Immunohistochemical predictors of local recurrence in breast carcinoma: development and sensitivity validation of an IHC-based risk score.

BACKGROUND

Local recurrence after breast-conserving surgery (BCS) remains clinically relevant and is associated with poorer long-term outcomes. While several prediction tools exist, many rely on costly genomic assays or omit key biological variables routinely assessed by immunohistochemistry (IHC).

PATIENTS, MATERIALS AND

METHODS

We retrospectively analyzed 100 consecutive patients with invasive breast carcinoma treated by BCS (2013-2018). IHC data included estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2∕neu) [0-3+, with 2+ confirmed by chromogenic in situ hybridization (CISH)], as well as hormonal phenotypes. Local recurrence occurred in 21 cases. An integrated IHC score (0-6 points) was constructed using weighted biological predictors (ER-, PR-, HER2+, and ER-∕PR- phenotype), stratifying cases into low (0-2), moderate (3-4), and high (≥5) risk categories. Although ER, PR, and HER2 status were available for all cases, case-level linkage between HER2 positivity and ER∕PR phenotypes was not consistently available; therefore, three sensitivity scenarios (optimistic, neutral, and pessimistic) were applied to assess the robustness of the findings.

RESULTS

Recurrence was higher in biologically unfavorable subgroups: ER- (26.47% vs. 9.09% in ER+), PR- (21.42% vs. 10.34% in PR+), ER-∕PR- phenotype (37.5%), and HER2-positive tumors (33.33% vs. 11.36% in HER2-). The integrated score achieved consistent separation of risk categories, with most recurrences concentrated in moderate- and high-risk groups. Sensitivity analyses showed stable stratification across all three HER2 allocation scenarios, supporting the robustness of the model despite uncertainty in HER2- phenotype overlap.

CONCLUSIONS

A pragmatic IHC-based risk score based on routinely available biomarkers stratified local recurrence risk in breast cancer patients treated with BCS and remained stable under sensitivity testing. External validation in larger, multicenter cohorts is warranted.