Advancements in Targeted Therapy and Immunotherapy for Human Breast Cancer

Breast cancer is the most frequent malignancy and the second most lethal cancer among women, according to the Centers for Disease Control and Prevention, despite recent medicinal advances.¹ Breast cancer is expected to afflict 2,811,550 women in the United States in 2021, resulting in the deaths of 43,600 people. Breast cancer, like other malignancies, has inter- and intratumor heterogeneity. The TNM staging method, the histopathologic categorization, and the tumor grade all reveal intertumor heterogeneity in different people. The breast cancer clinical staging system is based on tumor size, lymph node involvement, and distant metastases and ranges from I to IV. Histologic type and histologic grade, which consider the tumor’s development pattern and degree of differentiation, respectively, are used to assess the morphologic heterogeneity of breast carcinomas.¹

Invasive ductal carcinoma (50%-75%) and invasive lobular carcinoma (5%-15%) are the 2 most common histologic forms of breast cancer, with the rest showing mixed or other unusual histology.¹ The tumor grade, the other morphologic heterogeneity, is determined by 3 architectural features: tubule or gland development, nuclear pleomorphism, and mitotic rate.¹ Conversely, breast cancer intratumor heterogeneity can be seen at the morphologic, genomic, transcriptomic, and proteomic levels and is caused by the presence of different cellular phenotypes inside the same tumor.¹ Breast carcinomas exhibit the aforementioned heterogeneities, which have a negative impact on diagnosis, prognosis, and treatment. Several advancements have been made in the treatment of patients with breast cancer to improve their survival and slow tumor growth. Targeted medicines and combination therapies have been approved, with the first immunotherapy in conjunction with chemotherapy for metastatic triple-negative breast cancer being approved in 2019.¹

In targeted therapy, breast tumors that create too much of, or overexpress, a protein like HER2 may then be treated with biological response medicines in addition to chemotherapy treatments. If the HER2 gene is found in cancer cells by laboratory testing, the drugs may help shut it down, cutting the cancer cells off from their source of energy.² Breast cancer targeted therapy is frequently used in conjunction with other treatments, such as chemotherapy, to help control the spread of disease or avoid recurrence.²

In immunotherapy, checkpoint inhibitors may be an option for treating patients with breast cancer cells that have certain genetic characteristics.¹ For patients with inoperable, advanced triple-negative breast cancer that expresses the protein receptor PD-L1, the US Food and Drug Administration has approved the use of a checkpoint inhibitor in combination with a specific chemotherapeutic treatment.¹ Checkpoint inhibitors function by preventing receptors like PD-L1 from being activated.¹

More progress can be made, however, if a more tailored strategy is taken to address intra- and intertumor heterogeneities, and better biomarkers are identified to make personalization more therapeutically practical. More fundamental, preclinical, translational, and clinical research is needed to improve patients’ responses by further categorizing them based on tumor phenotypic and genotypic characteristics.

References

1. Bou-Dargham M, Draughon S, Cantrell V, et al. Advancements in human breast cancer targeted therapy and immunotherapy. J Cancer. 2021;12:6949-6963.
2. Cancer Treatment Centers of America. Targeted therapy for breast cancer. Updated September 21, 2021. www.cancercenter.com/cancer-types/breast-cancer/treatments/targeted-therapy. Accessed December 12, 2021.