Since the prognosis is good for both patients with ypT0 ypN0 and those with ypTis ypN0 breast cancer14, breast pCR in the present study was defined as the absence of residual invasive carcinoma in the breast, including ypT0 and ypTis. Our analyses revealed that the rate of patients with ypT0/is ypN0 after NST was 23.6%, which was not high. There are several possibilities to explain this finding. First, the present study included all molecular subtypes of breast cancer and 40.3% of the patients had HR-positive/HER2-negative breast cancer, who were less likely to achieve breast pCR (7.7%) compared to those with other molecular subtypes (P < 0.01), especially compared to patients with HER2-positive (43.8%) or TN (34.5%) breast cancer. This finding is in agreement with other reports15,16. In addition, HER2-positive patients received trastuzumab only as targeted therapy in the present study, because pertuzumab was not approved for NST in China until 2020. Third, the tumor burden was greater in the current study cohort. The median tumor diameter was 50 mm, 24.4% of the patients were in stage cT3–4, and the rate of cN + was 79.5%. These data reflect the real-world situation in China. Specifically, relatively more patients with advanced breast cancer have been selected to receive NST in recent years; however, those with operable breast cancer usually receive surgery first, even those patients with HER2-positive or TN breast cancer.
Due to the greater tumor burden, the rates of breast pCR were not high in the present study (18.2% and 8.9% in the ypT0 and ypTis subgroups, respectively). On the other hand, a greater tumor burden was also associated with a higher rate of tumor metastasis to axillary lymph nodes and only 20.5% of the enrolled patients had cN0. After NST, however, the rate of axillary pCR increased to 48.8%, indicating that NST could effectively reduce the stage of axillary lymph nodes and that nearly half of these patients may be able to avoid axillary surgery. Furthermore, determination of more accurate indicators can potentially facilitate the identification of patients who may avoid axillary surgery including ALND and SNB. Based on our analyses, the rate of patients achieving axillary pCR was higher in the breast pCR group than in the breast non-pCR group (87.1% vs 34.6%, P < 0.01), indicating that those who achieved breast pCR were more likely to achieve axillary pCR. This finding suggests that breast pCR might be a good indicator to determine patients who might be able to avoid axillary surgery, which requires for exploration in future studies.
In the present study, 18 of the 53 patients with initial cN0 achieved breast pCR after NST; all 18 patients (100%) achieved axillary pCR simultaneously. In comparison, only 30 of the 35 patients with breast non-pCR (85.7%) achieved axillary pCR. Although there was no statistical difference between the breast pCR and breast non-pCR groups, the high axillary pCR rate in the breast pCR group (100%) provides evidence to support that axillary surgery may be omitted in patients with initial cN0 who achieve breast pCR. The study from the MDACC1 have also confirmed that axillary surgery might be omitted in patients with initial cN0 who achieve ypT0. However, only patients with HER2-positive and TN breast cancer were enrolled and those with the ypTis status were not included in that study. In real-world settings, HR-positive/HER2-negative breast cancer comprises the largest subtype despite the low rate of pCR. Therefore, it is also especially important to explore whether axillary surgery can be omitted in patients with this breast cancer subtype. In the current study cohort, 104 (40.3%) of the 258 enrolled patients were HR-positive/HER2-negative, 23 of these 104 patients had cN0 breast cancer, and 3 patients who achieved breast pCR also achieved axillary pCR, with a success rate of 100%. This finding may indicate that axillary surgery can also be potentially omitted in patients with HR-positive/HER2-negative breast cancer and initial cN0 who achieve ypT0/is status, however, due to the small amount, this needs to be supported by larger data subsequently. This result is consistent with the analysis from other studies13,17, which also provides support that axillary surgery might be omitted in patients with initial cN0 breast cancer of any molecular subtype who achieve the ypT0/is status.
On the other hand, 153 of the 205 patients with initial cN + achieved breast non-pCR after NST and only 35 of these patients (22.9%) achieved axillary pCR. In comparison, the rate of axillary pCR was higher in patients who achieved breast pCR (43/52, 82.7%) (P < 0.01). However, since the rate of axillary pCR is less than 90%, axillary surgery omission is not safe in patients with initial cN + who achieve breast pCR. In addition, the subgroup analysis showed that only patients with TN breast cancer (12/13, 92.3%) might potentially be considered for axillary surgery omission. This finding is also consistent with the report from the MDACC1 which demonstrated that the omission of axillary surgery might be safe for patients with TN breast cancer (32/35, 91.4%). However, the subgroup analysis in the NCDB study13 led to a different result, wherein the omission of axillary surgery was not safe for all molecular subtypes including TN breast cancer. This discrepancy may be due to differences in the characteristics of patients enrolled in different studies. Therefore, prospective multicenter clinical trials are necessary to obtain more accurate results.
Furthermore, we analyzed patients with initial cN + breast cancer by categorizing into the ypT0 and ypTis subgroups. Our analyses demonstrated that the axillary pCR rate was higher in the ypT0 subgroup than in the ypTis subgroup (94.3% vs 58.8%, P < 0.01). Meanwhile, the high rate value (> 90%) was consistent across all molecular subgroups except for the HR-positive/HER2-negative subgroup, in which only four patients achieved ypT0, indicating that axillary surgery may also be potentially omitted if ypT0, rather than ypTis, is achieved in patients with initial cN + HER2-positive or TN breast cancer.
The limitations of the present study include a small-sized cohort in a real-world study, which was conducted at a single breast cancer center. Additionally, due to the retrospective study design, the patients with cN + breast cancer could not be analyzed further to distinguish those with cN1 disease from those with cN2 or cN3 disease. However, based on the postoperative pathology, nearly 1/3 of the patients were in ypN2–3, implying that many of the patients had advanced axillary tumor burden. Therefore, prospective multicenter clinical trials will be necessary to obtain more reliable evidence.