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Old 03-27-2010, 03:55 PM   #1
Christine MH-UK
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CEP17 seems to be key to anthracycline susceptibility

I figured that this one is a pretty important answer to a pretty major question: who actually benefits from those potentially cardiotoxic anthracyclines.

http://www.eurekalert.org/pub_releas...-nwd032410.php

As someone who had a very minimal response to anthracyclines and an unusually high level of side effects, I am glad to see that a charity I support Cancer Research UK, has helped answer this question. Might even send them a well done letter!
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Old 03-27-2010, 08:01 PM   #2
Debbie L.
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Re: CEP17 seems to be key to anthracycline susceptibility

I do so wish that we had an answer to this. But the waters remain muddy. Same conference (EBBC7):

http://cmwebcast.covr.be/presentatio...6/default.aspx

I need to watch this again, but what I heard was that they saw topo2a association with anthracycline response in ER negative cancers, not just HER+ cancers. Which would seem to say that it's not CEP17, and not HER2+ either.

Denny Slamon has so far maintained that the marker for additional benefit of anthracycline is topo2a (overexpression, amplification, deletion?) AND that the relevant topo2a mutations are limited to HER2+ cancers.

So although this link that I've provided seems to implicate topo2a (rather than CEP17), it does not limit the topo2a mutations to HER2+ cancers.

Whatever is the marker for additional benefit of anthracyline, we are talking about an important subgroup of cancer, because they are high-risk cancers. If anthracyclines do offer an additional benefit to some subgroup within these subtypes (ER-, HER2+, topo2a mutated), the absolute value of the additional benefit is high, because the risk is high.

Like I said, frustrating. All of these discussants (Slamon, Bartlett, Jules Bordet institute/Piccart) are well-respected experts. How to know what's the truth?!

I used to think that this was nitpicking. But the more I pay attention, the more women I meet who are post-treatment. When these wonderful women die from side effects of TREATMENT rather than from their breast cancer (Madubois on this list from anthracycline se's, Carolina Hinestrosa of NBCC from radiation se's), it forces me to pay more attention to the issue of treatment implications.
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4/01 ~ Bilateral mastectomies (LMRM, R elective simple) - 1.2cm IDC was found at pathology. 5 of 11 axillary nodes positive, largest = 6cm. Stage IIIA
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Old 03-30-2010, 02:39 PM   #3
AlaskaAngel
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Question Prevention

As you know, I share that concern, especially in terms of effect through the prolonged and repeated use of steroids for support with chemotherapy in causing obesity. What would the long-term survival rate be for stage I breast cancer patients, the majority of whom never need any treatment beyond surgery, if they never did the steroids that come with chemo?

Given that there is serious discussion about blanket treatment with steroids and chemotherapy even for stage 0, isn't it time that we considered ALL the components of therapy for their effects, before assuming that any negative effects are negligible?

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Old 03-30-2010, 04:11 PM   #4
Christine MH-UK
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Re: CEP17 seems to be key to anthracycline susceptibility

Yes, of course, these treatments should not be taken too lightly.

At the same time, some patients do benefit. In Bartlett's earlier work, it seems that at least 15 out of 100 women benefitted from the anthracycline if they had abnormal CEP17:
http://www.gbcc.kr/pdf/GBCC2009_Panel_5-1.pdf
There was no benefit to the normal CEP17 group. Anything that reduces patients getting treatments that will only give them side effects is a good thing, especially when the side effects are so serious.

And yes, there is a great deal of discussion about whether the predictor is her2 or topoIIa or CEP 17. Bartlett's point (see slide 25 above) is that cancers with abnormal CEP17 are more likely to have deleted topoIIa (over four times) or amplified topoIIa (1.5 times) and are twice as likely to be her2 positive. So, some of the connection between topoIIa and her2 and response may actually come from CEP17.

It's like when they found a link between coffee drinking and heart attacks, which seems to suggest that coffee is the problem. Then they discovered that heavy coffee drinkers are more likely to smoke, which turned out to be the cause of the heart attacks.

It would be a bit more convincing if they knew why CEP17 made such a big difference, since right now they only have a correlation without anything in the way of causation. I notice that in the scientific abstract he only says that CEP 17 may be important.
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