Creating a free account will enable you to subscribe to our daily and weekly email newsletters, as well as customize your reading experience to show only the categories most relevant to you.
Signing up only take a few minutes, so why not give it a try and see what you've been missing out on.
About three-quarters of breast cancers, the most common cancer in women in the U.S., are estrogen hormone dependent. Patients with this type of breast cancer are initially treated with drugs that block estrogen, such as Tamoxifen. However, one-third to half of these patients eventually become resistant to this treatment. For these patients and those whose tumors are not estrogen dependent to begin with, there are no alternative hormone treatment options.
In a new study directed by Tan A. Ince, M.D., Ph.D., associate professor of pathology at the University of Miami Miller School of Medicine and member of the Sylvester Comprehensive Cancer Center, researchers have developed a new breast cancer classification system that shifts the focus away from genetic mutations, a common approach of mainstream cancer research, but one that has been less effective than first imagined. The findings of this study, published online in the Journal of Clinical Investigation, offer a new approach to treating breast cancer, by using normal tissue and hormone receptors as a guideline to determine effective therapies.
In recent years, scientists have concentrated on identifying genetic mutations within breast cancers with the goal of developing a targeted therapy for each mutation. The clinical problem is that the average breast cancer has more than 200 mutations, and most patients share few, if any, commonalities. Researchers have believed that tumors differ from normal tissue, but Ince and the other team members found that not to be the case. "Everyone has just been studying tumors," said Ince. "They haven't been comparing normal tissue and tumors to this degree."
Ince, working with first author of the study Sandro Santagata, M.D., Ph.D., from Brigham and Women's Hospital, Harvard Medical School, and a team of researchers from both institutions found that about three-quarters of estrogen-dependent tumors and two-thirds of estrogen-independent tumors expressed hormone receptors for vitamin D and testosterone. The researchers showed that treatment of breast cancer cells with hormones that activate vitamin D and testosterone receptors reduced the growth of cancer cells. In addition, these hormones increased the efficacy of standard chemotherapy.
"These findings offer the possibility of expanding hormone therapy to patients who are otherwise treated with chemotherapy," said Ince, who is also a member of the Braman Family Breast Cancer Institute at Sylvester. With further work, he theorizes that it may also allow using lower doses of chemotherapy with the same effect and serve as a useful prognosticator.
Ince, who is a breast pathologist and cancer pharmacologist, began this study more than 10 years ago with funding from the Breast Cancer Research Foundation and meticulously described normal cell types in human breast tissue. Following on this lead, the research group eventually studied more than 15,000 normal breast cells and discovered 11 previously undefined normal cell subtypes. They grouped these 11 normal breast cell types into four new hormonal differentiation groups (HR 0, 1, 2, 3), which were characterized by vitamin D, androgen and estrogen hormone receptor expression.
In evolutionary biology, the ancestry of each species is determined based on key features that are inherited. Using this evolutionary principle, Ince constructed a tree of life for normal human breast cells. Next, the researchers took this information and compared it against 3,157 human breast tumors of patients and found that each patient's tumor could be placed precisely in this tree. Moreover, the tumors could also be grouped into four new hormonal differentiation groups (HR 0, 1, 2, 3), which were characterized by vitamin D, androgen and estrogen hormone receptor expression.
Importantly, the patients in different HR groups had different survival rates and responses to hormone treatments. The researchers found that nearly half of the breast cancer patients were in the HR3 group, meaning these patients' tumors had all three hormone receptors (estrogen, testosterone and vitamin D). Patients with these triple HR-positive tumors (HR3) were up to seven times more likely to survive compared with patients with triple HR-negative tumors (HR0). Compared with many existing genetic/molecular tests with 2-3 fold survival differences, "this cell-type based approach can become a powerful new tool in predicting patient outcomes," said Ince.
Since none of the existing genetic tests identify the HR0-3 subgroups, this will require translating the findings in this study into a clinically available new test. Additionally, description of these HR cell types raises the possibility of cell-targeted therapies. For example, with further work these findings could be translated into the clinic as triple hormone therapy for HR3 tumors. Hence, these studies may lead to cell-based diagnosis and treatment options as an alternative to gene-based approaches.
In this study the researchers also found that some of the standard breast tumor subtypes previously identified, called basal-like carcinoma, have been labeled erroneously due to incorrect classification of normal cell types.
Follow-up studies are underway in Ince's laboratory in collaboration with other researchers at Sylvester to translate these findings to the clinic.
This research was mainly supported with grants funding Ince’s laboratory from the Breast Cancer Research Foundation, founded by Evelyn Lauder, Play for P.I.N.K. and Sylvester Comprehensive Cancer Center. In addition, grants from the National Cancer Institute, Department of Health and Human Services, GlaxoSmithKline, National Institutes of Health, V Foundation for Cancer Research, Dana-Farber Cancer Institute Women’s Cancers Program, and Claudia Adams Barr Foundation were used.
University of Miami Miller School of Medicine
Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our Breast Cancer category page for the latest news on this subject.
Please use one of the following formats to cite this article in your essay, paper or report:
University of Miami Miller School of Medicine. "Researchers discover new hormone receptors to target when treating breast cancer." Medical News Today. MediLexicon, Intl., 27 Jan. 2014. Web.
7 Mar. 2014. <http://www.medicalnewstoday.com/releases/271634>
University of Miami Miller School of Medicine. (2014, January 27). "Researchers discover new hormone receptors to target when treating breast cancer." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
If you write about specific medications, operations, or procedures please do not name healthcare professionals by name.
For any corrections of factual information, or to contact our editorial team, please use our feedback form. Please send any medical news or health news press releases to:
Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.
This page was printed from: http://www.medicalnewstoday.com/releases/271634.php
Visit www.medicalnewstoday.com for medical news and health news headlines posted throughout the day, every day.
© 2004-2014 All rights reserved. MNT (logo) is the registered trade mark of MediLexicon International Limited.