Double Negative Breast Cancer

What is double negative breast cancer? Double negative breast cancer refers to tumors that lack the expression of estrogen (ER) and progesterone receptors (PR). Double negative cancers comprise 18-25% of breast tumors.

What is the clinical significance of double negative breast cancer?

Estrogen and progesterone receptors are immunohistochemical markers historically used to subtype breast cancer. 

Tumors with estrogen receptors are well-differentiated, less aggressive, and respond well to surgical management. They also respond better to anti-estrogen and aromatase inhibitors, such as tamoxifen and anastrozole, than estrogen receptor negative tumors.

Progesterone receptors in breast cancer are rarely present in tumors that lack estrogen receptors. Tumors with estrogen receptors may or may not have progesterone receptors. 

Double positive tumors (ER+PR+) are more responsive to endocrine therapy. Double negative tumors (ER-PR-) do not respond to endocrine therapy, are more aggressive, have a higher recurrence rate, and lower survival rate.

Since the subsequent discovery of the human epidermal growth factor receptor 2 (HER2), there is an additional marker that can be used to create targeted treatment in double negative tumors. 

HER2+ tumors (ER-PR-HER2+) can be treated with anthracycline-based chemotherapy, such as doxorubicin, but have a poorer prognosis than ER+PR+. 

HER2- tumors (ER-PR-HER-2), also known as triple negative tumors, are aggressive, poorly differentiated, have the poorest prognosis, and are the least likely to respond to hormone- based chemotherapy.

Source: Dai, X., Xiang, L., Li, T., & Bai, Z. (2016). Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. Journal of Cancer, 7(10), 1281–1294.