Case of the Month: March

Somatic Genomic Profiling in Breast Cancer-Insights Beyond Hereditary Testing

Clinical History:

A 39-year-old female was diagnosed with grade III invasive ductal carcinoma of the left breast and is a known case of hypothyroidism. She underwent left breast conservative surgery with axillary dissection in May 2024 followed by chemotherapy (4 cycles of AC regimen and 4 cycles of dose-dense Paclitaxel). Post-operative PET scan showed no evidence of metabolically active disease. Tumor pathology revealed ER+, PR+, HER2− status with a high Ki67 proliferation index (80%), along with lymphovascular emboli and 50% tumor infiltrating lymphocytes.

Family History:

There is no history of cancer reported on the patient’s side of the family. Although the patient’s mother-in-law had breast cancer, this does not contribute to the patient’s hereditary cancer risk assessment

Clinical Investigations:

Ultrasound of the breast showed a lobulated hypoechoic lesion with eccentric calcification in the outer zone of the left breast along with a few enlarged axillary lymph nodes (BIRADS 4). Mammography showed increased breast density bilaterally with calcific foci in the left breast.

Considering the relatively early age of onset, the patient underwent hereditary cancer testing, which did not detect any pathogenic or likely pathogenic variants. To further evaluate tumor-specific molecular alterations and potential therapeutic implications, somatic tumor profiling using the OncoCept Comprehensive Solid Panel was performed. Somatic mutations are genetic alterations that arise in tumor cells during a person’s lifetime and are not inherited or passed on to offspring.

This analysis identified a TP53 c.824G>A (p.Cys275Tyr) variant with a VAF of 27.62%, classified as Tier 2D, suggesting a potentially oncogenic alteration with possible prognostic or therapeutic relevance based on emerging evidence. Additionally, a H3-3A c.335C>T (p.Ala112Val) variant with a VAF of 3.91% was detected and classified as Tier 3, indicating limited evidence regarding its clinical significance.

Summary:

The patient with early-onset breast cancer underwent both hereditary and tumor genomic testing to better understand the genetic basis of her disease. While germline testing did not identify any inherited cancer predisposition, tumor profiling revealed somatic variants in TP53 and H3-3A genes, providing insights into the molecular characteristics of the tumor.

Conclusion:

This case highlights the complementary role of somatic tumor profiling when hereditary testing is negative, particularly in early-onset cancers. Identification of tumor-specific alterations can improve understanding of tumor biology and may help guide prognosis assessment, clinical trial eligibility, and personalized management strategies.