Development and Validation of a Nomogram for Predicting Survival of Breast Cancer Patients with Ipsilateral Supraclavicular Lymph Node Metastasis
Breast cancer remains a significant global health concern, with approximately 1.7 million new cases diagnosed annually. Among these, patients presenting with ipsilateral supraclavicular lymph node metastasis (ISLNM) are considered to have a particularly poor prognosis. Historically, ISLNM was classified as distant metastasis (M1) in the 1997 American Joint Committee on Cancer (AJCC) staging system. However, subsequent research indicated that the prognosis of patients with ISLNM is more akin to that of patients with stage-IIIB locally advanced breast cancer rather than those with distant metastasis. Consequently, the 6th edition of the AJCC-TNM staging system reclassified ISLNM as N3c.
Despite advances in systemic treatment, which have improved survival rates for patients with ISLNM, accurately predicting prognosis remains challenging. This study aimed to develop and validate a nomogram to predict the overall survival (OS) of breast cancer patients with ISLNM but without distant metastasis. The nomogram was designed to incorporate key clinicopathological variables identified through univariable and multivariable analyses, providing a tool for clinicians to estimate prognosis and make personalized therapeutic decisions.
The study retrospectively reviewed medical records of breast cancer patients who underwent surgical treatment at three hospitals in China between December 21, 2012, and June 30, 2020. A total of 345 patients with pathologically confirmed ISLNM and no evidence of distant metastasis were identified. These patients were randomized in a 2:1 ratio into training (n = 231) and validation (n = 114) cohorts. The nomogram was constructed based on clinicopathologic variables identified through univariable and multivariable analyses. The predictive accuracy and discriminative ability of the nomogram were assessed using calibration plots, concordance index (C-index), and risk group stratification.
Univariable analysis revealed that estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+) with Herceptin treatment, and a low axillary lymph node ratio (ALNR) were prognostic factors for better OS. Multivariable analysis confirmed that PR+, HER2+ with Herceptin treatment, and a low ALNR remained independent prognostic factors for better OS. These variables were incorporated into the nomogram to predict the 1-, 3-, and 5-year OS of breast cancer patients with ISLNM.
The C-indexes of the nomogram were 0.737 (95% confidence interval [CI]: 0.660–0.813) and 0.759 (95% CI: 0.636–0.881) for the training and validation cohorts, respectively. Calibration plots demonstrated excellent agreement between the nomogram prediction and actual observation for 3- and 5-year OS but not for 1-year OS in both cohorts. The nomogram also effectively stratified patients into different risk groups.
In the training cohort, the 1-year OS of the low-risk and high-risk subgroups was 98.0% and 86.9%, respectively; the 3-year OS was 87.3% and 57.3%, respectively; and the 5-year OS was 82.8% and 46.8%, respectively. Similar trends were observed in the validation cohort, with significant differences in OS between the low-risk and high-risk subgroups.
The study identified PR status, HER2 status with Herceptin use, and ALNR as independent prognostic factors for OS. Interestingly, while ER status was predictive of prognosis in the univariable analysis, it was not an independent predictor in the multivariable analysis. This finding contrasts with previous studies that suggested both ER and PR are independent prognostic factors. The study also found that HER2-positive patients treated with Herceptin had a better prognosis than HER2-negative patients, highlighting the importance of targeted therapy in improving outcomes.
The ALNR, defined as the ratio of the number of positive lymph nodes to the total number of lymph nodes removed, was found to be a significant prognostic factor. This study is one of the few to explore the prognostic significance of ALNR in breast cancer patients with ISLNM receiving neoadjuvant chemotherapy (NAC). The findings suggest that ALNR may be a superior prognostic factor than traditional pN staging in evaluating disease burden after NAC and tailoring postoperative treatment strategies.
The nomogram developed in this study provides a valuable tool for clinicians to estimate prognosis and make personalized therapeutic decisions for breast cancer patients with ISLNM. By stratifying patients into different risk groups, the nomogram can help identify those who may benefit from more aggressive systemic treatment. However, the study acknowledges limitations due to its retrospective nature and relatively small sample size. The calibration plots did not present an acceptable level of agreement for 1-year OS, and the short duration of follow-up may have impacted the discriminatory and predictive ability of the nomogram. Further prospective studies with larger sample sizes are warranted to validate the new nomogram.
In conclusion, this study established and validated a novel nomogram for predicting the survival of breast cancer patients with ISLNM. The nomogram incorporates key clinicopathological variables and effectively stratifies patients into different risk groups, providing a valuable tool for clinicians to estimate prognosis and make personalized therapeutic decisions. Despite its limitations, the nomogram represents a significant step forward in the management of breast cancer patients with ISLNM.
doi.org/10.1097/CM9.0000000000001755
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