Immune system and tumor microenvironment in early-stage breast cancer: different mechanisms for early recurrence after mastectomy and chemotherapy on ductal and lobular types [version 2; peer review: 2 approved]

Abstract

Background: The most common type of breast cancer is the ductal type (IDC), followed by lobular type (ILC). Surgery is the main therapy for early-stage breast cancer. Adjuvant chemotherapy might be given to those at high risk of recurrence. We aimed to determine the mechanisms in early local recurrence in both types. Methods: An observational case-controlled study was used. Early-stage IDC and ILC patients who received modified radical mastectomy (MRM) and adjuvant taxan and anthracycline base chemotherapy had recurrence within two years. We examined vimentin, α-smooth muscle actin (SMA), matrix metalloproteinase (MMP1), platelet-derived growth factor (PDGF), and clustered differentiation (CD95) Results: In the ductal type group, there were 25 samples revealing local recurrence and 25 samples that did not recur. The lobular type group comprised six participants who did not have a recurrence, while seven subjects had a recurrence. There were significant differences in the expression of vimentin (p = 0.000 and 0.021, respectively), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) in ductal and lobular cancer types, respectively. MMP1 (p = 0.000) and α-SMA (p = 0.000) only showed a significant difference in the ductal type. The pathway analysis showed that in the ductal type, the mechanism of recurrence was enabled by two factors: α-SMA and CD95. Meanwhile, for the lobular type, the recurrence mechanism was through the CD95 pathway. Conclusions: The tumor microenvironment and immune system both affect recurrence in IDC, whereas the immune system is more important in ILC. This study suggests that immune system enhancement may be an option for treating cancer.

Keywords

• Ductal Carcinoma
• Lobular Carcinoma
• Local Recurrence
• Early Breast Carcinoma
• eng