The Complex Role of Hormones in Breast Cancer Development and Treatment: A View from the Experts
Report of BCRF's 2010 Symposium and Scientific Retreat
With an all-star panel consisting of BCRF's Executive Board of Scientific Advisors and the 2010 Jill Rose Awardee, this year's public Symposium focused on The Many Faces of Hormones and Breast Cancer: Expert Views of Causation, Treatment and Prevention.
The experts traced the early path of treatments for hormone-receptor-positive breast cancer, which is the most frequently occurring type of breast cancer, continuing on to new lines of scientific inquiry emphasizing individualized treatment and preventive care. This signature event brought together a breast cancer brain trust, including 140 of the 172 BCRF 2010-2011 grantees, to help an overflow audience of more than 500 guests get to the bottom of hormones - specifically estrogen - and breast cancer and what people can do to minimize risk and maximize treatment options. The scientists reminded the audience that the presence of estrogen in itself is not a risk factor for breast cancer, but that about 80% of breast cancers express the estrogen receptor, also known as being "estrogen receptor positive" (ER+), whose growth is fueled by estrogen.
At the panel's center was Angela Hartley Brodie, PhD (Professor of Pharmacology and Experimental Therapeutics at the University of Maryland), who received the 2010 Jill Rose Award for Distinguished Scientific Achievement, in recognition of her seminal research in the development of aromatase inhibitors, drugs that stop the production of estrogen.
Joining her on the panel from BCRF's Executive Board were BCRF's Scientific Director, Larry Norton, MD, Director of Breast Cancer Programs at Memorial Sloan-Kettering Cancer Center; Nancy Davidson, MD, Director of the University of Pittsburgh Cancer Institute; Peter Greenwald, MD, Dr.PH, Director of the Division of Cancer Prevention and Control at the National Cancer Institute; and Gabriel Hortobagyi, MD, Chairman of the Department of Breast Medical Oncology at the University of Texas, MD Anderson Cancer Center. Clifford Hudis, MD, BCRF Scientific Advisory Committee Chair and Chief of Breast Cancer Medicine at Memorial Sloan-Kettering Cancer Center, moderated the lively presentations.
In the 1960s, when Dr. Brodie began her research, very little was known about the relationship between estrogen and breast cancer. Scientists knew that there was a connection; Dr. Hortobagyi provided the historical example dating to the 1890s, when it was noted that surgical removal of ovaries of young breast cancer patients seemed to "cure" some of these women of the disease.
Building on later work that elucidated more precisely the link between estrogen and breast cancer, Dr. Brodie's investigations spurred the development of aromatase inhibitors, used in post-menopausal women with breast cancer to stop the production of estrogen. Thanks to her work, there are three aromatase inhibitors on the market today and they are used to both treat breast cancer and prevent its return after surgery.
They may even have a role in prevention and research studies exploring this are underway. Dr. Brodie continues to focus on resistance to the aromatase inhibitors, since as many as one-third of breast cancer patients do not respond to hormone therapy and a significant percentage of ER+ tumors eventually become less responsive.
Linking hormone therapy, which was the first "targeted" treatment, to newer targeted therapies directed to specific characteristics of cancer cells beyond the estrogen receptor, Drs. Hortobagyi and Davidson spoke about their related work. The general guideline for treating women with ER+ breast cancer calls for tamoxifen when they are pre-menopausal and aromatase inhibitors after menopause.
This is a good example of the specificity that researchers have been able to achieve; however, they have not yet reached the ultimate goal of truly individualized therapy which might include patient-specific treatment selection based not only on the characteristics of the tumor but also on other factors related to the patient as a whole. Dr. Davidson then spoke of the need to address challenges facing survivors who have to confront not only the possibility of their cancer's recurrence and metastasis but also the long-term effects of therapeutics, such as chemo- or radiation therapy. Hormone therapies are typically associated with fewer side effects but studies continue to find even safer ways to use them.
Dr. Greenwald shared with the audience his expertise on cancer prevention, telling them that "breast cancer prevention starts with your life habits, including diet and exercise." He explained that data from the first generation of prevention studies showed that lifestyle changes, such as weight loss and reduced consumption of alcohol, lower the risk of developing cancer. With respect to weight, studies have shown that obesity increases estrogen and inflammation levels and therefore also increases the risk of breast cancer. As far as environmental factors that have been attributed to the incidence of breast cancer, Dr. Greenwald pointed out that it is very difficult to measure the level of toxins in a population, so direct cause and effect has not yet been demonstrated.
The Symposium concluded with a lively interchange with the audience, panelists, and many of the BCRF grantees.
Part of the discussion clarified the distinction between hormonal treatment for breast cancer, which works by blocking or lowering estrogen levels in the body, and hormone replacement therapy (HRT) after menopause, use of which has fallen off since clinical trials demonstrated that the estrogen in HRT can increase the risk of breast cancer development but also did not provide many of the benefits people thought it would.
"Cancer is complex but has an Achilles heel, and it is our job to find its weaknesses and exploit them," summarized Dr. Norton. "Are there easy answers? No. Are there hints? Absolutely!"
The enthusiasm at the Symposium matched the energy at the private Scientific Retreat for BCRF researchers that took place the day before. The annual Retreat followed a "think tank" format, and researchers participated in one of six sessions: Biomarkers; Cancer Stem Cells and Cancer/Stroma Interactions; Therapeutic Targets/Targeted Therapeutics; Cancer Susceptibility Genes; Molecular Classification, Prognostication and Prediction; and Prevention and Survivorship. In each group, investigators brainstormed the most important "next steps" in breast cancer research, and then the entire group met to hear summaries from group moderators. As a take-away to be shared among the participants, Dr. Norton requested that each researcher submit a sentence describing her or his "Zen wisdom" about the most important research advance discussed, and another describing the greatest impediment to progress. This event embodies BCRF's commitment to encouraging dialogue and fostering collaboration among breast cancer researchers from all corners of the globe.