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Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
Published on: October 2, 2014
Pathological response to herceptin-containing neoadjuvant therapy in HER2 IHC2+/ISH+ and IHC3+ early-stage invasive
Tristan Jordan1, Nay Nwe Nyein Chan1, David L Rimm2
1Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
Background:
HER2-positive breast cancers exhibit heterogeneous responses to neoadjuvant therapy. This study compared pathologic response between IHC 3+ and IHC 2+/FISH + invasive ductal carcinomas (IDCs) treated with trastuzumab/pertuzumab-containing chemotherapy.
Methods:
We identified 202 patients with HER2-positive early-stage IDC who received neoadjuvant T/P-containing chemotherapy followed by surgery between 2017 and 2024. Patients were categorized as IHC 3+ (n = 165) or IHC 2+/FISH+ (n = 37). Clinicopathologic parameters from pretreatment biopsies and post-treatment excisions were reviewed. Residual cancer burden (RCB) score and recurrence-free survival (RFS) at 36 months were analyzed.
Results:
The complete pathologic response (pCR) rate was significantly higher in IHC 3+ compared with IHC 2+/FISH + tumors (67% vs. 27%, p < 0.001). IHC 3+ tumors were more frequently ER-/PR- than IHC 2+/FISH + tumors (56% vs. 16%, p < 0.001). In the subset with complete FISH data (n = 49), increasing RCB class was inversely associated with both HER2/CEP17 ratio and HER2 copy number. At 36 months, recurrence rates were numerically lower in IHC 3+ compared with IHC 2+/FISH + tumors (1.7% vs. 9.4%, p = 0.07). Kaplan-Meier analysis demonstrated a non-significant trend toward improved RFS in IHC 3+ tumors among hormone receptor-positive cases (p = 0.14).
Conclusions:
Compared with IHC 3+ IDC, IHC 2+/FISH + IDC demonstrated lower pCR rates and inferior RFS in hormone receptor-negative subset following neoadjuvant trastuzumab/ pertuzumab-containing therapy. Pathologic response correlated inversely with HER2/CEP17 ratio and HER2 copy number. Reassessment of HER2 expression with more sensitive quantitative methods, particularly in IHC 2+/FISH + tumors, may improve therapeutic stratification.
Insights
HER2-positive breast cancer patients with IHC 3+ tumors showed better pathologic response and recurrence-free survival after neoadjuvant trastuzumab/pertuzumab therapy compared to those with IHC 2+/FISH+ tumors. Quantitative HER2 assessment may improve treatment selection.
Area of Science:
- Oncology
- Pathology
- Pharmacology
Background:
- HER2-positive breast cancers display varied responses to neoadjuvant therapy.
- This study investigates pathologic response differences in invasive ductal carcinomas (IDCs) based on HER2 expression levels (IHC 3+ vs. IHC 2+/FISH+).
Purpose of the Study:
- To compare pathologic response and recurrence-free survival (RFS) in HER2-positive IDCs treated with neoadjuvant trastuzumab/pertuzumab-containing chemotherapy.
- To evaluate the correlation between HER2 expression levels, tumor characteristics, and treatment outcomes.
Main Methods:
- Retrospective analysis of 202 HER2-positive early-stage IDC patients treated with neoadjuvant trastuzumab/pertuzumab.
- Patients were classified as IHC 3+ (n=165) or IHC 2+/FISH+ (n=37).
- Pathologic response (pCR), residual cancer burden (RCB) score, and 36-month RFS were analyzed.
Main Results:
- Complete pathologic response (pCR) rates were significantly higher in IHC 3+ (67%) versus IHC 2+/FISH+ (27%) tumors (p < 0.001).
- IHC 3+ tumors were more often ER-/PR- (56% vs. 16%, p < 0.001).
- Recurrence rates at 36 months were numerically lower in IHC 3+ (1.7%) compared to IHC 2+/FISH+ (9.4%) tumors (p = 0.07).
Conclusions:
- IHC 2+/FISH+ invasive ductal carcinomas showed lower pCR rates and inferior RFS compared to IHC 3+ tumors after neoadjuvant trastuzumab/pertuzumab therapy, particularly in hormone receptor-negative cases.
- Pathologic response correlated inversely with HER2/CEP17 ratio and HER2 copy number.
- More sensitive HER2 assessment methods may enhance therapeutic stratification for HER2-positive breast cancer.
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