Abstract
Background:
Breast density is an independent risk factor for breast cancer and affects the sensitivity of mammography screening. Therefore, new breast imaging approaches could benefit women with increased breast density in early cancer detection and diagnosis.
Objectives:
To assess the diagnostic performance of abbreviated breast MRI compared with mammography and other imaging modalities in screening and diagnosing breast cancer among Saudi women with dense breast tissue.
Methods:
A retrospective diagnostic study was conducted using anonymized medical images and histopathology information from 55 women, aged ≥30 years, who had dense breasts (Breast Imaging and Reporting Data System [BI-RADS] breast density categories C and D) and an abnormal mammogram. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for mammography, digital breast tomosynthesis (DBT), synthetic mammography (SM) derived from DBT, ultrasound, and abbreviated breast MRI (ABMRI).
Results:
A total of 19 women had pathology-proven breast cancer. Among all methods, ABMRI showed the highest sensitivity (94.7%) and specificity (58.3%), while mammography showed the lowest (84.2% and 44.4%, respectively). AUC for ABMRI was higher than all the methods including mammography (0.751 vs. 0.643; P < 0.05).
Conclusion:
ABMRI appears to be more accurate in cancer diagnosis than mammography and other modalities for women with dense breast tissue. Further research is advised on a larger sample of Saudi women to confirm the benefit of ABMRI in breast cancer screening and diagnosis for women with increased breast density.
Keywords: Abbreviated breast MRI, breast cancer, breast density, diagnostic accuracy, mammography, Saudi Arabia
INTRODUCTION
The majority of national breast cancer screening programs are primarily designed using age as the risk criteria for determining eligibility for mammography, with some also including family history of breast cancer.[1,2] Increased breast density, the higher proportion of fibroglandular tissue in the breast, lowers the sensitivity of mammography screening[3,4] and is known to be an important independent risk factor for breast cancer.[5,6] Therefore, recent European screening guidelines and legislation in the United States and Canada recommend that women with increased breast density should be offered additional breast imaging modalities to supplement mammography alone.[7,8] These recent advances in personalized breast cancer screening for women with dense breasts are based on higher cancer detection rates and greater diagnostic accuracy of supplementary imaging compared with mammography alone.[9]
Hand-held breast ultrasound, commonly used as an adjunct to mammography for diagnosing breast diseases in symptomatic patients,[10] increases cancer detection in mammography-negative women with dense breasts by 3.8 per 1000 but has limitations such as being time-consuming, operator-dependent, and having a low positive predictive value (PPV).[11,12,13] Digital breast tomosynthesis (DBT) improves breast radiographic examination by eliminating tissue overlap in 2D images and enhancing the analysis of fibroglandular tissue.[14] For women with dense breasts, DBT has higher sensitivity (84%–90%) than mammography alone (69%–86%) and results in more positive biopsies, improving diagnostic confidence.[15] Moreover, the use of DBT in diagnostic examinations has resulted in a higher rate of positive biopsies, improving diagnostic confidence.[16,17] While DBT increases cancer detection rates by up to 2.8 per 1000[18,19] and increases sensitivity by 2%,[20] it takes longer to interpret and increases radiation dose if combined with conventional mammography, an issue addressed by using synthetic mammography (SM) images.[21] Despite these advances, DBT’s sensitivity is lower for extremely dense breast tissue compared with other densities but better than mammography alone.[22,23]
Breast MRI is the most sensitive imaging modality for detecting and diagnosing breast cancer at its earliest stages.[24,25] The American College of Radiology (ACR) recommends MRI for women with genetics-based increased risk, a calculated lifetime risk of 20% or more, or a history of chest or mantle radiation therapy at a young age.[26] In line with this recommendation, women in Saudi Arabia with a higher risk of breast cancer due to genetic reasons are offered breast MRIs at tertiary care hospitals.[27,28] Recently, the European Society of Breast Imaging (EUSOBI) recommended that women of screening age with extremely dense breasts should be offered breast MRI every 2 to 4 years.[7] Additional MRI was found to detect more cancers 16.5 per 1000 screens and, as a consequence, there were fewer interval cancers (0.8/1000) for women who took up the invitation to attend breast MRI compared to women undergoing mammography alone (5.0/1000), thus reducing the interval cancer rate by 84%.[9] However, breast MRI is a costly modality, especially for screening purposes, in addition to the long time required to perform a full protocol contrast-enhanced breast MRI exam.[9,29] It is also unsuitable for women with a high body mass index (BMI) and those with cardiac implantable electronic devices such as pacemakers.[30]
The introduction of abbreviated breast MRI (ABMRI) permits a faster and shorter breast imaging process enabling MRI screening for a larger proportion of eligible women at a lower cost.[31,32] The first ABMRI introduced by Kuhl et al. used the FAST protocol (First contrast-enhanced Acquisition SubTracted), which consists of images of one pre-and one post-contrast acquisition and maximum-intensity projection (MIP) images. The diagnostic yield was found to be comparable with a full-breast MRI.[31]
Generally, studies of alternative imaging modalities for breast cancer screening have been conducted in Western and Eastern populations. It is unclear whether these findings apply to the Saudi breast screening population. This paucity of information about the Saudi screening population might be due to the fact that breast cancer screening in Saudi is opportunistic; women are not regularly invited but rather self-referred, which depends on a number of factors such as socioeconomic status or level of education.[33] To our knowledge, no study has compared ABMRI with other breast imaging modalities or with mammography alone in a Saudi population, particularly in women with dense breast tissue. Therefore, this study aims to assess the diagnostic performance of abbreviated breast MRI compared to mammography and other imaging modalities used to screen and diagnose Saudi women with dense breast tissue and abnormal mammogram.
METHODS
We undertook a retrospective diagnostic accuracy study that included mammography, SM, DBT, ultrasound, and ABMRI examinations for women attending King Saud University Medical City (KSUMC), Saudi Arabia, between May 2018 and May 2021. Ethical approvals were received from the Institutional Review Board at KSUMC and the University of Manchester, United Kingdom.
The study included anonymized medical imaging examinations and pathology information from Saudi women with dense breast tissue (ACR BIRADS 5th Edition categories C and D) and aged ≥30 years. The inclusion criteria were diagnostic or screening female cases who underwent contrast-enhanced breast MRI (only the abbreviated protocol was included) between 2018 and 202, who also had complete mammography, DBT, and ultrasound examinations within 6 months of the date of MRI. The exclusion criteria were women with incomplete breast imaging examinations and women with previous history of breast cancer surgery or treatment. All available breast cancer-related characteristics were recorded to provide information on the sample; this included age, BMI, menopausal status, presence of symptoms, family history, and number of children.
Mammography, synthetic mammography, and digital breast tomosynthesis images
The X-ray machine used for this study was a Fujifilm 3D digital mammography system. Image acquisition was obtained under the same compression for the left and right bilateral craniocaudal (CC) and mediolateral oblique (MLO) views of mammography and DBT. Thus, mammography, DBT, and the reconstructed images of SM were comparable.
Ultrasound images
Ultrasound images were collected from hand-held ultrasound machines at KSUMC (Aixplorer SuperSonic Imagine breast ultrasound machine; SuperSonic Imaging, Aix-en-Provence, France). The routine practice for a full bilateral breast ultrasound scan starts by dividing the breast into sections based on clock directions 12, 3, 6, and 9, the nipple and areolar area, and the axilla area. The transducers used are SL 15-4 linear with 8.5 MHz nominal center frequency and 5MHz pulse wave Doppler center frequency. All ultrasound examinations included in this study were performed by a senior technologist with 5 years of experience in breast ultrasound.
Abbreviated MRI images
Breast MRI examinations at KSUMC are performed on a 1.5-T MRI machine (GE Medical System, Optima MR450w) using a dedicated eight-channel breast coil. An abridged abbreviated FAST MRI protocol[34] was created from sequences obtained with the standard protocol for contrast-enhanced breast MRI with 1.4-mm slice thickness and 0.7-mm spacing between slices. These sequences are dual-echo (Dixon water/fat separation), dynamic contrast-enhanced MRI images of the unenhanced axial T1-weighted (pre), and the first (peak) and second (delay) post-contrast axial T1-weighted sequences. The total calculated acquisition time was <4 minutes. The contrast agent used was Dotarem (gadoterate meglumine) (Guerbet, Roissy CdG Cedex, France), a macrocyclic gadolinium-based contrast agent known for its high stability and safety profile, making it a preferred choice for breast MRI.[35]
In the full protocol of breast MRI, 7 phases were included for MIP generation. For this study, a senior MRI technologist performed the post-processing, including MIP of pre, peak, and delay phases of breast MRI images and generated the ABMRI examinations. The interpreting radiologist was provided with the abbreviated protocol images and the subtraction MIP images were only constructed from the abbreviated protocol’s sequences.
Image reading and presentation method
All images were viewed on mammography and breast imaging dedicated monitors in radiology reading stations. Six breast radiologists experienced in all breast imaging examinations (experience ranging from 5 to 20 years) assessed 6–11 cases for each modality, blind to each other’s results and original reports. Images were distributed randomly by dividing all images into six groups labelled A to F; these groups included 8, 10, 10, 6, 10, and 11 women, respectively. Therefore, each radiologist read 44–49 breast imaging examinations [Table 1]. Radiologists in this study were based outside KSUMC to ensure they had not previously seen the cases and pathology results. Images from DBT and SM were separated after construction and read independently.
Table 1.
Method of participant distribution among six radiologists
| Radiologist | Group code (number of women) | |||||
|---|---|---|---|---|---|---|
|
| ||||||
| Mammography | SM | DBT | Ultrasound | ABMRI | Total | |
| Radiologist 1 | A (8) | C (10) | B (10) | D (6) | F (11) | 45 |
| Radiologist 2 | F (11) | B (10) | A (8) | C (10) | E (10) | 49 |
| Radiologist 3 | E (10) | A (8) | F (11) | B (10) | D (6) | 45 |
| Radiologist 4 | D (6) | F (11) | E (10) | A (8) | C (10) | 45 |
| Radiologist 5 | C (10) | E (10) | D (6) | F (11) | B (10) | 47 |
| Radiologist 6 | B (10) | D (6) | C (10) | E (10) | A (8) | 44 |
SM – Synthetic mammography; DBT – Digital breast tomosynthesis; ABMRI – Abbreviated breast magnetic resonance imaging
Image interpretation method
Radiologists assessed the findings according to ACR BI-RADS for breast cancer diagnosis 5th edition.[36] For the purposes of processing the diagnostic yield of the five imaging modalities, test results were coded as negative (BI-RADS category 1, 2, or 3) or positive (BI-RADS categories 4 or 5). Radiologists were asked to mark all suspicious areas in the images by numbers (correlated lesions in different views should be given the same lesion number). Then a BI-RADS score was assigned for each lesion and for the full exam. If more than one lesion was present, radiologists were asked to mark the index and the most suspicious lesion first as lesion number one, and the second as number two, and so on.
Analysis
Pathological results were considered the gold standard. Cancer cases were defined as women with a confirmed malignant finding in the histopathology results such as ductal carcinoma in situ (DCIS), invasive mammary carcinoma including invasive ductal carcinoma (IDC) and/or invasive lobular carcinoma; other pathology findings were classified as non-malignant.
Cancer-free women were defined as women who were recalled but were negative for malignancy in the histopathology results or with normal findings in the follow-up examinations after at least 2 years. In case there was more than one lesion noted in the same examination, one lesion (the index lesion) per woman was considered in the analysis. Positive and negative results from each imaging modality were classified as true positive (TP), true negative (TN), false positive (FP), or false negative (FN), based on the gold standard. The outcomes were: sensitivity, specificity, PPV, and negative predictive value (NPV). Confidence intervals (95% CIs) were computed for the sensitivity and specificity using Clopper-Pearson confidence intervals and for PPV and NPV using the standard logit confidence intervals. Sensitivity, specificity, PPV, and NPV were calculated using TP, TN, FN, and FP values. The accuracy of each modality was compared with a non-inferiority null hypothesis based on the difference in the area under the receiver operating characteristic (ROC) curve (AUC). The difference between all the modalities in the differentiation between cancer cases and cancer-free women was assessed using Pearson’s Chi-square test. Multiple hypothesis testing was considered using the Bonferroni correction. P value <0.05 was divided by the number of statistical tests;[6] therefore, a P value (2-tailed) <0.008 was considered statistically significant. Statistical analyses were performed using SPSS version 25.
RESULTS
Between May 2018 and May 2021, 55 women met the inclusion criteria for the study [Figure 1]. The mean (±SD) age was 47.7 (±8.6; range 30-69 years) and the mean BMI was 32.9 (±7.3) kg/m2. Most of the women had heterogeneously dense breasts (category C) (90.9%). The distribution of other characteristics of the sample related to breast cancer risk is shown in Table 2.
Figure 1.
Number of women assessed by all imaging modalities and included in the study. KSUMC: King Saud University Medical City, DBT: Digital breast tomosynthesis
Table 2.
Characteristics of the study sample (women with dense breast tissue, breast imaging and reporting data system C and D) (N=55)
| Variables | n (%) |
|---|---|
| Age (years) | |
| Mean±SD | 47.7±8.6 |
| Median (25th–75th percentiles) | 49 (41–53) |
| BMI (kg/m2) | |
| Mean±SD | 32.9±7.3 |
| Median (25th–75th percentiles) | 31.6 (26.7–39.2) |
| Menopausal status | |
| Premenopausal | 37 (67.3) |
| Postmenopausal | 18 (32.7) |
| Symptomatic | |
| Yes | 35 (63.6) |
| No | 20 (36.4) |
| Original mammography BI-RADS breast density category | |
| C (heterogeneously dense tissue) | 50 (90.9) |
| D (extremely dense tissue) | 5 (0.1) |
| Family history | |
| Yes | 23 (41.8) |
| No | 32 (58.2) |
| Number of children | |
| None | 10 (18.2) |
| 1–4 | 24 (43.6) |
| 5–8 | 14 (25.5) |
| 8+ | 2 (3.6) |
| Unknown | 5 (9.1) |
BI-RADS – Breast Imaging and Reporting Data System; SD – Standard deviation; BMI – Body mass index
A total of 74 breast lesions were detected in this retrospective analysis from 36 women (all had previously been identified in normal clinical practice). Of these, there were 20 (28.5%) histologically proven malignant lesions, of which 80% were invasive carcinomas with or without DCIS; 33 benign lesions were histologically proven; and a further 21 had stable follow-up imaging at 1 and 2 years, showing no suspicious interval changes. Table 3 shows the histopathological characteristics of biopsied breast lesions for women who underwent biopsy. However, because one lesion per woman was considered in the analysis, the sample included 19 cancer cases (one woman had two grade 2 IDC lesions in the right breast, the largest was considered in this analysis) with histopathologically proven malignancies, and 36 cancer-free women (women with benign histopathological results: =17; women with a normal breast imaging exam at 2-year follow-up: 19).
Table 3.
Histopathological characteristics of cancer and benign lesions
| Characteristic | n (%) |
|---|---|
| Cancer type (n=20) | |
| IDC + DCIS | 2 (10) |
| IDC | 13 (65) |
| DCIS | 4 (20) |
| ILC | 1 (5) |
| Invasive grade | |
| 1 (low) | 0 |
| 2 (intermediate) | 5 (25) |
| 3 (high) | 10 (50) |
| Not applicable/reported | 5 (25) |
| DCIS grade | |
| 1 (low) | 1 (5) |
| 2 (intermediate) | 2 (10) |
| 3 (high) | 3 (15) |
| Lymph node involvement | |
| Yes | 9 (45) |
| No | 11 (55) |
| Cancer size (cm) | |
| ≤2 | 9 (45) |
| >2–4 | 7 (35) |
| >4 | 4 (20) |
| Benign lesion type (n=54) | |
| Fibrosis | 8 (14.8) |
| Ductal hyperplasia | 5 (9.2) |
| Stromal hyperplasia | 1 (1.9) |
| Fibrocystic change | 4 (7.4) |
| Adenosis | 2 (3.7) |
| Papilloma | 2 (3.7) |
| Hyalinised stroma | 1 (1.9) |
| Fibroadenoma | 4 (7.4) |
| Ductectasia | 1 (1.9) |
| Complicated cyst | 1 (1.9) |
| Benign mammary tissue | 4 (7.4) |
| Unknown | 21 (38.8) |
IDC – Invasive ductal carcinoma; DCIS – Ductal carcinoma in situ; ILC – Invasive lobular carcinoma
All imaging modalities missed at least one histopathologically confirmed breast cancer [Table 4]. Figure 2 shows breast cancer in a woman with dense breast tissue only detected in ABMRI and missed by all other modalities. ABMRI missed one breast cancer (5.3%); this was a low-grade DCIS seen as a non-enhancing mass (BI-RADS 2), which was detected by ultrasound and DBT as areas of altered echogenicity and by DBT as suspicious microcalcifications and was assigned BI-RADS 4 [Figures 3–6]. Mammography, SM, and ultrasound all missed three histologically proven malignancies (15.8%). Mammography missed only invasive ductal carcinomas (intermediate or high grade). Ultrasound missed one DCIS (high grade), one high-grade IDC, and one high-grade DCIS with IDC [Table 4]. Among the missed lesions, one high-grade IDC was missed by all modalities except for ABMRI, one DCIS was missed by SM and ABMRI only, and one intermediate IDC was missed by mammography and SM only.
Table 4.
Histopathological distribution of breast cancer cases missed on the imaging modalities
| Imaging modality | Missed cancers on imaging, n (%) | Histopathological diagnosis of missed breast cancers |
|---|---|---|
| Mammography | 3 (15.8) | IDC (high grade) (2) (sizes ≤2 cm and >2–4 cm) |
| IDC (intermediate grade) (1) (size >4 cm) | ||
| SM | 3 (15.8) | DCIS (low grade) (1) (size ≤2 cm) |
| IDC (high grade) (1) (size >2–4 cm) | ||
| IDC (intermediate grade) (1) (size >4 cm) | ||
| DBT | 2 (10.5) | DCIS (high grade) (1) (size ≤2 cm) |
| IDC (high grade) (1) (size >2–4 cm) | ||
| Ultrasound | 3 (15.8) | DCIS (high grade) (1) (size ≤2 cm) |
| IDC (high grade) (1) (size >2–4 cm) | ||
| DCIS + IDC (high grade) (1) (size ≤2 cm) | ||
| ABMRI | 1 (5.3) | DCIS (low grade) (1) (sizes ≤2 cm) |
SM – Synthetic mammography; DBT – Digital breast tomosynthesis; ABMRI – Abbreviated breast magnetic resonance imaging; IDC – Invasive ductal carcinoma; DCIS – Ductal carcinoma in situ
Figure 2.
Abbreviated breast MRI postprocessing maximum-intensity projection images of a 46-year-old woman with heterogeneously dense breasts. She attended the breast imaging clinic with a right breast palpable lump in May 2019. The radiological diagnoses at that time did not reveal any suspicious lesions (BI-RADS 2), and the lump was not biopsied. However, the follow-up histopathology diagnosis in December 2021 showed an interval invasive ductal carcinoma grade 3 in the right breast. The radiologist in this retrospective study assigned this abbreviated breast MRI exam a BI-RADS 4 for a suspicious right breast lesion (arrows), which was missed by all other imaging modalities
Figure 3.
Abbreviated breast MRI postprocessing MIR images of a 55-year-old woman with right breast nipple discharge (study ID is AC-10). She was diagnosed with BI-RADS 5 and was referred to histopathology for biopsy. Results showed a low-grade ductal carcinoma in situ in the right breast, which was missed in the retrospective evaluation of the abbreviated breast MRI protocol and assigned a BI-RADS 3 or probably benign lesion (arrow)
Figure 6.
Ultrasound images of the right breast of case AC-10. (a) a 10 o'clock oval hypoechoic mass with indistinct margin, (b) present vascularity on color Doppler and no posterior features. This low-grade ductal carcinoma in situ lesion was diagnosed in the retrospective analysis as suspicious mass (BI-RADS 4).
Figure 4.
Mammography images of the right breast, CC (a) and MLO (b), for case AC-10 with heterogeneously dense breasts (BI-RADS C). This exam was taken 13 days before the breast MRI in Figure 3. The retrospective diagnosis of the mammography exam showed microcalcification (arrowed) and was considered BI-RADS or highly suggestive of malignancy. CC: Bilateral craniocaudal, MLO: Mediolateral oblique
Figure 5.
Digital breast tomosynthesis MLO images of the right breast for case AC-10. This exam was performed after mammography and at the same position and compression [Figure 4]. The retrospective diagnosis in this study showed a visible suspicious microcalcification (arrowed) and the case was reported as BI-RADS 4 or suspicious for malignancy. MLO: Mediolateral oblique
ABMRI had the highest sensitivity (94.7%, 95% CI 73.9%-99.8%) followed by DBT (89.5%, 95% CI: 66.9%–98.7%). Mammography, SM, and ultrasound had the same sensitivity (84.2%, 95% CI: 60.4%–96.6%). ABMRI also had the highest specificity (55.6%, 95% CI: 38.1%–72.1%), while mammography had the lowest specificity (44.4%, 95% CI: 27.9%–61.9%). Table 5 summarizes each imaging modality’s sensitivity, specificity, PPV, and NPV.
Table 5.
Sensitivity, specificity, positive predictive value, and negative predictive value of the imaging modalities
| Imaging modality | Sensitivity, % (95% CI) | Specificity, % (95% CI) | PPV, % (95% CI) | NPV, % (95% CI) |
|---|---|---|---|---|
| Mammography | 84.2 (60.4%–96.6%) | 44.4 (27.9%–61.9%) | 44.4 (36.0%–53.1%) | 84.2 (63.9%–94.1%) |
| SM | 84.2 (60.4%–96.6%) | 58.3 (40.7%–74.5%) | 51.6 (40.9%–62.1%) | 87.5 (70.5%–95.3%) |
| DBT | 89.5 (66.9%–98.7%) | 52.8 (35.5%–69.6%) | 50.0 (40.6%–59.3%) | 90.4 (71.1%–97.3%) |
| Ultrasound | 84.2 (60.4%–96.6%) | 52.8 (35.5%–69.6%) | 48.4 (38.7%–58.3%) | 86.3 (68.1%–94.9%) |
| ABMRI | 94.7 (73.9%–99.8%) | 55.6 (38.1%–72.1%) | 52.9 (43.4%–62.2%) | 95.2 (74.3%–99.2%) |
BI-RADS score 4/5 was used as a threshold against the gold standard. SM – Synthetic mammography; DBT – Digital breast tomosynthesis; ABMRI – Abbreviated breast magnetic resonance imaging; PPV – Positive predictive value; NPV – Negative predictive value; BI-RADS – Breast Imaging and Reporting Data System; CI – Confidence interval
Accuracy in breast cancer diagnosis for women with dense breast tissue for each imaging modality is demonstrated in Figure 7. ROC curve analysis based on BI-RADS assessment for differentiating cancer cases and cancer-free women showed that the highest AUC was for ABMRI (0.751, 95% CI: 0.623–0.880), followed by SM (0.713, 95% CI: 0.572–0.853) and DBT (0.711, 95% CI: 0.573–0.849). Ultrasound also showed a higher AUC (AUC = 0.685, 95% CI: 0.540–0.829) than mammography (AUC = 0.643, 95% CI: 0.494–0.792).
Figure 7.
Receiver operating characteristic curves for mammography, synthetic mammography, digital breast tomosynthesis, ultrasound and abbreviated breast MRI. The operating points at BI-RADS 4 for all imaging modalities are indicated. ROC: Receiver operating characteristic
DISCUSSION
Mammography is considered as the primary breast cancer screening tool because it is widely available, inexpensive, and provides high-resolution images that can be interpreted quickly. However, due to limitations of the technique, especially for women with increased breast density, other imaging modalities have been investigated as an adjunct to, or replacement for, mammography in breast cancer screening and diagnosis.[37] In this retrospective diagnostic accuracy study, five diagnostic imaging modalities, mammography, DBT, SM, ultrasound, and ABMRI, were evaluated by comparing the diagnostic performance in 55 women with dense breast tissue (BI-RADS breast density categories C and D).
New EUSOBI guidelines suggest that women with increased breast density are eligible for additional imaging modalities rather than mammography alone, specifically breast MRI.[7] However, full MRI protocol examinations require a long time and higher costs, especially for population screening.[9,37,38,39] The results of this study showed that the accuracy of ABMRI was superior to mammography, which is consistent with previous literature.[31,32,40,41] ABMRI may provide more value in screening women with dense breast tissue, as assessed by sensitivity and AUC, than mammography, without compromising specificity. PPV was higher for ABMRI (52.9%) compared with other modalities and lowest for mammography (44.4%); this suggests an increase in the number of recalls or biopsies in screening settings for mammography screening. NPV, on the other hand, was highest for ABMRI (95.2%), meaning that women with positive results are less likely to be missed.
Mammography performance in breast cancer diagnosis was lower than SM, DBT, ultrasound, and ABMRI for Saudi women with dense breast tissue. In general, the sensitivity of breast cancer screening increases if an additional imaging modality is performed for women with dense breast tissue; however, more biopsies and recalls are reported.[42] The better sensitivity and specificity of ABMRI compared with mammography for women, irrespective of breast density, has been reported by previous studies with sensitivity ranging from 93.8% to 100% and specificity between 88.3% and 97.0%.[31,40] Comstock et al.[40] showed that ABMRI provided significantly higher sensitivity for women with dense breast tissue compared with DBT (95.7% vs. 39.1%, respectively; P < 0.001). However, ABMRI showed lower specificity than DBT (86.7% vs. 97.4%, respectively; P < 0.001) with a higher number of biopsies (107 ABMRI vs. 29 DBT). In the current study, the specificity of ABMRI was slightly lower than the constructed synthetic mammograms from DBT images (55.6% [95% CI: 39.4%–71.8%] vs. 58.3% [95% CI 42.2%-74.4%]; P = 0.007). Therefore, some argue that the cost of the ABMRI exam and additional investigations (i.e. biopsies) in breast cancer screening for women with dense breasts must be considered before adopting the modality in screening programs.[43]
DBT as a supplemental breast cancer screening modality to mammography has been extensively investigated and approved for clinical use.[44] DBT has been considered in breast cancer detection and diagnosis mainly to overcome the lower sensitivity in women with dense breast tissue in standard mammography due to tissue overlap.[45] In the TOMMY trial, Gilbert et al.[46] found that for women with dense breasts (percent density as assessed by visual analogue scale ≥50%), sensitivity was 93% for DBT plus mammography compared with 86% for mammography alone (P < 0.03). In another study, Rafferty et al.[23] showed that diagnostic accuracy was improved by the addition of DBT to mammography versus mammography alone for women with dense breast tissue (AUC: 0.877 vs. 0.786; P < 0.05).
The results of this analysis showed higher diagnostic performance of DBT alone in comparison with mammography. A study by Chae et al.[47] assessed the accuracy of DBT alone in comparison to mammography alone and found that the diagnostic performance for DBT was higher than that of mammography, particularly for women with dense breasts; AUC for DBT and for mammography were 0.95 (95% CI 0.93-0.97) and 0.92 (95% CI 0.90-0.94) (P = 0.006), respectively. In the current study, six radiologists assessed the screening views of SM alone (right and left CC and MLO) and found that the sensitivity was identical to mammography (84.2%, 95% CI: 60.4%–96.6% for both), while the AUC was higher (0.713 vs. 0.643 for SM and mammography, respectively) (P = 0.685). Previous studies have found similar results.[48,49,50,51] In the study by Choi et al., SM and mammography were compared by assessing the performance of three radiologists in the detection of T1 stage cancer (sized ≤2 cm). They found no difference in sensitivity between SM and mammography for all radiologists (62.6%–71.0% vs. 60.7%–71.0%, respectively, P > 0.05), while specificity was generally higher for SM compared with mammography (84.1%–96.3% vs. 72.9%–94.4%) and was significant for one reader (P = 0.02).[48] Three studies found that SM showed non-inferior performance compared with mammography in the detection of microcalcification, with better but non-significant conspicuity results.[49,50,51] Therefore, SM is considered a sufficient replacement for mammography if a DBT exam is conducted due to the comparable performance and less radiation exposure needed.[52]
In the current study, the sensitivity of breast ultrasound was identical to mammography for women with dense breasts. However, previous studies have found that supplemental ultrasound offers an overall increase in the detection rate (3.8 per 1000 women) among women with dense breasts and previously negative mammograms.[11] Such variation is likely due to the small sample size of the current study with more symptomatic women and larger lesions. However, other studies have shown similar results to the current study where additional MRI provides higher cancer detection rates than ultrasound (16.5 per 1000 women).[9] Moreover, the number of false-positive examinations in ultrasound is high, thereby decreasing the diagnostic accuracy.[53] The increased false positive recall rate is a drawback because it causes unnecessary distress to women and increases costs with possible further examinations that could include contrast administration and radiation dose. ABMRI for women with dense breast tissue in this study had fewer false positives than mammography and ultrasound. Similar results were reported in the second round of the DENSE trial; they showed that additional MRI for women with dense breast tissue provided a strong reduction in the number of false-positive results because images could be compared with those from prior MRI examinations.[54]
Limitations
This study has several limitations that should be acknowledged. The most significant is the relatively larger lesions included, which may not accurately represent the smaller lesions typically found in a screening setting. Consequently, the results may not be entirely applicable to such scenarios. In addition, the inclusion of cases with markers, while not problematic for larger lesions, could potentially alert radiologists to the exact position of smaller lesions or create artifacts that might reduce accuracy. The study involved both diagnostic and screening cases, which could impact the generalizability of the findings. Furthermore, due to the small sample size, the study did not evaluate lesion types or accuracy based on lesion type or patient age, which could have provided more comprehensive insights. Therefore, larger prospective studies should provide more definitive results. Nevertheless, this study provided, for the first-time, promising results of ABMRI in diagnosing Saudi women with increased breast density and compared multiple breast imaging modalities for those women.
CONCLUSION
This study found that among women with dense breasts, abbreviated breast MRI (ABMRI) had superior sensitivity and overall accuracy performance compared with mammography and other modalities in diagnosing breast cancer. This finding, along with the fact that ABMRI has lower cost and time requirements compared with full breast MRI protocol, suggests that Saudi women with dense breast tissue may benefit from ABMRI for breast cancer screening and diagnosis.
Ethical considerations
Ethical approvals were received from the Institutional Review Board at KSUMC, Saudi Arabia (Ref. no.: 21/0224/IRB) and the University of Manchester, United Kingdom (Ref. no.: 2021-5622-18502). Requirement for patient consent was waived owing to the study design. The study adhered to the principles of the Declaration of Helsinki, 2013.
Peer review
This article was peer-reviewed by two independent and anonymous reviewers.
Data availability statement
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Author contributions
Conceptualization: S.M.A., E.F.H., and A.S.A.; Methodology: A.S.A, R.S., E.F.H., and S.M.A.; Data analysis: N.K., F.A., S.H., S.S., D.A., F.A., S.A., M.A., and R.S.; Writing–original draft preparation: A.S.A.; Writing – review and editing: E.F.H., S.M.A., and A.S.A.; Supervision: N.K., E.F.H., and A.S.A.
All authors have read and agreed to the published version of the manuscript.
Conflicts of interest
There are no conflicts of interest.
Acknowledgements
We would like to thank Mr. Saud Al Nasser, Radiology Department, King Saud University Medical City, for his valuable assistance. The authors extend their appreciation to the Deanship of Scientific Research and the College of Applied Medical Sciences Research Center at King Saud University for supporting this work.
Funding Statement
This research project was supported by the NIHR Manchester Biomedical Research Centre (NIHR203308).
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.