vaccine results may not be as straight-forward as thought--a bit disconcerting!

[Lani]

Here, too, her2+er+ breast cancer/dcis seems to behave differently than her2+er- breast camcer/dcis and those who still have residual disease who are er+ may have more options for further treatment than those who started er-

Good thing these patients only had DCIS. As I said the results are somewhat disconcerting!

This study was of pulsed dendritic cell vaccine-- it is unclear it other vaccines would have similar effects. I previously reported much better results for other vaccines, but they worked differently and were used differently (against invasive disease vs dcis)

ABSTRACT: HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ
[Cancer]

Background: HER-2/neu overexpression plays a critical role in breast cancer development, and its expression in ductal carcinoma in situ (DCIS) is associated with development of invasive breast cancer. A vaccine targeting HER-2/neu expression in DCIS may initiate immunity against invasive cancer.

Methods: A HER-2/neu dendritic cell vaccine was administered to 27 patients with HER-2/neu-overexpressing DCIS. The HER-2/neu vaccine was administered before surgical resection, and pre- and postvaccination analysis was conducted to assess clinical results.

Results: At surgery, 5 of 27 (18.5%) vaccinated subjects had no evidence of remaining disease, whereas among 22 subjects with residual DCIS, HER-2/neu expression was eradicated in 11 (50%). When comparing estrogen receptor (ER)neg with ERpos DCIS lesions, vaccination was more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ERneg subjects compared with 5.9% in ERpos subjects. Sustained HER-2/neu expression was found in 10% of ERneg subjects compared with 47.1% in ERpos subjects (P = .04). Postvaccination phenotypes were significantly different between ERpos and ERneg subjects (P = .01), with 7 of 16 (43.8%) initially presenting with ERposHER-2/neupos luminal B phenotype finishing with the ERposHER-2/neuneg luminal A phenotype, and 3 of 6 (50%) with the ERnegHER-2/neupos phenotype changing to the ERnegHER-2/neuneg phenotype.

Conclusions: Results: suggest that vaccination against HER-2/neu is safe and well tolerated and induces decline and/or eradication of HER-2/neu expression. These findings warrant further exploration of HER-2/neu vaccination in estrogen-independent breast cancer and highlight the need to target additional tumor-associated antigens and pathways.

[Sandra in GA]

The AE37 vaccine that is being tested in the Walter Reed study for HLA-A2 neg. subjests is showing that it can stimulate the body's defense. This is a peptide vaccine and it is also being tested in prostate cancer with positive results. I hope that is what I am getting and will complete this trial in September of this year.

['lizbeth]

Hello SandraGA,

Nice to see your post. I'm finished with all my trips to San Antonio and am suffering from withdrawals from my amazing nurses and the beautiful Riverwalk. Plus I don't get to see my niece and nephews often anymore.

I think Lani's post is wonderful news. The vaccines are very effective for Her2+/ER-. That's me!

I'm so grateful I was able to participate in the AE37/GP2 vaccine trial. I suspect I am still NED today due to the injections.

Lani, I don't understand this line in the results: Postvaccination phenotypes were significantly different between ERpos and ERneg subjects (P = .01), with 7 of 16 (43.8%) initially presenting with ERposHER-2/neupos luminal B phenotype finishing with the ERposHER-2/neuneg luminal A phenotype, and 3 of 6 (50%) with the ERnegHER-2/neupos phenotype changing to the ERnegHER-2/neuneg phenotype.

Is it possible for you to translate it into English for me?

[Lani]

They gave the vaccine after diagnosing the DCIS by core biopsy but prior to doing the definitive surgery. Thereafter they did the definitive surgery and looked at the DCIS specimen and tested it for ER, PR and her2/

Underinfluence of the her2 vaccine, the patients immune systems fought back against the her2+ cells, but in some patients the residual tumor was made up of other types of cells this was not so bad for those with Er+her2+ breast cancer as they were left with ER+her2- breast cancer for which there was still antiestrogen treatment avaiable. For those with her2+er- disease, what was left was her2-er- for which there were few good drugs (they are trying cisplatin, antiEGFR drugs, PARP inhibitors etc but Triple Negative disease remains difficult to treat.

Again this was DCIS, not IDC and may behave differently and these were pulsed dendritic vaccines and not peptide vaccines.

It is just to make one wonder that some vaccines may not be as "harmless" as thought. Even if they work well, they may have the effect of some weedkillers.



If they don't kill all weeds, what weed aren't affected and aren't left won't have the other weeds to compete with and may end up taking over.

Simiilarly even though this vaccine was more effective in completely clearing away the DCIS for those with her2+er- DCIS, those whose DCIS did not disappear completely were left with triple negative DCIS. If the same thing would hold true for invasive breast cancer as for DCIS, that could be a significant problem.

Again don't compare apples with oranges, ie DCIS with IDC, pulsed dendritic vaccines with peptide vaccines.

Again, we know there is more her2+dcis than her2+idc, so not all will progress. I am not sure how much we know about triple negative DCIS.

Hope this helped.

[Debbie L.]

Maybe if we could see the full text this would all be more easily grasped. Anyone have access? I get that they all began as HER2+ DCIS and that the ER- ones were more likely (although not ALL that likely) to end up with no disease.

But then the changing of phenotype -- what do we make of that? Is that GOOD news, to initially be HER2+/ER- and end up with TNBC phenotype? It doesn't seem like it would be good news. I may well be missing something.

I agree, Lani -- not very straightforward, but then the whole immunology field is SO complex. Plus, in this particular study, the numbers were very small, especially when they got to the subgroups.

As for vaccine studies that show "positive results" when what that means is a measurable immune response -- that is a pet peeve of mine. Cancer vaccines have been showing that for many years now, but when it comes to positive CLINICAL results (some effect on cancer and/or recurrence) there has been much less success. Like almost none.

I remain hopeful but often frustrated, re: cancer vaccines. It seems like the outlook is most rosy for primary and secondary prevention, and perhaps less hopeful (at least so far) for treatment of existing disease.

Debbie Laxague

['lizbeth]

Lani,

I wasn't following the disconcerting part. I see now with the triple negative DCIS.

And you are right, I'm mixing apples and oranges again with dendritic and peptide vaccines. Still, it seems an important piece of research - even if it creates more questions than answers. And 18.5 ER+ to 40% ER- were NED as a result.


I do see only 50% effective with the Her2 eradication - which reminds me of Herceptin. I wonder if it would be the same 50% for whom Herceptin is not very effective, and I wonder if the reason is the same. Perhaps the other "weeds/phenotypes" are taking over?

I just found the phase I for the MUC1 breast vaccine trial for the triple negatives has 37 enrolled, but too early for results. Maybe someday in the future we will be see a treatment combination of more than 1 vaccine.

[Sandra in GA]

Hi 'lizbeth,
So you have no return visits after we finish? I know I will miss my nurse and the trips toNorth Carolina.

Lani,
Are familiar with the study being conducted at MD Anderson using a peptide vaccine along with Herceptin in the neo-adjunctive setting. There was someone on this board enrolled in that. I just have not heard from her lately.

Thank you for all you do to keep us informed.
Sandra

[Lani]

'lizbeth I previously reported some good results for a dual her2 peptide vaccine.

It seems blocking several routes of escape is the way to go whether with monoclonal antibodies or vaccines.

Again, I don't know how many triple negative DCISs turn into Triple negative invasive breast cancers, but will now look into if there are paper which might give us an idea. It was my impression that her2+ breast cancer was relatively unique in often having an adjacent area of DCIS. Perhaps the natural history of other subtypes is different, perhaps not.

['lizbeth]

Lani,

and so you did, and I even read it, then forgot. Sorry chemo brain.

I'm not familiar with the other peptide vaccine. I see it is already being used for ovarian cancer:


Active immunization with VEGF peptides elicits antibodies that inhibit tumor growth by blocking VEGF-dependent angiogenesis.


Hmmm interesing.

[shelleyd]

Hi Lani, I think I can clear this up. I am an actual participant in this trial for the DCIS pulsed DC vaccine for DCIS/Her2/neu+you are mentioning. When the trial began all patients with DCIS and Her2+ were eligible. After Phase I the data started to indicate that patients who were Er receptor negative had ZERO recurrences while the patients who were Er receptor positive had three recurrences. So the trial was ammended and now the Er receptor positive group have been getting Tamoxifin during the trial. The first two who were done this way had complete pathological responses and it is hoped they will achieve the same great lasting immunity that the Er receptor neg Her2 positive group has. The PI is Dr. Brian Czerniecki and these results were published in the Journal of Immunology and Cancer this January. The trial is soon to be Phase III in mulitple sites. His next vaccine with be a multi valent targeting Her1,2,3 and 4 and he expects it to be effective against ALL SOLID TUMORS, both therapeutic and preventative. Check out my website www.shelleydodt.com and Penniesinaction.org.

['lizbeth]

Abramson Cancer Center

Researchers at the Perelman School of Medicine and the Abramson Cancer Center at the University of Pennsylvania reported last month that a short course of vaccination with an anti-Her2 dendritic cell vaccine made partly from the patient’s own cells triggered complete tumor eradication in nearly 20% of women with ductal carcinoma in situ (DCIS). Brian Czerniecki, M.D., Ph.D., surgical director of the immunotherapy program for the Abramson Cancer Center, enrolled 27 women with Her2-positive DCIS in the vaccine study.
The investigators isolated lymphocytes from patients’ blood, then activated dendritic cells, priming them with small segments of the Her2/neu protein. Each patient then received four injections one week apart. After two weeks patients had surgery to remove any remaining disease, the standard of care for DCIS patients.
At surgery, 5 of 27 (18.5%) vaccinated subjects had no evidence of remaining disease. In the 22 subjects with residual DCIS, Her2/neu expression was eradicated in 11 (50%) of them, and reduced by 20 percent or more in another two. “We are continuing to see this pattern in our second, ongoing trial,” Dr. Czerniecki says. When comparing estrogen receptor (ER) negative with ER-positie DCIS lesions, vaccination was more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ER-negative subjects compared with 5.9% in ER-positive patients.
In analyzing patient immune responses, the investigators found that 85% had Her2-reactive CD4 and CD8 T cells. This suggests that the patients developed a robust and relatively complete immune response after vaccination. Some patients maintained their immune responses for as long as 52 months.
“Previous vaccines targeted tissue antigens that were expressed on the cancer cells but were not necessary for tumor survival,” Dr. Czerniecki noted. “So a vaccine response would cause the tumor to just stop expressing the antigen and the tumor would be fine. Here we’re going after Her2/neu, which is critical for survival of early breast cancers. If we knock it out with the immune response, we cripple the tumor cells.”
Regarding Herceptin, Dr. Czerniecki told GEN, “Herceptin is an anti-Her2/neu antibody. This autologous vaccine activates anti-Her2 CD4, CD8, and antibodies.” Because of the nature of the vaccine, patients’ immune responses are maintained against Her2. “Herceptin lasts few months and is gone; it is only antibody therapy,” Dr. Czerniecki explained.
“Eventually if we get this working a little better with some combinations such as vaccine plus trastuzumab or lapatinib, this could be a standalone therapy alternative, allowing the immune response to last longer,” Dr. Czerniecki added. “Ultimately the goal is to prevent disease recurrence and avoid radiation therapy.”


http://www.genengnews.com/keywordsan...print/3/26221/

['lizbeth]

Here is the clinical trial link:

http://clinicaltrials.gov/ct2/show/N...ne+dcis&rank=1

Shelley, I didn't see any information on the addition of Tamoxifin mentioned in the different treatment arms. I would love to see the interim data for this trial. Would you be so kind to post it when it becomes available?

Thanks!

[shelleyd]

Hi lizabeth, I will be happy to keep you posted. My email is sdodt@me.com. I speak with Dr. C.frequently so these first few patients results have not yet been published. We are about 10 patients away from phase III but i do know results have been excellent. We have seven patients in trial right now and only two can be processed since the vaccine production is quite extensive. My own immune response has not diminished. Email me any time. I am happy to discuss and currently follow many other cancer vaccines in trials. Shelley

['lizbeth]

Great Shelley,

Would love to learn more about your vaccine trial, mine is the Walter Reed AE37/GP2 vaccine trial for primary breast cancer. Am so please to hear about treatments for DCIS and will be in touch.

[shelleyd]

will be happy to send you recent pulbications on the DCIS/Her2 Dc vaccine trial. I am interested in the AE37 too. These vaccines will be the future of BC treatment once FDA approved. We are the pioneers testing them out! Shelley sdodt@me.com

[Sandra in GA]

Thanks, Shelly. I am most interested in learning all I can. You are right, we are the pioneers. I feel so lucky to be able to be a part of this trial.

[shelleyd]

We should start an area on this site for those of us participating in vaccine trials. I will be happy to share published articles I have with any one. Just email me at sdodt@me.com.
I volunteer as a patient advocate helping women navigate through possible trials. Many physicians (including the one I had at the time) did not have a clue. I started emailing the researchers myself and asking questions. I've met so many wonderful people who are willing to teach and explain. I will share this though, Dr. Czerniecki is working on a multi valent vaccine Her1,2,3,4 that he believes will work for 90% of BC. The best results will most likely be for early disease at first and it will work for prevention, but some vaccines have been made that can eat up pounds of tumor burden so there is hope for everyone!

['lizbeth]

We can hang out in the clinical trial section. I just bring up the new posts each time.

My 2nd oncologist was helpful in getting me into the trial, the first NOT! How do you volunteer as a patient advocate?

I'm certainly glad there are vaccine trials for early breast cancer. So much better than the old wait and see technique, and then treating patients in trials only at Stage IV.

This website has opened my eyes to what the Stage IV ladies suffer through. Very motivated to do everything I can to avoid a recurrence. Going to work more on the weight loss. The news today reported that even a 6 lbs weight loss was equal to a 25% reduction in recurrence.

I was just at an ENERGY seminar at UCSD and Shoshi told us that because of this study that diet and exercise help are being included in the Standard of Care.

Pertuzumab, Vaccines, TDM1, diet & exercise - so much positive progress coming. I just can't believe the difference from 5 years ago when I was first diagnosed.

[shelleyd]

I got started as a patient advocate by volunteering to speak with anyone in the trial who asked to speak with another participant. Some people have questions and concerns and want to hear others experiences. Then once I was finished with my own vaccine, I told everyone in my town and started to volunteer with Pennies in Action 501c3 to help raise funds for the trial. I asked my doctor how I could help others. Soon newly diagnosed patients in my hometown started calling me and one referral led to another. I also participated in NBCC LEADS course, and took another patient advocacy course by the Alliance for Cancer Clinical Trials. Also, I enrolled at the University of Miami Online course for Patient Advocacy. This is a one year post bach certificate program offered online for people who want to set up advocacy practices. I also started to attend SABCS and other immunological meetings to learn more.

I am very grateful for my own experience and I strive to help the researchers develop and get other cancer vaccines FDA approved. I also want to provide support to women not as fortunate as I have been. I am involved in Complementary and Integrated care through Annie Appleseed Project. They are wonderful and offer many non-tradtional options for those who do not want or cannot tolerate traditional treatments. Ann Fonfa is a wonderful leader and teacher who managed to find her way out of Stage IV lobular BC through non-traditional means.

I think you had asked the question about Dr. Czerniecki's trial. They did add tamo for Er rec positive patients but I don't think they needed to ammend the trial since there was no inclusion or exclusion for these kinds of drugs. I will ask him. Keep in touch. Shelley