In early breast cancer, assessing axillary lymph node involvement is critical for prognosis and treatment planning. ALND, as a standard treatment approach, enables accurate assessment of axillary lymph node metastasis in patients. However, despite the clear therapeutic efficacy of ALND, its associated complications such as lymphedema, nerve injury, and shoulder dysfunction need to be considered (12–14). In recent decades, there has been significant progress in developing less invasive approaches for axillary staging, facilitating more tailored treatments for breast cancer patients (15, 16). Consequently, the utility of ALND has been undergoing transformation. While omitting ALND in cases of node-positive disease has become increasingly accepted, the question persists as to whether the findings from the ACOSOG Z0011 trial can be extrapolated to broader patient cohorts, particularly those undergoing total mastectomy.
Furthermore, the occurrence of lymph node metastases outside the SLN in the axilla is notable. The residual tumor burden in the axilla poses a significant risk factor for axillary failure, warranting increased attention. While patients with SLN micrometastases may present with a low axillary disease burden, it does not preclude the possibility of additional axillary node involvement (17). Data from the SJTUBCDB in our study reveal that among patients with SLN showing N1mi status, further axillary dissection resulted in an additional non-sentinel lymph node metastasis rate of 19.4%. This incidence is comparable to previous reports of non-sentinel lymph node metastases ranging from 10–20% (18, 5, 19, 20). In our study, despite the presence of non-sentinel lymph node metastases, the incidence of local recurrence was reassuringly low in cases where the axilla remained undissected, comparable to that in patients who underwent axillary dissection (p = 0.28). This outcome was consistent with findings from other studies, underscoring the importance of these observations (21, 22).
Patients with SLN micrometastases who did not undergo axillary dissection exhibit not only a lower rate of axillary recurrence but also similar survival outcomes compared to those undergoing axillary dissection. Studies such as IBCSG 23 − 01 and AATRM, which exclusively enrolled patients with SLN micrometastases, compared observation with ALND (5, 23). These trials revealed a 5-year OS exceeding 97% across all groups, with no significant increase in axillary recurrence at the 5-year mark. Research indicates that tumor biology plays a pivotal role in disease progression among patients with micrometastases, rather than merely the extent of nodal involvement (24, 25). Therefore, these trials support the idea that contemporary adjuvant therapies for breast cancer, encompassing chemotherapy, endocrine therapy, and whole-breast radiotherapy, effectively control regional axillary disease and yield excellent long-term survival for women with SLN micrometastases who forego ALND (26). Based on these findings, it is deemed safe to observe women with only micrometastatic disease identified during SLNB evaluation, provided they have access to adjuvant therapy (24).
In comparison to the well-established efficacy of chemotherapy, endocrine therapy, and targeted treatment, the utilization of postmastectomy radiotherapy (PMRT) in this cohort remains a subject of debate (25). Current guidelines suggest strong consideration of PMRT to the chest wall and regional lymph nodes for mastectomy patients with one to three positive nodes (7). However, uncertainty persists regarding whether micrometastases should be factored into the node count. Moreover, both ALND and axillary radiotherapy are linked to heightened risks of complications such as ipsilateral upper limb lymphedema and shoulder stiffness when compared to SLNB alone. Therefore, it is imperative to identify the subset of patients who stand to benefit from the judicious reduction of axillary therapy.
In multivariable survival analysis, the receipt of adjuvant chemotherapy emerged as an independent predictor for improved OS in breast cancer patients. Additionally, various other factors were identified as influential on survival outcomes, including age, marital status, income, race, tumor stage (T2), tumor location in the upper outer quadrant, Grade III tumor, molecular subtype (HR-/HER2-), and the number of metastatic sentinel nodes. Subgroup survival analysis revealed that only patients with incomes below $75,000, Black race, and HR-/HER2- subtype exhibited survival benefits among those with SLN micrometastases treated with Non-ALND or ALND. These findings contribute to the surgical management of the axilla in patients with early-stage breast cancer undergoing mastectomy and provide support for less extensive axillary surgery in select patients. They provide valuable support for the implementation of less extensive axillary surgery in appropriately selected patient cohorts.
The current study has several limitations that warrant acknowledgment. Firstly, as it is a retrospective analysis, it lacks the randomization typically found in prospective studies. Moreover, utilizing telephone follow-up may introduce the potential for missing information. Additionally, due to the prolonged study duration, some patients were lost to follow-up, leading to a lack of contact with the clinic. Furthermore, the limited data within the SJTUBCDB dataset resulted in a low number of events, which precluded subgroup analysis. Secondly, concerning the SEER database, patients have not been categorized based on the type of axillary surgery. Consequently, we relied on the number of regional lymph nodes examined as a proxy, which may introduce errors.