HRT With Estrogen Added Raises Breast Cancer Risk

According to a study published March 15 in the Journal of the National Cancer Institute, thoughts about how estrogen alone or estrogen in addition to progestin influence the risk of developing breast cancer has considerably changed in the past 10 years due to results from the Women's Health Initiative (WHI) randomized placebo-controlled hormone therapy trials, and from large prospective cohort studies.

At present, concerns are still being raised regarding hormone therapy-induce breast cancer risk, even though the therapy is used for menopausal symptoms by millions of women. Furthermore, researchers are still not clear on the effects of estrogen in addition to progestin vs estrogen alone on breast cancer.

Rowan T. Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet Anderson, Ph.D., at Fred Hutchinson Cancer Research Center, examined data from 2 randomized, placebo-controlled clinical trials carried out in the WHI, in order to examine the effects of estrogen in addition progestin vs estrogen alone on the risk of developing breast cancer.

The first study assessed estrogen alone in post-menopausal women with prior hysterectomy, and the second study assessed estrogen plus progestin in post-menopausal women who had not undergone hysterectomy.

The researchers found that the risk of developing breast cancer was statistically considerably increased by using estrogen in addition to progestin, while the risk was statistically significantly decreased in post-menopausal women with previous hysterectomy who took estrogen alone.

According to the researchers, findings from the randomized human trial and those from the majority of observational studies differ, with the observational studies indicating that both estrogen alone and estrogen plus progestin increase the risk of developing breast cancer.

The researchers explain that:

"An imbalance in the use of mammography with greater screening for hormone users could explain some of the increase in breast cancer incidence with estrogen alone seen in cohort studies because screened populations have more cancers detected than unscreened populations."

Even though the authors do not fully understand the mechanisms underlying the different effects of estrogen alone and estrogen in addition to progestin, they said:

"The findings in the clinic, taken together with preclinical evidence, indicate that many breast cancers in post-menopausal women can survive only a limited range of estrogen exposures."

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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Surprising Connection Between Breast Cancer Cells And Surrounding Tissue

Rensselaer Polytechnic Institute Biologist Lee Ligon has found a previously unknown connection between breast cancer tumor cells and the surrounding healthy tissue. The results provide new information on the earliest stages of breast cancer metastasis.

The results were published in the journal PLoS One, in a paper titled " Cadherin-23 Mediates Heterotypic Cell-Cell Adhesion between Breast Cancer Epithelial Cells and Fibroblasts." Ligon was joined in the research by Rensselaer doctoral student Maria Apostolopoulou. The research was funded by the American Cancer Society.

The research shows that a specialized type of molecule called Cadherin-23 can be found in and around breast cancer tumors. The molecule, which had never been associated with breast tissue or cancer, helps connect cancerous tumor cells to its neighboring healthy tissue, called the stroma.

"Something happens once cancerous cells enter the stroma and the cancer can very quickly become invasive," Ligon said. "Pathologists studying cancerous tissues have often noted that tumor cells make contact with the cells in the stroma, but they assumed the connections were unimportant."

Ligon and her team sought to uncover exactly what molecules were involved in attaching the tumor cells to the surrounding tissue to determine if those initial points of contact play a role in the progression of cancer through the body.

In the human breast, tumors most often originate in what are known as epithelial tissues. These tissues are made up of a specialized type of cell called epithelial cells. Epithelial cells line the interior of many structures and organs within the human body. In the breast, they line the interior of milk ducts. When epithelial cells start to divide uncontrollably, they eventually break out of the duct and literally spill into the surround tissue or stroma. The stroma is comprised of cells called fibroblasts and extracellular material such as collagen fibers. In many cases, the invading cancerous epithelial cells will glom onto nearby fibroblasts in the stroma.

Ligon and Apostolopoulou worked to pick apart how the epithelial cells attached themselves to the fibroblasts. One of the primary tools the body uses to glue cells together is a family of molecules called cadherins. In the human genome there are over 80 different cadherin family members. In most cases, cadherins stick two cells of the same type together. In the case of the breast cancer tumor cells and fibroblasts, two very different cells were sticking together. Ligon sought to determine which cadherins were involved in this odd interaction.

At first, their findings were not surprising. They found cadherins associated with epithelial cells as well as cadherins associated with fibroblasts. It was the discovery of the highly specialized and unusual cadherin, Cadherin-23, that really surprised them, according to Ligon.

"Cadherin-23 has never before been associated with cancer," Ligon said. "In fact, it has previously only been shown in the sophisticated inner workings of the ear and retina."

It is still largely unknown what happens once the cells have made a connection, but the appearance of Cadherin-23 in elevated levels in cancerous tissues suggests that it might play a real role in the earliest stages of metastasis, according to Ligon. Cadherin-23 is a new and potentially very important new component in the progression of cancer for scientists to investigate, she said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject. Ligon is a member of the Center for Biotechnology and Interdisciplinary Studies and the Department of Biology at Rensselaer.
Published March 14, 2012
Rensselaer Polytechnic Institute Please use one of the following formats to cite this article in your essay, paper or report:

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