The mornings often start with a presentation about a particular topic before the research reports. Thursday started with a terrific presentation Macrophages as Novel Targets for Therapy in Breast Cancer, by Lisa Coussens, PhD, a pathologist at the University of California, San Francisco.
In order to develop cancer, you need both mutated cells and for the cells to be in a local environment, or neighborhood, that is egging them on. A lot of attention has been paid at this meeting to how cancer cells differ from normal cells and how we can develop targeted therapies that exploit that difference to kill them. Dr. Coussens presentation looked at one part of the neighborhood the immune system.
Dr. Coussens started with the observation that breast cancers that have a lot of associated macrophages (a kind of white blood cell) have a worse prognosis than those that do not. This is counterintuitive, since we always think of the immune system as protecting us. It turns out there are two kinds of macrophages, bad ones and good ones, and the bad ones appear to both encourage metastases and blunt the benefits of radiation and chemotherapy. These bad macrophages seem to be most important in breast cancers that are HER2+ or triple negative (ER-, PR-, HER2-). Dr. Coussens is now studying whether it is possible to either deplete or reprogram the bad macrophages in order to improve outcomes.
The research presentations today were interesting, often confirming previous reports. The first was a large European study looking at whether a full axillary dissection was necessary when there was a micrometastases in the sentinel node. The answer was that it is NOT necessary, confirming an earlier American study. The disease free survival was the same as was local recurrence and overall survival. Moreover, the full axillary dissection had increased side effects. The conclusion is that we should stop doing axillary dissections in tumors where the sentinel node is microscopically positive.
An interesting study looked at whether you can use a tumors response to neoadjuvant chemotherapy (given before surgery) to decide whether to change drugs. In this study, which was completed several years ago, they found that it was worth changing drugs. Although this sounds pretty obvious, it had not been shown before and might encourage more doctors to use chemotherapy upfront, where you can evaluate the tumor’s sensitivity.
Joyce OShaughnessy, MD, a medical oncologist at the Baylor-Sammons Cancer Center in Dallas, Texas, is always at the cutting edge of new approaches. She presented very interesting information about an approach her team used on 12 women with metastatic triple negative breast cancer that involved sequencing the DNA in the tumors to see if they could identify dominant molecular drivers that they could exploit. They found that in some of the women they were able to identify a pathway that could be interrupted by a specific drug and see a response. This is truly personalized medicine, where the treatment is matched to the exact molecular biology of your tumor, and it undoubtedly will be the wave of the future, at least for women who have been failed by traditional approaches.
There were two studies on everolimus (brand name Affinitor), a drug that is currently used in kidney cancer and that works by binding to an intracellular protein kinase called mTOR. In one study, everolimus was added to paclitaxel (brand name Taxol) in patients whose tumors were not responding to their current therapy. The second study, called BOLERO, demonstrated a better response rate by adding everolimus to the aromatase inhibitor exemestane (brand name Aromasin), in ER+ metastatic breast cancer that has stopped responding to hormone therapy. Since everolimus is already FDA approved, it adds another option in metastatic disease.
The afternoon symposium Environmental Exposures, Epigenetics and Epidemiology was disappointing. It focused on looking at exposures over the lifetime particularly on windows of susceptibility that may be significant but then the presenters talked about gynecological cancers rather than breast cancer. That is because we don’t have enough data on the breast. But the breast is NOT the uterus. We need to start studying the normal breast, if we are going to understand these interactions yet all the speakers said it was too hard and reverted to rats.
The Foundation has an active research program focused on the breast, and we presented a poster at the meeting about our research that found that the cytokines (immune markers) are different from duct to duct within the same breast. Could these differences be an indicator of which duct might go bad? We are continuing our work on this and will let you know!
The afternoon sessions started with a study showing that the risk of contralateral breast cancer in women who carry a BRCA mutation is higher than in women who do not. While this is not surprising, the researchers were able to show that the risk to the second breast in non-mutation carriers is 6% while that of BRCA1 carriers is 20% and BRCA2 carriers is 11%. The risk is highest in women who have a triple negative breast cancer diagnosed between ages 41-50.
Of note, most of the women in this study had not had their ovaries out, which decreases the risk of second cancers significantly (70%). The study also found that both chemotherapy and hormonal therapy for the first cancer seemed to reduce the chance of getting a second cancer in the other breast. In this era of bilateral mastectomies, it was a good reminder that the risk to the other breast is not the same in everyone.
For me the most interesting presentation of the day was Genomic Health’s new DCIS score. We know from retrospective data that not all women with ductal carcinoma in situ (DCIS) will go on to get an invasive cancer, if left untreated. However, we have not had a good way to tell which is the good kind and which is the bad kind.
Genomic Health, which developed the Oncotype Dx test, has now developed a test that can be done on biopsy slides to determine whether the DCIS has a low recurrence score and may not need radiation and or tamoxifen or has a high recurrence score and needs more therapy. In the research they discussed, they applied their test to data from a previous study comparing wide excision alone to wide excision with tamoxifen in small DCIS lesions (less than 2.5 cm). In this study, 70% of women had a low recurrence score. This is an important step in helping us put the treatment of DCIS on a more biological basis and will certainly provide support for some women who might want to forego radiation therapy and/or tamoxifen.