Immunohistochemical Subtype Conversion After Neoadjuvant Chemotherapy and Its Impact on Breast Cancer Survival: A Systematic Review and Meta-analysis
. Antonini M. 12/10/25; 4192143; 1160
Topic: Other
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Abstract
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Background: Neoadjuvant chemotherapy (NAC) may alter tumor biology, leading to immunohistochemical (IHC) subtype conversions between diagnosis and residual disease. The prognostic impact of such changes remains unclear. This systematic review and meta-analysis evaluated the effect of NAC-induced IHC subtype conversion on overall survival (OS) and disease-free survival (DFS) in patients with residual disease (non-pCR).
Methods: This study was registered in PROSPERO (CRD42024558811). PubMed, EMBASE, and Cochrane Library were searched through 2025 for studies reporting IHC subtype conversions after NAC and associated survival outcomes in non-pCR patients. Eligible studies included randomized trials and observational cohorts of adult women with primary breast cancer. Two reviewers independently selected studies and extracted data. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane tool. Pooled risk ratios (RRs) were calculated using random-effects models. Heterogeneity was quantified with I², and publication bias was assessed by Egger’s test.
Results: Twenty-five retrospective studies (n=5,263 non-pCR patients) were included. Mean patient age ranged from 46-54 years, and tumors were predominantly T2-T3. IHC subtype conversion occurred in 20% [95% CI: 0.17-0.24], with high heterogeneity (I²=89.8%). Common conversions included luminal-to-TNBC (35%), luminal-to-HER2+ (25%), HER2+-to-luminal (20%), and TNBC-to-luminal (20%).Patients without subtype conversion had significantly better OS (RR=1.13 [95% CI: 1.01-1.26], p=0.03; I²=62%). Luminal tumors showed the greatest OS benefit without conversion (RR=1.19 [1.01-1.41], p=0.04), while HER2+ (RR=1.11 [0.95-1.31], p=0.19) and TNBC (RR=0.98 [0.84-1.16], p=0.85) showed no significant OS impact. DFS was not significantly affected by conversion overall (RR=0.95 [0.80-1.14], p=0.58; I²=79%). Sensitivity analysis confirmed OS findings. Egger’s test revealed no publication bias for OS (p=0.33) but suggested bias for luminal DFS (p=0.044).
Conclusion: IHC subtype conversion after NAC occurs in 1 in 5 patients with residual disease and is associated with worse OS—particularly in luminal breast cancer. Routine post-NAC IHC reassessment should be considered to improve prognostication and guide adjuvant treatment. Prospective studies with standardized reporting are needed to validate these findings and refine treatment algorithms.
Methods: This study was registered in PROSPERO (CRD42024558811). PubMed, EMBASE, and Cochrane Library were searched through 2025 for studies reporting IHC subtype conversions after NAC and associated survival outcomes in non-pCR patients. Eligible studies included randomized trials and observational cohorts of adult women with primary breast cancer. Two reviewers independently selected studies and extracted data. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane tool. Pooled risk ratios (RRs) were calculated using random-effects models. Heterogeneity was quantified with I², and publication bias was assessed by Egger’s test.
Results: Twenty-five retrospective studies (n=5,263 non-pCR patients) were included. Mean patient age ranged from 46-54 years, and tumors were predominantly T2-T3. IHC subtype conversion occurred in 20% [95% CI: 0.17-0.24], with high heterogeneity (I²=89.8%). Common conversions included luminal-to-TNBC (35%), luminal-to-HER2+ (25%), HER2+-to-luminal (20%), and TNBC-to-luminal (20%).Patients without subtype conversion had significantly better OS (RR=1.13 [95% CI: 1.01-1.26], p=0.03; I²=62%). Luminal tumors showed the greatest OS benefit without conversion (RR=1.19 [1.01-1.41], p=0.04), while HER2+ (RR=1.11 [0.95-1.31], p=0.19) and TNBC (RR=0.98 [0.84-1.16], p=0.85) showed no significant OS impact. DFS was not significantly affected by conversion overall (RR=0.95 [0.80-1.14], p=0.58; I²=79%). Sensitivity analysis confirmed OS findings. Egger’s test revealed no publication bias for OS (p=0.33) but suggested bias for luminal DFS (p=0.044).
Conclusion: IHC subtype conversion after NAC occurs in 1 in 5 patients with residual disease and is associated with worse OS—particularly in luminal breast cancer. Routine post-NAC IHC reassessment should be considered to improve prognostication and guide adjuvant treatment. Prospective studies with standardized reporting are needed to validate these findings and refine treatment algorithms.
Background: Neoadjuvant chemotherapy (NAC) may alter tumor biology, leading to immunohistochemical (IHC) subtype conversions between diagnosis and residual disease. The prognostic impact of such changes remains unclear. This systematic review and meta-analysis evaluated the effect of NAC-induced IHC subtype conversion on overall survival (OS) and disease-free survival (DFS) in patients with residual disease (non-pCR).
Methods: This study was registered in PROSPERO (CRD42024558811). PubMed, EMBASE, and Cochrane Library were searched through 2025 for studies reporting IHC subtype conversions after NAC and associated survival outcomes in non-pCR patients. Eligible studies included randomized trials and observational cohorts of adult women with primary breast cancer. Two reviewers independently selected studies and extracted data. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane tool. Pooled risk ratios (RRs) were calculated using random-effects models. Heterogeneity was quantified with I², and publication bias was assessed by Egger’s test.
Results: Twenty-five retrospective studies (n=5,263 non-pCR patients) were included. Mean patient age ranged from 46-54 years, and tumors were predominantly T2-T3. IHC subtype conversion occurred in 20% [95% CI: 0.17-0.24], with high heterogeneity (I²=89.8%). Common conversions included luminal-to-TNBC (35%), luminal-to-HER2+ (25%), HER2+-to-luminal (20%), and TNBC-to-luminal (20%).Patients without subtype conversion had significantly better OS (RR=1.13 [95% CI: 1.01-1.26], p=0.03; I²=62%). Luminal tumors showed the greatest OS benefit without conversion (RR=1.19 [1.01-1.41], p=0.04), while HER2+ (RR=1.11 [0.95-1.31], p=0.19) and TNBC (RR=0.98 [0.84-1.16], p=0.85) showed no significant OS impact. DFS was not significantly affected by conversion overall (RR=0.95 [0.80-1.14], p=0.58; I²=79%). Sensitivity analysis confirmed OS findings. Egger’s test revealed no publication bias for OS (p=0.33) but suggested bias for luminal DFS (p=0.044).
Conclusion: IHC subtype conversion after NAC occurs in 1 in 5 patients with residual disease and is associated with worse OS—particularly in luminal breast cancer. Routine post-NAC IHC reassessment should be considered to improve prognostication and guide adjuvant treatment. Prospective studies with standardized reporting are needed to validate these findings and refine treatment algorithms.
Methods: This study was registered in PROSPERO (CRD42024558811). PubMed, EMBASE, and Cochrane Library were searched through 2025 for studies reporting IHC subtype conversions after NAC and associated survival outcomes in non-pCR patients. Eligible studies included randomized trials and observational cohorts of adult women with primary breast cancer. Two reviewers independently selected studies and extracted data. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane tool. Pooled risk ratios (RRs) were calculated using random-effects models. Heterogeneity was quantified with I², and publication bias was assessed by Egger’s test.
Results: Twenty-five retrospective studies (n=5,263 non-pCR patients) were included. Mean patient age ranged from 46-54 years, and tumors were predominantly T2-T3. IHC subtype conversion occurred in 20% [95% CI: 0.17-0.24], with high heterogeneity (I²=89.8%). Common conversions included luminal-to-TNBC (35%), luminal-to-HER2+ (25%), HER2+-to-luminal (20%), and TNBC-to-luminal (20%).Patients without subtype conversion had significantly better OS (RR=1.13 [95% CI: 1.01-1.26], p=0.03; I²=62%). Luminal tumors showed the greatest OS benefit without conversion (RR=1.19 [1.01-1.41], p=0.04), while HER2+ (RR=1.11 [0.95-1.31], p=0.19) and TNBC (RR=0.98 [0.84-1.16], p=0.85) showed no significant OS impact. DFS was not significantly affected by conversion overall (RR=0.95 [0.80-1.14], p=0.58; I²=79%). Sensitivity analysis confirmed OS findings. Egger’s test revealed no publication bias for OS (p=0.33) but suggested bias for luminal DFS (p=0.044).
Conclusion: IHC subtype conversion after NAC occurs in 1 in 5 patients with residual disease and is associated with worse OS—particularly in luminal breast cancer. Routine post-NAC IHC reassessment should be considered to improve prognostication and guide adjuvant treatment. Prospective studies with standardized reporting are needed to validate these findings and refine treatment algorithms.
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