At the 2025 San Antonio Breast Cancer Symposium (SABCS), investigators from The University of Texas MD Anderson Cancer Center reported that key breast cancer biomarkers frequently change following neoadjuvant therapy in patients with inflammatory breast cancer (IBC). The study was presented by Savitri Krishnamurthy and focused on the stability of prognostic and predictive biomarkers between baseline diagnostic biopsies and residual invasive tumor in mastectomy specimens after completion of neoadjuvant therapy.
Limited guidance for a high-risk population
Current ASCO CAP guidelines do not mandate routine retesting of ER, PR, or HER2 in residual disease following neoadjuvant therapy for breast cancer. While biomarker discordance has been reported in other breast cancer subtypes, there have been no prior studies specifically evaluating this issue in inflammatory breast cancer, a rare but highly aggressive form of the disease.
To address this gap, the investigators evaluated paired baseline core biopsy samples and post treatment mastectomy specimens from patients with IBC who had residual invasive disease after neoadjuvant therapy. Standardized immunohistochemical assays were used to assess ER, PR, and HER2 expression, ensuring consistency across samples.
One in five patients showed biomarker changes
The analysis demonstrated that alterations in ER, PR, and or HER2 status occurred in 22% of patients. Importantly, these changes resulted in a shift in invasive tumor subtype in 22% of cases, potentially altering prognosis and therapeutic decision making.
Loss or gain of hormone receptor expression and changes in HER2 status were observed, underscoring that residual disease biology may differ meaningfully from pretreatment assessments. These findings suggest that reliance solely on baseline biomarker testing may not fully capture the biology of treatment resistant disease in IBC.
Implications for evolving targeted therapies
Beyond subtype switching, the study also identified low levels of HER2 expression in a substantial proportion of patients. HER2 low or HER2 ultralow expression was observed in 36% of cases, a finding with increasing clinical relevance as antibody drug conjugates targeting HER2 low disease become more widely available.
The investigators concluded that reassessment of ER, PR, and HER2 in residual tumor after neoadjuvant therapy may be clinically informative in inflammatory breast cancer. Identifying biomarker changes could influence prognosis assessment and guide selection of adjuvant systemic therapies, particularly in a disease where treatment options remain limited and outcomes are often poor.
Reference
Krishnamurthy S et al. Stability of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in residual invasive tumor after neoadjuvant therapy in inflammatory breast cancer. Abstract PD2-02-01. SABCS 2025; 9-12 December.
