Several characteristics, including tumor biology and demographics, vary between Asian and Western patients with breast cancer [17, 18]. Racial differences could affect the adoption of current surgical strategies established in Western countries. Although our study, based on a large Korean nationwide database, revealed downward trends of ALND in our breast cancer patients who met the Z0011 criteria, the downward trend was significantly more gradual than that in the Dutch cohort. To the best of our knowledge, this is the first study to report the downward trend of axillary surgery in Asian patients with breast cancer and to compare the degrees of the downward trend of axillary surgery between Asian and Western countries.
Compared to the Z0011 participants, those in our study had larger tumor size, more frequent lymphatic invasion, and younger age. In the Z0011 cohort, approximately 30% of patients had T2 lesions, 28% of patients had lymphatic invasion, and 25% of patients were < 50 years old [6]. In contrast, in our study cohort, approximately 45% of patients had T2 lesions, 49% of patients had lymphatic invasion, and 47% of patients were < 50 years old. In the Dutch cohort, 37% of patients had T2 lesions, no information on lymphatic invasion was reported, and only 20% of patients were < 50 years old, similar to the Z0011 cohort [21]. A recent Japanese study by Kittaka et al. evaluated Japanese patients who met the Z0011 criteria and reported that their patients had larger tumors and more frequent lymphatic invasion than the Z0011 participants [22], which is consistent with our study findings. These differences in tumor biology and demographic characteristics between the Asian and Z0011 cohorts might underlie the difference in the trend of the surgical management of the axilla. We speculate that more unfavorable tumor characteristics in Asian women might be the reason why surgeons in Asia are less willing to omit ALND even in some patients who meet the Z0011 criteria. Our multivariate analysis revealed that larger tumor size and lymphatic invasion were associated with a higher odds ratio of performing ALND, indicating that surgeons preferred to perform completion ALND over SLNB alone in such cases.
Consistent with our findings, Liu et al. reported that many surgeons in China preferred to perform completion ALND even in patients who met the Z0011 criteria [19]. Although Chinese surgeons were aware of the Z0011 trial results, 42% of them still performed ALND in most cases considering that clinical situations in many areas of China were different from those in Western countries. For example, many patients do not receive standard adjuvant treatment following surgery in suburban areas of China due to patient intention, financial issues, and medical conditions. Thus, some Chinese surgeons have argued that the Z0011 trial results may not be applicable in the clinical setting in China and that they prefer to choose radical surgery for any number of positive sentinel lymph nodes. In addition, some Chinese surgeons were uncertain whether the Western trial results could be applicable to the Chinese population due to differences in clinical characteristics between Asian and Western patients. Furthermore, there have been some debates on the potential selection bias related to the enrollment of patients in the Z0011 trial. Patients with a good prognosis alone were enrolled, and the trial was closed early with < 50% target accrual [23, 24]. The aforementioned explanations may also explain the downward trend of ALND in the Korean cohort that is not as fast as that in the Dutch cohort.
Several recent studies in large Asian cohorts have validated that the Z0011 strategy could be safely applied to Asian patients. Jung et al. reported that ALND omission in the Asian cohort did not increase the risk of disease recurrence during a median follow-up period of 50 months [20]. A prospective single-arm study by Kittaka et al. showed that the 5-year cumulative rate of locoregional recurrences was only 1.3% in patients undergoing BCS with SLNB alone followed by radiotherapy [22]. Although prolonged follow-up is needed to determine the oncologic safety with regard to late recurrences, it might be feasible to apply the Z0011 strategy in Asian patients. Taken together, despite of differences in tumor biology and demographics along with clinical situations in Asian countries, more efforts are needed to spread the Z0011 strategy.
Previous studies have reported several factors associated with performing ALND in early breast cancer. According to recently published data from the European Society of Breast Cancer Specialists, the factors associated with a higher odds ratio of performing ALND in patients meeting the Z0011 criteria were earlier year of surgery, younger age, larger tumor size, and a higher tumor grade [11]. In a Dutch population-based study, younger patients with invasive lobular subtype, those with a higher tumor grade, and those treated in a general non-teaching hospital underwent completion ALND more frequently. Our results similarly demonstrated that patients with poor prognostic tumor biology, such as large size and lymphatic invasion, underwent ALND more frequently than other patients. With regard to surgeons’ preferences, a survey study by Morrow et al. reported that surgeons in higher patient volume centers and those participating in a multidisciplinary tumor board had a lower propensity for performing ALND, suggesting the need for education targeting breast surgeons working in lower-volume centers [25].
Our study is limited by its retrospective design and lack of data on the clinical T and N stages. Instead, we postulated that patients with T1-2 N1-3 M0 disease who had undergone SLNB and BCS would best meet the Z0011 criteria. Despite these limitations, our study has a strength in analyzing population-based nationwide data, including diverse surgeons’ preferences. To our knowledge, this is the first study reporting real-world data on trends of axillary surgery in Asian patients with breast cancer.
In summary, our study demonstrated a downward trend of ALND in Korea patients with breast cancer who met the Z0011 criteria. However, the rate of decrease was significantly slower than that in Dutch cohort, indicating the need to spread the Z0011 strategy in Asia.