Triple Negative Breast Cancer: An Analysis of the Subtypes and the Effects of Menopausal Status on Invasive Breast Cancer

Abstract

Background: Triple negative breast cancer (TNBC) is a subtype of breast cancer which lacks hormone receptor (HR) expression and HER2 gene amplification and is the most aggressive subtype, with a heterogeneous genetic profile. The aim of this retrospective study was to evaluate the clinical significance of menopausal status in breast cancer cases with TNBC.

Methods: Primary breast cancer patients who underwent curative surgery were enrolled in this retrospective study. A total of 5153 invasive breast cancer cases with Stage I-III were analyzed. The distribution of cases according to the menopausal status and subtypes was investigated and the clinicopathological characteristics and prognosis were compared between pre- and postmenopausal TNBC patients.

Results: TNBC was frequently seen in postmenopausal patients and Luminal B and Luminal/HER2 subtypes were more common in premenopausal patients. There was no difference in DFS in the Luminal A/B and HER2 subtypes, but a significant difference was seen in the TNBC patients. Premenopausal patients with TNBC frequently had an overexpression of the p53 protein, a significantly higher Ki-67 index value, and a higher nuclear grade. A multivariate analysis revealed that menopausal status, nodal status, and tumor size were significant factors for DFS in TNBC cases.

Conclusion: Menopausal status significantly correlates with breast cancer subtypes. TNBC was often seen in postmenopausal patients and these patients tend to have more favorable factors and a better DFS than premenopausal patients. These findings suggest that menopausal status is an important factor for evaluating biology and prognosis in TNBC cases.

Keywords: Ki-67; breast cancer; disease-free survival; menopausal status; triple negative.

Figure 1

DFS according to Menopausal Status in Each Subtype and OS in TNBC. There was no difference in DFS between pre- and postmenopausal patients with the HER2 positive and Luminal A/B subtypes (A,B), but a significant difference (p = 0.01) was seen in patients with TNBC (premenopausal patients had a poorer DFS than postmenopausal patients; (C)). Moreover, postmenopausal patients had a more favorable OS than premenopausal patients, but the difference was not significant.

Figure 1

DFS according to Menopausal Status in Each Subtype and OS in TNBC. There was no difference in DFS between pre- and postmenopausal patients with the HER2 positive and Luminal A/B subtypes (A,B), but a significant difference (p = 0.01) was seen in patients with TNBC (premenopausal patients had a poorer DFS than postmenopausal patients; (C)). Moreover, postmenopausal patients had a more favorable OS than premenopausal patients, but the difference was not significant.

Figure 1

DFS according to Menopausal Status in Each Subtype and OS in TNBC. There was no difference in DFS between pre- and postmenopausal patients with the HER2 positive and Luminal A/B subtypes (A,B), but a significant difference (p = 0.01) was seen in patients with TNBC (premenopausal patients had a poorer DFS than postmenopausal patients; (C)). Moreover, postmenopausal patients had a more favorable OS than premenopausal patients, but the difference was not significant.

Figure 2

DFS according to Menopausal Status and Ki-67 Index Value in TNBC. There was no difference in DFS between the menopausal status in cases with a high Ki-67 index value (≥50%). On the other hand, in the cases with a low Ki-67 index value (<50%), the postmenopausal patients had a significantly higher DFS rate.

Figure 2

DFS according to Menopausal Status and Ki-67 Index Value in TNBC. There was no difference in DFS between the menopausal status in cases with a high Ki-67 index value (≥50%). On the other hand, in the cases with a low Ki-67 index value (<50%), the postmenopausal patients had a significantly higher DFS rate.