Clinicopathological Characteristics Of HER2 Low Expression Breast Cancer And Factors Influencing Its Efficacy With Neoadjuvant Chemotherapy

Objective:Breast cancer(BC)is a heterogeneous group of malignant tumors,and clinical treatment is guided by different molecular typing.For human epidermal growth factor receptor 2(HER2)-positive BC,anti-HER2-targeted therapeutic agents can be used to improve patient prognosis,while HER2-negative breast cancer is deprived of targeted therapeutic opportunities.As the development of antibody-coupled drugs(ADCs)progresses,HER2 low-expressing breast cancer is becoming more widely recognized,however,the understanding of the biological behavior and prognosis of HER2low-expressing breast cancer is incomplete and controversial.The aim of this paper is to compare the clinicopathological biology of HER2-negative locally advanced breast cancers with different HER2 protein expression status and the factors associated with their neoadjuvant chemotherapy(NAC)efficacy,and to assess whether HER2 low-expressing breast cancer can be considered as a different biological subtype of breast cancer.Methods:The clinicopathological data of 348 patients with neoadjuvant and surgically treated breast cancer in the First Affiliated Hospital of Gannan Medical College between January 2016 and July 1,2022 were retrospectively collected.According to the inclusion and exclusion criteria,195 HER2-negative breast cancer patients were used as study subjects,and the included HER2-negative breast cancer patients were divided into HER2 zero expression,HER2 1+and HER2 2+/ISH-groups according to IHC and ISH results for analysis,and the baseline clinicopathological characteristics of each group were compared;the patients were further divided into pathologic complete remission group according to postoperative pathology(pCR)and non-pathological complete remission group(non-pCR),and the relationship between pCR and HER2 protein expression status as well as baseline clinicopathological characteristics was investigated using one-way and multi-way logistic models,and P<0.05 was considered a statistically significant differencResults:1.195 HER2-negative breast cancer patients were included,94 cases(48.2%)had zero HER2 expression;101 cases(51.8%)had low HER2 expression,most of them were Luminal type in HER2 low expression and most of them were TNBC in HER2 zero expression(P=0.015).Compared with HER2 zero expression,HER2 low expression estrogen receptor(P=0.029)and progesterone receptor(P=0.004)were more positive,and HER2 low expression breast cancer had less axillary lymph node metastasis(P=0.027),lower Ki67 value-added index(P<0.05),and lower histological grade(P=0.029).2.There were more HER2 low-expressing BC in the HR-positive group compared to the estrogen-progestin receptor(HR)-negative group(P=0.018);HER2protein expression levels were positively associated with the HR-positive rate(X~2=12.221;P=0.015),with the highest percentage of HR positivity in HER22+/ISH-breast cancers(76.1%),followed by HER2 1+(58.1%)and the lowest HR positivity rate in HER2 zero expression.3.The pCR rates of HER2 zero expression,IHC 1+and IHC 2+/ISH-were inversely correlated with HER2 protein expression levels,and decreased with increasing HER2 expression levels,and the comparison between groups showed significant differences between HER2 zero expression and HER2 2+/ISH-(P=0.048).The pCR rate gradually decreased with increasing HER2 protein expression levels in both luminal and triple-negative breast cancers(P>0.05),however,the difference was not statistically significant.4.Stratified according to different estrogen and progesterone receptor status,HR-negative had higher pCR rate than HR-positive BC regardless of HER2 zero expression or low expression group(P<0.05).pCR rate was negatively correlated with estrogen and progesterone receptor expression level,and the higher the HR expression level,the lower the pCR rate of HER2-negative breast cancer,and the comparison between groups showed a significant difference between HR negative and HR strong positive(P=0.02).5.Univariate and multifactorial logistic analyses revealed that molecular typing/estrogen and progesterone receptor status was an independent factor influencing the efficacy of neoadjuvant therapy for HER2-negative breast cancer(P=0.021).Conclusion:1.HER2 low expression has unique clinicopathological characteristics compared to HER2 zero expression breast cancer,with significant differences in efficacy for neoadjuvant therapy.2.The biological behavior of HER2 low expression can vary depending on hormone receptor status,and estrogen and progesterone receptor expression status/molecular typing relative to HER2 expression status may be a determining factor in the efficacy of neoadjuvant therapy for HER2 low expression breast cancer.3.The results of this study are not sufficient to demonstrate HER2low-expressing breast cancer as a unique biological subtype,while more exploration is needed to standardize HER2 low-expressing breast cancer,and future national multicenter prospective randomized controlled studies with large samples are necessary to further explore the relationship between HER2 protein and HR.