By: Dr. George Sledge, Jr., MD.
Guest Blog by Komen Chief Scientific Advisor Dr. George Sledge, Jr., MD. Dr. Sledge is a Professor of Medicine and Pathology, and Chief of the Division of Oncology in the Department of Medicine at Stanford University.
As a physician and cancer researcher I am often asked, “when will we find a cure for breast cancer?” The answer is complicated, in part because of what we have learned over the last decade or so: breast cancer is not one disease, but many, and as such will require not one cure, but many.
Are we making progress towards the “cures” of breast cancer? I believe so, though there is much work to be done. In the clinic, we deal with three basic types of breast cancer: one dominated by the presence of the estrogen receptor (hence, estrogen-driven in terms of its growth), one whose growth is driven by the growth factor receptor HER2, and one where HER2 and ER are absent (which we often call “triple negative”, because it lacks the progesterone receptor as well).
Estrogen receptor positive breast cancer was the first human cancer where we had targeted therapy, in the form of drugs that remove estrogen or prevent estrogen binding to its receptor. These drugs clearly reduce the risk of recurrence in early stage, estrogen receptor-positive breast cancer patients, but they do not cure everyone with this type of breast cancer. In the past decade we have learned much about how breast cancers become resistant to estrogen-targeting drugs, and this has led to new drugs to thwart resistance. The first of these,everolimus, recently entered clinical care, and others are rapidly being developed. For instance, we know that estrogen drives growth through something called CDK4/6, and early studies suggest that blocking CDK 4/6 significantly lengthen the time patients with advanced breast cancer remain in remission.
HER2-positive breast cancers are the second major “family” of breast cancers for which we have developed targeted therapies. HER2-targeting drugs entered clinical practice with the use of the antibody trastuzumab, initially for advanced breast cancers, but during the last decade for early stage breast cancers as well. HER2-positive breast cancers have gone from being the most feared to being among the most treatable. New HER2-targeting drugs have joined our treatment tool kit in the past three years, and we are already seeing impressive evidence that these drugs improve survival for patients with advanced disease. Several of these drugs (pertuzumab, T-DM1 and neratinib) are now being tested for early stage breast cancer, and the hope (I think a realistic hope) is that these new drugs will largely eliminate HER2-positive breast cancer as public health problem.
The third group of breast cancers, so-called “triple negative breast cancer”, has proved the most intractable. While the combination of local therapies (surgery and radiation) and adjuvant chemotherapy cure many of the women with this disease, the picture for patients with advanced (or metastatic) disease remains daunting. While we have many chemotherapy agents for women with advanced disease, these drugs are toxic and eventually fail to control the disease.
Several new approaches to triple negative breast cancer are being tried. For instance, women with BRCA1 mutations (most of whom have triple negative disease) appear to be more sensitive to drugs that interfere with DNA repair, and several of these are being tested. In addition, new approaches that involve interfering with the metabolism of these drugs, as well as novel approaches that make use of the body’s immune system, are now underway.
Many of these new approaches represent small steps in the right direction. Will they collectively result in a “great leap” forward towards our goal of a cure for breast cancer? Only time will tell, but I am optimistic that we will continue to improve the fate of women with the disease, through the efforts of a dedicated army of breast cancer researchers.Komen researchers have been at the forefront of many of the major advances in breast cancer research, both in understanding the biology of the disease, and applying this knowledge to the clinic.
Ultimately, of course, part of the cure should involve preventing, as opposed to treating, breast cancer. This has also been an exciting research area, and one that Komen has invested a great deal of resources in. We could give no greater gift to our children than using novel prevention approaches to consign breast cancer to the dustbin of medical history.
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