Researchers at Weill Cornell Medical College, New York, have found the hormone estrogen plays a major role in about half of all prostate cancers. Their findings were published in the May 27 online edition of the Journal of the National Cancer Institute.

They have found that the estrogen-linked signaling helps drive a discrete and aggressive form of prostate cancer caused by a chromosomal translocation. This mutation causes the fusion of two genes.

The senior author, Dr. Mark A. Rubin, professor of pathology and laboratory medicine and vice chair for experimental pathology at Weill Cornell Medical College said “Fifty percent of prostate cancers harbor a common recurrent gene fusion, and we believe that this confers a more aggressive nature to these tumors. Interfering with this gene fusion — or its downstream molecular pathways — will be crucial in the search for drugs that fight the disease. Based on our new data, we now believe that inhibiting estrogen may be one way of doing so.”

Dr. Rubin first discovered and described the common fusions between the TMPRSS2 and ETS family member genes subset of prostate cancer in the journal Science in 2005. “The discovery showed that these malignancies occur after an androgen (male hormone)-dependent gene fuses with an oncogene — a type of gene that causes cancer,” he explains.

It is common knowledge that male hormones help spur prostate cancer, thus a first line treatment for prostate cancer recurrences is often androgen-deprivation therapy (ADT). Despite the ADT, prostate cancer usually will continue to progress. This simple reality clearly indicated that there are other molecular pathways at work, pathways we need to study.

“So, we wanted to learn more — what is the genetic and molecular ‘fingerprint’ of this aggressive subset of prostate tumor” Dr. Rubin said.

Four hundred and fifty five (455) prostate cancer samples from trials in Sweden and the United States were analyzed. The analysis was the largest gene-expression microarray ever performed in prostate cancer research. The work amassed information on more than 6,000 genes. “This allowed us to obtain a robust, 87-gene expression ‘signature’ that distinguishes fusion-positive TMPRSS2-ERG cancers from other prostate malignancies.” said Dr. Rubin.

The work yielded a surprise: that estrogen-dependent molecular pathways appear to play a crucial role in regulating (and encouraging) this aggressive form of prostate cancer. “Now, we show for the first time that this natural estrogen can stimulate the production of the cancer-linked TMPRSS2-ERG transcript, via the estrogen receptor (ER)-alpha and ER-beta. These receptors are found on the surface of some prostate cancer cells,” Dr. Rubin explains.

The finding could have significant implications including drug development for prostate cancer. According to Dr. Rubin, “We now believe that agents that dampen estrogen activity (ER-beta antagonists) could inhibit fusion-positive prostate cancers. Alternatively, any intervention that boosts estrogen activity (ER-alpha) might also give a boost to these aggressive malignancies.”

Additional, this research calls into question the use of any estrogen containing supplement as well as the use of estrogen patches as an androgen blockade (ADT). Again, speak to your doctor, discuss this finding before you decide to use estrogen related therapy. Also, remember, estrogen does increase your risk for breast cancer, and yes, men do get breast cancer.

Joel T Nowak MA, MSW