Abstract
Background
Previous studies have confirmed that the higher axillary lymph node metastasis rate, the worse the prognosis. This study aimed to determine the key factors associated with axillary lymph node metastasis and prognosis of T2 breast cancer, which ultimately provides a scientific basis for precise risk stratification, optimized treatment decision-making, and improved prognosis in T2 patients.
Methods
Multivariate logistic regression was used to explore the influencing factors of axillary lymph node metastasis in patients with T2 breast cancer. Univariate and multivariate Cox regression were used to explore the prognostic factors of T2 breast cancer patients, and the nomogram was used to predict the survival probability of patients. Kaplan-Meier survival curve was used to analyze the influence of influencing factors on survival.
Results
A total of 150,730 patients with T2 breast cancer were included in this study. Age ≥65 years old, and other races were protective factors for axillary lymph node metastasis, while black race, infiltrating cancer, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, luminal B subtype, human epidermal growth factor receptor-2 (HER2)-positive subtype, and triple-negative subtype were risk factors. Other race, married, right primary site, chemotherapy, ER-positive, PR-positive, HER2-positive subtype, and triple-negative subtype were protective factors for overall survival (OS) of patients with T2 breast cancer, while age ≥65 years old, black race, other marital status, stage II, stage III, axillary lymph node metastasis, and luminal B subtype were risk factors for OS of patients with T2 breast cancer. The same results were also found in the breast cancer-specific survival (BCSS) of patients with T2 breast cancer. The nomogram constructed based on these factors affecting OS and BCSS can be used as a tool to predict OS and BCSS for T2 breast cancer.
Conclusions
Black race, infiltrating cancer, ER-positive, PR-positive, luminal B subtype, HER2-positive subtype, and triple-negative subtype were independent risk factors for axillary lymph node metastasis. Old age, black race, other marital status, stage II, stage III, axillary lymph node metastasis, and luminal B subtype were risk factors for the prognosis of patients with T2 breast cancer.
Keywords: Axillary lymph node metastasis, breast cancer, T2, overall survival (OS), breast cancer-specific survival (BCSS)
Highlight box.
Key findings
• Black race, infiltrating cancer, estrogen receptor-positive, progesterone receptor-positive, luminal B subtype, human epidermal growth factor receptor-2-positive subtype, and triple-negative subtype were independent risk factors for axillary lymph node metastasis. Old age, black race, other marital status, stage II, stage III, axillary lymph node metastasis, and luminal B subtype were risk factors for the prognosis of patients with T2 breast cancer.
What is known, and what is new?
• It is known that axillary lymph node metastasis has an important influence on the progression and survival rate of breast cancer patients.
• This study revealed that several factors, such as black race, luminal B subtype, can influence the axillary lymph node metastasis and prognosis in patients with T2 breast cancer.
What is the implication, and what should change now?
• Medical staff should pay more attention to these factors in the process of diagnosis and treatment.
Introduction
Breast cancer is a common female cancer, and it is a disease in which abnormal breast cells grow out of control and form tumors (1). At present, breast cancer is a major public health problem all over the world because of its high morbidity and mortality. According to the World Health Organization report, the number of new cases of breast cancer in 2022 exceeded 2.31 million, with the disease becoming the second most prevalent type of cancer after lung cancer (2). In 2022, it was estimated that 287,850 new cases of breast cancer in women in the USA were diagnosed, accounting for 31% of new cases of cancer. Additionally, it was estimated that 43,250 cases in women of breast cancer patients died, accounting for 15% of cancer deaths (3). In 2022, it was estimated that 0.3572 million new cases of breast cancer occurred in China, with an incidence rate of 51.17%, and 75 thousand breast cancer patients died, with a mortality rate of 10.86% (4).
With the progress of science and technology, more than half of breast cancer patients are diagnosed at an early stage (3). Tumor metastasis or tumor cells spreading all over the body is the main cause of death in breast cancer patients. Axillary lymph node metastasis is the most common breast cancer metastasis. It was found that axillary lymph node metastasis has an important influence on the progression and survival rate of breast cancer patients (5). Song et al. selected 75 patients with recurrent breast cancer after initial breast-conserving surgery as study subjects and found that axillary lymph node metastasis can affect the prognosis of those breast cancer patients, because it can result in a reduction in the postoperative survival rate, a shortening of the overall survival (OS) time of the patients, and an increase in the risk of distant metastasis after recurrence (6). The higher the axillary lymph node metastasis rate, the worse the prognosis (7).
At present, few studies focus on the influencing factors of axillary lymph node metastasis in patient with T2 breast cancer, so this study studies the influencing factors of axillary lymph node metastasis and prognosis of patients with T2 breast cancer based on the Surveillance, Epidemiology, and End Results (SEER) Program database, to better prevent and control the occurrence and development of breast cancer. We present this article in accordance with the TRIPOD reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-214/rc).
Methods
Data source
Patient data were from the SEER database, which was established by the National Cancer Institute in 1973. It is a common cancer database in the United States, including various tumor types, such as lung cancer, breast cancer, gastric cancer, colorectal cancer, prostate cancer, and so on. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Variables and grouping
The variables included in the research were as follows: age (<65 years old, ≥65 years old), race (White, Black, Others), marital status (single, married, others), stage (I, II, III), primary site (left, right), chemotherapy (no, yes), pathological types (others, infiltrating cancer), estrogen receptor (ER) (negative, positive), progesterone receptor (PR) (negative, positive), human epidermal growth factor receptor-2 (HER2) (negative, positive), axillary lymph node metastasis (no, yes), subtypes (luminal A, luminal B, HER2-positive, triple-negative).
The grouping was as follows: according to whether axillary lymph node metastasis occurs, the collected patients were divided into those without axillary lymph node metastasis and those with axillary lymph node metastasis.
The main outcome indicators of prognosis were OS and breast cancer-specific survival (BCSS).
Inclusion and exclusion criteria
In this study, we initially collected data from 677,743 female patients aged over 20 years diagnosed with primary breast cancer between 2011 and 2021, then applied predefined inclusion and exclusion criteria to refine the cohort: inclusion was limited to T2-stage patients (n=158,894), while exclusions comprised patients with unclear N-stage classification (n=2,335), missing survival time records (n=11), distant metastases (n=927), bilateral breast cancer (n=892), or incomplete key variables (n=3,999), resulting in a final analytical cohort of 150,730 patients, with the detailed selection process visualized in Figure S1.
Statistical analysis
R language was used for data analysis. Qualitative data were described by composition ratio and analyzed by the Chi-squared test. Collinearity analysis was used to explore whether there was collinearity between influencing factors. Multivariate logistic regression was used to explore the influencing factors of axillary lymph node metastasis in patients with T2 breast cancer. Univariate and multivariate COX regression were used to explore the prognostic factors of T2 breast cancer patients, and the nomogram was used to predict the survival probability of patients. C-index and calibration curve are used to evaluate the consistency and accuracy of the nomogram, respectively. Area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to evaluate the predictive performance of the nomogram. In addition, 50% of the patients with T2 breast cancer were randomly selected for internal verification of nomograms. Kaplan-Meier (KM) survival curve was used to analyze the influence of influencing factors on survival. P<0.05 was considered to be statistically significant.
Results
Patient baseline information
A total of 150,730 patients with T2 breast cancer were included in this study, among whom 86,358 patients did not have axillary lymph node metastasis, accounting for 57.393% of the total patients, and 64,372 patients had axillary lymph node metastasis. There were differences in age, race, marital status, stage, pathological types, ER, PR, HER2, and subtypes between the two groups (all P<0.001) while there was no difference in the primary site (Table 1).
Table 1. Baseline characteristic of patients.
| Variable | Without axillary lymph node metastasis (n=86,358) | With axillary lymph node metastasis (n=64,372) | P |
|---|---|---|---|
| Age, years | <0.001 | ||
| <65 | 47,818 (55.372) | 42,882 (66.616) | |
| ≥65 | 38,540 (44.628) | 21,490 (33.384) | |
| Race | <0.001 | ||
| White | 65,842 (76.243) | 48,121 (74.755) | |
| Black | 9,803 (11.352) | 8,279 (12.861) | |
| Other | 10,713 (12.405) | 7,972 (12.384) | |
| Primary site | 0.88 | ||
| Left | 43,954 (50.897) | 32738 (50.858) | |
| Right | 42,404 (49.103) | 31634 (49.142) | |
| Stage | <0.001 | ||
| I | 25,830 (29.910) | 12,165 (18.898) | |
| II | 60,528 (70.090) | 36,934 (57.376) | |
| III | 0 (0.000) | 15,273 (23.726) | |
| Marital status | <0.001 | ||
| Single | 14,261 (16.514) | 11,466 (17.812) | |
| Married | 45,496 (52.683) | 35,136 (54.583) | |
| Other | 26,601 (30.803) | 17,770 (27.605) | |
| Pathological types | <0.001 | ||
| Other | 15,780 (18.273) | 7,989 (12.411) | |
| Infiltrating cancer | 70,578 (81.727) | 56,383 (87.589) | |
| ER | <0.001 | ||
| Negative | 19,837 (22.971) | 12,905 (20.048) | |
| Positive | 66,521 (77.029) | 51,467 (79.952) | |
| PR | <0.001 | ||
| Negative | 29,649 (34.333) | 20,105 (31.233) | |
| Positive | 56,709 (65.667) | 44,267 (68.767) | |
| HER2 | <0.001 | ||
| Negative | 71,993 (83.366) | 51,742 (80.380) | |
| Positive | 14,365 (16.634) | 12,630 (19.620) | |
| Subtypes | <0.001 | ||
| Luminal A | 57,542 (66.632) | 43,356 (67.352) | |
| Luminal B | 10,276 (11.899) | 8,882 (13.798) | |
| HER2-positive | 4,089 (4.735) | 3,748 (5.822) | |
| Triple-negative | 14,451 (16.734) | 8,386 (13.027) |
Data are presented as n (%). ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; PR, progesterone receptor.
Influencing factors of axillary lymph node metastasis in patients with T2 breast cancer
A variance inflation factor (VIF)>5 is considered to have multiple collinearity in collinearity analysis. We conducted a collinearity analysis and found that HER2 had serious collinearity, so HER2 was excluded from the follow-up study. Because the number of patients with stage III T2 breast cancer who did not have lymph node metastasis was zero, the stage was not included in the subsequent analysis of risk factors for axillary lymph node metastasis. We further conducted the multivariate logistic regression analysis, as shown in Table 2, those factors, including age ≥65 years old, black race, other race, infiltrating cancer, ER-positive, PR-positive, luminal B subtype, HER2-positive subtype, and triple-negative subtype, were independently related with axillary lymph node metastasis. Age ≥65 years old, and other races were protective factors for axillary lymph node metastasis, while black race, infiltrating cancer, ER-positive, PR-positive, luminal B subtype, HER2-positive subtype, and triple-negative subtype were risk factors.
Table 2. Influencing factors of axillary lymph node metastasis in patients with T2 breast cancer.
| Variable | OR (95% CI) | P |
|---|---|---|
| Age, years | ||
| <65 | Ref. | |
| ≥65 | 0.635 (0.621–0.649) | <0.001 |
| Race | ||
| White | Ref. | |
| Black | 1.158 (1.120–1.196) | <0.001 |
| Other | 0.935 (0.906–0.965) | <0.001 |
| Marital status | ||
| Single | Ref. | |
| Married | 1.014 (0.985–1.044) | 0.34 |
| Other | 0.991 (0.960–1.024) | 0.60 |
| Pathological types | ||
| Other | Ref. | |
| Infiltrating cancer | 1.525 (1.480–1.571) | <0.001 |
| ER | ||
| Negative | Ref. | |
| Positive | 1.489 (1.360–1.631) | <0.001 |
| PR | ||
| Negative | Ref. | |
| Positive | 1.115 (1.079–1.151) | <0.001 |
| Subtypes | ||
| Luminal A | Ref. | |
| Luminal B | 1.044 (1.012–1.078) | 0.008 |
| HER2-positive | 1.736 (1.561–1.930) | <0.001 |
| Triple-negative | 1.113 (1.007–1.230) | 0.04 |
CI, confidence interval; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; OR, odds ratio; PR, progesterone receptor; Ref., reference.
Influencing factors of the prognosis of patients with T2 breast cancer
As can be seen from Table 3, other race, married, right primary site, chemotherapy, ER-positive, PR-positive, HER2-positive subtype, and triple-negative subtype were protective factors for OS of patients with T2 breast cancer, while age≥65 years old, black race, other marital status, stage II, stage III, axillary lymph node metastasis, and luminal B subtype were risk factors for OS of patients with T2 breast cancer. The same results were also found in the BCSS of patients with T2 breast cancer (Table 4). Besides, infiltrating cancer was a protective factor for OS of patients with T2 breast cancer. Figure 1A,1B were nomograms of OS and BCSS of patients with T2 breast cancer, respectively. In OS, age, stage, and chemotherapy made great contributions, while in BCSS, stage, subtypes, and ER were the most important factors. C-index of nomograms of OS and BCSS were 0.701 and 0.712, respectively. The C-index indicated that the nomograms of OS and BCSS have medium accuracy. In addition, the calibration curve results showed that the risk prediction results of the two nomograms were reliably consistent with the actual results, with no significant deviation from the reference line (Figure 1C,1D). The ROC results showed that the AUC of the nomogram for predicting OS was 0.686, and the AUC of the nomogram for predicting BCSS was 0.704 (Figure 2A,2B). The AUCs of the two nomograms in the validation set are 0.728 and 0.710, respectively (Figure 2C,2D). In addition, we further analyzed the influence of a single factor on prognosis. The results of KM analysis were similar to those of COX regression analysis (Figures 3,4).
Table 3. Influencing factors of the OS of patients with T2 breast cancer.
| Variables | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | ||
| Age, years | |||||
| <65 | Ref. | Ref. | |||
| ≥65 | 3.153 (3.060–3.249) | <0.001 | 2.529 (2.445–2.615) | <0.001 | |
| Race | |||||
| White | Ref. | Ref. | |||
| Black | 1.238 (1.188–1.290) | <0.001 | 1.210 (1.160–1.262) | <0.001 | |
| Other | 0.639 (0.605–0.675) | <0.001 | 0.769 (0.728–0.813) | <0.001 | |
| Marital status | |||||
| Single | Ref. | Ref. | |||
| Married | 0.745 (0.713–0.778) | <0.001 | 0.733 (0.702–0.766) | <0.001 | |
| Other | 1.704 (1.633–1.778) | <0.001 | 1.185 (1.134–1.238) | <0.001 | |
| Stage | |||||
| I | Ref. | Ref. | |||
| II | 1.644 (1.540–1.754) | <0.001 | 1.535 (1.436–1.641) | <0.001 | |
| III | 2.702 (2.515–2.903) | <0.001 | 2.684 (2.484–2.900) | <0.001 | |
| Primary site | |||||
| Left | Ref. | Ref. | |||
| Right | 0.963 (0.935–0.991) | 0.01 | 0.970 (0.942–0.999) | 0.04 | |
| Chemotherapy | |||||
| No | Ref. | Ref. | |||
| Yes | 0.506 (0.492–0.521) | <0.001 | 0.509 (0.492–0.528) | <0.001 | |
| Pathological types | |||||
| Others | Ref. | ||||
| Infiltrating cancer | 1.009 (0.970–1.049) | 0.67 | |||
| ER | |||||
| Negative | Ref. | Ref. | |||
| Positive | 0.751 (0.726–0.776) | <0.001 | 0.560 (0.499–0.630) | <0.001 | |
| PR | |||||
| Negative | Ref. | Ref. | |||
| Positive | 0.720 (0.699–0.742) | <0.001 | 0.714 (0.684–0.746) | <0.001 | |
| Axillary lymph node metastasis | |||||
| No | Ref. | Ref. | |||
| Yes | 1.196 (1.162–1.232) | <0.001 | 1.376 (1.330–1.423) | <0.001 | |
| Subtypes | |||||
| Luminal A | Ref. | Ref. | |||
| Luminal B | 0.805 (0.767–0.844) | <0.001 | 1.095 (1.041–1.151) | <0.001 | |
| HER2-positive | 0.931 (0.870–0.997) | 0.04 | 0.571 (0.496–0.657) | <0.001 | |
| Triple-negative | 1.413 (1.361–1.466) | <0.001 | 0.822 (0.724–0.934) | 0.003 | |
CI, confidence interval; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; HR, hazard ratio; OS, overall survival; PR, progesterone receptor; Ref., reference.
Table 4. Influencing factors of the BCSS of patients with T2 breast cancer.
| Variables | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | ||
| Age, years | |||||
| <65 | Ref. | Ref. | |||
| ≥65 | 1.980 (1.902–2.062) | <0.001 | 1.846 (1.765–1.930) | <0.001 | |
| Race | |||||
| White | Ref. | Ref. | |||
| Black | 1.416 (1.341–1.496) | <0.001 | 1.236 (1.168–1.308) | <0.001 | |
| Other | 0.682 (0.633–0.734) | <0.001 | 0.770 (0.715–0.829) | <0.001 | |
| Marital status | |||||
| Single | Ref. | Ref. | |||
| Married | 0.741 (0.700–0.784) | <0.001 | 0.757 (0.715–0.802) | <0.001 | |
| Other | 1.371 (1.294–1.453) | <0.001 | 1.125 (1.060–1.194) | <0.001 | |
| Stage | |||||
| I | Ref. | Ref. | |||
| II | 2.922 (2.608–3.273) | <0.001 | 2.423 (2.158–2.721) | <0.001 | |
| III | 7.087 (6.296–7.977) | <0.001 | 4.820 (4.256–5.458) | <0.001 | |
| Primary site | |||||
| Left | Ref. | Ref. | |||
| Right | 0.948 (0.910–0.987) | 0.01 | 0.960 (0.922–0.999) | 0.047 | |
| Chemotherapy | |||||
| No | Ref. | Ref. | |||
| Yes | 0.825 (0.792–0.860) | <0.001 | 0.641 (0.611–0.673) | <0.001 | |
| Pathological types | |||||
| Others | Ref. | Ref. | |||
| Infiltrating cancer | 1.225 (1.153–1.300) | <0.001 | 0.572 (0.545–0.601) | <0.001 | |
| ER | |||||
| Negative | Ref. | Ref. | |||
| Positive | 0.556 (0.533–0.581) | <0.001 | 0.462 (0.398–0.537) | <0.001 | |
| PR | |||||
| Negative | Ref. | Ref. | |||
| Positive | 0.531 (0.510–0.553) | <0.001 | 0.584 (0.551–0.620) | <0.001 | |
| Axillary lymph node metastasis | |||||
| No | Ref. | Ref. | |||
| Yes | 1.831 (1.758–1.908) | <0.001 | 1.823 (1.738–1.912) | <0.001 | |
| Subtypes | |||||
| Luminal A | Ref. | Ref. | |||
| Luminal B | 0.904 (0.845–0.967) | 0.003 | 1.014 (0.946–1.087) | 0.70 | |
| HER2-positive | 1.182 (1.082–1.292) | <0.001 | 0.421 (0.351–0.504) | <0.001 | |
| Triple-negative | 1.984 (1.890–2.081) | <0.001 | 0.697 (0.592–0.821) | <0.001 | |
BCSS, breast cancer-specific survival; CI, confidence interval; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; HR, hazard ratio; PR, progesterone receptor; Ref., reference.
Figure 1.
Nomogram of the prognosis of patients with T2 breast cancer. (A) Nomogram of OS of patients with T2 breast cancer; (B) nomogram of BCSS of patients with T2 breast cancer; (C) calibration curve of nomogram of OS of patients with T2 breast cancer; (D) calibration curve of nomogram of BCSS of patients with T2 breast cancer. Each variable in the figure corresponds to a line segment with marked scale divisions, representing the possible value range of that variable, while the length of the segment reflects the magnitude of that factor’s contribution to the outcome event. The “points” in the diagram indicate the individual score associated with each value of the variable. “Total point” refers to the sum of individual scores from all variables after their values are assigned. “5 years” in the figure represents the 5-year survival probability. The nomogram demonstrates that among T2 patients: (I) for 5-year OS, age, stage, and chemotherapy contributed significantly; (II) for 5-year BCSS, stage, subtypes, and ER status emerged as the most important factors. BCSS, breast cancer-specific survival; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; OS, overall survival; PR, progesterone receptor.
Figure 2.
ROC curve to evaluate the predictive performance of the nomogram in patients with T2 breast cancer. (A) ROC of nomogram of OS in the entire patients with T2 breast cancer; (B) ROC of nomogram of BCSS in the entire patients with T2 breast cancer; (C) ROC of nomogram of OS in internal validation of patients with T2 breast cancer; (D) ROC of nomogram of BCSS in internal validation of patients with T2 breast cancer. Half of the patients with T2 breast cancer were randomly selected for internal verification of nomograms. AUC, area under the curve; BCSS, breast cancer-specific survival; OS, overall survival; ROC, receiver operating characteristic curve.
Figure 3.
KM curves of OS of patients with T2 breast cancer. (A) Age. (B) Race. (C) Marital status. (D) Pathological types. (E) ER. (F) PR. (G) Subtypes. (H) Stage. (I) Primary site. (J) Chemotherapy. (K) Axillary lymph node metastasis. The KM survival curve is formed by connecting the survival rates at each time point, with follow-up time on the X-axis and survival rate on the Y-axis. Different colored lines represent different subgroups, and the survival curve positioned higher indicates a better survival rate for that group of patients. The log-rank test is used to compare survival curves between two or more groups. All KM curves in this figure demonstrate that each variable has a statistically significant impact on the OS of patients (all P<0.05). ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; KM, Kaplan-Meier; OS, overall survival; PR, progesterone receptor.
Figure 4.
KM curves of BCSS of patients with T2 breast cancer. (A) Age. (B) Race. (C) Marital status. (D) Pathological types. (E) ER. (F) PR. (G) Subtypes. (H) Stage. (I) Primary site. (J) Chemotherapy. (K) Axillary lymph node metastasis. The KM survival curve is formed by connecting the survival rates at each time point, with follow-up time on the X-axis and survival rate on the Y-axis. Different colored lines represent different subgroups, and the survival curve positioned higher indicates a better survival rate for that group of patients. The log-rank test is used to compare survival curves between two or more groups. All KM curves in this figure demonstrate that each variable has a statistically significant impact on the BCSS of patients (all P<0.05). BCSS, breast cancer-specific survival; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; KM, Kaplan-Meier; PR, progesterone receptor.
Discussion
Breast cancer is one of the most common malignant tumors in women, and the incidence of breast cancer in women has been increasing globally over the past 30 years (8). The age of incidence has also expanded from old age to middle-aged and young people. This study explored the influencing factors of axillary lymph node metastasis and the prognosis of T2 breast cancer based on the SEER database.
In this study, the incidence of axillary lymph node metastasis in patients with T2 breast cancer was 42.707%. Old age was a protective factor for axillary lymph node metastasis. A large retrospective study based on the SEER database also found that old age was a protective factor for axillary lymphatic metastasis in patients with triple-negative breast cancer (9). Regarding the relationship between age and axillary lymph node metastasis of breast cancer, Chinese scholars found that the rate of axillary lymph node metastasis was lowest at 11.8% in the older age group, highest at 17.2% in the middle-aged group, and 13.8% in the young people (10). Some studies have also found that age is not an influencing factor in axillary lymph node metastasis (11,12). This occurrence may be related to the size of the sample size. Black race, infiltrating cancer, ER-positive, PR-positive, luminal B subtype, HER2-positive subtype, and triple-negative subtype were risk factors for axillary lymph node metastasis. Liu et al. also found that ER-positive and PR-positive were risk factors for axillary lymphatic metastasis in breast cancer patients (13). Black race, PR-positive was found to be a risk factor for axillary lymphatic metastases in patients with stage T1 locally advanced breast cancer (13).
In the analysis of influencing factors of prognosis of breast cancer patients, we found that other race, being married, right primary site, chemotherapy, ER-positive, PR-positive, HER2-positive subtype, and triple-negative subtype were protective factors for the prognosis of patients with T2 breast cancer. The research results have certain similarities with those reported in previous studies. For example, it was found that chemotherapy was a protective factor against OS in patients with brain metastasis of triple-negative breast cancer (14). Zhang et al. analyzed the prognosis of young breast cancer patients and found that the HER2-positive subtype is a protective factor of OS in breast cancer patients, but it has nothing to do with BCSS (15). Old age, black race, other marital status, stage II, stage III, axillary lymph node metastasis, and luminal B subtype were risk factors for the prognosis of patients with T2 breast cancer. Zhou et al. found that the elderly, black race, stage II, stage III, axillary lymph node metastasis were significantly related to poor prognosis, while other races and married people had better prognosis (16). Zhao et al. retrospectively selected 80 patients with breast cancer who received radiotherapy in Jiangsu Cancer Hospital from April 2015 to April 2018 and found that age ≥60 years old and grade II-III were independent risk factors affecting the 5-year prognosis of breast cancer patients (P<0.05) (17).
In this study, we also found that ER-positive and PR-positive, HER2-positive, and triple-negative breast cancer all promote axillary lymph node metastasis. However, those factors are beneficial to the patient’s OS and BCSS. This result may be due to multiple reasons. (I) Advances in treatment methods. HR-positive tumors can significantly and persistently reduce the risk of recurrence and death with the help of long-term endocrine therapy (5–10 years of tamoxifen/extended treatment) and modern multi-drug chemotherapy (anthracycline/taxane regimen), thereby offsetting the adverse effects of their stronger lymphatic tropism on survival (18,19). HER2-positive patients have achieved significant improvements in OS/BCSS across trials and generations due to trastuzumab-based adjuvant/neoadjuvant therapy, transforming this traditional “high-risk” subtype into a high-cure population in contemporary treatment. Therefore, even with a higher tendency for axillary lymph node metastasis, systemic therapy can still bring net benefits in overall and specific survival (20,21). In addition, although triple-negative breast cancer is biologically aggressive, it is highly sensitive to chemotherapy (± platinum/immunotherapy), and the long-term outcomes of patients who achieve pathological complete remission (pCR) are significantly improved, which also provides a reasonable explanation for the cohort observation of promoting axillary lymph node metastasis but survival is not worse (22). (II) Subtypes are inherently heterogeneous in terms of lymphatic tropism—HER2-positive and luminal B breast cancer cases demonstrated higher frequencies of axillary nodal metastasis (23); under T2 stratification, this difference can be amplified or reversed in the sample by factors such as grade, lymphovascular invasion and detection sensitivity. (III) Advances in the detection of axillary lymph node metastasis. The popularization of sentinel lymph node biopsy has brought about “stage migration” (Will Rogers phenomenon) (24), significantly increasing the detection rate of micro/submicroscopic metastasis, resulting in the statistical phenomenon of “increased axillary lymph node metastasis rate and improved survival in each stage”, further weakening the superficial correspondence of “axillary lymph node metastasis = worse survival”. In summary, under the background of T2 tumor burden, the axillary pCR rate of HER2+ and triple-negative breast cancer population is higher; and axillary pCR is closely related to better OS/BSCC, which explains that even if axillary lymph node metastasis is present at initial diagnosis, long-term OS/BCSS can still be improved as long as it is highly sensitive to neoadjuvant/systemic treatment, which confirms our finding that chemotherapy is a protective factor for OS/BCSS.
This study has some limitations. First of all, in the SEER database, the available demographic information was limited, and other demographic information that cannot be obtained may also be influencing factors of lymphatic metastasis and prognosis of patients with T2 breast cancer. Secondly, there were few related indicators of breast cancer immunohistochemistry, only ER, PR, HER2, and lack of Ki-67 and other related indicators. Thirdly, the study lacks data on important prognostic factors such as endocrine therapy, targeted therapy, and recurrence, due to missing data. Fourthly, temporal changes in the management over the study period could introduce bias.
Conclusions
Black race, infiltrating cancer, ER-positive, PR-positive, luminal B subtype, HER2-positive subtype, and triple-negative subtype were independent risk factors for axillary lymph node metastasis. Old age, black race, other marital status, stage II, stage III, axillary lymph node metastasis, and luminal B subtype were risk factors for the prognosis of patients with T2 breast cancer.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Footnotes
Reporting Checklist: The authors have completed the TRIPOD reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-214/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-214/coif). The authors have no conflicts of interest to declare.
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