The San Antonio BreastÂ Cancer Symposium is the most important breast cancer meeting that takes place each year.Â It attracts close to 9,000 participants from more than 90 countries who are interested in hearing and discussing the most recent breast cancer research findings. The 33rd annual Symposium is being held December 8-12, 2010, and Dr. Love will be posting daily blogs about the meetingâ€™s most interesting research reports and discussions.
The first session of this yearâ€™s Symposium focused on hormonal drugs. Researchers reported findings from studies that showed that exemestane (brand name Aromasin) and anastrozole (brand name Arimidex) are about the same, with slightly less side effects for exemestane; that goserelin (brand name Zoladex) has the same benefit as tamoxifen when given to ER-positive premenopausal women for two years; that there was no benefit from taking goserelin and tamoxifen together; and that the benefit from goserelin, but not tamoxifen, was greater in tumors that were strongly estrogen receptor (ER) positive.
The next presentation, which reviewed two studies looking at the CYP2D6 test and the benefits of tamoxifen, were more interesting. The CYP2D6 test, also called the “tamoxifen resistance” test examines a gene called 2D6, which produces the enzyme CYP2D6. This enzyme is necessary for the body to metabolize a number of drugs, including tamoxifen. Tamoxifen has to be metabolized to endoxifen in order to work.Â This is done in the body by enzymes. Some people have variations in these genes that result in them making less endoxifen, and there has been some data suggesting that these people donâ€™t do as well when they take tamoxifen. This was noted at the 2007 San Antonio Breast Cancer Symposium, when researchers presented data that showed that women who inherited a certain variation of the 2D6 gene were almost twice as likely to have their breast cancer recur, even though they were more likely to complete their tamoxifen treatment.
To explore this question further, researchers took advantage of two large studies that were done to look at the benefit of tamoxifen versus an aromatase inhibitor (which is metabolized differently, and is not affected by CYP2D6).Â Their findings refuted the previous data, showing that the presence of common mutations in the genes that control the enzymes that metabolize tamoxifen did not have an effect on whether women were likely to have a recurrence.Â Â They also found that antidepressants that are thought to inhibit CYP2D6 actually had no effect on whether women taking tamoxifen had a recurrence. In sum, the researchers concluded that for postmenopausal patients with hormone-sensitive early breast cancer, CYP2D6 testing is not justified to determine whether to give tamoxifen. They also found that, in contrast to what has been suggested, the presence or absence of hot flashes should not be used as an indicator of whether tamoxifen is effective.
This meeting is a combination of basic science and clinical science. I always love the basic science sessions because I learn a lot.Â One of todayâ€™s sessions focused on how cells metastasize, and what happens next.Â The data shows that this is actually a very inefficient process, withÂ only 2% of the metastatic cells actually arriving at a new organ and with about one-third of these cells remaining completely dormant in the new organ for as long as 20 years or more.Â Interestingly, in the researchersâ€™ models, chemotherapy had no effect when the cells were dormant, but it did have an effect once the cells woke up.
Dormant means asleep, and the second speaker talked about how that dormancy works. This research team looked to see whether dormancy was related to blood supply (it wasnâ€™t) or the balance between cell death and growth.Â They found that the cells were basically just not dividing when they were dormant.Â They then went on to see if there were molecular differences between the cells that woke up and those that did not, hoping that they could then go on to develop new drugs that target and stop the molecules that only are in the cells that wake up.Â While that would be great, it made me think that we should also be looking at the environment that keeps the cells asleep.Â After all, the goal is not to kill dormant cells but to live your life and die a natural death with the cells still dormant.
Obesity & Breast Cancer Survival
The talks that followed may have given us a clue to one factor in the cellâ€™s environment that stimulates metastasis.Â Researchers reported findings from three studies that analyzed the effect that being overweight or obese has on a womanâ€™s risk of having a recurrence or dying of their disease.
The first set of studies looked at women with ER-positive, HER2-positive, or triple negative breast cancer.Â These studies found a significantly higher risk of death from breast cancer in women who had a body mass index (BMI) over 25 (these are women considered overweight) who were ER positive. In fact, in premenopausal ER-positive women there was a 51% increased chance in death in the women who were obese!Â This higher risk of death was not seen in women with a BMI over 25 who had HER2-positive or triple negative tumors.
A second study looked at women with locally advanced node positive (3 or more positive nodes) breast cancer.Â This study also showed a worse prognosis in women who were obese. It was mentioned that the goal is not to become skinny, and it was reported that the Womenâ€™s Intervention Nutrition Study (WINS) showed that losing just 6 pounds made a difference in survival. The last study looked to see if it mattered whether women who were overweight were on an aromatase inhibitor or on tamoxifen. The researchers reported that it didnâ€™t matter which therapy they were on, as the risk of death was the same for both treatments.
I couldnâ€™t help but think that if we had a drug that had that much effect as obesity on womenâ€™s risk of dying of breast cancer we would be writing headlines! At this point I believe there is enough data to suggest that obese women should routinely be entered into a weight loss and exercise program as part of their treatment.