jeffntate

SUNDAY, April 13 (HealthDay News) -- A breast cancer vaccine significantly reduced the risk of recurrence for patients who have a high expression of the protein HER2-neu.

This type of breast cancer, representing about one-quarter of all cases, tends to be deadlier than other forms of the disease. In this group, the vaccine reduced mortality by 50 percent.

Even better, however, the vaccine lowered mortality by 100 percent in women with breast cancer and low or intermediate expression of HER2/neu. Currently, these women have no therapies other than conventional cancer treatments such as surgery and chemo.

"We now have something we think works in the majority of women with breast cancer who are currently underserved," said Dr. George Peoples, senior author of the study, which is expected to be presented at the American Association for Cancer Research annual meeting, in San Diego. "It's also very, very well-tolerated, like a flu shot."

Peoples is chief of surgical oncology at Brooke Army Medical Center in San Antonio and director of the Cancer Vaccine Development Program at the U.S. Military Cancer Institute.

According to study lead author, Dr. Linda Benavides, a resident in general surgery at Brooke Army Medical Center, the biotech firm, Apthera, has licensed the vaccine, named it NeuVax, and is currently planning phase 3 clinical trials.

But there's still no guarantee the vaccine will reach the market.

"It is a very exciting area of research, but it's very exploratory and not ready for prime time," said Dr. Minetta Liu, a translational researcher/breast oncologist at Georgetown's Lombardi Comprehensive Cancer Center.

Other cancer vaccines have been tested, mostly to treat tumors that have already spread, with little success.

"We've been studying vaccines in the setting of metastatic cancer, but the immune system has already been effective, and the cat's out of the bag already," Liu said. "Many of us believe the time to get rid of them is as they're developing. It's just so hard to study it in that setting."

This vaccine (also known as E75), which stimulates the immune system to recognize the cancer as foreign, aims to prevent a recurrence in women who have already had one round of cancer. It is the furthest along of all the cancer vaccines.

This trial involved 165 breast cancer patients with HER2/neu tumors and lymph node involvement; 94 were vaccinated (initial shot plus boosters) and 71 served as controls.

Immunity was raised in all women who received the vaccine, but the biggest benefit was seen in those women with low and intermediate expression of HER2/neu or those who are not eligible for Herceptin, the drug currently used to treat this type of cancer.

After a follow-up of about 30 months, recurrence rates were similar between high overexpressors in both the vaccine and control groups (18.2. percent and 13.8 percent, respectively). But, there was a greater than 50 percent reduction in mortality rates.

In those with low or intermediate expression of the protein, results were more startling. Less than 11 percent of low HER2/neu expressors had a recurrence, versus 18.2 percent in the control group. The mortality rate in the vaccine group was zero, compared with 38 percent in the control group.

The downside of leaving it in is the additional time the tumor has to spread.  Like atomic decay, it's a probability equation that increases the chance of spread the longer it is left in the body.  My wife was triple neg, and the tumor actually grew while she did DD taxotere.  Yes it is nice to know the tumor shrinks but even if you get a pathological complete response, there still is no guarantee it has been totally destroyed if spread elsewhere already.  It's a tradeoff and no human being knows the true answer.  I was personally relieved to know the monster inside had been eradicated from my wife's body.  Hopefully it was taking out before it spread but that is why they do post-op chemo and radiation.  I've read thousands of research papers only to conclude it's all a gave of chance and there is no 100% anything about cancer.  Look forward to things like eating right and exercising which according to papers I read this summer  reduced recurrence by as much as 50%. 

Jeff

My wife Karen has completed her T-AC and was hospitalized for four days for GI issues and not being able to eat.  Now the diaherra has subsided but she still wakes up naused and requires both Zofran and Phenegran to get up and about.  Anyone else have this post-chemo nausea problem and how did you lick it?  Also, she has occassionally vomited (more like spit up) some white looking junk that I think is stomich acid.  Not violent vomiting, just stuff coming up.

Thanks,
Jeff for Karen

You can get the full prereleased (28 page) report at this web site:

http://jco.ascopubs.org/cgi/reprint/JCO.2007.14.2364v1

Maybe this is what I'll send to my wife's oncologists to push for more information on her tumor ;)

Thanks for the lead on this Tender!

Jeff

Well they did the BNP tests and my wife's score was well below the threshold for concern of heart damage.  Perhaps the anticipatory ACE inhibitor mitigated some of this risk or she has an Angel on her side.  It's a relief and a blessing to know with these BNP results that we no longer need be concerned with cardiotoxicity and can return our focus to killing the cancer and preventing recurrence!

The advice my wife was given was specifically to NOT take a multivitamin with either Iron or Copper.  If you do some research you will find out that both potentiate the adriamycin (A in the AC) and contribute to cellular damage in the heart muscles.  She was also told by the Professor of medical oncology to take vitamins only (no minerals) and to take the ones with 100% and no extras to avoid getting too much antioxidants that can decrease the effectiveness (tumor killing property) of the adriamycin.  Taking this is no different than eating a well balanced meal, so it's OK to take the one a day type vitamins.  When in doubt, ask before doing anything with supplements while in chemotherapy, and do your own research.  You'll be amazed what you will find with google.  Use the term doxorubicin rather than AC or Adriamycin and you will find more of the information the oncologists are reading.

Jeff 

My wife is triple negative and during the first 3 taxotere treatments her tumor was not growing, but after the 4th it took off and they decided to go to immediate mastectomy rather than onto AC (she was in a clinical trial to determine the biomarkers that would correlate to taxotere response so an ideal case for tumors that do not respond).  We pushed and got the tumor board to "agree" to try carboplatin and gemzar due to some research at Dana Farber that indicated a possible sensitivity of triple negs to the platins.

Here is what a cardiologist told our oncologist:

I was at the meeting where Dan Lenihan presented this.  As he points out in the story, there isn't enough data out there to say whether you should change your plan based upon a BNP.  If you find one that's high, are you going to alter her therapeutic plan?  At this point, the biggest change a rise in BNP might trigger is reaching for ACEI or Beta blocker.  

The indication for ACEI or beta-blocker are small clinical studies, but if I were to undergo anthracycline Rx I would put myself on one.  My bias would be to take a beta blocker. 

The doctor said the same thing.  I registered to get on Medscape (you don't have to be a doctor but you do fillout a registration).

Here is the article:

Serial Natriuretic Peptide Testing Can Predict Anthracycline Cardiotoxicity Risk

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September 27, 2007 (Washington, DC) - Measurement of brain-type natriuretic peptide (BNP) levels in cancer patients receiving anthracyclines can predict the treatment's risk of cardiotoxicity more reliably than troponin levels or echocardiographic assessment of LV function, according to a small prospective study [1].

For example, a BNP reading >100 pg/mL on two occasions signaled an 18-fold increase in risk of heart failure, arrhythmias, or other cardiovascular complications. The risk was much steeper if levels exceeded >200 pg/mL only once.

Even though oncologists well know to watch for the cardiotoxic effects of doxorubicin and other anthracyclines, "there's a range of how vigilant they might be," Dr Daniel J Lenihan (MD Anderson Cancer Center, Houston, TX), a cardiologist, told heartwire. "Some might look for them aggressively and others may not. The good thing about this is that it's a point-of-care test, so even in a small oncology practice, they can easily check a blood sample in their office while they're waiting to get the IV in. You can get the results in 15 minutes."

Serial BNP testing probably isn't enough on its own to indicate withdrawal of the drugs but can help identify patients who should be watched more carefully for cardiac side effects, according to Lenihan, who presented the study here at the Heart Failure Society of America 2007 Scientific Meeting.

A lot of its 109 patients, under treatment for various malignancies, also had cardiovascular risk factors, which may help promote anthracycline cardiotoxicity, Lenihan and his colleagues speculate. A tenth of the patients had documented CAD, a third had hyperlipidemia, 50% had hypertension, 35% were obese, and 12% had diabetes. Patients with unstable angina, a recent history of MI or acute heart failure, or an LVEF <40% were excluded.

Biomarkers were normal at baseline in virtually everyone; echocardiography was performed at baseline and at 18 and 24 weeks.

The patients received up to six courses of chemotherapy, each three weeks apart and preceded and followed by measurements of BNP and troponin I; 71 patients completed all six courses.

Eleven patients experienced cardiac events over a median of six months; the events included symptomatic heart failure in five, symptomatic arrhythmias in four, and ACS in two patients. All 11 had BNP levels >150 pg/mL on at least one occasion.

Unadjusted odds ratio (OR) for a cardiac event (95% CI) by BNP and LVEF finding <table><tbody><tr><td>Risk factor </td><td>OR (95% CI) </td><td>p </td></tr><tr><td>1 BNP test >200 pg/mL </td><td>88 (10-761) </td><td><0.0001 </td></tr><tr><td>2 BNP tests >150 pg/mL </td><td>23 (5-97) </td><td><0.0001 </td></tr><tr><td>2 BNP tests >100 pg/mL </td><td>18 (4-88) </td><td>0.0005 </td></tr><tr><td>LVEF indicative of cardiotoxicity </td><td>2.2 (0.1-9) </td><td>0.29 </td></tr></tbody></table>

Troponin levels remained normal in all but two patients, both of whom were among those experiencing cardiac events.

In multivariate analysis, significant predictors of cardiac events included BNP levels >100 pg/mL, >150 pg/mL, and >200 pg/mL (p<0.0001 for each) prior to any such event. History of MI also emerged as a significant predictor (p=0.05), but it's hard to make anything of it, since it was present in only four patients, Lenihan said.

Most studies in oncology assess cardiotoxicity according to echocardiographic changes in LV function, he said; but a decline in LVEF considered indicative of cardiotoxicity was not a significant predictor of events in this study (p=0.376).

Whether elevated BNP levels by themselves are enough to justify stopping anthracycline chemotherapy remains an open question, according to Lenihan. They can help, he said, but it would depend on the patient's entire clinical picture. "I think it's a marker of risk. It doesn't necessarily mean you have to stop therapy, but it definitely identifies a group you should be more worried about."

Lenihan reports being a consultant for St Jude Medical and receiving honoraria from Novartis.

1. Lenihan DJ, Massey MR, Baysinger KB, et al. Superior detection of cardiotoxicity during chemotherapy using biomarkers. J Cardiac Failure 2007; 13(Supple 2):S151. Heart Failure Society of America 2006 Scientific Meeting; September 17, 2007; Washington, DC. Abstract 265.

The complete contents of Heartwire, a professional news service of WebMD, can be found at http://www.theheart.org/, a Web site for cardiovascular healthcare professionals.

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This article contains a new way that is per the report is much more accurate than a MUGA in predicting heart damage from Adriamycin.

http://www.medscape.com/viewarticle/563469

Jeff