A modified molecular typing approach for breast cancer based on immunohistochemical staining

Introduction: Anti-HER2 antibody drug conjugates (ADCs) have demonstrated positive results in the treatment of breast cancer with HER2 low expression; however, traditional molecular typing does not evaluate HER2 low expression. Therefore, modified methods need to be designed to promote the use of ADCs for breast cancer treatment. This study propose a modified molecular typing approach for breast cancer based on immunohistochemical (IHC) staining of estrogen receptor (ER), progesterone receptor (PR), and HER2 to guide the application of ADCs for the treatment of breast cancer with low HER2 expression. Methods According to the classification criteria for the modified molecular typing based only on IHC staining of ER, PR, and HER2 status, 1448 breast cancer specimens were divided into luminal HER2 positive (LH+); luminal HER2 low positive (LH±); luminal HER2 negative (LH−); non-luminal HER2 positive (NLH+); non-luminal HER2 low positive (NLH±); and non luminal HER2 negative (NLH−). Results Among 1448 breast cancer specimens: 7.8% (113/1448) were LH+; 51.2% (741/1448) LH±; 16.5% (238/1448) were LH−; 10.4% (151/1448) were NLH+; 7.5% (109/1448) were NLH±; and 6.6% (96/1448) were NLH−. Significant differences were identified in the age at onset, lymphatic metastasis, TNM stage, and Ki67 index among the six molecular types of breast cancer according to the modified molecular typing approach. Conclusions Based only on IHC staining of ER, PR, and HER2 status, this study classifies breast tumors with low HER2 expression as an independent molecular subtype and proposes a modified molecular typing approach to divide breast cancer into six types, including luminal HER2+, luminal HER2 low positive, luminal HER2−, non-luminal HER2+, non-luminal HER2 low positive, and non-luminal HER2−. This molecular typing approach not only better distinguishes the molecular and biological characteristics of different molecular types of breast cancer, but it also guides the application of ADCs for breast cancer treatment.