The Relationship of Reproductive Risk Factors and Histologic Patterns with Molecular Subtypes of Breast Cancer

Abstract

Background: The close link between molecular subtypes and different histological types of breast cancer has recently been taken into consideration. Objectives: The present study aimed at evaluating the reproductive risk factors in relation to molecular subtypes and histological features of breast cancer in a large group of Iranian patients. Methods: This historical cohort study was conducted on 1988 women diagnosed as different subtypes of breast cancers recruited in 2011 to 2016 from cancer research center in Shahid Beheshti University of Medical Sciences, Iran. Data on molecular markers were obtained from hospital files obtaining originally from immunohistochemical staining technique. Based on the pathological reports in hospital recorded files, the histological patterns of the cancer was also determined. The patients were followed for 5 years to assess the 5-year survival and compared the survival across the different molecular subtypes. Results: The highest mean age was found for the group with HER2-overexpression and the lowest for those with luminal A (P = 0.045). The most and the least tumor size was revealed in triple negative group and luminal A group, respectively (P = 0.035). The mean number of lymph nodes involved in breast cancer was significantly higher in luminal B subtypes compared to luminal A and triple negative subtypes (P = 0.004). The tumor stages III-IV were found in 31.6% of patients with luminal A subtype, 42.2% in patients with luminal B, 34.3% in patients with HER2 overexpression, and 26.0% in those with triple negative subtype (P = 0.006). The histological patterns of the tumor were powerfully different in terms of the molecular subtypes of tumor so that luminal A subtype was found more in ILC pattern, luminal B subtype was found more in DCIS pattern, HER2-overexpression subtype was revealed more in DCIS pattern, and triple negative subtype was found more in IDC pattern. Based on the long-term survival analysis, 5-year survival was found to be 98.3% in luminal A group, 98.3% in luminal B group, 100% in HER2 overexpression, and 98.1% in triple negative with no difference between different molecular subtypes. The lowest 5-year survival was found in the patients aged higher than 30 years at first pregnancy and live birth with triple negative subtype (survival rate of 75.0%). The long-term survival was adversely associated with the tumor stage but independent to tumor molecular subtypes. Conclusions: Age at first live birth, tumor size, lymph node involvement, tumor stage, and histological pattern of breast cancer are linked to its molecular subtype. The lower long-term survival of breast cancer can be predicted by advanced age (especially in triple negative subtype) and by higher tumor stage independent to molecular subtype.