Dr. Jack Cuzick is director of the Wolfson Institute of Preventive Medicine and head of the Center for Cancer Prevention at the Queen Mary University of London, where he holds the title of John Snow Professor of Epidemiology.
He is internationally known for his research showing tamoxifen can be used to treat estrogen-receptor-positive breast cancer, as well as his work to help develop the Tyrer-Cuzick breast cancer risk evaluation tool, which helps women and their doctors estimate a woman’s risk of developing breast cancer.
At the 2019 San Antonio Breast Cancer Symposium, he presented the latest results from the International Breast Cancer Intervention Study II Prevention Trial, looking at whether 5 years of Arimidex (chemical name: anastrozole) can reduce breast cancer risk in postmenopausal women who have higher-than-average risk of the disease but have not been diagnosed.
Listen to the podcast to hear Dr. Cuzick discuss:
- how much Arimidex reduced risk after about 11 years of follow up
- why Arimidex is better than tamoxifen at reducing risk in high-risk postmenopausal women
- the side effects seen in the study and why side effect rates were the same in women who took Arimidex and women who took a placebo
- why it’s unlikely that Arimidex will be approved by the U.S. Food and Drug Administration for this use, but why doctors will be able to prescribe it off-label
Running time: 9:25
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This podcast is made possible by the generous support of Lilly Oncology.
Jamie DePolo: Hello! I’m Jamie DePolo, senior editor of Breastcancer.org. We’re podcasting on location from the 2019 San Antonio Breast Cancer Symposium. My guest is Dr. Jack Cuzick, director of the Wolfson Institute of Preventive Medicine and head of the Center for Cancer Prevention at the Queen Mary University of London, where he holds the title of John Snow Professor of Epidemiology. He is internationally known for his research showing that tamoxifen could be used to treat estrogen-receptor-positive breast cancer as well as his work to develop the Tyrer-Cuzick model for breast cancer risk evaluation, which helps women and their doctors estimate a woman’s risk of developing breast cancer.
At this conference, he is presenting the latest results from the International Breast Cancer Intervention Study II Prevention Trial. The study looked at whether 5 years of the aromatase inhibitor Arimidex, which has the chemical name of anastrozole, can reduce breast cancer risk in women who have higher-than-average risk of the disease. Dr. Cuzick, welcome to the podcast.
Jack Cuzick: Thank you.
Jamie DePolo: So in 2003 you presented results that showed Arimidex reduced risk by about 53% compared to placebo. Can you sort of summarize these latest results? And this was after almost 11 years of follow-up, correct?
Jack Cuzick: Yes, that’s right. So that original study showed a very big effect but primarily during the period in which the patients were taking treatment. This now looks at the post-treatment interval and goes out… we have good data that goes out to about 12 years. The median follow-up is just 11 years but there’s adequate follow-up to go out to 12 years. The results were very, very encouraging. They showed a continued benefit carrying on right out to that period and no indication it was dropping off near the end. Now, when you just look at just the first five years we’re finding now about a 60% benefit. And if you look at the period from year 5 to year 12 it’s about a 36% benefit year-on-year.
So that’s still bigger than the tamoxifen benefit, which was about 30% in the longer term. So we think the efficacy looks very, very good.
Jamie DePolo: Okay. And there were about 4,000 women in the study, is that right?
Jack Cuzick: Yeah. Just under 4,000.
Jamie DePolo: And how did you determine if they had a high risk of breast cancer?
Jack Cuzick: Well, there were a number of ways in which you could be high risk. The most common was to have a mother or sister with breast cancer under the age of 50 or to have two breast cancers in the family. The other approaches, which were not so common, were to have dense breasts, which we know are high risk but was not used so widely then, or to have a benign breast lump that had atypical features, which indicated a subsequent high risk of breast cancer as well. So those were the primary criteria.
Jamie DePolo: I don't know if you have this number in the study, but was there an average amount of increased risk for the women in the study that you could say…?
Jack Cuzick: Yeah. They had about a doubling of risk compared to the general population, yeah.
Jamie DePolo: Okay. And we know that now based on this study Arimidex seems to be better than tamoxifen in reducing risk, at least with these results so far.
Jack Cuzick: Yeah. So we knew that for the treatment of breast cancer, postmenopausal breast cancer, some time ago, primarily with the ATAC trial. This is a follow-on now looking at prevention in postmenopausal women. This is the only trial with Arimidex. There’s one other trial with exemestane, which also shows a substantial — 60%, roughly — benefit, but that was a short-term follow-up. This is the only long-term follow-up study, and again the results are really very promising.
Jamie DePolo: Now I know there seems to be some suggestion in the results, because while the women were taking it the effect seemed to be higher. While it was still good after they stopped taking it, it maybe suggested that would taking Arimidex for longer than 5 years offer more or better results?
Jack Cuzick: I think that’s a very interesting question. We didn’t anticipate what was going to happen, and we’ve just seen these results now, which do suggest that potentially longer treatment or possibly some kind of intermittent schedule, which maybe you stop for a few years and then you restart again, might be better. Now, that’s a really exciting prospect but it will be a difficult one to evaluate properly.
Jamie DePolo: Now, I want to talk about side effects because we know that a lot of women who have been diagnosed with breast cancer don’t take their either tamoxifen or aromatase inhibitor as prescribed. Women who are at high risk are maybe a little hesitant to take medicine because they’ve heard about the side effects and they’re concerned. Now, in your study you had about 70% adherence, which was really high compared to the numbers we see talked about...
Jack Cuzick: Yeah. We had 77% adherence in the placebo arm and 75.6% in the anastrozole/Arimidex arm. So the differences were really very, very small and they bring out a point, which I think isn’t well recognized, that a lot of these side effects are usually musculoskeletal aches and pains, arthralgias, or hot flashes. These are quite common, of course, in women of early postmenopausal age. In fact, they were so high in the placebo that most of that effect was nothing to do with the drug. So for example, we looked at musculoskeletal aches and pains, 64% reported them in the Arimidex arm, but it was 58% in the placebo arm.
So there’s a small increase but most of those effects are actually just to do with aging and the fact that as we get older we all get aches and pains. If you could blame it on something you certainly would, but that doesn’t mean it’s true.
Jamie DePolo: Okay. Now, I do want to ask, too, you were very careful to look at the women’s bone health in this study. All the women had a DEXA scan before they went into the study. Then if they did have osteoporosis or osteopenia they were treated with a bisphosphonate. I don’t know, I’m not a doctor, but could that in any way have lessened the severity of any joint pain that they might have been experiencing?
Jack Cuzick: We don’t think so because in fact the effect of Arimidex is to actually reduce the density of the bone. It’s inside the bone. It’s nothing to do with the joints, and the bisphosphonate actually builds up the density of the bone itself. But it shouldn’t have much to do with joints, so we don’t think that’s likely to have happened.
Jamie DePolo: I also want to ask, too, there has been some suggestion that bisphosphonates may help reduce the risk of breast cancer. So do you think that played any role in the study results at all?
Jack Cuzick: Well, that’s an interesting question. Not that many women were actually taking bisphosphonates. It was only the ones that were osteoporotic or some of the ones that were osteopenic, not all of them. So it would have been on the order of 15-20% of the population that would be taking them. So we don’t think that’s the case. We’ve looked very carefully at that because we thought that the bisphosphonates are a potential drug to be used for breast cancer prevention. There’s been a couple of studies that are not randomized that have found an effect of women taking bisphosphonates. But if you look at the contralateral breasts in women with breast cancer where bisphosphonates are used for treatment we found no effect there at all. That’s been a very good measure of the effects of other drugs. It's still a possibility, but I think it’s looking less likely than we had hoped.
Jamie DePolo: Then finally, the last few questions. Now, Arimidex, or anastrozole, is not approved in this country, in the United States, by the Food and Drug Administration to be used as a preventive medicine. But your results in 2003, I know a lot of doctors thought, “We could prescribe this off label and use it that way.” Do you think anybody would ever petition for it to be approved in that way?
Jack Cuzick: Well, the challenge is that only the manufacturer can actually seek a license for an extended indication. With a drug that’s off patent, the costs of that make it very difficult for AstraZeneca to do that. Now, in the United States it has been recommended by the U.S. Preventive Service Task Force to be used, so there is some formal recognition that this is a good idea in the United States in addition to the same kind of formal approval we’ve had from the NICE committee, the National Institute for Clinical Excellence, which recommends it for postmenopausal women at high risk.
Jamie DePolo: And that’s in Europe?
Jack Cuzick: In the United Kingdom.
Jamie DePolo: Just in the UK. Okay. But I want to make sure I understand it right. Even if it isn’t approved specifically for that use, if a doctor had a patient that felt might benefit, the doctor could prescribe it.
Jack Cuzick: The doctors are free to make those decisions. They have enough backing now because of the fact that major bodies have recommended it. The reason doctors are cautious is if something happens for an off-label use they’re more liable for problems. But it’s been recommended by several important bodies. So that I think is not a major problem.
Jamie DePolo: All right. Thank you very much for your time.
Jack Cuzick: My pleasure.