The only reason I accepted his invitation to circle the dance floor is that his latest foray into temptation has to do with pluripotent stem cells, a highly interesting, extremely complex, and promising area of serious scientific investigation. But before I attempt to follow Dr Sears’ complicated dance routine, there’s another bit of news that I want to put before you. It is, in the considered opinion of Doc Gumshoe, one of the most important news items in the medical field to have emerged in quite some time.
What the results of the TAILORx trial might mean for thousands of women
The results of the trial have not actually been published yet. They were scheduled to have been presented at the American Society of Clinical Oncology (ASCO) a couple of days ago, but the news has trickled out and hit the front page of the New York Times. In a nutshell, it is this: for thousands of women with early stage breast cancer who would, following the current treatment guidelines, have been treated with chemotherapy, this form of treatment may not be necessary. And, given that chemotherapy is in its essential nature a highly toxic form of treatment, if it is possible to treat these patients without resorting to chemotherapy with no sacrifice to treatment outcomes, then by all means, chemotherapy should be avoided.
The trial, TAILORx, (Trial Assigning IndividuaLized Options for Treatment (Rx), was announced in 2006. Its initial objective was not specifically to evaluate the benefits of chemotherapy versus other forms of therapy, but to examine whether genes that are frequently associated with risk of recurrence for women with early-stage breast cancer can be used to assign patients to the most appropriate and effective treatment.
What the trial found was that in a significant percentage of women with early stage breast cancer, perhaps as high as 70%, chemotherapy provides no benefit whatever over drugs that inhibit the action of estrogen or prevent the body from generating estrogen. Tamoxifen and related drugs, termed endocrine therapy, are very widely used; even though these agents do have side effects, including a slight increase in the risk of developing uterine cancer, the side effects of endocrine therapy are quite mild compared with the side effects of chemotherapy. The almost inevitable side effects of chemo include extreme nausea and hair loss. Less frequent but more serious side effects include cardiac and nervous system damage, increased susceptibility to infectious diseases, and perhaps also increased risk of leukemia.
The trial evaluated nearly 10,000 women with early stage breast cancer who had genetic analyses of their cancers. Of these, about 70% had disease marked by the following characteristics: 1), early stage breast tumors measuring one to five centimeters; 2), that have not spread to the lymph nodes; 3) these tumors are sensitive to estrogens; 4), and do not demonstrate the presence of the HER2 protein; 5), finally, an intermediate score on a genetic test that estimates the activity of a group of genes that are known to predict cancer recurrence.
One group of women in this cohort, those with intermediate test scores, was randomly assigned to receive either hormone therapy alone or hormone therapy together with chemotherapy. After nine years of follow-up, the overall survival rates were 93.9% in the women who got hormone therapy alone, versus 93.8% in those women who were treated with the combined therapy regimen. The rates of survival free of any evidence of invasive cancer in those two groups were 83.3% versus 84.3%.
That one percent difference favoring the cohort of women who got the combined therapy suggests that there may be a very few women who get a tiny benefit from chemotherapy. The authors note that these women are substantially younger than the age at which women usually develop breast cancer, and that further study is necessary before arriving at any conclusion.
Based on the overall evidence, the conclusion of the authors as well as that of a number of recognized experts was that the addition of chemotherapy offers no advantage over adjuvant hormone therapy. This helps to resolve an area of doubt in treating early stage breast cancer. Previous studies had indicated that women with scores at the low end of the genetic test could be successfully treated with hormone therapy alone, but uncertainty remained regarding women with intermediate scores. Might it be possible that chemotherapy provided a benefit in terms of survival, albeit a small benefit? The TAILORx study indicates that in women in that range, chemotherapy adds zero benefit while significantly increasing adverse effects. And the great majority of women with early stage breast cancer fall into that category. Estimates are that every year about 60,000 women in the United States who would otherwise receive chemotherapy can now be free from that ordeal.
There are a couple of other interesting and perhaps important take-aways from the TAILORx study. One is that this large, long, and expensive trial was sponsored not by pharmaceutical companies, but by the National Cancer Institute (NCI), which is part of the National Institutes of Health (NIH). If we think about it for just a moment, it’s evident that the pharmaceutical companies are not likely to put their money at stake in a trial of this kind because they’re liable to lose. Having government agencies step up to the plate is the obvious first choice. But Doc Gumshoe wonders about getting some Silicon Valley Billionaires to foot the bill for studies that would potentially be of great benefit to real live patients, and not just to the drug makers. (How about that guy who want to dedicate his $100-billion-plus to putting colonies of humans on planets here and there in the galaxy?)
And another take-away that makes me a trifle sentimental is the fact that thousands of women volunteered to take part in a clinical trial in which they might at random be assigned to a cohort that did not receive the standard treatment. Yes, chemo is an ordeal, but the doctrine supporting it has always been that it could save your life. And now women are being asked to take the chance that they won’t get chemo, and indeed, that chance could cost them their lives. But they said “yes;” they volunteered to enter the trial. In my view, those women acted heroically.
Now, let’s get back to Dr Al Sears and those stem cells. When he implies that stem cells can reverse every disease or medical condition that afflicts us, he’s doing no more than wildly, extravagantly exaggerating. The scientific community certainly recognizes the promise of stem cells, but it also recognizes that at this time, it’s a promise, and the date at which this promise might come true is likely a long way in the future.
A brief introduction to stem cells and what (we hope!) they can do
It must have been obvious to anyone with an elementary understanding of biology that there had to be something like original cells from which other cells developed. The entire living organism, whether a mouse or an elephant, develops from a single egg fertilized by a single sperm. Those first cells divide and multiply in number, and from those entirely undifferentiated cells evolve all parts of the fully developed living being. Those o