Bilateral Breast Discordance in Immunohistochemistry
The question appears to be asking about discordance between bilateral breast cancers (left vs. right breast), but the available evidence primarily addresses discordance between primary tumors and metastases, or between different testing laboratories—not specifically bilateral primary breast cancers. Based on the evidence provided, I cannot give precise percentages for bilateral breast IHC discordance, as this specific scenario is not directly addressed in the guidelines or research presented.
What the Evidence Actually Shows
Interlaboratory Discordance (Not Bilateral Breast Discordance)
The evidence focuses on discordance between different laboratories testing the same specimen:
- Interlaboratory concordance for HER2 testing ranges from 74-92% for IHC, with discordance rates of 8-26% depending on the study 1
- Central laboratory concordance is approximately 96% for IHC and 97% for FISH when comparing three central laboratories 1
- Local versus central laboratory discordance occurs in approximately 4-8% of cases for HER2-negative specimens 1
Primary Tumor vs. Metastasis Discordance
- Discordance between primary breast cancer and distant metastases ranges up to 50% in some studies using IHC or FISH for HER2 status 1
- For HER2 specifically, discordance between primary and metastatic sites is 6-7% by IHC and 7% by FISH 2
- ER discordance between primary and recurrent/metastatic disease ranges from 3.4-60%, while PR discordance ranges from 7.2-31% 1
- In one study of 107 patients, HER2 discordance was 10.6%, while PR discordance was 23.3% between primary and recurrent/metastatic lesions 3
Heterogeneity Within Single Tumors
- Heterogeneous HER2 gene amplification occurs in at least 4-5% of breast cancers, with some studies showing rates of 1-50% depending on methodology 1
- Unusual ISH patterns ("rogue cases") occur in approximately 10% of cases, posing interpretative challenges 1
Clinical Implications
When Discordance Matters Most
- Discordance is most clinically significant when it changes treatment decisions, particularly denying patients HER2-targeted therapy or endocrine therapy 1
- Borderline or equivocal results account for most discordant findings 1
- False-negative results may deprive patients of potentially beneficial therapy, while false-positive results expose patients to unnecessary toxicity 4
Recommendations for Clinical Practice
- Retesting of metastatic or recurrent disease is recommended, especially when biomarkers were previously unknown, originally negative, or not overexpressed 1
- Reliance on a single negative test is not advisable—retesting with the alternative method (IHC vs. FISH) may help identify patients who would benefit from targeted therapy 1
- Clinicians should be aware of unusual patterns and seek expert advice for diagnostic dilemmas 1
- Current NCCN guidelines emphasize awareness of unusual/discordant or borderline results and recommend correlation with histology 1
Important Caveats
- The evidence does not specifically address bilateral synchronous breast cancers, which would be the true definition of "bilateral breast discordance"
- Most discordance data comes from comparing different testing methodologies or different time points (primary vs. recurrence), not different anatomic sites in the same patient
- Quality control and laboratory proficiency significantly impact discordance rates 1