Anthracyclines: what does one do?

11-13-2007, 07:53 AM

"Then Dr. Slamon's closer inspection found that not all Her2 patients are alike — and only those who have a second overactive gene, called TopoII, derive special benefit from anthracyclines. That's about 8 percent of breast cancer patients."

The above quote is from an article I read recently, probably on this site. My question is, if you find out that someone recently diagnosed with breast cancer will begin treatment with an anthracycline, do you point out the recent research or do you keep quiet? I did extensive research before I began my treatment and rejected adriamycin up front, but not all women have the time to do the same. I have no medical credentials and I don't feel I have any right to issue recommendations if not asked specifically, yet there's a part of me that thinks I have a moral obligation to point people to the latest research. Since Anthracyclines are particularly tough on the heart and are also, I believe, the main culprits in women who later get blood cancers I really don't know what to do, and it's been bothering me quite a bit. What would you do?

janet11 · 11-13-2007, 10:13 AM

I had the test for the Topo II gene and as a result, had a chemo that did NOT include an anthracycline. Turned out good for me since just having Herceptin hit my heart and I had to stop that treatment early. I hate to think what an anthracycline would have done.

However (and I discussed this with my onc), I understand that the tests with the topo II gene have only had a very few people to substantiate this theory, and simply... it may or may not be true. There's just not enough results yet and it's too early to tell for sure. However, my onc thought it was worth doing and I'm glad she did.

janet11 · 11-13-2007, 10:15 AM

Ahh.. but what I meant to include is: not all doctors are willing to order this test when there are very few labs that do it and not everyone agrees that this research is definitive. I know others who have had oncs that will NOT do it because of this.

vickie h · 11-13-2007, 10:27 AM

HI Grace, You bring up a very important subject. I had to stop and think about whether I had that test done, I never did the AC as was suggested by Stanford, but not by UCLA. I wonder if that was the reason. I see my Onc on the 29th of this month and will ask her. And here I thought I was being so pro active......
Happy Thanksgiving to you, dear sister, Love, Vickie

suzan w · 11-13-2007, 11:49 AM

I wonder if it matters as to what type of breast cancer one has...when I made the decision to do A/C, it was based on my oncotype results and the fact that I had invasive lobular carcinoma-which, according to my research and backed up by my oncologist, has a higher chance of recurrance. There are just so many variables, eh??!! I did have a TERRIBLE time with the A/C and only had 4 treatments instead of the originally prescribed 6...and at the time I was going through it I seriously questioned if I was doing the right thing!

Hopeful · 11-13-2007, 12:01 PM

Grace,

I believe there was a thread on this board a month or so ago about the fact that anthracyclines were not beneficial to Her2-, ER+ patients, as well. I feel the same as you do, I am not a medical professional, but I also do not want to see people subjected to unnecessary toxicity. I would favor mentioning the research with the caveat that the person should take a copy of it to their doctor and get the doctor's opinion, or also a second opinion, before proceeding with treatment.

Hopeful

mimiflower07 · 11-13-2007, 12:37 PM

sooo glad that this is the topic. i'm struggling on what to do. I see the onc tomorrow for the first time. after reading about the group of a/c not sure thats the combo i would want.

please share more of your thoughts. Here's my situation once again
bilat mast, tumor 2.5 cm with satellite nodes in rt breast. clr margins, neg nodes, no lymph vascular invol seen. Bone, ct scan and back xray neg(except arthritic changes) 42 yrs old. Any suggestions? Do you think a/c is what they'll suggest? I will no more info tommorow when bld work back..ie fish...etc

Is it possible that taxol and herceptin would be enough?
suzanne

Brenda_D · 11-13-2007, 01:54 PM

I was not tested for TOPO II, and did get A/C last year. But I feel that it was the right thing for me, as my IDC was aggressive and fast growing (KI 67- 70%). I did and still do have concerns about heart damage and complications later on, but for now I am NED, afaik, and that's given me the will to keep fighting. I can't say whether it was the A/C, the rads, the Herceptin, the prayers! , or all of the above, but something got rid of the BC in my IM node and I am thrilled that I am living right now. I will deal with the future a day at a time, and not regret any treatments, or decisions by me or my doctors.

ckeesling · 11-13-2007, 01:59 PM

When I was diagnosed one year ago, the Cancer Conference in Texas had not concluded. My onc wanted to wait and see what they determined was the benefit, if any ,to include or not include AC. It was determined by my onc, that the benefit of Taxotere w/Carbo and Herceptin was the same as with the AC, but a reduced chance of heart issues. So we chose the TCH only, with heart ultra's every 3 months. Luckily I haven't had any negative effects.

Good luck with what you choose as your best defense!!!
Cat

11-13-2007, 02:49 PM

Suzan,

I can only tell you what I did prior to treatment. Before my first visit with oncologist--I already knew my pathology--I did extensive research on various chemos, treatments, including herceptin, to understand what I was likely to be offered. I wanted to know all the benefits and the disadvantages of each treatment. I had determined during my research that I wanted only herceptin. My oncologist agreed with that conclusion, but when my tumor markers were elevated I changed my mind and decided on chemo: taxol and carboplatin. Again, my oncologist agreed. I have a long history of heart disease in my family and my research lead me to conclude that I did not want any type of anthracycline, in particular adriamycin, as my reserch indicated that they were very hard on the heart, particularly when coupled with herceptin.

In the sixteen months since my original research, additional papers have been published (check Lani's posts as she posts most of the research on this site) on the dangers and benefits of anthracyclines--apparently the benefit is small to women with primary breast cancer, but you should check this out yourself. Recent research also suggests that taxol is of particular benefit to women with HER2 cancers, but again please check this out for yourself.

I suppose I would say be prepared with lots of questions when your treatment options are presented to you. Ask why a particular chemo (or why not) and what benefit it provides to you in particular, based on your pathology. Also ask how recent the research is for the treatment being suggested. It's very important, I think, to be active in your own treatment.

I'm comfortable with the decisions I made although I might not have made the same decisions if I were deciding today. I'm particularly happy that I did herceptin for a year. Good luck in whatever you decide.

dlaxague · 11-13-2007, 04:07 PM

Back to Grace's original and excellent question:

How do you make a decision whether to tell someone else about information that you believe to be true, and that may be of use to them? We are not medical professionals. When we use information we've gathered, for our own benefit that's one thing. But to challenge or question medical advise third-hand gets mucky.

What if the "friend" who we advise had a great relationship with her provider, and our meddling ruins that, and there's still no change in tx recommendations? What if we say nothing and the friend goes blissfully (ignorantly) along and what we had to offer could have made an important difference - even saved a life?

I agree that it's an awkward place to be. For me, for many reasons, most often I keep my mouth shut unless it's blatant error/bad advice that I'm hearing. Only with people who are already close friends do I go into detail about my thoughts or understanding, and even then only when I perceive that they are interested and receptive.

Debbie Laxague

11-14-2007, 09:24 AM

Thanks Debbie--that was what I had hoped to hear, as it reflects what I did, although I still have some guilt about it. But you're correct, we should only give advice when it's asked, and even there, we need to be fine tuned enough to know if advice is really wanted. Often it's not!

StephN · 11-14-2007, 02:35 PM

As one who did NOT have the benefit of the TOPO II test (not yet discovered) AND took an anthracycline being Adriamycin, I can speak up and say that I have a strong feeling I am one of those 8% this drug class does not work for.

My cancer was stage II at diagnosis and one year later, after Adriamycin, Taxotere and radiation, my cancer was back in a very big way. I also did not have the benefit of Herceptin with my first round treatments, but obviously the taxane could not stop the progression either.

I am hopeful that the TOPO II assay will be more widely available, as I am not the only one to progress quickly and many on this site have also progressed on Herceptin or just after completing their year.

More of us would have a better chance at achieving and staying in remission with more precise testing and pathology.

chrisy · 11-14-2007, 03:13 PM

Again, back to the original question, I would share the information (get the article if you can) and let her show this to her onc. Many oncologists who are VERY GOOD doctors are not breast specialists. There is so much research, so much news all the time, it is impossible for anyone to know it all, and a good doctor will not be offended by the question. This is serious business, and you should use all the knowledge you can to get the right treatment. Just my opinion.

weezie1053 · 11-14-2007, 07:38 PM

I see my Oncologist on Friday for my last Herceptin treatment. I would love to have access to the articule...does anybody have it? This is the first I have heard about TOPO II. StephN, I too am Stage II, and it is natural to think you may be out of the woods. After reading your thread, I realize we need to keep informed.

11-14-2007, 07:56 PM

Actually Stephanie, I believe Dr. Slamon's research showed that it worked for only 8% of BC patients, which would leave the other 92% in the cold. I gather that his research showed that it worked for only women with Topo II and that's about 8% of BC patients. I'll look to see if I can find the original article. I believe Lani posted it, so perhaps if she reads this thread, she'll post it again. I'm relying on memory, which after chemo often leaves me high and dry.

dlaxague · 11-14-2007, 11:10 PM

I don't have the exact figures at hand, either, although it seems like it was in the 92/8 range. But some of these posts are leaving out an important part - no one nor no study said that anthracyclines DON'T WORK for 92%. They said that anthracyclines don't work BETTER (than CMF, I think) for 92%. And since anthracyclines have a worse side effect profile, it wouldn't make sense to use a drug that didn't work better and had worse side effects.

Debbie Laxague

SoCalGal · 11-14-2007, 11:31 PM

If you are on AC you can take COQ10 to protect your heart.
Good luck,
Flori

StephN · 11-15-2007, 05:28 AM

Yes, Grace, I see that I got my number mixed up. I am not sure how the 92% vs 8% numbers were arrived at (an estimate by Dr. Slamon I think), and also do not think there has yet been enough testing in our breast cancer subtype to establish those firmly.

Also a function of how exhausted I am from these months of my dad's poor health. Details slip out of my head.

11-15-2007, 06:20 AM

Yes, Debbie is correct regarding anthracyclines. And Stephanie is correct as well. I can't find the original post where I read about Dr. Slamon's recent research, but here's a review from Medscape:

Anthracyclines May Not Be Necessary in Adjuvant Therapy of Breast Cancer

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December 18, 2006 (San Antonio) — Anthracyclines have formed the backbone of adjuvant treatment for breast cancer, but new data presented at the 29th Annual San Antonio Breast Cancer (SABC) Symposium have raised the provocative question of whether they are necessary. A large study has shown that a regimen of taxane plus trastuzumab (Herceptin, Roche/Genentech) is similar in terms of prolonging survival to a regimen containing an anthracycline plus trastuzumab but has much less toxicity. The data offer a new option for women with early-stage HER2+ breast cancer and will influence daily clinical practice, predicted cochair of the study, Dennis Slamon, MD, PhD, from the University of California, Los Angeles Jonsson Comprehensive Cancer Center. However, other experts were less enthusiastic. At a separate session, Gabriel Hortobagyi, MD, from the University of Texas MD Anderson Cancer Center, in Houston, said he wasn’t convinced enough yet to stop using anthracyclines.

In an interview with Medscape, David Cameron, MD, from the Western General Infirmary, in Edinburgh, Scotland, said he thought that anthracyclines will continue to play a major role in the treatment of breast cancer, but he agreed that their role is being challenged in the treatment of HER2+ breast cancer (a subgroup representing some 20% to 25% of all breast cancers) by these new data.

Study in Early-Stage HER2+ Breast Cancer

The new findings come from the Breast Cancer International Research Group (BCIRG) 006 study, which involved 3233 women with early-stage HER2+ breast cancer, with or without axillary lymph node involvement. Supported by Sanofi Aventis with funding from Genentech, the study had 3 groups, comparing standard therapy with 2 experimental ones, as follows:

Group A, the control group — 4 cycles of doxorubicin (Adriamycin) and cyclophosphamide followed by 4 cycles of docetaxel (Taxotere, Sanofi-Aventis).

Group B — Trastuzumab added to the group A regimen.

Group C, the group without an anthracycline — 6 cycles of the taxane docetaxel with carboplatin and trastuzumab.

At the meeting, Dr. Slamon presented results from a second interim analysis of this trial, with a median follow-up of 3 years. The results confirm the findings of the first interim analysis, announced in April 2005. Dr. Slamon noted that since that time, only 17 patients from 1073 randomized to group A (1.6%) have crossed over to receive trastuzumab, which leaves 98.4% of the control group intact.Both experimental groups had significantly better outcomes than the control group in reducing the risk for death and improving disease-free survival. The differences between the 2 experimental groups were not statistically significant, Dr. Slamon noted. Second Interim Analysis of BCIRG 006, Median 3-Year Follow-Up
<table border="1" frame="box" rules="all"> <colgroup> <col width="146"> <col width="146"> <col width="146"> <col width="146"> </colgroup> <tbody><tr valign="top"> <td colspan="1" rowspan="1" valign="top" width="146"> </td> <td colspan="1" rowspan="1" valign="top" width="146"> Group A
</td> <td colspan="1" rowspan="1" valign="top" width="146"> Group B
</td> <td colspan="1" rowspan="1" valign="top" width="146"> Group C
</td> </tr> <tr valign="top"> <td colspan="1" rowspan="1" valign="top" width="146"> Patients, n
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 1073
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 1074
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 1075
</td> </tr> <tr valign="top"> <td colspan="1" rowspan="1" valign="top" width="146"> Deaths, n
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 80
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 49 (P = .004)*
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 56 (P = .017)*
</td> </tr> <tr valign="top"> <td colspan="1" rowspan="1" valign="top" width="146"> Relapses, n
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 192
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 128 (P < .0001)*
</td> <td colspan="1" rowspan="1" valign="top" width="146"> 142 (P = .0003)*
</td> </tr> </tbody></table>
*P for comparison of experimental group with control group (A).Significant Differences in Toxicity However, the 2 experimental groups, while similar in efficacy, showed significant differences in toxicity. This was particularly apparent with cardiotoxicity, which was 5 times lower in with the nonanthracycline regimen (group C) compared with group B, which had the double whammy of cardiac damage from the anthracycline and from trastuzumab. Congestive heart failure (grade 3/4) developed in 20 patients in group B, compared with 4 patients in group C group and 5 patients in group A. An asymptomatic decline in cardiac function was seen in 8.6% of patients in group C, compared with 10% in group A and 18% in group B. Group C also showed significantly lower toxicity than both anthracycline-containing groups with regard to several other side effects, including arthralgia and myalgia, hand-foot syndrome (none seen in group C), stomatitis, vomiting, nail changes, and neuropathy. Hematological toxicity showed different patterns between the groups, with group C showing significantly less neutropenia and leukopenia but more anemia and thrombocytopenia. Dr. Slamon noted secondary leukemia developed in both of the anthracycline-containing groups — in 3 patients in the group A and in 1 patient in group B, but no cases have been seen in group C.In summary, Dr. Slamon said the updated results show a difference in the number of disease-free survival events and breast cancer deaths in favor of the group B regimen, but neither is statistically significant, and they are now exceeded by the number of critical adverse events, including CHF, loss of cardiac function, and anthracycline-related leukemia, all of which are highly statistically significant. Thus, the trial demonstrates an optimal therapeutic index for these patients with the use of the group C regimen, he concluded. Dr. Slamon noted that, quite separately, a recently published trial has shown significantly superior efficacy in breast cancer for an anthracycline-free regimen of docetaxel plus cyclophosphamide compared with doxorubicin plus cyclophosphamide (Jones SE et al. J Clin Oncol. 2006;24:5381). In view of this reported superior efficacy and now the equivalent efficacy but milder toxicity reported from his own study, he threw out the provocative question of whether anthracyclines were necessary for adjuvant therapy.29th Annual SABC Symposium: Abstract 52. Presented December 14, 2006.