A real-world study in Japan confirmed that low HER2 expression is a poor prognostic factor in patients with stage I triple-negative breast cancer.
Triple negative breast cancer (TNBC) is a specific subtype of breast cancer that accounts for approximately 15-20% of all breast cancers [1]. Due to the lack of ER, PR and HER2 expression in its tumor cells, treatment options are limited and the prognosis is relatively poor except for conventional chemotherapy. HER2 expression status is an important factor to be considered in the treatment of early TNBC, and studies have shown that there is a difference in the prognosis of patients with early TNBC between low HER2 expression and no HER2 expression. A real-world study exploring the impact of low HER2 expression on the risk of recurrence and prognosis in patients with stage I TNBC showed that low HER2 expression was associated with shorter disease-free survival (DFS) and shorter overall survival (OS) compared with zero HER2 expression, and low HER2 expression was a poor prognostic factor for stage I TNBC [2]. This study clarified the impact of HER2 low expression on the recurrence risk and prognosis of patients with early-stage TNBC, and provided new evidence-based evidence for the development of personalized treatment plans. The important contents are summarized below for the benefit of readers.
Research Methods:
In this study, patients diagnosed with TNBC and underwent surgery at the National Cancer Center Hospital of Japan from June 2004 to December 2009 were included to further screen out patients with stage I TNBC, and patients with TNBC who received chemotherapy and axillary lymph node metastasis before surgery were excluded. At the same time, the patient's medical record information was extracted, including: DFS, OS, patient age, tumor grade, disease stage, HER2/ER/PR status, surgery, adjuvant radiotherapy, and adjuvant chemotherapy. Clinical data were retrospectively evaluated and predictors of DFS, OS, risk of recurrence, and prognosis were detected based on different HER2 expressions in stage I TNBC cases.
The HER2 test material was provided by the biobank with specimens from patients at the time of surgical admission, and the specimens were fixed with formalin and embedded with paraffin. The samples were anonymized and re-evaluated by the pathologist and the HER2 status was determined.
Figure 1.Study screening method
Findings:
In this study, 42 patients were female, with a median age of 60.5 years and a medium-term follow-up of 121 months, 11 (26.2%) were patients with TNBC with low HER2 expression and 31 (73.8%) were patients with zero HER2 expression. Thirty patients received adjuvant therapy, of which 26 (61.9%) received chemotherapy and 12 (28.6%) received radiotherapy. Relapse occurred in 8 patients. The HER2 status in the patient's medical record was more consistent with the HER2 1+/2+ (ISH negative) positive rate as reassessed by the pathologist than in previous studies.
DFS analysis of the two groups showed that the median DFS was shorter in the HER2-low group than in the HER2-no expression group (118 versus 185 months, HR: 7.0, 95% CI 1.2-40.2, P=0.0016). The results showed that patients with HER2-low stage I TNBC had a worse prognosis than patients with HER2-zero stage I TNBC, which may be due to the false negative of IHC and differences in molecular subtypes.
Figure 2.DFS analysis results of the study
OS analysis of both groups showed that median OS was shorter in the HER2-low group than in the HER2-no expression group (166 months vs NE, HR: 4.2, 95% CI 0.58-31.4, P = 0.082), which may be due to the reduced risk of death with appropriate treatment, and the results would be more reliable with longer follow-up. Adverse events during the treatment period were manageable in all cases.
Figure 3.Results of OS analysis for the study
In univariate analysis, adjuvant therapy, undifferentiated (NG), and HER2 status were identified as prognostic factors affecting DFS. According to univariate and multivariate analysis, there was no correlation between other influencing factors, and low HER2 expression was an important factor leading to poor prognosis of patients.
Table 1.Results of one-way analysis
Table 2.Results of multivariate analysis
Conclusions of the study
This study showed that patients with HER2-low stage I TNBC had shorter DFS and OS than patients with HER2-low stage I TNBC, and the Log-rank test showed that there was a statistically significant difference in DFS between patients with HER2 low expression and patients with HER2 zero expression, but there was no significant difference in OS. Univariate and multivariate analyses showed that low HER2 expression was a poor prognostic factor for patients with stage I TNBC. This study clarified the relationship between low HER2 expression and the prognosis of patients with stage I TNBC, which provides a new evidence-based basis for clinical practice, which is helpful for predicting patients' treatment response and formulating personalized treatment plans.
Bibliography:
[1] Li Y, Zhang H, Merkher Y, et al. Recent advances in therapeutic strategies for triple-negative breast cancer. J Hematol Oncol. 2022 Aug 29; 15(1):121. [2] Sanomachi T, Okuma HS, Kitadai R, et al. Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer. Front Oncol. 2023 Mar 27;13:1157789.
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