In this spotlight, Dr. Jose Claudio Casali, Head of the Department of Oncogenetics, and Dr. Dirce Maria Carraro, Head of the Clinical and Functional Genomics Group at A. C. Camargo Cancer Center share an extraordinary case that highlights the critical role of comprehensive multigene testing in hereditary cancer care. By using a custom SOPHiA DDM™ Hereditary Cancer Solution, their team was able to generate rare and clinically relevant findings that helped shape a new course of treatment and preventative care — not only for the patient, but for her entire family.

Watch the interview:

Case Overview

A 51-year-old woman was recently diagnosed with breast cancer — her second breast cancer diagnosis in 10 years.

Tumor characteristics were completely different:

• First tumor: Triple-negative breast cancer
• Second tumor: Luminal B breast cancer

Strong family history:

• Mother and three aunts died early of breast cancer.

Variant analysis powered by the SOPHiA DDM™ Platform

A comprehensive 112-gene panel was used for genetic testing.

Three variants were identified:

• BRCA1 pathogenic variant (high-penetrance gene)
• ATM pathogenic variant (copy number variation, CNV, one copy deletion)
• CHEK2 variant of uncertain significance (VUS) with strong suspicion of pathogenicity

Implications

• Extremely rare case: Identification of multiple clinically significant variants in a single patient.
• Highlights the importance of performing broad multigene panel testing to obtain a more complete hereditary risk profile.
• Findings contributed to the healthcare team's decision to initiate personalized risk management strategies.

Family Screening and Management

Relatives were tested:

• Son inherited all three mutations.
• Daughter inherited the ATM mutation only.

The inheritance pattern confirmed that the variants were authentic (not technical artifacts).

Clinical Management Decisions

Based on risk assessment, the patient underwent:

• Contralateral risk-reducing mastectomy.
• Salpingo-oophorectomy to reduce ovarian cancer risk.

Family members were enrolled in an annual whole-body MRI screening program.

Key Takeaways

• Ten years ago, hereditary testing was often limited to BRCA1/2, leading to potentially incomplete risk assessments.
• This case illustrates the evolving landscape of hereditary cancer risk evaluation:
  • The need for multigene panel testing.
  • The importance of detecting CNVs using reliable analytic tools like the SOPHiA DDM™ Platform.
• SOPHiA DDM™ enabled the healthcare team to interpret complex genetic findings, supporting a more comprehensive approach to patient and family management.

Click through to learn more about SOPHiA DDM™ hereditary cancer solutions.

SOPHiA DDM™ is for Research Use Only (RUO), not for use in diagnostic procedures unless otherwise specified. Clinical interpretation and patient management decisions are the sole responsibility of qualified healthcare professionals. Patient case shared with permission and anonymized for educational purposes.