The effect of HER2 expression on treatment response in patients with metastatic breast cancer using cyclin-dependent kinase (CDK) 4/6 intibitors

Introduction: Breast cancer is the cancer with the highest incidence (11.7%) and prevalence (15.4%) in all genders in the world. Approximately 60-70% of breast cancers are hormone receptor positive. The main treatment in hormone positive disease is endocrine therapies. In the treatment of hormone-positive HER2-negative metastatic breast cancer, the use of CDK 4/6 inhibitor combined with endocrine therapies is standard as first-line therapy. Studies have shown that this combination has positive results on progression-free survival and overall survival. HER2 amplification is an important prognostic factor in breast cancer by reducing overall survival and increasing the risk of recurrence, and plays a role in treatment selection. Recently, in immunohistochemical staining; In the HER2 1+, HER2 2+ FISH method, breast cancers without amplification are defined as 'HER2 low disease', they constitute approximately 55% of patients with breast cancer. In this study, we aimed to investigate the effect of CDK 4/6 inhibitors on HER2 low disease in patients with metastatic breast cancer. Recent studies have shown that treatments targeting HER2 can be effective in patients with low HER2 disease definition. In this study, we aimed to investigate the effect of CDK 4/6 inhibitors on HER2 low disease in patients with metastatic breast cancer. Materials and Methods: A retrospective study was designed by scanning the hospital database and files of patients diagnosed with breast cancer using cyclin-dependent kinase inhibitors, who were treated at Akdeniz University Hospital Oncology Clinic, Meram University Hospital Oncology Clinic and Okmeydanı Hospital Oncology Clinic.Between December 2018 and October 2022, patients diagnosed with breast cancer were screened and 214 patients were identified, who received cyclin-dependent kinase inhibitor therapy and were receiving cyclin-dependent kinase inhibitor therapy and completed the 6th month control.By accessing the pathology data of these patients, patients with clear His-2 expression levels were included in the study. In the patients included in the study; 'Her-2 low' status, patient characteristics (age, comorbidity, ECOG, menopausal status), presence of visceral metastases, presence of endocrine resistance, presence of CNS metastases, treatment before CDK 4/6 inhibitor in the metastatic period were evaluated.In these patients, the 6th month response to treatment, progression-free survival, and overall survival were evaluated according to the status of 'HER2 low', presence of visceral metastases, presence of endocrine resistance, presence of CNS metastases, treatment before CDK 4/6 inhibitor in the metastatic period. Results: In our study, we evaluated 214 patients. While 73.8% of them were HER2-0, 26.2% were HER2-low patients. When the HER2 Low group and the Her2-0 group were compared, no statistically significant difference was found between the two groups in terms of progression-free survival and overall survival (p= 0.479), (p=0786). When the 6th month response to CDK 4/6 inhibitor treatment was evaluated, it was observed that HER2 status did not significantly affect the response to treatment (p>0.999). Although it was shown in our study that progression-free survival was negatively affected in the presence of visceral metastases (p=0.013), its effect on overall survival was not significant (p=0.092). In our study, the presence of visceral metastases had no effect on the response to CDK 4/6 inhibitor treatment at 6th month. In our study, no significant correlation was found between the presence of HER2 low and visceral metastasis (p=0.21). In our study, the presence of endocrine resistance had no effect on progression-free survival, overall survival, and response to cdk 4/6 inhibitor at 6th month. In our study, CNS metastasis was seen in 2.3% of the patients. No significant correlation was observed between the presence of Her-2 low and CNS metastasis (p>0.999).In our study, although the effect of the presence of CNS metastasis on PFS and the 6th month response of the CDK 4/6 inhibitor was not significant, it was shown to negatively affect overall survival. Although the presence of CNS metastasis was not significant for progression-free survival, the presence of CNS metastasis was found to significantly reduce overall survival (p=0.035). In our study, it was shown that the use of CDK 4/6 inhibitor as first-line therapy in the metastatic period significantly increased progression-free survival and overall survival (p=0.038 and p=0.02, respectively). The use of the CDK 4/6 inhibitor in first-line therapy did not have a significant effect on the 6th month response to the CDK 4/6 inhibitor. Conclusions: It is known that CDK 4/6 inhibitors are effective in hormone positive, HER2 0, HER2 1+, HER2 2+ (FISH negative) patients with metastatic breast cancer . In our study, it was observed that treatment with CDK 4/6 inhibitors did not create a significant difference between the HER2 low group and the HER2 0 group in terms of response to treatment, progression-free survival and overall survival. Key Words; metastatic breast cancer, CDK 4/6 inhibitors, ' HER2 Low'