Multifocal/multicentric breast cancer: Does each focus matter?

Abstract

Background: Multifocal (MF) and multicentric (MC) breast cancer cases have been increasingly diagnosed owing to the extensive use of improved preoperative breast imaging. The current tumor-node-metastasis staging system uses the dimension of the largest tumor and recommends reporting the pathological features of the largest tumor in MF/MC breast cancers.Aim: This study aimed to explore whether the largest or aggregate dimensions of MF and MC breast cancers can better predict tumor behavior. We also attempted to study the histological and biological heterogeneities of separate foci in MF and MC breast cancers to determine whether it was necessary to examine each lesion. Methods:We retrospectively analyzed 121 patients with MF/MC (103 with MF and 18 with MC) breast cancers and 484 patients with unifocal breast cancer who were treated at the First Affiliated Hospital of Nanjing Medical University.Two methods were used to record the T stage (using the dimensions of the largest lesion and aggregate dimensions of all lesions). The histological grade, immunohistochemical parameters, and molecular subtypes of the largest lesion and other lesions in MF/MC breast cancers were studied to assess intertumoral heterogeneity. Results:The use of aggregate dimensions upstaged 63 patients with MF/MC breast cancers to a more advanced stage and removed the independent effect of cancer multiplicity on lymph node positivity compared with the use of the largest dimension. Mismatches were found in the pathological type (9.9%), histological grade (4.1%), and molecular subtype (8.3%) among different foci. Conclusion:The tendency of MF/MC breast tumors to metastasize may be related to tumor load, which can be better predicted by the aggregate dimensions of all foci. The use of the current staging systems may require further evaluation and modification. Intertumoral heterogeneity indicates the necessity for pathological and immunohistochemical assessments of each lesion in patients with MF/MC breast cancers.

Characteristics of multifocality/multicentricity in breast cancer and its effect on axillary lymph node metastasis

“…In our study, MF/ MC, T sum , T max , LVI, PNI and invasive lobular histology had a significant effect on ALNM in univariate analysis (Table 3). Previous studies also show that multiplicity, T sum , T max , LVI and histological grade are associated with lymph node metastasis [5,17,29]. In our multivariate analyses, MF/MC had no significant effect on ALNM in either model using T sum or T max .…”

“…While MF/MC had a significant effect on ALNM in the model using T max , it was observed that this effect disappeared when T sum was used [17]. In Tong et al's study, it was observed that MF/MC lost its significant effect on ALNM when T stage was calculated based on T sum [5]. In our study, MF/ MC, T sum , T max , LVI, PNI and invasive lobular histology had a significant effect on ALNM in univariate analysis (Table 3).…”

“…Therefore, some of the tumors considered MF may be MC tumors originating from different clones. In addition, it has been shown that there may be mismatches in tumors defined as MF in terms of histopathological type, histological grade, receptor status and molecular subtypes, as in MC tumors [5,13]. The occurrence of mismatches in MF tumors reduces the reliability of these definitions based on tumor location.…”

“…However, in this method, ambiguity may occur because lesions in different quadrants may be very close to each other. For this reason, some authors use the definition of MC if there is a 90° angle between the lesions and the nipple [5]. With the increased use of magnetic resonance imaging, the frequency of MF/MC tumors has increased [6,7].…”

“…Therefore, information about the behavior of multiple tumors is quite narrow compared to unifocal tumors. There is no full consensus on the approach to MF/MC tumors [5]. In this study, we aimed to compare the clinical characteristics of MF and MC tumors, and especially their tendency to lymph node metastasis, among themselves and with UF tumors.…”