Anthracyclines: what does one do?

[AlaskaAngel]

My vote goes with Chrisy and StephN.

Some people feel more comfortable with the physicians entirely taking care of the details, especially since as we know they can be complicated. Others want to be more involved in the process. We don't always know which people will want more info. I like to provide others with the choice. If they have no clue that there is always some new info that some docs may not yet be aware of because each cancer is so specific, then they can't really take advantage of various ways to improve their chances.

When I was diagnosed my onc did not tell me about my HER2 status, and I had just assumed that if I was HER2 positive he would have said so, since I was told about my ER and PR status. That piece of information can make a big difference.

I think it is beneficial to mention the general drift and then back it up by providing direction to access to the detailed discussion about it so that they can either pass it by or pursue it further.

[StillHere]

I wish someone would have mentioned the serious risks involved w/ AC therapy. My oncologist stated he felt that AC, Taxol, radiation & mastectomy would give me the best chance for survival and also he felt these were the gold standard at the time in May of 05. If I had to do everything all over again, I would not have used A/C. I later had to stop Herceptin after 7 mos due to low right ventricle heart ejection fraction (dropped to 40). I must also mention I would want someone to tell me if they knew my husband was fooling around. I would rather have all the info up front to make my decision on what to do next for my future. I may not believe or follow the messenger's advise, but I still would like to hear it if my friend thought it was worthwhile info.

[TSund]

Opening this up again because I missed this thread. I fought our first onc like crazy about her rec of the "golden AC/TH standard" because I had read Slamon's research. She treated me like I was a blogging idiot. I refused to back down and I insisted we seek another opinion. I left xeroxes of studies at her office the next day. (I should send her RUth's path report now! or would that be spiteful?) Our new onc is a noted researcher, and although she too first recommended the "standard", after much discussion and careful thought gave us the go-ahead on TCH. Ruth responded wonderfully beyond anyone's hopes. I still feverently believe in getting the Herceptin in the equation ASAP. I'm just a musician, but it seems totally illogical to give AC when you don't know if it will help but there is a strong possibility that Herceptin could be a lifesaver and the AC delays the Herceptin. And the AC could end up getting in the way of the Herceptin if heart complications arise. For us the decision was simple but it is absurd that I had to be the one to find the info. THis should be standard information presented in any HER2+ initial consult.

I asked for Ruth to be given the TOPO ll test after we were under way in the TCH and new onc said there was no point, as TOPO + do better IN GENERAL ?? I still don't know what to make of this, but this onc is excellent in her breadth of knowledge and I decided to trust her. Any thoughts?

I believe too many doctor's are covering their rears and feel they must prescribe the "standard" even when there is evidence pointing in another direction. Our new onc said TCH wasn't proven over the long term yet, but when I asked her if she thought the evidence would prove out in the long run she paused and said "YES, I believe it will". WE decided as a team to go for it.

[TSund]

<TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD class=breadbanner vAlign=top float="left">

• Symposium Meeting

</TD><TD vAlign=top align=left><TABLE cellSpacing=0 cellPadding=5 width=220><TBODY><TR><TD>Coverage of The San Antonio Breast Cancer Symposium is supported in part by an unrestricted educational grant from </TD></TR><TR><TD></TD></TR></TBODY></TABLE> </TD></TR></TBODY></TABLE><!--startclickprintinclude--><TABLE cellSpacing=0 cellPadding=0 width=500 align=center border=0><TBODY><TR><TD style="FONT-WEIGHT: bold; FONT-SIZE: 17px; COLOR: #003399; FONT-FAMILY: georgia" vAlign=top height=40>SABCS: A Call to Scrap Anthracyclines for Breast Cancer <!--startclickprintexclude--><!--endclickprintexclude--></TD></TR><TR><TD style="BORDER-TOP: #ccc 1px solid; BORDER-BOTTOM: #ccc 1px solid" height=40><TABLE width="100%" border=0><TBODY><TR><TD style="PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 5px; PADDING-TOP: 5px">By Michael Smith, North American Correspondent, MedPage Today
Published: December 13, 2007
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco </TD><TD style="PADDING-TOP: 5px" align=right>

Earn CME/CE credit
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</TD></TR></TBODY></TABLE></TD></TR><TR><TD style="PADDING-TOP: 10px"><TABLE width=120 align=right border=0><TBODY><TR><TD vAlign=top align=right><TABLE><TBODY><TR><TD vAlign=top bgColor=white><OBJECT id=mpt_280x170_v2 codeBase=http://download.macromedia.com/pub/shockwave/cabs/flash/swflash.cab#version=9,0,0,0 height=239 width=280 align=right classid=clsid:d27cdb6e-ae6d-11cf-96b8-444553540000>
























<embed src="http://www.medpagetoday.com/mpt_280x170_v2.swf?gTag=/upload/2007/12/13/7682_wide.flv&gType=flv&gTime=11" quality="high" bgcolor="#ffffff" width="280" height="239" name="mpt_280x170_v2" align="right" allowScriptAccess="sameDomain" allowFullScreen="false" type="application/x-shockwave-flash" pluginspage="http://www.macromedia.com/go/getflashplayer" /> </OBJECT></TD></TR></TBODY></TABLE></TD></TR><TR><TD style="FONT-SIZE: 9px; LINE-HEIGHT: 11px"> Dennis Slamon, M.D., Ph.D., UCLA

</TD></TR></TBODY></TABLE>SAN ANTONIO, Dec. 13 -- The anthracycline drugs -- long a mainstay of breast cancer chemotherapy -- only benefit a minority of women and should be mostly scrapped, a researcher said here.

The continued use of the drugs "on a one-size-fits-all approach is just crazy and it's medically dangerous," said Dennis Slamon, M.D., Ph.D., of the University of California at Los Angeles.

Both retrospective and prospective data show that the anthracyclines only benefit women with amplification of both the HER2 receptor and the topoisomerase IIa gene (Topo IIa), Dr. Slamon told an oral session at the San Antonio Breast Cancer Symposium.<?XML:NAMESPACE PREFIX = O /><O:P></O:P> Action Points <!--- ---> <HR style="BORDER-TOP-WIDTH: thin; BORDER-LEFT-WIDTH: thin; BORDER-LEFT-COLOR: #9b9b9b; BORDER-TOP-COLOR: #9b9b9b; BORDER-BOTTOM: #9b9b9b thin dotted; BORDER-RIGHT-WIDTH: thin; BORDER-RIGHT-COLOR: #9b9b9b" width="90%">

• <LI class=APP>Explain to interested patients that anthracycline drugs, including doxorubicin (Adriamycin), have been a mainstay of adjuvant breast cancer chemotherapy for decades, but are associated with long-term toxicity, including cardiotoxicity.<O:P></O:P>
  
  <LI class=APP>Note that this study suggests that the benefit seen with anthracyclines is limited to a small proportion of women with two genetic changes.<O:P></O:P>
  
• This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.<O:P></O:P>

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The amplification of Topo IIa appears only to occur when HER2 is amplified, but not always, he said, so that women with both changes account for about 8% of all women with breast cancer.<O:P></O:P>
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"When we didn't have an alternative and when we didn't know how to identify the women who would benefit, it made sense to use the drugs," he said.<O:P></O:P>
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Now, he said, anthracycline-based adjuvant treatment should be reserved for women who don't have access to therapy targeted to the HER2 receptor, which doesn't apply to women in the U.S.<O:P></O:P>
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The anthracyclines -- notably doxorubicin (Adriamycin) -- yield about a 5% improvement in survival overall, Dr. Slamon said, but they are also associated with cardiac and bone marrow morbidity and mortality.<O:P></O:P>
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"The reality is that there's probably a 25% to 30% benefit for a small subgroup" while the remaining patients do not benefit, Dr. Slamon said.<O:P></O:P>
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The reason, he said, is that the Topo IIa protein is a "major target" of the anthracyclines and the Topo IIa gene is amplified only in a minority of women who are also HER2-positive.<O:P></O:P>
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Dr. Slamon said data from the registrational trial of trastuzumab (Herceptin), which he led, showed clearly that patients with co-amplified Topo IIa were the only ones who benefited from anthracyclines.<O:P></O:P>
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Among HER2-positive women treated with doxorubicin and cyclophosphamide (Cytoxan), those with a normal or deleted Topo IIa gene had a median survival of 18.2 months. In contrast, women with amplified Topo IIa had a median survival of 38.5 months -- a difference that was significant at P=0.004.<O:P></O:P>
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When trastuzumab was added in the experimental arm of the study, the difference disappeared, he said.<O:P></O:P>
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Similar results have been seen in eight other studies, he said, leading to his conclusion that HER2-positive women with amplified Topo IIa are a "unique niche" in which the anthracycline drugs can be used.<O:P></O:P>
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But it may be too soon to consign the drugs to the scrap heap, countered Eric Winer, M.D., of Boston's Dana-Farber Cancer Center, who moderated the session and was not involved in Dr. Slamon's research.<O:P></O:P>
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"It will make me very happy if we can get rid of Adriamycin and its inherent cardiac toxicity," Dr. Winer said. "But I'm not ready to say that this is an agent that doesn't have a role -- yet."<O:P></O:P>
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Dr. Winer said the debate doesn't signal a "rift in the breast cancer community." <O:P></O:P>
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Instead, he said, it's a question of timing: "Most people feel they'll be using a lot less in the way of anthracycline-based therapy in the years ahead," he said, "and there are some people who are running to that goal post."<O:P></O:P>
<O:P></O:P>
Others, he said, are waiting for more than "a bunch of retrospective studies and one prospective trial."<O:P></O:P> <O:P></O:P><TABLE style="BORDER-RIGHT: #8dabbc 1px solid; PADDING-RIGHT: 5px; BORDER-TOP: #8dabbc 1px solid; PADDING-LEFT: 5px; FONT-SIZE: 12px; PADDING-BOTTOM: 5px; BORDER-LEFT: #8dabbc 1px solid; PADDING-TOP: 5px; BORDER-BOTTOM: #8dabbc 1px solid; FONT-FAMILY: arial; BACKGROUND-COLOR: #dbe9f2" cellSpacing=0 hspace="1"><TBODY><TR><TD>The research was supported by the Revlon Foundation, Genentech, and Amgen. Dr. Slamon reported financial relationships with Genentech and sanofi-aventis. </TD></TR></TBODY></TABLE>

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Primary source: Breast Cancer Research and Treatment
Source reference:
Slamon DJ, et al "Role of anthracycline-based therapy in the adjuvant treatment of breast cancer: efficacy analyses determined by molecular subtypes of the disease" Breast Cancer Res Treat 2007; 106 (Supp1): Abstract 13.

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[Lani]

Dr Slamon got his numbers by estimating her2+ivity at 24% and saying that 1/3 of her2+s were also TOPOIIa positive hence 1/3x24%=*% THat left the other 92%of bc patients, her2+s without TOPOIIa and her2- who did not benefit. Even the 8% he said, did no better with the anthracycline and herceptin than with TCH --just equally well, so why risk the toxicity he asked?

[TSund]

Amen. This also explains why our onc. didn't feel necessary to do the TOPO test.

[StephN]

OK. Did not realize that these figures include ALL breast cancer patients.

I thought that 8% was an awfully low number for just HER2+'s. Thanks for the clarification.

Seven years later I can't see that it is the Adriamycin that has affected me long term since I took several other chemos following that.

Also I was in a trial that was trying to minimize Adria side effects while giving a greater total amount. TWELVE weekly infusions. So more smaller doses more often. I never had ANY nausea that way.

Just trying to maintain a reasonable level of health, and would have liked to have had a less toxic regimen.

[madubois63]

Grace - I have read the replies and then reread your question several times. I have to agree with Debbie, this can be a very sticky situation!! I think it all depends on the person that you may or might not be offering the advise too. Not everyone wants to be proactive in their care. For all the members here at this site learning and discussing their own treatments WITH the doctors, there are 10 or 100 times more people that don't want to know anymore than what the doctor offers. I have friends that let husband's and family deal with the doctors and just do the treatments without even knowing what they were getting. I think that you should tell the person that you read a lot about the subject and that you would be glad to help find information if the person was interest. Great opportunity to give out this site...

I did not have the test. I do not regret any chemo or treatment I've done. I did have to stop Herceptin for a few months because of a drop in the MUGA, but that fixed itself; and of course, I did get that blood cancer you mentioned. Genetic testing says it was from the carboplaten and not the adriamycin. Funny thing, several anthracyclines were used to fight my leukemia.

[janet11]

Interesting -- I hadn't heard of blood cancer from the carboplatin. In fact, i hadn't heard of any major side effects from the 'c' at all.

Wish my LVEF had reversed after stopping the Herceptin though. It turns out that for some people, it looks like the heart damage is permanent. And apparently I'm one of those. After hearinga bout all the problems with Andriamycins, I didn't even think that the Herceptin would cause problems. Funny.

Anyway, it was still worth it I think. At least how that I've stopped the Herceptin, it's not getting worse (and heart function is improving with meds).