Treatment strategies for early breast cancer depend on the typing and staging of early breast cancer. Based on gene expression profiles and immunohistochemical characteristics, early breast cancer can be classified into the following major molecular subtypes, with significant differences in biological behavior, treatment response, and prognosis among the subtypes. Breast cancer is further classified into hormone receptor-positive, triple-negative breast cancer (TNBC), and human epidermal growth factor receptor 2-positive type. Luminal A type: about 40% - 50% of early breast cancers, hormone receptor (ER and/or PR) positive, HER2 negative, with a low Ki-67 index (typically ≤ 14%). This subtype grows slowly, has low malignancy, is sensitive to endocrine therapy, has a good prognosis with a 5-year disease-free survival rate of over 90%, and is a major beneficiary of downgrading treatment. Luminal B type: accounting for 20% - 30%, it can be further divided into HER2-negative and HER2-positive subtypes. All are hormone receptor-positive and have a high Ki-67 index (>14%); HER2-positive subclasses are accompanied by HER2 overexpression or amplification. This subtype of tumor has high proliferative activity, and some may require combined chemotherapy or targeted therapy. Downgrading therapy should be carefully evaluated in combination with tumor size and lymph node status. HER2-positive type: about 15% - 20%, hormone receptor-negative, HER2-positive. The tumor is highly aggressive, but with the use of targeted drugs such as trastuzumab and pertuzumab, the prognosis has improved significantly, and the pathological complete response (pCR) rate after neoadjuvant therapy can reach more than 60%, creating favorable conditions for surgical downgrading. Triple-negative type: 10% - 15% of cases, negative for both hormone receptor and HER2. Highly invasive, with a high risk of recurrence, and relatively sensitive to chemotherapy, with a neoadjuvant chemotherapy pCR rate of about 30% to 40%; those with pCR may consider downgrading surgery, but those without pCR require more aggressive local treatment [2] .

The current breast cancer staging principles are based on the American Joint Committee on Cancer (AJCC) 8^th edition breast cancer staging system (including traditional anatomical staging and prognostic staging). Stage 0 (Tis): carcinoma in situ, including ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS), is confined within the ducts or lobules, does not break through the basement membrane, and has no lymph node or distant metastasis. Stage IA: maximum diameter of the tumor ≤ 2 cm, no lymph node metastasis (T1N0M0); Stage IB: tumor with maximum diameter ≤ 2 cm and microlymph node metastasis (≤0.2 cm, T1N1miM0), or no evidence of primary tumor but microlymph node metastasis in the axillary area (T0N1miM0). Stage II: Stage IIA: tumor with a maximum diameter > 2 cm and ≤5 cm, no lymph node metastasis (T2N0M0); or tumor ≤ 2 cm with 1 - 3 lymph node metastases in the axillary area (T1N1M0); Stage IIB: tumor maximum diameter > 2 cm and ≤5 cm with 1 - 3 lymph node metastases in the axillary area (T2N1M0); or tumor > 5 cm but no lymph node metastasis (T3N0M0). The stage of early breast cancer directly affects the choice of treatment strategy. For example, patients with stage IA Luminal A type may be treated with breast-conserving surgery alone combined with endocrine therapy, while patients with stage IIB triple-negative may need neoadjuvant chemotherapy to determine the extent [2] .

Sentinel lymph node biopsy (SLNB) replaces traditional axillary lymph node dissection (ALND) as the standard assessment method for clinically axillary-negative patients by identifying the “first stop” lymph nodes of tumor lymphatic drainage. Some patients have sequelae such as lymphedema, limb pain and numbness, and limited upper limb movement after ALND surgery, while the lymph node metastasis rate of all stages of breast cancer is only 40% to 50%. Therefore, routine ALND may cause 50% to 60% of patients to undergo unnecessary surgery . The concept of the sentinel lymph node (SLN) emerged in 1960, defined as the regional lymph nodes in the primary tumor that receive lymphatic drainage first and have tumor cell metastasis first. The use of SLNB in patients with clinically negative lymph nodes in breast cancer undoubtedly avoids postoperative complications to a large extent and has no significant impact on the prognosis of patients. For patients with clinically negative lymph nodes and SLNB-negative, global multicenter studies unanimously support exemption from ALND, with an axillary recurrence rate of only 0.6% 1.2% [10] . For example, a European registry study involving 5000 patients showed that the 5-year axillary recurrence risk for such patients was only 0.8%, without the need for further surgical intervention. With the widespread use of SLNB in clinical practice, the concept of further surgical downgrading treatment is also expanding the applicable population. First, for patients with axillary downstaging after neoadjuvant therapy, can the implementation of SLNB after neoadjuvant therapy accurately assess the pathological state of axillary lymph nodes and thus also provide an opportunity for exemption from ALND? Previous studies suggest that for patients evaluated as cN1 stage before neoadjuvant therapy, neoadjuvant therapy can turn lymph nodes negative in about 40% of patients, especially in TNBC or HER2-positive cN1 stage breast cancer patients, where about two-thirds of patients show no axillary lymph node metastasis after treatment. Three multicenter prospective clinical trials, ACOSOG Z1071, SENTINA, and SN FNAC, evaluated the feasibility and accuracy of SLNB in patients with initially positive axillary lymph nodes after neoadjuvant chemotherapy, and the results suggested that biopsy of ≥3 SLNs, double-tracer lymphangiography, and an axillary biopsy technique for marking metastatic lymph nodes before neoadjuvant therapy can effectively reduce the false-negative rate of SLNB after neoadjuvant therapy. Patients who meet these conditions have a negative SLN after neoadjuvant therapy and can safely be exempted from ALND.

Adjuvant therapy refers to systematic systemic treatment carried out after surgery. At present, the prognosis of patients with different subtypes of early breast cancer has improved significantly after treatment. A number of studies have shown good therapeutic outcomes for patients with breast cancer at medium to high risk of recurrence. Neoadjuvant therapy has become the standard treatment for locally advanced and some high-risk early-stage breast cancer by reducing tumor size and downstaging before surgery, creating conditions for surgical downgrading. The MonarchE study enrolled 5637 patients. The treatment group received adjuvant abeciclib combined with standard endocrine therapy regimens, with a median follow-up of 54 months. The results showed a 32% reduction in the risk of recurrence and 5 years of invasive disease-free survival (iDFS). The iDFS rate increased significantly compared to the control group (83.6% vs 76.0%). The NATALEE study further confirmed that among 5101 high-risk patients with positive or negative lymph nodes, 3-year adjuvant rebociclib reduced the risk of recurrence by 29% compared with conventional endocrine therapy, and the 4-year absolute benefit rate of iDFS was 4.9%;a team from Fudan University Shanghai Cancer Center conducted stratified treatment for TNBC patients and found that low-risk patients had a 3-year disease-free survival (DFS) rate of up to 90.1% after receiving conventional chemotherapy, while high-risk patients received anthracyclines and taxanes followed by an enhanced chemotherapy regimen of gemcitabine and platinum-based drugs. The 3-year disease-free survival rate reached 90.9%, significantly higher than 80.6% in the conventional chemotherapy group. The APHINITY study reported the follow-up of patients who received trastuzumab and pertuzumab in combination with chemotherapy after surgery. The results showed an 8-year iDFS rate of 86.1% in patients with positive axillary lymph nodes and 92.3% in patients with negative axillary lymph nodes. For high-risk HER2-negative early breast cancer patients with germline BRCA mutations, the Phase III randomized controlled clinical trial OlympiA confirmed that one year of olaparib adjuvant therapy could further reduce the risk of recurrence by 42%, and the 3-year iDFS rate increased from 77.0% to 85.9%. All of the above studies enrolled patients with clinically high-risk subtypes of early breast cancer. After optimized systemic adjuvant therapy, the overall prognosis improved significantly, which also laid the foundation [11] for the formation, promotion, and popularization of the surgical downgrading treatment concept. There are significant differences in response to neoadjuvant therapy among different molecular subtypes, and accurate prediction of efficacy is a prerequisite for surgical downgrading. For HER2-positive breast [12] cancer: dual-targeted therapy with trastuzumab combined with pertuzumab yields a pathological complete response (pCR) rate of 60% to 70% . NeoSphere studies showed [14] that breast retention in pCR patients increased to 70%, and the 5-year disease-free survival rate reached 90%. Hormone receptor-positive breast cancer: 45% of postmenopausal patients who received neoadjuvant therapy with aromatase inhibitors (such as anastrozole) for six months experienced a tumor reduction of ≥50%, with a pCR rate of about 10% - 15%, but even without pCR, tumor regression still increases the chance of breast preservation. Triple-negative breast cancer: The PCR rate for neoadjuvant chemotherapy (such as the TC regimen) is about 30% to 40%, and the local recurrence rate 5 years after breast-conserving surgery for pCR patients is only 3.2%, significantly lower than that for non-PCR patients (8.5%).

The “watch-and-wait” exploration for patients with clinical complete response (cCR) was for those who achieved cCR after neoadjuvant therapy (with no clinical or imaging evidence of tumor) with a pCR predictive value of ≥90%, and some studies attempted to exempt surgery. As shown in the I-SPY2 study subgroup, the 2-year local recurrence rate of HER2-positive cCR patients was approximately 3.1%, but this strategy still requires larger-scale studies for validation and is currently only recommended for clinical trials. The management after axillary lymph node downstaging refers to axillary-positive patients before neoadjuvant therapy. If it turns negative after treatment, the false-negative rate of SLNB re-evaluation is about 5%, and combined ultrasound or MRI evaluation can be reduced to less than 3%. As shown in the SENTINA study, the 5-year axillary recurrence rate of patients exempted from ALND was 1.5%, comparable to that of the ALND group (1.3%) [14] - [16] . At present, breast cancer has entered an era of individualized treatment based on molecular subtypes, and the choice of neoadjuvant therapy drugs also needs to be based on the patient’s tumor burden and the expression levels of ER, PR, and HER2, as well as the Ki-67 proliferation index. From different perspectives, the advantages of neoadjuvant therapy include: 1) from the perspective of tumorigenesis and development mechanisms, neoadjuvant therapy enables earlier and more effective treatment of distant micrometastases of the tumor; preventing postoperative tumor recurrence and metastasis due to reduced angiogenesis inhibitors and an increased number of drug-resistant cells; 2) from a clinical perspective, neoadjuvant therapy downstages the primary lesion and regional lymph nodes of breast cancer, allowing tumors that were previously inoperable to be cured through neoadjuvant therapy; it gives patients who were previously unable to undergo breast-conserving surgery the opportunity to do so; to prevent axillary dissection (auxiliary lymph node dissection, ALND) for patients who would otherwise need axillary dissection after axillary downstaging; monitoring tumor sensitivity to treatment regimens provides a basis for the selection of postoperative adjuvant therapy; 3) from a scientific perspective, neoadjuvant therapy provides a research platform to accelerate the discovery of biomarkers, establish indicators for predicting efficacy and biomarkers related to residual tumor or tumor drug resistance; testing the efficacy of new combination therapies can rapidly assess the efficacy of new drugs and accelerate the development of new anti-tumor drugs. Based on current evidence-based medical evidence, the effect of neoadjuvant therapy with the same regimen and course is the same as that of adjuvant therapy. If the treatment is effective and surgery is performed after completing the full course of neoadjuvant therapy without achieving pathologic complete remission, patients with pCR have the opportunity to use intensive treatment regimens to further reduce the risk of relapse and death [17] . In terms of TNBC, the KEYNOTE522 study showed that chemotherapy combined with pembrolizumab achieved a 64% pCR rate [18] . Similarly, in patients with HER2-positive breast cancer, the combination of taxane and platinum-based drugs with trastuzumab and pertuzumab yields a pCR rate of more than 60%, providing a broader exploration space for surgical downgrading, especially for local treatment downgrading after neoadjuvant therapy [12] [19] .