You are looking at DCIS, now this is not breast cancer but it’s being treated with anastrozole or tamoxifen. First of all, can you tell me what is the case for treating DCIS like this?
DCIS, there are cancerous cells but they haven’t actually left the breast yet, they’re still so-called in situ cancers. Now, if left untreated it’s very clear that about 30-40% of them will progress to invasive cancer so the option of just doing nothing with DCIS overall is not a good option. There’s very good evidence from many studies that the detection and treatment of DCIS actually lowers the rate of invasive cancer in the future and deaths from breast cancer.
And this fits in with other ways of approaching high risk breast cancer and preventing it with these same agents, tamoxifen and anastrozole.
One of the challenges, of course, is determining which women are going to benefit and which women are at sufficiently low risk that they don’t need aggressive therapy. So the story is quite a long one; there are two studies, again one from ourselves and one from the NSABP, looking at the role of tamoxifen in DCIS. Both of them overall showed about a 30% reduction in recurrences with tamoxifen. So there clearly is a benefit. If you look just at ER positive DCIS, which has not been done so thoroughly in those trials, it’s probably a bigger effect so oestrogen receptor positive DCIS there’s probably of the order of a 40-50% reduction in recurrence with tamoxifen.
So what did you do in this study that you’re quoting right here in San Antonio?
In this study we actually evaluated whether or not an aromatase inhibitor, that is anastrozole, would be more effective than tamoxifen in oestrogen receptor positive DCIS. This has been seen in invasive cancers, it’s very clear that anastrozole is more effective than tamoxifen, and there is indirect evidence in the prevention setting that you prevent more new cancers with an aromatase inhibitor than you do with tamoxifen. So the missing link was what about DCIS which is early, early cancer or high risk for cancer.
What did you find?
We found in our own study a small benefit for anastrozole over tamoxifen. It was an 11% lower recurrence rate which was not significant. One of the problems that both of these studies suffered was that when they were designed recurrence rates were much higher in DCIS than they are now so they’re a little bit underpowered. So when you put our study together with the B-35 study you see a 21% reduction which is statistically significant. So I think the evidence does support the fact that aromatase inhibitor will prevent more recurrences than tamoxifen.
So what should doctors make of this, do you think? Because many of them might have looked for stratifying their patients with DCIS and not treating some of them.
Yes. So every aspect of the treatment of DCIS is controversy at the moment now. There are studies saying do you even need surgery; there’s a lot of interest in whether or not radiotherapy is over-treatment, undoubtedly it is for many women. Then this area of hormonal treatment is also controversial. We focussed only on oestrogen receptor positive DCIS where the effects are certain to be bigger. There is clearly a reduction in recurrence although recurrence rates are sufficiently low it may not be necessary for all women.
What sort of symptoms do you get? The symptoms are actually a bit different with the two agents, aren’t they?
One of the most interesting findings was that although there wasn’t a big difference in recurrence rates there were very different side effect profiles. Adherence to treatment overall was identical in the two arms, it was 67% at five years, but the actual side effect profiles were very different. So, for example, tamoxifen is associated with gynaecologic problems, more endometrial cancers which is the major concern for women that still have a uterus, more thromboembolic events which are important as well, whereas anastrozole was associated with more musculoskeletal aches and pains and arthralgias and bone loss leading to a higher fracture rate. So these were very balanced overall but they were very different.
So the overall preventive effect, the efficacy of anastrozole, seems to be slightly better than tamoxifen but how should doctors view these data and perhaps choose one or other of these agents in prevention of breast cancer after DCIS?
Because the results are quite similar doctors need to individualise the choice for patients. So, for example, if a woman has had a deep vein thrombosis previously then tamoxifen is typically not a good choice and an aromatase inhibitor would be better. If there were problems with musculoskeletal aches and pains or concerns about bone density loss which can, of course, be ameliorated by using a bisphosphonate as well, but if that’s still a concern then tamoxifen emerges as probably the treatment of choice. So it really does depend on prior history of other conditions and then coupled with the fact that once you start one of these drugs it’s not a lifetime commitment. If you’re having problems or side effects with one of these drugs there’s now another option, you can try something else. So I think it really just provides another effective option for treating DCIS which should be in the armamentarium of what to offer, particularly for women that have trouble with tamoxifen.
What’s the take home message for cancer doctors?
The overall message is that anastrozole, the aromatase inhibitors, are somewhat more effective than tamoxifen at preventing recurrence but the differences are small and considerations of side effect profiles emerge as probably the most important determinant for which of these drugs to offer.