By: Susan G. Komen
In the quest for better patient outcomes, scientists have been studying why some breast cancers stop responding to therapies and develop resistance. Dr. Myles Brown, the recipient of this year’s prestigious Brinker Award for Scientific Distinction in Basic Science, has been studying the role of hormones in breast cancer treatment, and his years of successful accomplishments started with one patient. We recently had a chance to chat with Dr. Brown and learn more about what motivates him in his work.
Myles Brown, M.D., Winner of the 2015 Brinker Award for Scientific Distinction in Basic Science
1. What made you decide to focus your research on steroid hormones and their receptors in breast cancer?
When I was a first-year oncology fellow in 1986 I cared for a young woman, Anne V., who had ER+ breast cancer that had recurred in the skin of her chest wall. I started her on tamoxifen and could see the tumors in her skin regress over a period of only a few months. The gene for ER had just been cloned and for me this was a visible example of the efficacy of a molecularly targeted therapy. Despite having a complete clinical response in her skin, Anne’s breast cancer recurred a year later, and she eventually died of her disease. My entire career since has been focused on understanding why patients like Anne initially respond to endocrine therapy only to become resistant.
2. How could your research help individuals facing breast cancer today and in years to come?
Our work is focused on understanding what makes most breast cancers depend on steroid hormones such as estrogen. Drugs that block estrogen’s ability to bind its receptor such as tamoxifen and fulvestrant or ones that block the production of estrogen such as anastrozole, letrozole and exemestane are among the most effective and least toxic therapies we have for breast cancer. While these drugs work for many women with estrogen receptor-positive (ER+) breast cancer, there are still too many women who die from ER+ disease. We are defining the reasons why some tumors fail to respond to these treatments and are developing new approaches to overcome endocrine resistance including new combination therapies and new ER-targeted drugs.
3. What was the biggest challenge that you had to overcome in your career?
Starting out in my career I was investigating how tamoxifen worked and how it was able to block estrogen action in the breast, yet mimic estrogen action in other organs such as the uterus and bone. In my initial grants I proposed that this difference might be due to proteins we called coactivators that would interact physically with ER and might be differentially expressed in various tissues. My first application to the NIH that proposed cloning these coactivators was not well received to say the least. Fortunately for me the ACS and Komen were willing to take a risk on me early in my career. These early non-government grants were crucial to my ability to build a successful research program.
4. What, in your opinion, is the most recent progress in breast cancer research that patients should be aware of?
Patients need to be aware of the progress in personalizing breast cancer treatments based on the specific breast cancer subtype and specific genetic alterations present in the tumor. There are new drugs and drug combinations in development targeting many of these changes. It is important to be able to sample a patient’s tumor when it no longer responds to a given therapy in order to find the resistance mechanisms and potential vulnerabilities present in that tumor. This can now be done for most patients using radiographically guided needle biopsies and modern high throughput gene sequencing. On the horizon are so-called liquid biopsies in which DNA either from circulating tumor cells or free tumor DNA can be purified from the blood and sequenced. If this technology proves reliable, it should be possible to genetically profile a patient’s tumor repeatedly over the course of therapy.
5. What would you predict will be the next big breakthrough for breast cancer patients?
There continues to be very considerable progress in the development of targeted therapies based on the specific sensitivities of the different breast cancer subtypes, defined both by the genes they express and the mutations they harbor. It is likely that novel combinations of these therapies will be shown to be active in the advanced disease setting and given the very strong adjuvant paradigm in breast cancer, will be tested there where the field has consistently made progress in curing increasing numbers of women.
Curing women with metastatic breast cancer will continue to be a challenge for this approach, however, because of the high level of heterogeneity present at this stage of the disease. Given the successes in metastatic melanoma, non-small cell lung cancer and other cancer types, a breakthrough in immunotherapy would have the potential to cure breast cancer patients with advanced disease. Figuring out how to prompt the immune system to attack breast cancer and how immunotherapy might be combined with targeted therapy will be the challenge of the coming decade.
6. What does receiving the Brinker Award for Scientific Distinction in Basic Science mean to you?
It is extremely gratifying to be recognized by one’s colleagues and to join the ranks of other members of the steroid receptor field who have won the award in the past, including Craig Jordan, Marc Lippman, Angela Brodie, Bert O’Malley, Elwood Jensen, Evan Simpson, Geoffrey Greene and Benita Katzenellenbogen. I have had the extreme good fortune to have had wonderful mentors, collaborators and trainees over my career. Without them, none of my work would have been possible.
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