In the present study, we assessed the clinical value of BCS for predicting axillary lymph node metastasis in breast cancer patients and the results showed that HR−/HER2− subtype was associated with a lower risk of lymph node metastasis as compared to other BCSs.
The status of the axillary lymph node is an important prognostic factor in breast cancer patients. Studies from Western countries showed that age, tumor location, tumor stage, grade, and LVI could be used to evaluate the axillary lymph node status.4–8 Our findings from a Chinese population showed that tumor stage, grade, and LVI were also factors affecting the axillary lymph node status, but no relationship with age. Similar findings were also observed in a study conducted in Korea.16 There is evidence showing that women are more likely to have positive lymph nodes with increasing age, but the age distribution of breast cancer patients in Eastern was different from those of Western countries.20,21 Thus, the value of age as a predictor of axillary lymph node status is influenced by other factors.22
In this study, 3471 patients were included from 2 cancer centers and the results showed that TNBC patients had a lower risk of axillary lymph node metastasis as compared to other BCS patients. The finding of this study was similar to the results of previous studies.14,15,23,24 A study of the Danish Breast Cancer Cooperative Group database that included 20,009 patients showed that TNBC patients had a reduced risk of axillary lymph node involvement than other BCSs when adjusted for other risk factors.14 Ugras et al15 investigated 11,596 patients with breast cancer and found that nodal metastases were least frequent in TNBC as compared with other subtypes. A Chinese National Cancer Center study that included 3,198 patients showed that the probability of positive lymph nodes in TNBC patients was significantly lower than that in patients with other subtypes (28.2% vs 43.3–44.8%), although without multivariate analysis.23 In a Surveillance, Epidemiology, and End Results study with 7,274 patients, the HR+/HER2– subtype had a higher rate of lymph node metastasis at diagnosis than the TNBC.24 However, the value of BCS for predicting axillary lymph node status is still controversial. TNBC patients had a higher risk of nodal positivity (OR 2.09) in a Korean study.16 In addition, Gangi et al17 investigated 2,967 patients and multivariate analysis failed to show a significant difference in the lymph node status among patients with 4 BCSs. Furthermore, Wiechmann et al18 reviewed the records of 6,042 patients and reported that TNBC tumors did not have involved lymph nodes more often than non-TNBC. Sample size variation across studies may produce disparate findings in the above studies.
Lymphovascular invasion has been found to be a risk factor for locoregional and distant recurrence in breast cancer patients.25,26 Lymphovascular invasion is an obligatory step in tumor metastasis, and therefore may be a surrogate marker for metastatic potential.27 However, therapeutic failure is frequently found at 3 to 5 years in TNBC patients with hematogenous metastasis.28 Our results showed the frequency of LVI in TNBC patients (7.3%) was statistically lower than that in patients with other BCSs (9.4–13.4%). Ugras et al15 also found that the risk for LVI in other BCSs (OR 1.7–2.5) was statistically higher than in TNBC. Based on these findings, we speculate that TNBC patients have a lower risk for axillary lymph node metastasis and might be susceptible to hematogenous metastasis, but not directly associated with lymphatic spread.
Sentinel lymph node biopsy is an important treatment for early breast cancer and is helpful to improve quality of life.29 However, a method to accurately evaluate axillary lymph node status is an important prerequisite for sentinel lymph node biopsy. In patients with positive sentinel lymph nodes, the risk for positive nonsentinel nodes in TNBC patients is significantly lower than in Luminal A and Luminal B patients, but similar to that in HER2 overexpressing patients.30 Freedman et al31 found that TNBC had the lowest risk of nonsentinel lymph node metastasis in breast cancer patients with positive sentinel lymph nodes as compared to other subtypes. This indicates that BCS may be an important factor determining the need for axillary lymph node dissection in patients with breast cancer, and dissection may not be necessary in some TNBC patients. However, breast cancer was not subtyped in the ACOSOG Z0011 clinical trial,2,3 and more studies are required to confirm our findings.
There are limitations in our study. First, it is a retrospective study and hence is subject to inherent biases. However, the patients included in this study were from 2 cancer centers, and the results of this study had potential impact of axillary lymph node management decisions in clinical practice. Second, because of the patients period spanned with >10 years, BCS were not determined according to the criteria developed in the St. Gallen International Breast Cancer Conference because some patients did not have immunohistochemistry for Ki-67.32 We have not found the value of Ki-67 in predicting lymph node metastases; this confirms findings from previous studies.33–35 In addition, the ER, PR, and HER2 expressions were mainly detected by immunohistochemistry, which may bias the results, but the results of immunohistochemistry have been widely used in the treatment option for patients with breast cancer.
In conclusion, our results show that BCS as determined by ER, PR, and HER2 status can predict axillary lymph node metastasis in breast cancer. Although TNBC is more aggressive, a lower risk for axillary lymph node metastasis compared to patients with other BCSs. The findings suggest that lymphatic metastasis is not a major pattern of metastasis in HR−/HER2− patients. Our findings may play an important role in guiding axillary treatment considerations if further confirmed in larger sample size studies.
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