females (<50 years) have Type d breast and as the age increases the glandular tissue is replaced by fat that is type a in >70 age group. (p value <0.0005)

Table 1: Age of the participants with each type of breast density

* Significant at 0.05 level of significance. One way ANOVA test used

In screening population (total 59 patients) , the detected breast lesions (BIRADS >3) on FFDM and DBT, 33.9% were benign and 66.1% were malignant.

In diagnostic group (total 79 patients), the detected lesions (BIRADS >3) on FFDM and DBT, 27.8% were benign and 72.2% were malignant.

Table 2: Results of histopathology (HPE) [n = 138] in the participants in the diagnostic and screening groups [Frequency (Percentage)]

#Significance level is 0.05. Chi-square test used.

It was observed that, in most cases DBT did not change the BIRADS scoring however, its addition increased the diagnostic confidence among readers. On addition of DBT to FFDM it was observed there is down gradation of the BIRADS score from 4A to 3 in 8 cases. And upgradation of BIRADS score from 4A to 4B in 1 case, 4A to 4C in 7 cases and to 5 in 2 cases.

Table 3: Nature of the breast lesions on histopathology (HPE) for each BIRADS score on FFDM plus DBT [Frequency (Percentage)]

This is in concordance to the study by Divya Singla, Arvind K. Chaturvedi et al, (27) which showed BIRADS was upgraded and downgraded in 14 and 31 cases, respectively, with the addition of DBT to FFDM.  Therefore, the addition of the DBT to FFDM increases the reader confidence and improves the lesion characterization.

Statistically significant increase in sensitivity was seen with the addition of DBT to FFDM in BIRADS ≥ 4B and ≥ 4C  (P = 0.004).

Statistically significant increase in positive predictive value was seen with the addition of DBT to FFDM in ≥ 4A.

Table 4: Diagnostic measurements - Positive Predictive value and Negative Predictive value for FFDM and FFDM plus DBT

Sensitivity of FFDM versus FFDM plus DBT in different breast densities is statistically significant in type b, c, d for BIRADS ≥ 4B and ≥ 4C. that is the detection rate of  BIRADS  ≥ 4B and ≥ 4C  lesions is improved on addition of DBT to FFDM.

Table 5: Comparison of sensitivity of FFDM versus FFDM plus DBT in different breast densities

There is no statistically significant increase in the specificity of lesion detection in different breast densities on addition of DBT to FFDM.

Table 6: Comparison of specificity of FFDM versus FFDM plus DBT in different breast densities

In both diagnostic and screening groups, significant increase in sensitivity, positive predictive value (P < 0.05) was seen with the addition of DBT to FFDM.

Table 7: Comparison of Negative predictive value of FFDM versus FFDM plus DBT in different breast densities

Increase in cancer detection rates by addition of DBT to FFDM was not statistically significant.

4 cases are shown from

Case 1) 2D Mammographic images [(a) & (c) magnified view of (a)] in CC view show microcalcifications in right breast laterally which are seen equally well on Tomosynthesis images in CC view [(c) & (d) magnified view of (c).

Case  2)  55  yr  old  female  showed  focal  asymmetry  in  right  breast  laterally  on 2D mammography images (a) & (c); which on 3D tomosynthesis images (b)&(d) was seen as density with spiculations changing BIRAD of lesion from III to IV. Histopathology report was suggestive of invasive ductal carcinoma grade I.

Case 3) A patient with heterogeneously dense breasts showed focal asymmetry in left breast medially [images (a)&(c)] which revealed density with spiculated margin on tomosynthesis [images (b)&(d)]. Histopathology report was suggestive of invasive ductal carcinoma grade II.

Case 4) Images (a) & (c) are mammographic images showing density with obscured margins in left breast which on 3D   tomosynthesis showed well circumscribed margins with perilesional radiolucent halo which was seen as simple cyst on sonography.

Breast cancer is a malignancy showing rising trend in its incidence. Earliest signs of breast carcinoma are seen on mammography. It is still the gold standard investigation for screening breasts. But being a 2D modality mammography has certain restrictions in evaluation of a 3D structure of a breast. In mammography overlap of normal breast parenchyma can mimic lesions causing false positive results. This will lead to unnecessary investigations like FNAC, biopsy MR-mammography or frequent follow up of patients causing patient anxiety till the diagnosis is reached. Similarly, overlap of normal breast parenchyma can hide or obscure lesions present in breast causing false negative results. This leads to delay in diagnosis which in case of malignant lesions leads to loss of vital lead time available from easily curable to noncurable stage. This produces grave implications on survival and quality of life of patients.  So, it is becoming increasingly important to pick up breast lesions early and then characterize them correctly. Though there are many factors which can cause false positive and false negative results in mammography like machine quality, breast density, radiologists experience etc  major factor considered responsible is overlap by normal breast parenchyma. It is thought that 3D imaging of breast can be of help as it will remove the effect of overlap of structures by taking multiple slices at varying levels.

This study is done to evaluate the effect of addition of tomosynthesis to mammography in feature  analysis of different  types of breast lesions and it‘s  effect  in BIRADS categorization of these lesions.

No significant difference was found in analysis of architectural distortions in our study, which was not in concordance with study by Raghavan B, Rajmohan M, Sivaramalingam G.et al(17)  that showed better analysis of architectural distortions with tomosynthesis as compared to mammography. However, this result may not be valid because of small sample size in our study. Only 13 architectural distortions were seen in all 141 patients out of it 5 were showing better architectural distortions on addition of tomosynthesis.

40 out of 141 patients in our study demonstrated calcifications. All of these were identified & characterized equally well on both 2D mammography & combined 3D tomosynthesis. These results matched partially with study done by Spangler ML,Zuley ML,Sumkin JH,Abrams  H,Ganott MA,Hakim C. et  al (26) ,  who  also  found  no  significant difference in identification & recognition pattern of distribution of calcification on both modalities.  However, characterization of calcification was better demonstrated on 2D mammography as compared to 3D tomosynthesis in their study.

New lesions were not detected on addition of DBT to FFDM.  The lesions seen on FFDM were better characterized and increased the confidence of reader in scoring the lesion according to BIRADS. However, since our study included subjects who were already showing lesions on mammography this is not the ideal study sample to decide about detection of new lesion on addition of tomosynthesis.

It was observed that, in most cases DBT did not change the BIRADS scoring however, its addition increased the diagnostic confidence among readers. On addition of DBT to FFDM it was observed there is downgradation of the BIRADS score from 4A to 3 in 8 cases. And upgradation of BIRADS score from 4A to 4B in 1 case, 4A to 4C in 7 cases and to 5 in 2 cases. This is in concordance to the study by Divya Singla, Arvind K. Chaturvedi et al, (27) which showed BIRADS was upgraded and downgraded in 14 and 31 cases, respectively, with the addition of DBT to FFDM.  Therefore, the addition of the DBT to FFDM increases the reader confidence and improves the lesion characterization.

Statistically significant increase in sensitivity was seen with the addition of DBT to FFDM in BIRADS ≥ 4B and ≥ 4C  (P = 0.004).

Statistically significant increase in positive predictive value was seen with the addition of DBT to FFDM in ≥ 4A.

Sensitivity of FFDM versus FFDM plus DBT in different breast densities is statistically significant in type b, c, d for BIRADS ≥ 4B and ≥ 4C. that is the detection rate of  BIRADS ≥ 4B and ≥ 4C  lesions is improved on addition of DBT to FFDM.

According to results in our study, addition of tomosynthesis to mammography increased the sensitivity from 80.2 % to 89.6 % in evaluation of in BIRADS ≥ 4B lesions and from 68.8% to 78.1% for in BIRADS ≥ 4C lesions (p value 0.004). Addition of tomosynthesis to mammography. These results were in concordance with results obtained in study done by Ingvar Andersson,Debra M. Ikeda,Sophia Zackrisson,Mark Ruschin, Tony Svahn, Pontus Timberg,Anders Tingberg.et al (20)  also showed higher sensitivity of breast tomosynthesis than digital mammography  in cancer visibility.  Also, they found better diagnostic accuracy of breast tomosynthesis than digital mammography in cancer evaluation. This shows addition of tomosynthesis to mammography causes increase in sensitivity in evaluation of benign as well as malignant lesions.

In our study, it was seen that FFDM plus DBT had better sensitivity, and positive predictive value, compared to FFDM alone in the overall study population as well as in diagnostic and screening setup. The results were similar to a previous study by Gennaro et al. who found that performance of tomosynthesis in one view at the same total dose as standard screen film mammography was not inferior to digital mammography in two views. (28) A study done by Rafferty revealed that diagnostic sensitivity and positive predictive values increased with addition of tomosynthesis (29).

Use of tomosynthesis is helpful in analysis and characterization of breast masses seen on mammography. Most of lesions can be classified either into overlapping normal breast parenchyma or densities with addition of tomosynthesis avoiding the need for unnecessary   follow   ups   or   delay   in   pathological   procedures   and   diagnosis.   So tomosynthesis should always be added while evaluating asymmetries on mammography.

1. Datta, K., Choudhuri, M., Guha, S., and Biswas, J. "Breast Cancer Scenario in Regional Cancer Centre in Eastern India over Eight Years - Still a Major Public Health Problem." Asian Pacific Journal of Cancer Prevention, vol. 13, 2012, pp. 809-813.
2. Lindhardt, F. Digital Breast Tomosynthesis. White paper by Siemens, June 2010.
3. Badgwell, B. D., et al. "Mammography Before Diagnosis Among Women Age 80 Years and Older With Breast Cancer." Journal of Clinical Oncology, Apr 21 2008. [Medline].
4. Kolb, T. M., Lichy, J., and Newhouse, J. H. "Comparison of the Performance of Screening Mammography, Physical Examination, and Breast US and Evaluation of Factors That Influence Them: An Analysis of 27,825 Patient Evaluations." Radiology, vol. 225, 2002, pp. 165-175.
5. Helvie, M. "Digital Mammography Imaging: Breast Tomosynthesis and Advanced Applications." Radiology Clinics of North America, vol. 48, no. 5, Sept. 2010, pp. 917-929.
6. Agur, A. M. R., and A. F. Dalley. Grant's Atlas of Anatomy, 12th ed., Lippincott Williams & Wilkins, Baltimore, MD, 2009.
7. Clemente, C. Anatomy: A Regional Atlas of the Human Body, 5th ed., Lippincott Williams & Wilkins, Baltimore, MD, 2006.
8. Moore, K. L., Dalley, A. F., and Agur, A. M. R. Clinically Oriented Anatomy, 6th ed., Lippincott Williams & Wilkins, Baltimore, MD, 2010.
9. Smithuis, R., and Pijnappel, R. "Differential Diagnosis of Breast Calcifications." Radiology Assistant, 11 May 2008, www.radiologyassistant.nl.
10. Wilson, J. J., and Evans, A. "The Breast." In Adam A. Dixon A. Grainger & Allison's Diagnostic Radiology Textbook, 5th ed., First vol., 2008.
11. Mahadevappa, M. "AAPM/RSN Physics Tutorial for Residents Digital Mammography: An Overview." Radiographics, vol. 24, Nov./Dec. 2004, pp. 1747-1760.
12. Simmons, M. A., Chavez, J., and Barke, L. D. "Patient Positioning and Mammography." E-radimaging, 13 Sept. 2012, www.eradimaging.com.
13. ACR BI-RADS Atlas® 5th Edition. Available from www.acr.org.
14. Zonderland, H. "Introduction to the Breast Imaging Reporting and Data System." Radiology Assistant, 1 Feb. 2006, www.radiologyassistant.nl.
15. Dongola, N. "Mammography in Breast Cancer." Medscape, 20 Sept. 2012, emedicine.medscape.com/article/.
16. Pisano, E. D., and Yaffe, M. J. "Digital Mammography." Radiology, vol. 234, 2005, pp. 353–362.
17. Raghavan, B., et al. "Role of Breast Tomosynthesis in the Morphological Analysis of Breast Lesions." European Society of Radiology, ECR 2012, SS 602 Tomosynthesis and FFDM.
18. Zuley, M. L., et al. "Digital Breast Tomosynthesis Versus Supplemental Diagnostic Mammographic Views for Evaluation of Noncalcified Breast Lesions." Radiology, vol. 266, no. 1, 2013, pp. 89-95. DOI: 10.1148/radiol.12120552.
19. Förnvik, D., et al. "Breast Tomosynthesis: Accuracy of Tumor Measurement Compared with Digital Mammography and Ultrasonography." Radiology, vol. 51, no. 3, 2010, pp. 240-247.
20. Andersson, I., et al. "Breast Tomosynthesis and Digital Mammography: A Comparison of Breast Cancer Visibility and BIRADS Classification in a Population of Cancers with Subtle Mammographic Findings." European Radiology, vol. 18, 2008, pp. 2817–2825.
21. Martínez, P., et al. "The Role of Breast Tomosynthesis Combined with Digital Mammography." European Society of Radiology, ECR 2012, SS 602 Tomosynthesis and FFDM.
22. Skaane, P., et al. "Comparison of Digital Mammography Alone and Digital Mammography Plus Tomosynthesis in a Population-based Screening Program." Radiology, RSNA, 7 Jan. 2013.
23. Svahn, T. M., et al. "Breast Tomosynthesis and Digital Mammography: A Comparison of Diagnostic Accuracy." The British Journal of Radiology, 6 June 2012.
24. Noroozian, M., et al. "Digital Breast Tomosynthesis Is Comparable to Mammographic Spot Views for Mass Characterization." Radiology, Oct. 2011.
25. Rafferty, E., and Niklason, L. "FFDM vs FFDM with Tomosynthesis for Women with Radiographically Dense Breasts: An Enriched Retrospective Reader Study." Presented at RSNA, 2011, MSVB31-10 Breast Series: Emerging Technologies in Breast Imaging.
26. Spangler, M. L., et al. "Detection and Classification of Calcifications on Digital Breast Tomosynthesis and 2D Digital Mammography: A Comparison." AJR, vol. 196, 2011, pp. 320–324.
27. Singla, D., et al. "Comparing the Diagnostic Efficacy of Full-Field Digital Mammography with Digital Breast Tomosynthesis Using BIRADS Score in a Tertiary Cancer Care Hospital." 2018, DOI: 10.4103/ijri.IJRI_107_17.
28. Gennaro, G., et al. "Digital Breast Tomosynthesis Versus Digital Mammography: A Clinical Performance Study." European Radiology, vol. 20, 2010, pp. 1545‑1553.
29. Rafferty, E. A., et al. "Assessing Radiologist Performance Using Combined Digital Mammography and Breast Tomosynthesis Compared with Digital Mammography Alone: Results of a Multicentre, Multireader Trial." Radiology, vol. 266, 2013, pp. 104‑113.
30.