INTERVIEW WITH DR. MICHAEL BAUM

DR. LOVE: I'm thinking that until this gets sorted out a little bit better, and thinking about historically at other times when we were going through this data coming out all of a sudden that we have to sort of think about. I think one of the big issues is going to be the risk for recurrence for the women. And I think when you look at a node-positive patient, those are the women who maybe are going to be thinking more about taking that kind of a leap of faith. But, I don't know.

DR. BAUM: Well, I'll come clean. Last week, I started my first patient on adjuvant anastrozole and when I describe this scenario it will become clear why I made that decision. She was a tiny little Indian lady, age 82, very frail, she had diabetes and aschemic heart disease, I think also she might have had a stroke in her past because there was something wrong with her speech. She had a superficial mucinous carcinoma. I excised it under local anesthetic. It was strongly ER PR-positive and without a second thought, a clear conscience, I put her on anastrozole. But that was the easy one.

DR. LOVE: There have already been patients out there who had previous history of thrombosis or intolerable hot flashes that people have been doing that.

DR. BAUM: Exactly, I've been speaking with my American colleagues over the last few days, and they've been telling me that just on the basis of the advanced studies in these high risk women without the adjuvant data they've been putting them on Arimidex. In these circumstances, I really do think it is legitimate. Where there are contra-indications to tamoxifen.

DR. LOVE: High risk in terms of tamoxifen?

DR. BAUM: High risk in terms of tamoxifen, I think that is legitimate.

DR. LOVE: Again, understanding that the only way to really understand the effect of this therapy is to wait for more data. But, if you look historically and compare these data to other trials, not just hormonal therapy, other trials where you've seen disease free survival advantages of this magnitude at this point and follow up. What do they tend to predict about what you are going to see several years later?

DR. BAUM: Well, by and large, the early improvement of disease free survival have translated in the long term to improvements in overall survival. There have been a few notable exceptions. The first trials with AC and Taxane, were hyped after two years, and haven't really lived up to their promise.

DR. LOVE: When I watched that presentation yesterday, and it was really neat to think about what the impact was going to be on adjuvant therapy, but my brain was just on fire about prevention. When I saw that second cancer data and then the toxicity profile and I thought back to when the P1 data came out and everyone was so excited, but in affect nothing happened because people were so concerned about endometrial cancer, deep pain thrombosis. Even in the low risk women, there was something sort of psychologically, about using an agent that causes that for prevention. Given the question about bone and given the question about cognition, I think that this is going to be a completely different ball game.

DR. BAUM: I think that qualitatively the adverse effects are very, very different. I can't envisage a dream scenario, you'd have to do the trial of the combination of raloxifene and anastrozole. I know that sounds bizarre bearing in mind the lack of affect we have seen in this trial. But raloxifene is not tamoxifen.

DR. LOVE: And you're talking about for prevention?

DR. BAUM: For prevention, yeah. Or, anastrozole and some other agent totally unrelated to endocrine mechanisms of protecting the skeleton.

TRACK…Impact on second breast cancers vs. recurrence

DR. LOVE: It looked like, and I don' know if this is just a numbers thing or not, but it looked like the impact on second breast cancers was greater than the effect on recurrence. Do you think that's for real?

DR. BAUM: I don't know. You can't compare one hazard rate with another. The hazard rate for relapse is of the order 20%, the odds ratio for contralateral breast cancers is about .460% reduction. They calculated through different statistical ways, one is the log rank analysis for the Kaplan-Meier life table on the relapse. For the contralateral breast cancer it's the comparison of odds ratios. I don't think you can cross compare. Remember that Tamoxifen has a greater impact in the reduction of the risk of the contralateral breast cancer then in the reduction of the risk of the primary cancer.

DR. LOVE: I thought they were both around 50%

DR. BAUM: Sorry, I may be thinking about survival. 30% for survival, 50% for preventing contralateral breast cancer. Sorry, you're right. For relapse free survival and reduction of contralateral breast cancer, they're close.

DR. LOVE: They're about 50%.

DR. BAUM: Yeah, something like that.

DR. LOVE: Is there any way to statistically estimate what anastrozole would do in terms of recurrences compared to control?

DR. BAUM: There is no reliable way of doing that because the populations are different. The populations of women going into trials where we had an untreated control are very different from the population going into the ATAC. But, you can make some crude estimate that if tamoxifen is associated with a 30% reduction in the risk of death and the hazard ratio for anastrozole continues at about 20%, I think you can summate those. So, it's 20% better than 50%. And 20% better than 50% is not 70%, it's 20% of 50% added to the 50%. It's still great, but in a period of 25 years we would have…I mean if you add in chemotherapy therapy, I think we can say with some confidence now that over a period of 25 years we will have reduced breast cancer mortality by 50%, as a result of systemic therapy. And in parenthesis, if I may, nothing to do with mammographic screening. But, my happiness this week, is absolutely complete with those headlines in the Saturday New York Times questioning the value of mammographic screening.

DR. LOVE: You don't think that mammographic screening has any impact on mortality?

DR. BAUM: I think mammographic screening has a great future behind it. And the better the results of systemic therapy the smaller the window of opportunity for screening. Even in the bad old days before successful adjuvant therapy, we had a 25% reduction in mortality from screening. That translates into saving one in a thousand lives over ten years of screening. That's when you're batting against say, 40% risk of death from breast cancer. I don't think mammographic screening has anywhere to go. The better the systemic treatments the less the impact of screening.

DR. LOVE: This is about the longest you ever went into an interview without saying something very controversial. You got pretty far this time.

DR. BAUM: Well, it used to be controversial even to question. It was considered controversial merely to question the value of mammographic screening. It was like questioning the American constitution, but I was delighted to hear Fran Visco open the meeting with a talk where she was shown to be sufficiently open-minded to question the value of mammographic screening.

DR. LOVE: How do you explain the randomized trials on mammography showing a mortality advantage.

DR. BAUM: Well, you compare the quality of the ATAC trial with the quality of the mammographic screening trials. The people setting up the mammographic screening trials, didn't know how to organize screening trials, and didn't know anything about how to organize trials. The Gotzsche Olsen analysis in the Lancet last month and particularly the more detailed analysis in the Cochrane collaboration systematic review took every trial apart. As a clinical trialist, if I had attempted to submit an abstract and give a paper on a trial of adjuvant therapy designed like a trial of screening, I wouldn't get past the committee. There is a double standard here, the quality of trials of treatment, is superb and are open scientific scrutiny. Yet, somehow we accept really shabby clinical trials to demonstrate the benefits of mammographic screening. And the chickens have come home to roost.

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