A systematic study on phenotypical characteristics of invasive breast carcinoma and surrounding ductal carcinoma in situ in multifocal breast cancers

Current understanding and distinct features of multifocal and multicentric breast cancers

“…The heterogeneity of ER, PR, and HER2 ranged from 0.0% to 18.0%, 6.0% to 11.1%, and 0.0% to 6.0%, respectively. [21][22][23][24]28 Several studies investigated the heterogeneity of axillary lymph node metastases and of the genetic profile of MF/MC breast cancers. Boros et al determined that axillary lymph node metastases could also be heterogeneous (e.g., regarding histological type) from the foci in the breast, regardless of whether the foci were heterogeneous or homogeneous.…”

“…The definitions of MF and MC breast cancers are inconsistent in the literature, especially regarding the location of foci in breast quadrants, the distance between foci, and the invasiveness of the foci (Table 1). Most authors accept that MF and MC breast cancers involve multiple distinct tumors in the same and different breast quadrants, respectively 3,5–7,12,21,28 . Some studies combine MF and MC cases (typically referred to as MMBC) and define the diseases as two or more invasive carcinomas that are separated by benign tissue, regardless of whether they are in the same or different breast quadrants 1,4,9,11,20,35 .…”

“…However, a wide range of distances between tumors has been reported, ranging from 1 to 5 cm 8,35,37 . Furthermore, most MF/MC cancers are defined as exclusively invasive carcinomas, including ductal and/or lobular breast cancers; however, some studies also included in situ lesions 5,7,8,12,16,20,28,35,37,38 . In addition to the non‐standardized criteria for MF/MC breast cancers, conventional mammogram and gross pathological examination seem to be unable to detect all MF/MC cancers 10,36 .…”

“…It remains unclear whether the multiple foci of MF/MC breast cancers develop simultaneously and independently or whether they originate from one primary tumor 20,22,23,25,27–29 . A subsequent question then arises: whether the cancer cells from these foci are heterogeneous or homogeneous.…”

“…In addition, recent investigations have focused on understanding the distinct biological differences between MF/MC and UF breast cancers that could elucidate the underlying causes of the increased aggressiveness and poorer prognosis associated with MF/MC cancers to aid in the selection of better treatment plans for these patients. Some studies have focused on studying the clonality of multiple MF/MC lesions via the homogeneity and heterogeneity of their grades, histological types, molecular subtypes, and genetic profiles and the impact of these features on the tumors' aggressiveness and patient prognosis 20–28 . Other studies have investigated the effects of MF/MC subtypes on the expression of molecular biomarkers, genes of canonical cancer pathways, and cancer stem cell biomarkers 8,25,27,29–34 .…”