Hormonal treatments produce similar quality of life outcomes in DCIS

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Published: 11 Dec 2015
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Prof Patricia Ganz - UCLA, Los Angeles, USA

Prof Ganz talks to ecancertv at SABCS 2015 about secondary end point data from the phase III NSABP B-35 clinical trial that compared 5 years’ treatment with anastrozole or tamoxifen in postmenopausal women with ductal carcinoma in situ (DCIS).

The primary end point results of the NSABP B-35 trial were reported at the American Society of Clinical Oncology 2015 annual meeting and showed that anastrozole was at least as effective and safe as tamoxifen. There was a slight advantage of anastrozole perhaps, Dr Ganz notes in the interview. Indeed women where more likely to remain breast-cancer free at 10 years if they had received the aromatase inhibitor.

Patient reported outcomes such as quality of life were reported in a sub-study of the trial and Dr Ganz reported data on more than 1000 women who has participated and completed the Short-Form 12. There were no differences, however, between the women treated with anastrozole and those treated with tamoxifen when using the Physical Component Summary (p=0.16) or the Mental Component Summary (p=0.38) of this questionnaire.

As expected there were differences in terms of the symptoms, with the typical tamoxifen side effects of hot flashes seen and more musculoskeletal pain and vaginal pain and discomfort during sex in those treated with anastrozole.

What these data show is that there are choices, Dr Ganz says. Before tamoxifen was the only approved option in DCIS but the NSABP B-35 and other trial data now show that aromatase inhibitor therapy, specifically anastrozole, is also of benefit.

ecancer's filming at SABCS 2015 has been kindly supported by Novartis through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

You’re looking at DCIS and you’re looking at what I gather is really a preventive role of either anastrozole or tamoxifen. Could you tell me what it was exactly you were trying to investigate in this NSABP B-35 study?

Yes. The trial was designed to look at whether giving either anastrozole for five years or tamoxifen for five years would prevent any kind of breast cancer recurrence in these women. Those events included distant metastatic cancer, invasive cancer in the breast, recurrent ductal carcinoma in situ and any local or regional changes. So we have to realise that this is a non-invasive cancer but the risk for a cancer event in the future was what was being prevented.

And what did you find? This is a big study, over 3,000 patients.

Yes, the trial was reported last June at ASCO and showed that overall there was a small benefit to anastrozole compared to tamoxifen but overall very long breast cancer event free survival for women. When we looked at who was benefitting it was the women younger than 60 years of age.

What about quality of life issues? What was happening there?

The quality of life was looked at and what we found were what we would now expect with these two agents, which is that with tamoxifen we saw more hot flashes occurring and more vaginal discharge and itching, those kinds of symptoms that we know are part of tamoxifen treatment. In contrast, for anastrozole we saw more musculoskeletal pain and symptoms and we saw more vaginal dryness and pain with intercourse.

So there was an age difference, age made a difference. So how would you choose between the two agents in typical patients then, do you think?

For women who were younger we saw a greater degree of hot flashes compared to older women on tamoxifen or on anastrozole. For vaginal dryness and pain with intercourse we saw also more difficulty in the younger women. Again, for those two drugs it was tamoxifen that was worse in the younger women and it was anastrozole that was worse for vaginal dryness in the younger women.

So how do you choose between these two agents then? Give me a typical example of what kind of woman.

As an example, if an older woman has osteoporosis, and I didn’t get a chance to talk about some of the more medical outcomes from the trial, but anastrozole leads to lower bone density and fractures, tamoxifen can lead to uterine cancer, so that’s a risk for that drug. But if you had an older woman who had had a hysterectomy and she had established osteoporosis and had now DCIS one might prefer tamoxifen over anastrozole because you would have accelerated bone loss with the anastrozole and if she has osteoporosis already and does not have a uterus she’s not at risk for uterine cancer, tamoxifen might be the preferable treatment. In contrast, for the younger woman she might say, ‘I really am worried about preventing the cancer, it looks like anastrozole is better in preventing the cancer. I’d like to try that. I’m going to try to take that drug.’ But she takes the drug and has bad joint pains, has bad vaginal dryness and pain with intercourse, well then we could switch her to tamoxifen and know that the drug was only slightly less effective but would have a better symptom profile.

Of course, age comes into it in a different way too because an older woman might well say, ‘Well DCIS is not such a high risk condition, do I really need to take anything?’ Do you have any help there to offer?

We didn’t really address that in this study and I think that’s a clinical question. I think physicians are often facing this with patients. We don’t know which kinds of DCIS are serious and are going to go on to have problems. Clearly in my own practice if a person has a few millimetres of DCIS on a biopsy and let’s say she was on hormone replacement therapy when this occurred, I might just take her off that hormone replacement therapy and say let’s just excise this and we can go on with things. On the other hand, if the DCIS is 3-4cm in size, has high grade features we might want to consider this kind of preventive therapy as being very important to potentially prevent a recurrence of the disease.

So how would you summarise what doctors should be doing for their patients with DCIS who are having local excision and radiotherapy? What should they also be doing? It still is a close-run race between anastrozole and tamoxifen, isn’t it?

Yes, it’s very close and again what our trial did not look at was a group of women who didn’t get any treatment simultaneously. So it’s hard to extrapolate but we know from earlier trials done by the NSABP that tamoxifen incrementally improves the reduction in risk of recurrence. So, again, if a woman is in good shape and she says, ‘I don’t ever want to have this experience again and I want to do whatever I can to prevent this. I want to preserve my breast, I don’t want to have a recurrence and have to have a mastectomy. I don’t want to have to worry about getting it in my other breast,’ then we need to offer her one of these two drugs for prevention of recurrence. On the other hand, if she’s not concerned about this, she’s worried about the side effects, she has other comorbid conditions that might be more prominent for her, then not taking any therapy might be a choice.

So in a nutshell, how would you sum up what doctors should remember coming out of this very interesting and very large NSABP B-35 study?

The important thing to know is now that we have choices, we don’t have one drug. Previously tamoxifen was the only drug approved for the treatment of women with DCIS, now we have a second drug that is equally efficacious, certainly in women over 60 and perhaps better in women less than 60. We know a lot now about the side effect profiles so we can really tailor and personalise the choice of therapy.

But in fact preventive therapy seems to be very well established in your view?

Yes, we have had multiple breast cancer prevention trials around the world which have all shown the benefits in certain high risk populations and these are discussions that we hope would go on more frequently. Unfortunately the uptake of breast cancer preventive therapies has been much less than we would like but again sometimes it takes time to get the message out.

But the uptake could be greater if you have DCIS?

Yes, it’s a much more serious condition, it’s in the breast that we have evidence of disease. Certainly for women with atypical ductal hyperplasia in the breast their motivation is better. But I think when you do a hypothetical calculation of risk it’s harder for a woman to say, ‘I want to take something.’ But if you have a breast biopsy that shows either atypical hyperplasia, lobular carcinoma in situ or DCIS an active discussion about breast cancer preventive therapy needs to go on.