Local Treatment of Residual Disease

zarovka

I have minimal residual disease after a year on Ibrance/Letrozol. The protocol probably eliminated all metastatic disease (7 liver tumors <2cm and a small bone met in my sternum). I am left with a dormant and much smaller primary breast tumor and maybe one or two impacted lymph nodes. In general, we don't treat residual disease unless it is causing pain or interfering with the function of something important like an organ artery or nerve. However, when you have very little residual disease, some practitioners will remove the remaining tumors with surgery or radiation.

One specialist said I have to get the tumor in my breast and lymph nodes out with surgery ASAP but my regular onc says surgery will do nothing. She says the last thing I need is a major medical procedure. The papers I have read are inconclusive. So far I have cast the deciding vote against surgery.

I did inquire briefly about radiation. I am interested in Stereotactic Body Radiation Treatment (SBRT) because it also stimulates the immune system to attack cancer. I have seen people with stunning responses to SBRT that extend beyond the area directly treated. However, the one radiologist/SBRT specialist I consulted with said that breast cancer is not generally immunogenic nor is SBRT done on the primary tumor. One generally removes the primary tumor with surgery, if that is the plan, and then you clean up with radiation. I disagree that breast cancer is never immunogenic and the conversation generally left the radiation question open in my mind.

So I pulled the string one more time while talking to a naturopathic oncologist I recently added to the team. He wants me to try to get rid of the remaining tumors, but he recommends hyperthermia. Hyperthermia is well supported in the literature with multiple small trials but it doesn't have FDA approval yet. It looks to me like no single company can control the technology and get the profits necessary to pay for FDA approval.

Whatever the cause, I have to fly to Canada and pay for it myself. The idea of getting rid of the tumors without radiation or surgery seems worth it. I could imagine myself on the beach for the entirety of this procedure and that is a big plus given my medical phobia. This is the clinic in Canada i am investigating.

In addition to getting rid of the tumors, hyperthermia may be a systemic treatment that will support the Ibrance/letrozol treatment. I am PR- which means I am likely to develop resistance to hormone therapy sooner rather than later. The idea of hitting the cancer hard in this first round feels important.

Interested in anyone's thoughts or experience with local treatment of residual disease and/or hyperthermia.

>Z<

BellaTassie15

Hi Zarovka, I had stage 4 breast cancer de novo like you, so I have not had surgery or radiotherapy. I've just had chemo and targeted therapy. I live in Hobart in Tasmania, Australia, a small capital city. I'm not aware of a naturopathic oncologist here but I have seen there is a naturopathic GP who offers hyperthermia. I have not consulted with him but was considering doing this in the new year when things settled down at home. I guess this is now? I would be very interested in the experiences of others

MSL

Like you guys I was diagnosed de novo, but I didn't have a scan until the week after my mx so I'm one of those de novos who had the full surgery from the get go.

I agree that there is no settled view about whether surgery is good or bad or indifferent to long term outcomes. My sense is that it seems to be swinging towards surgery being good (reducing tumour burden etc) but that's just a perception.

I've also looked back through these boards and know many others have wrestled with this issue.

I have no insights to add other than my experience. I'm really, really glad I had the surgery and got the thing out. I believe it's good for your body's immune system and overall capacity to fight this long journey with the primary gone. I know some people have completely the opposite view and choose a different path and I absolute respect that. There is no clear answer either way.

BTW, I also had lung surgery for the biopsy and an ooph within a couple of weeks of the mx. It was not a ton of fun but honestly it was ok and I recovered quickly from them all. I'm sure that your fitness and stamina will see you get through really well if you do decide to have surgery.

Wish I could give you some more definitive advice dear Z. On the big upside, it's great that your very good scans mean this is an issue you are confronted with!

Good luck

zarovka

MSL - there is no definitive approach, just intelligent perspectives like yours. Thank you for your thoughtful response. I am indeed in a reasonably good position with a lot to be grateful for. I understand the mental benefit of getting rid of the tumors and I'd definitely lose a boob for a little better odds. If I could just get two experts to agree on whether and how.

Bella Tassie - Although hyperthermia may be a good idea, I would steer clear of naturopathic generalists as they are well meaning but don't have the training. I have been consulting by Skype with Grace Gawler of Australia to get an international perspective on treatment options (US treatment is good but a bit myopic as well). I appreciate her perspective. I haven't asked her about hyperthermia but it is on my list.

>Z<

Cure-ious

Hi Z- Important question! I would vote to get rid of the primary tumor and lymph nodes, by lumpectomy if possible and have insurance pay for it. The main reason is to get the most out of immunotherapy, whenever you do get it, for which it is important to get the tumor burden as low as possible. The primary tumor must have a ton of cells and be hard for immune system to penetrate it and get all the cells out. I'm not sure but also think this is maybe why they do the bone marrow transplant technique in the NCI protocol?, ie to flush out latent transformed cells and give immunotherapy a chance to work. And hopefully it does work for you, because the PR- phenotype is luminal B, and preliminary data indicates that this subtype iis nearly as responsive as are the triple negative cancers, so hopefully some combination of immuno and other targeted drug may be in your future. Anyway, that's my 2 cents...

zarovka

Cure-ious - I was wondering if PR- was effectively TNBC as far as immunotherapy goes. That is good news. TNBC responds to immunotherapy better than HR+ but it is still only 20% to 30% response. I hope I can hang on until they figure out where the brakes are.

In the meantime I am indeed pondering options for reducing the tumor load.

>Z<

Cure-ious

Yes, immunotherapy on its own is not terrific, but in combination they are getting some high response rates- trials are underway combining it with chemo/abraxane, targeted drugs- I am waiting to hear about immuno in combination with anti-CD47 antibody, although it will be awhile because CD47 is only in phase I as monotherapy, where nobody expects much to happen. But the combination could be great- CD47 antibody 'unmasks' the tumor cell so it can be much more efficienty killed, whereas immunotherapy revs up the immune system so overall killing is more effective.

zarovka

Thank you Cure-ious. It looks like CD47 disables one of the important brakes.. I read up on it. They are shooting for clinical trials of CD47 and immunotherapy for brain cancer in 18 months.

>Z<

MSL

Hey Z and Cure-ious

It's fascinating to read your exchanges. You both have a very sophisticated understanding of the complexities of the treatment of this disease and we all learn a lot from you.

My primary was ER - 60%, PR - 85%, HER neg. The Ki score was 19%. The Grade was 3. I did a lot of reading (before I knew I was St IV) and figured I was probably Luminal B, although the PR vs Ki thing meant it was debatable.

The biopsy of my lung mets showed ER - 95%, PR - 95%, HR neg. Your discussion about immunotherapy/luminal status etc has raised very important issues. How do you know whether you are Luminal A or B and how significant is it?

Be most grateful for your thoughts

Apg

I am in a trial at Cleveland Clinic where they are going to take a piece of my tumor and study the mutation for immunotherapy. This was where I went for my 2nd opinion. I am not being treated there however the dr is still putting me in the trial. He said it is a $5000 test I'll get done for free. It will be necessary to have done he said for any immunotherapy I do in the future! I'm very hopeful in this area of treatment.

Misty

Heidihill

http://www.ascopost.com/issues/january-15-2014/using-hyperthermia-for-cancer-treatment-proofs-promises-and-uncertainties.aspx

I was looking into hyperthermia at some point and remember reading the above.

As for local control, this was integral to my treatment, although it was for unseen residual disease.  I had two opinions, one locally and one from MGH. I had one boob and lymph nodes removed and had my chest burned with rads with zaps as well to axilla, clavicle and spine. I am barely PR+ and responded well to chemo. I think with PR- (and low PR+) there's maybe a greater likelihood some cells are TN given the heterogeneity of tumors. My guess.

Cure-ious

Z- Your question reminds me that it was recently reported that immunotherapy appears to be much more effective (in mice) if given while the tumor is still present (ie before surgery);

http://www.abc.net.au/news/2016-12-06/cancer-study...

so perhaps the tumor instructs the immune system in some way about which cells to kill? You still have the primary tumor, so it would be good to goose up the immune system, but how? There is one trial at Mayo clinic where they add Keytruda to the Ibrance/Femara, but that clearly ithat s too far away from you- before you get it removed, you might want to try to stimulate your immune system with probiotics to get a partial immune response activation going. Am going to look up which ones, will post later

Also, anti-CD47 antibodies are in clinical trial in combination with a targeted drug for colon cancer; the last two San Antonio conferences have been very disappointing in this area, not much happening?, maybe the breast cancer advocates are not pushing as hard as they should be to get it going for breast cancers. There is no reason why breast should not be 'immunogenic'. they just have to find the good biomarkers and drug combinations

Cure-ious

Here are the strains you want in your probiotic:

These alone are like a low dose of immunotherapy, and are synergistic with immunotherapy

Bifidobacterium breve, Bifidobacterium longum and Bifidobacterium adolescentis apy

zarovka

Misty - I appreciate it that you share the details of your treatment. I am definitely not having the same experience at my local regional hospital in Northern New Mexico. I have to google, skype and travel to get access to next generation strategies. It is very helpful to know what options the Cleveland Clinic offers. Also very glad you are getting great care.

There are two main genetic tests, Foundation One and Caris. I am pondering having one of them done. I am interested in how your doctor will use them. I am not contemplating a change in my treatment in systemic therapy right now and I think that I should wait untili I get new growth to test (If I do). But I have a lot to learn about these tests and how they are used and I am interested in your doctor's thinking.

Heidi - One doctor I consulted with last week noted research that showed that the estrogen receptor doesn't work in the absence of the progesterone receptor. The upshot of that line of thinking is that if you are PR-, you are effectively TNBC. My liver biopsy was PR-. My breast biopsy was PR low (20%). This sent me into a funk for a day or two over the holidays as TNBC is challenging to treat. However, I have responded to Ibrance and letrozol. Someone on this thread pointed out that Ibrance didn't do much as a monotherapy, so the A/I must be doing something. Bestbird pointed out that TNBC often does respond to hormone therapy. Another person pointed out that being PR- may give me immunotherapy trials to consider. I find working through these issues and developing a strategy all really interesting. I am stilling processing the situation. I do wish I didn't have so much on the line.

Cure-ious - How kind of you to research the probiotics that promote an immune response for me. I work with a naturopathic oncologist who works with many patients on Ibrance. He has seen that one can improve Ibrance outcomes with "complementary" immunotherapy and we are working on a plan.

At the same time there is a startup in my town called Viome that has developed a test to completely characterize the gut biome. Their goal is to treat disease by tweaking the gut biome. Viome is not shipping kits yet, but I am friends with the team and I will be starting the beta in January. Being ambitious, I'd like my gut biome to get an A+ in my friends test. Thanks for the tip. My gut biome is sure to impress now, and I am increasingly convinced the gut biome plays a huge role in health.

And a third idea ... I have friend with cancer who is baking gluten free sourdough bread with a very specific sourdough starter at the suggestion of an awesome doctor. I wasn't sure why and I have to say that gluten free sourdough is very hard to do. As I researched sources of Bifidobacterium breve, Bifidobacterium longum and Bifidobacterium adolescentis apy, I found that these bacteria are present in high concentrations in gluten free sourdough. I am thinking the doctor is trying to give a cheap source of these bacteria.

Interesting how things come together. I found the strains in this bulgarian yogurt starter and this capsule probiotic. Going for the yogurt option because it sounds cool to make yogurt.

>Z<

Bestbird

This is an old (2005) but interesting article that may be of interest: three times as many ER⁺/PR⁻ tumors as ER⁺/PR⁺ tumors expressed HER-1 (25% versus 8%; P<.001) and 50% more overexpressed HER-2 (21% versus 14%; P<.001). From: http://jnci.oxfordjournals.org/content/97/17/1254.full

Cure-ious

Hi Bestbird,

I have a question about her2 status; when I visited FHCRC last year and I happened to catch a bit of conversation between two oncologists at dinner, something to the effect that the trials with herceptin were done so long ago that they didn't properly carry out the 'control' analysis, the upshot of which (I think) was that they were suggesting is that other breast cancer subtypes, beyond those that overexpress HER2, might similarly benefit from herceptin and related drugs affecting that pathway- did you ever hear anything about that? Your comment made me wonder about that, and the heterogeneity that exists in that pathway in these tumors...thanks, Kathy

Cure-ious

Z- the bacterial strains I mentioned are the ones from the Science paper that they found to be required for immunotherapy, if they reconstitute mice that do not respond to immunotherapy with those gut bacteria, then they can respond, and other strains of bacteria didn't do that- those are in particular required to activate the immune cells, and the levels of those bacteria can go down with age and with chemo and drugs, etc. I think it is an excellent idea to get our gut microbiome scoped out. I did see there was a clinical trial underway to combine immuno with a general high-quality gut probiotic, so that's probably the most sensible way to go when you have no idea what is or is not resident in your body..

Heidihill

Microbiome changes can take awhile, Z, so you should start with the probiotic program ASAP if you want an A+.

I had tests of my circulating tumor cells done a few years back and pathology was about 20 percentage points higher for PR than in my original breast tumor. It is possible to raise progesterone naturally and Vitamin C (which I took through tons of fruit and vegetables) may be one way.

zarovka

Thank you Heidi. Happy New Year.

>Z<

Bestbird

Cure-ious, your question is indeed an interesting one! I do know that the tests for hormonal and HER2 status can be equivocal, and of course we're also aware that different areas of the same tumor as well as tumors elsewhere in the body can express different pathological profiles. Plus, tumors can change over time, and re-testing (which can be valuable) is often not done. These findings would lead a rational scientific thinker to believe that it wouldn't hurt to try, for instance, a HER2-targeted drug on someone who is TNBC if they've already failed a few therapies.

LisaY

This thread came up when I did a search for 'hyperthermia' today.

Zarovka, did you decide to pursue hyperthermia further? I recently saw a naturopath (FABNO) who recommended a combination of locoregional hyperthermia, IV vitamin C, intermittent fasting, and various supplements for my residual disease. At the moment, it's not clear that I have any active disease at all, so I'm not sure how aggressively to utilize these expensive complementary approaches.

zarovka

LisaY - I will pursue it, but later this year. I have the same dormant residual disease, getting pretty much the same advice from a FABNO. My thinking is to treat the aggressively now, while it is on the defensive. Odds are it's going to come back. I want to hit it hard and try to delay that return, at least.

My complementary docs want me doing Vitamin C IV's but it's expensive and I am not into the IV lifestyle. We compromised on a highly bioavailable oral form. PM me if you are interested.

But if you don't feel that you need this stuff, you probably don't . Go with your gut, with a sharp eye on your pocket book.

>Z<

Heidihill

LisaY, intermittent fasting is cheap and does help with weight loss. I did it for a whole year. For me this meant fasting at least 17 hours from 7pm to 12pm.

Back on topic of local treatment, another option for small tumors is cryoablation. Worth looking into as there seem to be several places in the US offering it. There is also the possibility of generating an immune response depending on freeze rate. It is imaging-guided and surgery can be performed if there is residual disease. I think this is an important step as it is akin to getting clean margins which is crucial for effective local control with surgery.

http://www.medscape.com/viewarticle/824379

zarovka

Thanks Heidi! - No medscape account, however. If it would be possible to cut and past the abstract into this forum I am sure many would be interested.

>Z<

LisaY

I'm looking at intermittent fasting to starve the cancer, but not for weight loss. I'm hoping to maintain my weight. As you point out, Heidi, it's a cheap intervention that has shown some promise:

https://news.usc.edu/103972/fasting-like-diet-turn...

I'm aiming for 48 hours of fasting timed to coincide with my Herceptin & Perjeta treatments every 3 weeks. I tried 24 hours with my last treatment, and that went fine. I don't think I can fast for 17 hours every day, but every 3 weeks is feasible forme.

BellaTassie15

I've been doing intermittent fasting with a low carbohydrate diet for about 12 months trying to lose weight. I do understand that this will also starve the cancer of sugar, so I have several incentives to stick to this diet I did multiple days a few times, which I found was fine. I lost about 5 kg, which was great! But then I had to start on prednisolone for an autoimmune disease triggered by herceptin and Perjeta, and it needed to be taken with food so I started to fast from about 7pm till about 11 am or later, depending on my activity level. (I always eat protein soon after moderate to heavy exercise.) I'm almost off prednisolone now and finally starting to lose weight again . Once I'm off it completely in June I will do multiple day fasts again. I hadn't thought to do it with HP infusions, I thought it was only good with chemo. But after reading that article I will make sure to time it with infusions also. So do you start the day before or how do you time it?

ShetlandPony

Gosh, I can't imagine fasting for very long. I'm always hungry. I would be sitting outside the chemo room, waiting for them to call me, eating a turkey and kale sandwich and drinking red grape juice. I did not know about the research on fasting. But I got a complete metabolic response after three cycles, so I guess that was ok. But based on the research, I am trying to skip the bedtime snack now. I've lost a few pounds and the vitals nurse who checks me each month before my onc visit is watching me with suspicion. Sorry, off the thread topic.

LisaY

I'm going to aim for a 48-hour fast starting the day before my infusion. I may have a tablespoon of coconut oil in the morning with my Tamoxifen so that I don't take it on an empty stomach. I also will have some bone broth and green tea during the day. Since I'm generally always hungry, a more strict fast is better than a 5-day fasting mimicking calorie restricted diet. And I swear I'm much more hungry since I started Tamoxifen last month.

Heidihill

Cryoablation 'Quite Successful' for Small Breast Cancers

Nick Mulcahy

| April 30, 2014

 

• Breast Cancer News & Perspectives
• Cryoablation Safe, Well-Tolerated for Early-Stage Breast Cancer

Freezing breast cancers to death with cryoablation could be a viable option for small lesions, and might allow some women to forgo surgery in the future, according to a multi-institutional phase 2 study.

Of 16 patients with invasive breast cancers smaller than 1 cm, 15 had complete tumor ablation with the technique, reported principal investigator Rache M. Simmons, MD, from Weill Cornell Medical College in New York City.

She spoke at a presscast today at the American Society of Breast Surgeons (ASBS) 15th Annual Meeting in Las Vegas.

The technique had an ablation rate in small tumors of 93.8%. "It was quite successful," Dr. Simmons said in an interview with Medscape Medical News.

The rate of complete tumor ablation was the primary outcome in the open-label single-group study, known as the American College of Surgeons Oncology GroupZ1072 trial.

Of the 99 patients enrolled, 86 women (with a total of 87 breast cancers) were evaluable. All patients had unifocal invasive ductal breast cancer that was 2 cm or smaller, an intraductal component of less than 25%, and no extensive calcifications.

The overall ablation rate was only 69%; the procedure was much less successful in larger breast cancers and in patients who had some measure of ductal carcinoma in situ (DCIS).----

Google medscape and the article number or title and you can read the full article.

zarovka

Thank you Heidi!

>Z<