Unique Estrogen
Receptor Linked to Metastatic Breast Cancer
Behind the Cancer Headlines®
A new study led by researchers at
"We found that a novel estrogen receptor, termed GPR30,
is linked to breast tumor progression and increased tumor size," says lead
author Edward J. Filardo, PhD, research associate at
Estrogen receptors act like ears on a breast cancer cell; estrogen attaches to the receptor and transmits signals that tell the cell to grow and multiply. Physicians test for receptors to help determine the most appropriate treatment for breast cancer patients. Typically, the more estrogen receptors present, the more likely the patient will respond to hormone therapy, such as tamoxifen.
However, approximately one in four patients that test positive for estrogen receptors do not respond to hormone therapy, prompting scientists to propose that there may be additional types of estrogen receptors that play a role tumor growth. Filardo and co-author Jeffrey Quinn, PhD, first identified GPR30 as a potential alternate estrogen receptor capable of triggering breast cancer cell growth in 2000.
In an effort to further refine the classification of GPR30, researchers in this study analyzed 361 tumor samples from breast cancer patients to compare the distribution patterns of standard estrogen receptors (ER) and GPR30. They examined how the various estrogen receptors associated with each other and their relationship with size of the primary breast tumor, lymph node invasion, and development of metastasis.
Results showed that while the two types of receptors, GPR30 and the standard ERs, were commonly found together, their expression was not interdependent. This was best evidenced by the fact that approximately half of the ER-negative tumors remained positive for GPR30.
"This suggests that tumors traditionally viewed as
being unreceptive to estrogen, may in fact, remain
estrogen responsive," says co-author Edmond Sabo, MD, pathologist at
Researchers also found that GPR30 was positively associated with tumor size, and that primary tumors from patients with metastatic disease were twice as likely to express GPR30.
Alternatively, an inverse relationship was measured between the standard estrogen receptors (ERƒÑ and ERƒÒ) and tumor size, and no significant association was found between receptor expression and the presence of metastatic disease.
"Our data indicates that GPR30 promotes tumor growth and is linked to metastatic disease, but also evidences GPR30's autonomy from the standard estrogen receptors," says Filardo. "It strengthens the concept that GPR30 and standard estrogen receptors promote distinct biological responses and invokes a new paradigm regarding our current understanding of breast cancer biology."
Interestingly, although GPR30 was strongly associated with the development of metastatic disease, there was not a connection between the presence of GPR30 and if breast cancer cells had invaded the lymph nodes of a patient.
"Further research is needed to determine if there is a relationship between GPR30 and lymph node invasion," says Filardo. "Given that tumor size and lymph node invasion are well-known predictors of metastases, future studies will focus on determining how cells that test positive for GPR30 spread throughout the body."
SOURCE:
Clinical Cancer
Research,