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Published on: December 5, 2017
What Proportion of BRCA-Associated Breast Cancer Is Human Epidermal Growth Factor 2-Low and Eligible for Additional
Emily Forester1, Aakash Belsare2, Dong Won Kim3
1Division of Breast Surgical Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Rowan-Virtua School of Osteopathic Medicine, Stratford, New Jersey.
Introduction:
DESTINY B04 provided clinical meaning to a new classification of human epidermal growth factor 2 (HER2) expression in breast cancer: HER2-low. Patients with germline breast cancer type 1 gene pathogenic variants (gBRCA1) often develop triple negative breast cancer (TNBC), but the proportion who could be classified as HER2-low and qualify for an additional targeted therapy option is unknown. This study aims to characterize the proportion of gBRCA1 or germline breast cancer type 2 gene pathogenic variants patients for whom these novel targeted therapies may be an option.
Methods:
We performed a retrospective chart review of patients with gBRCA1/2 treated at our institution for invasive breast cancer from 2000 to 2021. Synchronous or metachronous contralateral breast cancers were recorded separately. HER2 status was determined by immunohistochemistry and fluorescence in situ hybridization. We excluded patients without complete HER2 data.
Results:
Among the 95 breast cancers identified in our cohort of 85 gBRCA1/2 patients, 41 (43%) were TNBC, 38 (40%) were hormone receptor positive (HR+)/HER2-negative, and 16 (17%) were HER2-positive based on standard conventions. We found that 82% of the HR+/HER2-cancers and 66% of TNBCs would be reclassified as HER2-low. After stratifying by BRCA gene status, 64% of cancers in patients with gBRCA1 and 58% of cancers in patients with germline breast cancer type 2 gene pathogenic variants were HER2-low.
Conclusions:
A significant portion of gBRCA1/2 patients who were previously diagnosed with TNBC or HR+/HER2- breast cancer would now be classified as HER2-low and could be considered for the use of trastuzumab deruxtecan in the metastatic setting. Outcome differences from therapy changes in this cohort should now be assessed.
Insights
A significant proportion of patients with germline BRCA1/2 (gBRCA1/2) variants, previously diagnosed with triple-negative breast cancer (TNBC) or hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer, are now classified as HER2-low. This reclassification may offer new targeted therapy options for these patients.
Area of Science:
- Oncology
- Genetics
- Breast Cancer Research
Background:
- The DESTINY-B04 trial established the clinical significance of HER2-low expression in breast cancer.
- Germline BRCA1 (gBRCA1) pathogenic variants are frequently associated with triple-negative breast cancer (TNBC).
- The potential for gBRCA1/2 patients to benefit from HER2-low targeted therapies remains largely uncharacterized.
Purpose of the Study:
- To determine the proportion of patients with germline BRCA1 or BRCA2 (gBRCA1/2) pathogenic variants who could be classified as HER2-low.
- To assess the eligibility of gBRCA1/2 patients for novel targeted therapies based on HER2-low status.
Main Methods:
- Retrospective chart review of invasive breast cancer patients with gBRCA1/2 from 2000-2021.
- Separate recording of synchronous or metachronous contralateral breast cancers.
- HER2 status determination using immunohistochemistry and fluorescence in situ hybridization; exclusion of cases with incomplete HER2 data.
Main Results:
- Of 95 breast cancers in 85 gBRCA1/2 patients, 43% were TNBC, 40% HR+/HER2-, and 17% HER2-positive.
- 82% of HR+/HER2- and 66% of TNBC cases were reclassified as HER2-low.
- HER2-low classification was observed in 64% of gBRCA1 and 58% of gBRCA2 cancers.
Conclusions:
- A substantial number of gBRCA1/2 patients with prior TNBC or HR+/HER2- diagnoses now meet HER2-low criteria.
- These patients may be candidates for trastuzumab deruxtecan in the metastatic setting.
- Further assessment of treatment outcomes following this therapy shift is warranted.
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