Ductal carcinoma in situ: Anastrozole versus tamoxifen

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Published: 15 Dec 2015
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Dr Terry Mamounas - UF Health Cancer Center, Orlando, USA

Dr Mamounas talks to ecancertv at SABCS 2015 about the outcomes of a study comparing the use of adjuvant anastrozole versus tamoxifen in postmenopausal patients with estrogen-receptor (ER) positive ductal carcinoma in situ (DCIS).

Traditionally women with estrogen-receptor (ER) positive DCIS undergoing lumpectomy have been treated with adjuvant tamoxifen. So the aim here was to see if treatment with anastrozole was as good at preventing local recurrence, Dr Mamounas explains.

Postmenopausal women under the age of 60 years particularly seemed to benefit from anastrozole rather than tamoxifen, he observes, but there was no advantage of one treatment over the other in older women. Anastrozole and tamoxifen have different side effect profiles, he notes, which would also influence treatment choice.

You’ve been looking in the study at the use of anastrozole versus tamoxifen and this is in patients with DCIS. Could you tell me what was the big issue you were particularly looking at there?

The study that we actually have presented at the ASCO meeting then soon to be published, and there is also another study in this meeting about the same topic, relates to the use of aromatase inhibitors for patients with DCIS. Traditionally patients with oestrogen receptor positive DCIS treated with lumpectomy are also treated with tamoxifen and that reduces the risk of recurrence in the breast or development of a contralateral breast. But then for several years now we have accepted aromatase inhibitors for invasive breast cancer as an equivalent or better drug than tamoxifen for post-menopausal women. So the natural question was to ask whether the same drug, aromatase inhibitors, anastrozole in this case, is as good or better as tamoxifen for the treatment of patients with DCIS.

And which category of patients with DCIS?

These are post-menopausal patients with oestrogen receptor positive DCIS.

Is there not a risk of overtreatment of this condition?

It is always a risk of overtreatment in cancer with everything we do, we treat the majority of the patients to prevent a few recurrences. However, this is more of a preventative treatment to begin with because patients that develop breast cancer, including DCIS, are at risk for subsequent events in the opposite breast or the same breast if you preserve it. So these treatments are inclined to actually reduce the risk of new events occurring in the breast so the patient doesn’t have to undergo another lumpectomy or a mastectomy in the future.

What did you find in the study?

What we found was that anastrozole actually was superior to tamoxifen in reducing the risk of recurrence and contralateral breast cancer. In our study we found that this was particularly true for patients under the age of 60, so post-menopausal patients but under the age of 60, essentially between 50-60. This was the group of patients that had actually the most benefit from anastrozole over tamoxifen. For the older post-menopausal patients tamoxifen and anastrozole were equally effective. Now, that doesn’t take anything away from anastrozole because anastrozole also was associated with less side effects. Tamoxifen has the long-term effects of potentially endometrial cancer, thromboembolic events, anastrozole does not. On the other hand, anastrozole can decrease your bone density and you have to be careful about that and potentially institute therapy if you have to.

Now, can you take me through the decision-making tree because you diagnose DCIS, one possible course of action is to do nothing but it seems you’re going for prevention using hormone therapies. What should doctors bear in mind when they’re making up their minds?

That’s a good question because DCIS, as you know, is a very early demonstration of breast cancer and the survival of these patients is actually excellent, it’s the same as the normal population. However, these patients are at risk for subsequent events in the same breast and the opposite breast. So typically how we approach DCIS is to excise it and then, depending on how aggressive the disease looks in the breast, the size of the tumour, the age of the patient, the oestrogen/progesterone receptor status and more recently now a genomic score such as the DCIS score, we can make the decision on what is the risk of recurrence in the same breast. If that risk falls, and it depends on your level of comfort but usually it’s under 10%, we feel comfortable potentially avoiding radiotherapy after lumpectomy. But if it falls above that then usually radiotherapy is indicated. And then in addition to radiotherapy for the oestrogen receptor positive patients we look at their hormonal manipulation to see if we can further reduce the risk of recurrence.

This is not just a scientific issue, is it? How are the patients concerned about this?

Yes, the patients, sometimes they are reluctant to receive hormonal therapy because that potentially has side effects. However, most of the time the side effects are constitutional effects such as menopausal symptoms which go away if you stop the treatment. So I always tell my patients you can always try it because the majority of the patients may now have minimal to no symptoms. But if you’re one of those patients that you actually exhibit some of the symptoms, for example menopausal symptoms, mood changes, other constitutional symptoms, you can always stop the treatment. There are some long-term rare side effects, as I mentioned – endometrial cancer, thromboembolic events – that can be serious but those are very, very uncommon.

So how would you sum this up in a few words for what doctors need to be doing about this knowledge?

You have to assess the patient globally to make sure that there are no comorbid conditions that preclude you from using one of those. For example, if somebody has a history of clots then you don’t want to use tamoxifen, if somebody has a uterus you have to be cognisant of the risk of endometrial cancer. If somebody has osteoporosis you may not want to use an aromatase inhibitor because it can worsen osteoporosis. But I can also monitor the patient and be able to adjust or take the medication away if they develop serious side effects. But in general most of the patients tolerate those medications well and, depending on their life expectancy, which is a factor of their age at the time of diagnosis, this can be very helpful in the future because most of these patients in their 50s and 60s have a long life expectancy after the diagnosis of DCIS so they’re at risk of subsequent events and that’s what we’re trying to prevent.