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Multigene Germline Testing in Patients with DCIS vs Invasive Breast Cancer in a Large, Integrated Health Care System.

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Germline genetic testing for breast cancer reveals similar risks for moderate-risk genes in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). This supports current genetic testing guidelines for both conditions.

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Area of Science:

  • Oncology
  • Genetics
  • Public Health

Background:

  • Germline pathogenic variants (PV) and likely pathogenic variants (LPV) identify breast cancer risk, guiding risk-reducing strategies.
  • National guidelines for germline testing are uniform for invasive breast cancer (IBC) and ductal carcinoma in situ (DCIS).
  • Limited data exist comparing germline testing uptake and results between DCIS and IBC patients.

Purpose of the Study:

  • To compare germline genetic testing rates and variant prevalence between patients with DCIS and stage I-III IBC.
  • To evaluate differences in pathogenic variant (PV) and likely pathogenic variant (LPV) detection in breast cancer-related (BCR) genes between DCIS and IBC cohorts.

Main Methods:

  • Retrospective cohort study analyzing multigene panel germline testing data.
  • Comparison of women diagnosed with DCIS versus stage I-III IBC between September 2019 and September 2022.
  • Analysis of testing rates and PV/LPV prevalence in moderate- and high-risk BCR genes.

Main Results:

  • Genetic testing was more common in IBC (38%) than DCIS (28.5%) patients (p < 0.00001).
  • Overall PV/LPV prevalence in BCR genes was higher in IBC (9.1%) than DCIS (6.1%) (p=0.041).
  • PV/LPV prevalence in high-risk genes was significantly higher in IBC (5.8%) versus DCIS (3.1%) (p=0.0189), while moderate-risk gene prevalence was similar (3.4% vs 3.3%).

Conclusions:

  • Despite lower high-risk variant prevalence in DCIS, similar moderate-risk variant prevalence supports current uniform genetic testing guidelines for DCIS and IBC.
  • Germline variants in moderate-risk genes impact treatment and surveillance decisions for both DCIS and IBC patients.
  • Continued use of the same genetic testing guidelines for DCIS and IBC is supported by these findings.