Presentation on several new therapies for HER2-positive metastatic breast cancer including kinase inhibitors, antibody drug conjugates, and immunotherapies, as well as patient-friendly resources for exploring clinical trials.
View the presentation or view on SlideShare.
Presentation on several new clinical trials for triple negative metastatic breast cancer including antibody drug conjugates, and immunotherapy combinations, as well as patient-friendly resources for exploring clinical trials.
View the presentation or view on SlideShare.
Ending Metastatic Breast Cancer for Everyone (EMBRACE) is a research study conducted at Dana-Farber Cancer Institute. This study began recruiting patients in 2009, with the aim of learning more about the biology of advanced breast cancer, as well as the
treatment experiences of patients living with it.
Each patient's progress is tracked by a study coordinator, and the information collected is used to help doctors understand more about the long-term journey of the metastatic breast cancer patients in this group. Investigators hope the study will bring
them closer to finding a cure for this disease.
The study also sponsors a metastatic breast cancer forum every year, as well as webcasts of topics relevant to patients with metastatic disease.
The study is not sponsored by drug companies, and patients are not required to be on any drug trials.
For more information on EMBRACE, please email
Research Advances in Metastatic Breast Cancer
Research is particularly vital when it comes to cancer that has spread beyond the breast (metastatic). One hallmark of the
Susan F. Smith Center for Women's Cancers is the integration of research and patient care, and the equal investment in both. At a basic level, scientists seek to understand the basic
biology of how and why breast cancer can spread, and at a clinical level, clinician/scientists test potential therapies in patients. More than 30 clinical trials are now underway for women with metastatic breast cancer.
Research conducted through the
Specialized Program of Research Excellence (SPORE) led by
Eric Winer, MD, encompasses several metastatic breast cancer projects. This prestigious five-year grant funded by the National Cancer Institute includes projects aimed at identifying drug "targets" on breast
Here are some examples of our current metastatic breast cancer research advances.
- Numerous trials focus on metastatic breast cancer that is driven by the hormone estrogen. A promising candidate for treating such "ER-positive" tumors is a class of drugs known as PI3-kinase (or PI3K) inhibitors, which inhibit a pathway that is often
overactive in these cancers. A recent phase 2 trial led by
Ian Krop, MD, PhD, showed that adding a PI3K inhibitor to a hormone blocker may partially restore the blocker's effectiveness and delay the advance of the disease.
- ER-positive, metastatic breast cancer is often characterized by unregulated cell growth and division, a process linked to an oversupply of the protein cyclin D. Drugs known as CDK4/6 inhibitors block cyclin D, and stop tumor cell growth. A recent
phase 1 clinical trial led by
Sara Tolaney, MD, MPH, found that a CDK4/6-inhibiting drug called abemaciclib caused tumors to shrink or stop growing in one-third of participants with ER-positive metastatic breast cancer.
- A phase 2 clinical trial led by
Beth Overmoyer, MD, found that a daily dose of the drug enobosarm shows promise for women with metastatic breast cancer that is driven by both estrogen and androgen. One advantage of the drug is that
it produces even milder side effects than those associated with standard hormonal therapy.
- Ian Krop, MD, PhD, Sara Tolaney MD, MPH, Eric Winer, MD, and their colleagues have launched a series of clinical trials of drugs designed to unleash an immune system attack on
triple-negative breast cancer that has metastasized. (Triple-negative breast cancer cells lack the HER2 receptor, as well as receptors for the hormones estrogen and progesterone.)
The drugs target PD-1, a protein on immune system cells that normally restrains them from attacking cancer cells. Although the initial trial is still underway, the approach is showing promise and has led to the additional studies, a welcome sign
in a disease where long-lasting results have been difficult to attain with chemotherapy.
- Susan F. Smith Center researchers are also focused on metastatic breast cancer fueled by the presence of the growth-promoting protein HER2.
Nancy Lin, MD, and her colleague
Otto Metzger-Filho, MD, have recently completed enrollment to a phase 1 clinical trial of the drugs ARRY-380 and trastuzumab (Herceptin) in patients with HER2-positive breast cancer that has metastasized
to the brain, and final results are expected later in 2017.
- Hormonal therapy, which deprives ER-positive breast cancers of estrogen, is part of after-surgery therapy for early ER-positive breast cancer, and is often successful at preventing return of the disease. However, ER-positive breast cancer can recur
many years later, often at a site far from the original tumor. Researchers led by
Myles Brown, MD, have discovered that breast tumor cells can carry an abnormal "receptor" for estrogen, potentially allowing them to grow even when estrogen is absent. Researchers hope to use this finding
to guide the development of new drug agents.
- Brown and his colleague
Rinath Jeselsohn, MD, are studying a particularly promising class of drugs for metastatic, ER-positive breast cancers. Known as selective estrogen receptor degraders (or SERDs), they clamp onto
the estrogen receptor and cause it to crumble, so the tumor cells no longer respond to estrogen.
- Other research is focusing on the molecular makeup of breast tumors — the presence of genetically distinct cells within a single tumor. Tumors with the most "heterogeneity" — the greatest diversity of cell types within them — are often more likely
to resist treatment and to metastasize. Researchers led by
Kornelia Polyak, MD, PhD, have discovered that the fastest-proliferating cells within a tumor aren't necessarily the main drivers of tumor growth, suggesting that efforts to develop new drugs should
focus on targeting the actual driver cells.
- Up to 50 percent of HER2-positive breast cancers spread to the brain, but scientists have known little about how the process occurs. Recently a team of researchers including
Nikhil Wagle, MD, Eric Winer, MD, Ian Krop, MD, PhD,
Jean Zhao, PhD, Nancy Lin, MD, and Shom Goel, MD, PhD, found that approximately 12 percent of such tumors contain mutations that may explain why they don't respond well to the target drug trastuzumab, also
known as Herceptin. Researchers in Zhao's lab have implanted patients' metastatic tissue into animal research models, making it possible to test various drugs to see which may be most effective against the disease.