The Prognostic Impact of Synchronous Ipsilateral Multiple Breast Cancer: Survival Outcomes according to the Eighth American Joint Committee on Cancer Staging and Molecular Subtype

Abstract

Background: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer.

Methods: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012.

Results: Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS.

Conclusions: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1-2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.

Keywords: Breast neoplasms; Disease-free survival; Molecular subtype; Multiplicity; Prognosis.

Fig. 1.

The Kaplan-Meier curves for disease-free survival in patients with single and multiple masses according to T category. (A) Survival curve of all patients. (B) Survival curve of the T1 category. (C) Survival curve of the T2 category. (D) Survival curve of the T3 category. A significant difference is observed in the T1 category.

Fig. 2.

The Kaplan-Meier survival curves for disease-free survival of patients with single and multiple masses in different Anatomic and prognostic staging groups. (A) Survival curve of the anatomic staging group I. (B) Survival curve of the prognostic staging group IA. (C) Survival curve of the prognostic staging group IB. The anatomic staging group I and prognostic staging group IA show a significant difference.

Fig. 3.

Molecular subgroup analysis of the association between multiplicity and disease-free survival. The Kaplan-Meier survival curve of luminal A (A), human epidermal growth factor receptor 2 (HER2)–positive (B), luminal B1 (C), luminal B2 (D), and triple-negative groups (E). The difference is significant in patients of the luminal A and HER2-positive groups.

Fig. 4.

The Kaplan-Meier survival curves for disease-free survival in patients with T1–2 N0 M0, hormone receptor–positive, and human epidermal growth factor receptor 2 (HER2)–negative cancer. Comparison between patients with single mass and multiple masses.