Clinical and molecular characteristics of human epidermal growth factor receptor 2-positive breast cancers: a meta-analysis

Breast cancer is the most common malignancy in women worldwide. One type of breast cancer called human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for almost 40% of them, it is an aggressive cancer with a poor prognosis.
A patient with HER2-positive breast cancer tests positive for a protein called human epidermal growth factor receptor 2. The cancer cells have extra copies of the gene that makes the protein, and the protein promotes the growth of cancer cells.

Breast cancer cells may also have proteins on their surface called hormone receptors. Whether these are present or not determines if the cancer is hormone receptor positive (HR+) or negative (HR-).

Currently, therapy for the disease is greatly improving survival outcomes in this group of patients, however, there are still many unmet needs, such as differences in the efficacy of neoadjuvant therapy in patients with HR+/HER2+ cancer versus those with HR-/HER2+ cancer. Neoadjuvant therapy is a drug treatment given to the patient before their main treatment which may for example be surgery. The aim of neoadjuvant therapy is to shrink the tumor.

HR+/HER2+ patients exhibit distinct biological characteristics and responds less favorably to conventional neoadjuvant therapy in comparison to HR-/HER2+ patients. Thus, we want to deeply explore the differences in the data collected from these patients such as response rates and prognosis through an of a large number of similar clinical studies in Vivli database. Finally, we can treat these two subtypes of breast cancer patients with different and specified methods and provide the new basis for the classification of HER2+ breast cancer patients, so as to find the potential mechanism and the precision treatment strategy for these two different subtypes of HER2+ breast cancer patients.

乳腺癌是全球女性最常见的恶性肿瘤。其中，人表皮生长因子受体2阳性（human epidermal growth factor receptor 2-positive, HER2+）乳腺癌约占所有乳腺癌病例的40%，属于侵袭性强、预后较差的癌症类型。
HER2阳性乳腺癌患者的肿瘤细胞会过量表达人表皮生长因子受体2蛋白：编码该蛋白的基因存在额外拷贝，而该蛋白可促进肿瘤细胞的增殖与生长。
乳腺癌细胞表面还可能表达激素受体（hormone receptor），根据该受体的表达与否，可将乳腺癌分为激素受体阳性（hormone receptor positive, HR+）与激素受体阴性（hormone receptor negative, HR-）两种亚型。
当前，针对该疾病的治疗手段已显著改善了此类患者的生存结局，但仍存在诸多未被满足的临床需求——例如HR+/HER2+与HR-/HER2+乳腺癌患者对新辅助治疗（neoadjuvant therapy）的疗效存在显著差异。新辅助治疗指在患者接受主要治疗（如外科手术）前开展的药物治疗，其核心目标为缩小肿瘤体积。
相较于HR-/HER2+患者，HR+/HER2+患者具有独特的生物学特征，且对常规新辅助治疗的响应效果更差。因此，本研究拟通过整合Vivli数据库中的大量同类临床研究数据，深入分析两类患者的响应率、预后等临床数据差异。最终，我们将针对这两种HER2阳性乳腺癌亚型制定差异化的精准治疗方案，为HER2阳性乳腺癌患者的分型诊疗提供新的科学依据，以期揭示两种亚型的潜在发病机制与精准治疗策略。