A 40-year-old woman with a family history of breast cancer (mother) and confirmed checkpoint kinase 2 (CHEK2) mutation presented for routine tests. Previous annual ultrasonography (US) examinations, including 2 studies performed in the preceding year, showed only benign cysts without suspicious features. Despite negative findings, the patient enrolled in the ongoing DICES (Dyspnoeic Individuals with COPD: Electrical Stimulation or Strength Training) clinical trial at the University Hospital in Kraków for multimodality screening.

US identified benign cysts, which points to its limited sensitivity in dense breasts and in cancers presenting primarily as microcalcifications.

Contrast-enhanced mammography (CEM) showed a dense glandular pattern (type D according the American College of Radiology1 classification). Low-energy images (equal to standard mammography) demonstrated linear, powdery microcalcifications in the left upper outer quadrant, measuring over 19 mm in diameter (Figure 1A). Subtraction images showed a regional, heterogeneous nonmass enhancement (NME) measuring 42 mm × 26 mm, overlapping the microcalcification site (Figure 1B).

Figure 1. A – contrast-enhanced mammography (CEM), low-energy image of linear microcalcifications in the left upper outer quadrant (arrow); B – subtraction CEM image of regional, heterogeneous nonmass enhancement (NME) in the region of calcifications (arrow); C – breast magnetic resonance showing multifocal enhancing foci (NME type) with restricted diffusion (arrow)

Breast magnetic resonance (BMR) confirmed pathologic NME at 3 o’clock, measuring 27 mm × 12 mm, with a plateau-type kinetic curve and diffusion restriction. Additional linear enhancement (20 mm in diameter) was identified at 2 o’clock, and further small foci were observed in the lower and upper outer quadrants, consistent with multifocal disease (Figure 1C).

Vacuum-assisted biopsy of the calcification area was performed under mammographic guidance. Histopathology showed invasive carcinoma of no special type, Nottingham grade 1. Immunohistochemical profile of the invasive carcinoma cells was as follows: estrogen receptor with strong, moderate, and weak expression in 90% of the tumor cells; progesterone receptor with strong, moderate, and weak expression in 80% of the tumor cells; negative human epidermal growth factor receptor 2 status; and proliferative activity, as measured by the Ki-67 index, of 5%. Also, extensive ductal carcinoma in situ component, associated with microcalcifications, was found. No lymphovascular invasion was observed. The histopathology result is typical in patients with the CHEK2 mutation.2

This case illustrates the limitations of US as a screening modality in genetically predisposed women, and underscores the complementary role of advanced imaging in such cases. While US is valuable for palpable lesions and interventional guidance, mammography remains the standard modality for detecting microcalcifications. In high-risk patients, annual BMR is recommended from the age of 30 years, with CEM emerging as a reliable alternative when BMR is unavailable.

Carriers of pathogenic CHEK2 mutations are at an increased risk of breast cancer and require enhanced surveillance involving both self-examination and extended diagnostic imaging. US has limited sensitivity for cancers manifesting as microcalcifications. Mammography and CEM are superior for detecting early lesions in dense breasts. BMR provides additional staging information and improves detection of multifocal diseases. In genetically predisposed women, such as those with CHEK2 mutations, combined mammography/CEM and BMR represent the optimal screening approach.3-5