Thursday was an interesting day at the San Antonio Breast Cancer Symposium. The NeoAllto study that I mentioned yesterday presented the data that many had been waiting for. This was a study where women with HER-2 positive breast cancer were randomized between trastuzumab (Herceptin) or lapatnab (Tykerb ) or both, given before surgery. First they looked at what effect these drugs, separately and in combination had on the amount of tumor left at surgery. It was clear that the combination was better than either one alone. The other question, however, was whether making the tumor in the breast disappear with drugs translates to a better long-term survival. Martine Piccart presented the data which confirmed that a pathological complete remission (i.e., no tumor left at surgery) does indeed reflect a better prognosis overall. This is good news because it suggests that we don’t always have to wait for years to figure out whether a drug works but can get hints within months whether a drug is having a positive effect.
Aromatase Inhibitors (AI’s)
An interesting paper regarding collateral damage and aromatase inhibitors was presented. The study showed that 20-30% of women stop taking aromatase inhibitors prior to the prescribed 5-10 years and for 75% of those women, it is because of musculoskeletal symptoms (joint pain). Other symptoms include insomnia, chemo brain, mood disorders and fatigue. The hypothesis of the study was that they could predict who would have problems and stop taking AI’s. And indeed, women who had poor sleep quality and difficulty concentrating prior to taking AI’s were more likely to have worse symptoms on AI’s and then to discontinue taking them. While their recommendation was to anticipate the people who were likely to have problems and look at alternatives, e.g., tamoxifen, or to add more drugs to treat the side effects, I think there is another approach. To figure out exactly what the benefit is for an individual woman and let her decide whether it is worth it!
Other studies also looked at why women don’t take their AI’s. They found that cost was a factor for 45% of women. They also found that women who took generic drugs such as tamoxifen or generic aromatase inhibitors were more likely to continue taking their drugs. The list below caused a gasp to go up in the auditorium. Note the first two drugs are generic and the rest are not.
Oral Therapy Price Comparison
DRUG 30-Day Supply
A second study about collateral damage took a different tack. They randomized women on AI’s with arthralgia to an exercise program or not. The women who were in the exercise program had a decrease in symptoms as well as weight and decrease in inflammatory markers. Yet another reason to exercise.
Finally there was an interesting study of the use of the AI anastrozole to prevent breast cancer in postmenopausal women. Not surprisingly, this drug when given to high risk postmenopausal women reduced the chance of developing breast cancer by 50%. This made the headlines but deserves a bit more discussion. What most of the stories neglected to point out is the fact that the group of high risk women given a placebo had a 4% risk of developing breast cancer while those on anastrozole had a 2% risk. When put that way it is less impressive, especially in light of all of the studies about the side effects of these drugs.
Another big story from Thursday involved the use of bisphosphonates. This has been an area of discussion over the years and the presentation was a meta-analysis of individual data from all the randomized controlled trials. Bisophosphonates are drugs that were developed to prevent osteoporosis. Bone is continuously being remodeled during our lives to adjust to weight loss or gain, fractures, and growth. This remodeling involves cells that resorb bone, osteoclasts, and others that put down bone, osteoblasts. With age and particularly menopause, many people have more active osteoclasts than osteoblasts and bone gets weaker. Bisphosphonates are drugs that block osteoclasts and therefore help prevent fractures. They are often used along with aromatase inhibitors to help protect bone from the effect that estrogen deprivation has on bone density. What has become even more interesting is the role of these drugs in bone metastases. Several studies have noted that women on these drugs who are postmenopausal either naturally or through drugs, have less metastatic disease particularly in bone. The hypothesis is that we need the osteoclasts to dig a hole in the bone for the metastatic breast cancer cells to find their niche.
This particular study combined all the women who had been included in previous studies and reanalyzed them. They found that in postmenopausal women, there was a 34% decrease in the risk of bone recurrence and a 17% reduction in the risk of breast cancer death. This was true regardless of the hormone status of the tumor, node status or use of chemotherapy. It was the same for the IV drugs commonly used in the U.S. and the oral type used in Europe. This certainly supports the use of these drugs. There was no breast cancer effect in premenopausal women and no significant effect on breast cancer deaths or local recurrence in the other breast or the same breast.