October 8, 2008 — Tamoxifen chemoprevention is already known to reduce the incidence of estrogen-receptor-positive (ER+) breast cancer, but a new analysis suggests that it might also speed up the diagnosis of estrogen-receptor-negative (ER–) breast cancer.
This was an unexpected finding, commented lead author Yu Shen, PhD, professor of biostatistics at MD Anderson Cancer Center, in Houston, Texas. "We found that in women who were at high risk of breast cancer, tamoxifen shortened the time to diagnosis of ER– breast cancer by about a year."
"This is potentially another positive effect from tamoxifen chemoprevention, and it is good news for women at high risk of breast cancer who are considering whether to take it or not," commented Therese Bevers, MD, associate professor of clinical cancer prevention and medical director at MD Anderson's Cancer Prevention Center. She was not involved in the latest analysis of data, but was involved in the original clinical trial.
The finding was published online October 7 in the Journal of the National Cancer Institute. It comes from a retrospective analysis of data from the Breast Cancer Prevention Trial, which involved 13,388 women at high risk for breast cancer who were randomized to either tamoxifen or placebo.
This was the largest ever placebo-controlled trial of tamoxifen, and when the original results were published 10 years ago, they caused great excitement, Dr. Shen explained, because they showed that the drug halved the incidence of breast cancer when compared with placebo. Further analysis showed that the reduction in incidence was solely in ER+ tumors, with no effect on the incidence of ER– tumors.
"This was a landmark trial; we showed for the first time that we could reduce the risk of developing cancer by taking a pill," added Dr. Bevers.
Time to Diagnosis Shortened by 1 Year
The new analysis carried out by Dr. Shen and colleagues looked at the time to diagnosis of breast cancer. The overall results showed no difference between the tamoxifen and placebo groups in time to diagnosis, and no difference for women who where diagnosed with ER+ tumors (n = 174).
However, there was a significant difference in the time to diagnosis for women with ER– tumors (n = 69), with those in the tamoxifen group being diagnosed at a median time of 24 months and those in the placebo group at 36 months (P = .037).
"I was very nervous when I saw these results, as they were so unexpected," Dr. Shen commented in an interview. She checked back in the literature, but no effect on ER– breast cancer had been reported previously.
Dr. Shen said the finding is important. Women in the tamoxifen group were diagnosed a year earlier than those in the placebo group, and earlier diagnosis is associated with better survival, she pointed out.
Dr. Bevers agreed. Currently, there is no way to predict whether a woman will develop ER+ or ER– breast cancer, she told Medscape Oncology. "As a clinician, when I prescribe tamoxifen to women who are at high risk of developing the disease, I know that there is likely to be a benefit for women who would develop ER+ tumors, but until now, there appeared to be no benefit for women who would develop ER– tumors."
Now, it appears that there may be a benefit for this group also. Although tamoxifen had no effect on the incidence of ER– cancer, it appears to shorten the time to its diagnosis. "So now we can say that there may be a benefit, because detecting the tumor at an earlier more treatable stage means improved outcomes," Dr. Bevers comments.
Does Tamoxifen Make Detection Easier?
The finding can be explained in 2 different ways, Dr. Shen continued. Either tamoxifen was having a detrimental stimulatory effect on ER– tumors and they were growing faster, or tamoxifen was having some effect that made these ER– tumors easier to diagnose. Analysis showed that the ER– tumors in the tamoxifen group were smaller in size than those in the placebo group, which suggests that the first explanation — a detrimental effect — was unlikely, she said.
"Thus, it appears that tamoxifen is making these ER– tumors easier to diagnose," Dr. Shen commented. She speculated that 1 way in which the drug might do so is through its effect on breast-tissue density. Other studies have shown that tamoxifen reduces breast density, and this makes it easier to spot breast cancer on a mammogram, she added.
"However, all of this is conjecture, and we need further data from clinical trials," she added. "Also, the puzzling part is that there was no similar effect on the time to diagnosis of ER+ tumors."
Opens Up Whole New Angle for Research
"Nobody has looked at this before — the time to diagnosis — and whether the intervention may improve the diagnosis of the cancer," Dr. Bevers commented in an interview. "Until now, we have focused on incidence, and whether it was reduced or not."
"This finding has opened up a whole new angle of research," she said. It is hypothesis-generating, and is likely to stimulate a lot more research in this area. It would be interesting to perform similar analyses on the data that already exist for raloxifene and the aromatase inhibitors from other breast cancer trials, and also the data on Proscar in prostate cancer. "This is something new that we can look for — does the intervention have an effect on the time to diagnosis," she said.
The researchers have disclosed no relevant financial relationships. The study was supported by a National Cancer Institute grant.
J Natl Cancer Inst. Published online October 7, 2008.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου