HR-positive breast cancers accounts for about 50% to 60% of all breast cancer patients. Neoadjuvant Chemotherapy is the core treatment mode for this type of breast cancer, and endocrine therapy can be used in some low-risk patients. However, the pathological complete response (pCR) rate obtained is low. HER2 is an important prognostic indicator and therapeutic target for breast cancer. Nearly 60% of HR-positive breast cancers have low expression of HER2, and antibody-drug conjugates (ADC) targeting HER2 may achieve better efficacy in this subtype.

This prospective, single-arm study is being conducted to evaluate the efficacy and safety of SHR-A1811 for early-stage or locally advanced breast cancer patients with HR-Positive, Low HER2 Expression. Subjects will receive the neoadjuvant therapy of SHR-A1811 for eight cycles, and then undergo surgery within 4 weeks after neoadjuvant therapy. The follow-up visit will last for at least 5 years.

Inclusion Criteria:

1. Patients aged 18 to 70 years old (inclusive);
2. Treatment-naive patients with clinically confirmed T2-T3, any nodal status and M0;
3. HR-positive, HER2 low expression, the expression of Ki-67 exceed 14% invasive breast cancer confirmed by histology or cytology;
4. ECOG performance status of 0-1;
5. Normal organ and bone marrow function;
6. Patients of childbearing age must consent to use highly effective contraception for 7 months from the start of study screening until the last study medication and agree not to breastfeeding;
7. Patients voluntarily joined the study and signed informed consent;

Exclusion Criteria:

1. Patients have evidence of metastatic breast cancer, or inflammatory breast cancer;
2. Patients previously received antineoplastic therapy or radiotherapy for any malignancy, excluding cured malignancies such as cervical carcinoma in situ, basal cell carcinoma, or squamous carcinoma;
3. Patients received any other anti-tumor therapy at the same time, including endocrine therapy, bisphosphonates or immunotherapy;
4. Patients have major surgical procedures unrelated to breast cancer within 4 weeks before the first medication, or not fully recovered from surgical procedures;
5. Clinically significant pulmonary or cardiovascular disease;
6. Failure to swallow, chronic diarrhea, intestinal obstruction, or presence of other factors affecting drug administration and absorption;
7. Known to be allergic to any study drug or any of its excipients;
8. History of immunodeficiency, including HIV-positive, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
9. Pregnant and lactating women;
10. Patients with serious concomitant diseases or other comorbidities that will interfere with the planned treatment, or any other condition that is not suitable for participation assessed by investigator.