Clinical value of contrast enhanced mammography in breast cancer surveillance: Early detection of disease recurrence in two cases

INTRODUCTION

Contrast-enhanced mammography (CEM) is an emerging functional imaging modality that combines conventional mammography with dual-energy contrast imaging to highlight areas of neovascularity, thus improving lesion detection and characterization. With a diagnostic sensitivity approaching that of breast magnetic resonance imaging (MRI), CEM is increasingly being integrated into clinical practice for screening, preoperative staging, and diagnostic problem-solving, especially in women with dense breasts or inconclusive findings on standard imaging modalities.^[1]

While breast MRI remains the gold standard for its high sensitivity in detecting breast cancer, its cost, availability, and patient tolerability pose significant limitations in many clinical settings. CEM, as a relatively accessible and cost-effective alternative, offers promise, particularly in intermediate-to-high-risk populations and for the surveillance of breast cancer survivors.^[2]

This report presents two cases in which CEM was pivotal in the early detection of clinically occult recurrent or new breast cancer in post-operative patients undergoing routine cancer surveillance.

CASE SERIES

The study is exempted from consent from the Institutional Review Board (IRB) due to anonymization. Permission from the department of radiology was obtained to utilize the anonymized images for the case report.

Case 1

A 68-year-old woman with a history of right mastectomy for invasive breast cancer was undergoing routine surveillance with annual mammograms. Her mammogram showed heterogeneously dense breast tissue but was otherwise unremarkable [Figure 1a and b]. The patient subsequently presented with significant unexplained weight loss, prompting further evaluation for occult malignancy. A contrast-enhanced CT of the thorax, abdomen, and pelvis revealed a small enhancing lesion in the left breast. A targeted second-look ultrasound failed to identify a corresponding abnormality.

Close

Figure 1: A 68-year-old woman with a history of right mastectomy underwent routine surveillance. The left mammogram in (a) craniocaudal (CC) and (b) mediolateral oblique (MLO) projections appeared unremarkable. However, contrast-enhanced mammography (CEM) in the corresponding (c) CC and (d) MLO views revealed an 11 mm area of focal non-mass enhancement in the upper outer quadrant of the left breast, located in the anterior third of the breast tissue (red arrows). Given its suspicious appearance, a biopsy was recommended.

Export to PPT

To further evaluate the CT finding, a contrast-enhanced mammogram was performed. This revealed an 11 mm area of focal non-mass enhancement in the upper outer quadrant of the left breast, approximately 1 cm from the nipple [Figure 1c and d]. In the absence of a sonographic correlate, a CEM-guided biopsy was performed [Figure 2], which was reported as intermediate-grade ductal carcinoma in situ (DCIS). The patient subsequently underwent a left mastectomy with sentinel lymph node biopsy. Final histopathology confirmed an 8 mm, intermediate-grade DCIS, ER/PR positive; sentinel nodes were negative (pTisN0).

Close

Figure 2: In the same patient, absence of a correlate on conventional imaging prompted a contrast enhanced mammogram (CEM)-guided biopsy. (a) The enhancing lesion was re-demonstrated on contrast-enhanced mammography (red arrows in a and b), and (b) stereotactic biopsy was subsequently performed. (c) A post-biopsy marker clip is seen in a satisfactory position (dashed red arrow). Histopathological analysis confirmed intermediate-grade ductal carcinoma in-situ (DCIS).

Export to PPT

Case 2

A 51-year-old woman with a history of right breast wide local excision for DCIS 2 years earlier was on routine imaging surveillance. Mammography and ultrasound were reported as normal. Given her high-risk profile and scattered fibroglandular tissue noted on the mammogram, the patient was offered annual CEM surveillance. Her first year postoperative CEM was unremarkable [Figure 3a and b]. However, the second-year surveillance CEM revealed a new 15 mm intensely enhancing focal non-mass enhancement in the upper outer quadrant of the right breast [Figure 3c and d]. Second-look ultrasound failed to identify any definite correlate. A CEM-guided biopsy [Figure 4] was performed that confirmed high-grade DCIS with microinvasion, ER/PR-positive.

Close

Figure 3: A 51-year-old woman with a history of right breast wide local excision for cancer underwent high-risk surveillance. First-year contrast-enhanced mammography (CEM) in (a) mediolateral oblique (MLO) and (b) craniocaudal (CC) projections was unremarkable. However, second-year surveillance CEM in (c) MLO and (d) CC projections revealed a new, intensely enhancing focal non-mass lesion in the upper outer quadrant of the right breast, located at mid-third depth (red arrows). The lesion was considered suspicious, and a biopsy was recommended.

Export to PPT

Close

Figure 4: In the same patient, due to the absence of a correlate on conventional imaging, a contrast-enhanced mammography (CEM)-guided biopsy was recommended. (a-b) The enhancing lesion was re-identified and stereotactic biopsy was performed (red arrows). (c-d) The post-biopsy marker clip is seen in a satisfactory position (dashed red arrows). Histopathology confirmed high-grade ductal carcinoma in-situ (DCIS).

Export to PPT

DISCUSSION

Women with a personal history of breast cancer face an elevated risk of both ipsilateral recurrence and metachronous contralateral disease. A meta-analysis of 10,801 women treated with breast-conserving therapy reported a 10-year recurrence rate of 19.3% and a 15-year breast cancer-specific mortality rate of 21.4%.^[3] Younger age at diagnosis further compounds risk, with all women diagnosed at or before age 50 and treated with breast conservation demonstrating a ≥20% lifetime risk for a new breast cancer.^[4] Dense breast tissue independently increases breast cancer risk and impairs detection, especially in women with heterogeneous or extremely dense breasts.^[5]

Surveillance in this population is challenging. Post-therapeutic changes—such as architectural distortion, fibrosis, fat necrosis, and skin thickening—can obscure or mimic malignancy, lowering the sensitivity and specificity of mammography.^[6] This limitation is compounded in dense breasts, where overlapping fibroglandular structures reduce lesion conspicuity. Consequently, mammography alone has suboptimal performance for detecting early recurrence or second primaries in breast cancer survivors.^[3]

Breast MRI, with its high sensitivity, improves cancer detection in women at elevated risk, including those with a personal history of breast cancer. Studies consistently report high detection rates in this cohort (10–29 cancers/1,000 examinations), with particular benefit in younger women (<65 years, especially <50 years) and those with dense tissue.^[7,8] However, MRI implementation is limited by high cost, constrained availability, longer examination times, and the need for specialized acquisition and interpretation expertise. Contraindications such as gadolinium allergy or severe claustrophobia further restrict use.

CEM, a dual-energy technique combining morphological and functional imaging, has emerged as a valuable alternative in such scenarios. Increasingly, CEM is being used for indications previously reserved for MRI, supported by evidence of comparable diagnostic performance in various clinical settings.^[9,10] It is more widely available, quicker to perform, relatively affordable, and interpretable by radiologists already trained in mammography. Importantly, CEM performance is not affected by breast density, and contrast subtraction suppresses post-surgical changes, improving detection of subtle recurrence or new lesions.

The two cases presented in this study illustrate CEM’s diagnostic advantage. In both, recurrence or new disease was occult on mammography and ultrasound but detected on CEM as early-stage DCIS, enabling timely intervention. CEM also reduces diagnostic ambiguity compared with ultrasound, which may otherwise lead to frequent follow-ups or unnecessary biopsies for Breast Imaging Reporting and Data System (BI-RADS) 3 lesions. Moreover, it permits targeted biopsy under CEM guidance for lesions occult on ultrasound.

While current guidelines, including those from the American College of Radiology, recommend MRI for breast cancer survivors with additional risk factors (dense breasts, young age, strong family history),^[11] real-world access to MRI remains variable. In such contexts, CEM offers a practical, effective, and evidence-based alternative that may enhance early detection, optimize healthcare resources, and improve patient outcomes in survivorship surveillance.^[12,13]

CONCLUSION

These cases underscore the clinical value of CEM in detecting clinically occult malignancy during post-treatment surveillance in breast cancer survivors. By combining high sensitivity with greater accessibility, lower cost, and ease of integration into existing mammographic workflows, CEM offers a practical alternative in settings where MRI is unavailable, contraindicated, or resource-limited. Incorporating CEM into surveillance protocols may enable earlier detection of recurrence or new primary cancers, supporting more timely intervention and potentially improving long-term outcomes in this high-risk population. However, prospective studies are needed to further validate the role of CEM in the surveillance setting before its inclusion as an appropriate imaging modality in clinical guidelines.