by Lori Marx-Rubiner and Dr. Emil Lou

The 2015 meeting of the American Association for Cancer Research was held in Philadelphia April 18th – 22nd. Lori Marx-Rubiner attended the conference – here are her thoughts:

In the “Breaking News” department – at least as pertains to breast cancer – I thought this year’s AACR was a bust. There just isn’t much new going on, but here is what I did find:

– A number of new targets have been identified, which will hopefully lead quickly to low-impact, high-benefit therapies. The advantage to these targeted therapies is that there is less “collateral damage” to healthy cells.
– I think researchers have heard the demands of the patient community for more triple negative breast cancer (TNBC) research and that it’s starting to pay off. Each year I’m seeing more studies focused on TNBC, which is particularly important since we have no reliable targets.
– One such potential advance is the use GDC-0425, an agent which blocks the protein kinase Chk1 and prevents cell repair. The inhibitor is being given alongside the chemotherapy agent gemcitabine. This data is from a Phase I trial.
-There was also a promising Phase I study evaluating immunotherapy in TNBC. MPDL3280A targets the immune system’s T-cells, enabling them to return to attacking cancer cells. There have been some serious side effects that must be watched, but one can hope…

Speaking of immunotherapies, if there was a buzz about anything this year, I think immunotherapy is it. Researchers are realizing that creating something as effective as the human immune system to kill human cancer hasn’t been working. Instead, they are turning attention to why the immune system stops functioning and how to support its reactivation. According to one researcher, “Many patients who are on immunotherapy don’t even feel like they are taking a treatment.” Sounds good to me if we can make it happen!

On the prevention front I found two breast-cancer specific studies: One suggesting that extended overnight fasting (this study looked at 12 hours from dinner to breakfast) stabilized glucose levels and might thereby reduce cancer rates. I wouldn’t call this clinically relevant yet, but they are looking to investigate further. Perhaps curb the midnight munchies for now? Also, if you’ve been using aspirin for 16 years or more, you might also benefit from a reduced risk of breast cancer. Again, it’s early and they are not recommending a change without consulting your physician.

In my personal opinion, the need for new therapies to benefit metastatic breast cancer patients remains urgent. I didn’t see much that impressed me in terms of treatments poised to make a clinical impact. The focus was in broader areas of investigation, such as immunotherapies and circulating tumor cells, or CTCs.

CTCs are measurable cells in the bloodstream that correlate with cancer progression to metastasis, and may also allow ongoing and careful monitoring of cancer through phases of metastasis. Blood tests are obviously far easier than taking sequential biopsies, and allow for more frequent assessment. Labs are working on correlating CTC results with comparable tissue biopsies to ensure the reliability of the markers – but I honestly believe they are a game-changer.

Getting to these new kinds of progress is being done in large part thanks to integrative investigation. The shear volume of genomic information demands the attention of biologists, geneticists, engineers, computational scientists, microscopic imaging specialists, database managers, and computer manufacturers, to name just a few. Today the very physical space of researchers is being arranged to address these collaborative efforts. One research implied that there more contributor names you have on the last slide, the better you’re doing in cancer research today. When incredible minds from biological, physical, engineering and computational perspectives, come together to tackle the challenges of cancer we can make new kinds of progress – at last. Lori Marx-Rubiner

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The AACR Annual Meeting held recently in Philadelphia (April 18-22) brought to the forefront a lot of exciting developments and progress in cancer research, including in the field of breast cancer. As can be expected from a meeting hosting more than 16,000 researchers and physicians from around the world, there was a lot of breadth of studies, from epidemiology, to basic research on cancer cells and in animal models of cancer, to translational and clinical studies in patients. One interesting study (Abstract # 2770) examined racial differences in breast density between black and white women. This is pertinent because higher breast density has been associated with a higher risk (as high as 4 to 6 times higher) of breast cancer. The researchers – from Massachusetts General Hospital and the University of Pennsylvania– studied thousands of patients using two and three-dimensional measurements of breast density; their study provided evidence supporting higher breast density in black women as a strong risk factor for breast cancer. This study was interesting for several reasons, including the fact that the software was developed for this NIH-funded research project, and is being made widely available at no cost to other researchers. This is a good example of the research community committing to readily sharing resources to advance progress with other groups.

An epidemiological study estimated that breast cancer cases in the U.S. may rise by as much as 50% by the year 2030 (Abstract # 3699). Dr. Philip Rosenberg and colleagues from the National Cancer Institute noted that this overall increase includes variation in different histologic subtypes of breast cancer, and that in the era of targeted therapy, treatment is being tailored depending on the subtype. For example, the researchers stated expectations that cases of estrogen receptor (ER)-negative breast cancers may decrease by nearly half (from 17% to 9%) by 2030, and the reasons for this shift in cases remains unclear. This is especially important to understand, as some ER-negative tumor types (eg triple-negative breast cancers) are especially aggressive and don’t respond as well to current standards of therapy. Recognition of the shifting landscape in the decades to come will help oncologists and researchers tailor future targeted therapies while helping us understand the biologic reasons underlying these changes in the larger population of patients.

There was progress in clinical trials in breast cancer as well. There has been mounting excitement the past few years regarding “checkpoint-inhibitors” and immunotherapy to treat cancer in general. One example is immunotherapy drugs targeting PD-L1, which is found on T cells (cells which are vital to immune response to infection). PD-L1 is a protein, or “ligand”, found on T cells normally; PD-L1 can interact and lock with the protein PD-1 found on the surface of cancer cells. While this interaction normally serves as a “brake” that prevents excess involvement of the immune system against cells in the body (ie the rationale for calling it a “checkpoint”), antibodies (immunotherapy) blocking this interaction have come to the forefront and proven to be effective treatments in cancers including melanoma and lung cancer. For breast cancer, an antibody called MPDL3280A was used in a phase I trial (Abstract # 2859); this antibody was studied in 54 patients with metastatic triple-negative breast cancer, and showed a 27% progression-free survival rate, leading to objective response rate of 19%. While phase I trials are generally smaller and are designed primarily to determine the safe doses that can be administered to patients, this kind of response seen on CT Scans provides a lot of promise for future large studies in phase II and III trials. Every year there emerges one or a few main “themes” at large research or clinical oncology meetings, like AACR and ASCO. This year, Immunotherapy was arguable the single hottest topic – and expect more results to be shared, hopefully with even more positive news, in the years to come. Dr. Emil Lou

4/27/15 Tweet Chat Transcript

Lori Marx-Rubiner is a breast cancer advocate and metastatic breast cancer patient. She is currently serving as president of METAvivor, is an avid blogger, live-tweets many breast cancer conferences, serves on scientific peer review and is working on a memoir. She lives in Los Angeles with her husband John and son Zachary.

DR. EMIL LOU is an Assistant professor of Medicine in the Department of Hematology, Oncology and Transplantation at the University of Minnesota. HIs RESEARCH INTERESTS include tumor heterogeneity and intercellular communication. Follow him on Twitter: @CANCERASSASSIN1