Isolated tumor cells in lymph nodes with ILC

Cliffyw

Hi, my wife recently had her surgery (BMX with sentinel lymph node dissection). Although the intraoperative pathology on the nodes was negative, the more thorough post-operative analysis showed isolated tumor cells (ITC) in 4 of the 5 nodes removed (they thought they had removed 3 nodes initially but it turned out to be 5). Clinically, that means her nodes are clear and her N status is pN0(i+) (technically 0 affected nodes for purpose of staging).

However, I have been doing some reading on this and it sounds like for ILC, the cells are more likely to be disperse and less likely to form masses in the nodes leaving micrometastasis more difficult to assess. According to this paper (https://www.ncbi.nlm.nih.gov/m/pubmed/20347308/) the ITC diagnosis should not be made in ILC tumors because of the way ILC cells spread.

I am worried it means my wife will be undertreated. They are not currently planning to perform any further axillary dissection. She is being staged at IIB (her primary tumor was 5.6cm). However, if they had classified her nodes as positive she would have been IIIA. I'm not sure if I should push for further axillary node removal ( at the cost of the additional side effects) or maybe try to ensure that radiation will include the area.

It also seems that guidelines for treatment for ITC has changed in the past 5-7 years. Previously, they were more likely to perform a full axillary dissection if ITC were discovered. Has anyone here had multiple nodes with isolated cells with no other lymph node involvement? Did the doctors perform additional dissection as a result?

Lab-girl

Cliffyw,

I did have ITC in 2 of 3 lymph nodes. I had a 1.8 cm tumor and a .9 cm tumor (one IDC, one ILC). I got opinions at 2 major research hospitals, another regional hospital and talked to a friend who is a radiation oncologist. In short, the current thinking is that ITCs don't mean much and they do not recommend radiation or further axillary dissection. In general, I think the research I've read (pretty much all of PubMed, as I was very worried about this) backs that up but I've read the article you mentioned and others and it does concern me, especially with ILC presentation. I mentioned this to my oncologist and her thought was that the purpose of endocrine therapy (tamoxifen or AI) was to mop up tumor cells that might be roaming around anyway. I also think the genomic tests like oncotype and Breast Cancer Index are helpful to better understand what you are dealing with as far as aggressiveness, etc.

Peregrinelady

I was told that I had ITCs in one of two nodes. Since my oncotype was 12, I did not receive chemo, so I thought I should at least have radiation. I got 3 different opinions and they all said not worth the risk. Also, one of those ROs mentioned that actually I had micromets, so not sure what difference that makes. So now I am on Arimidex, my only treatment besides surgery and it does feel like I am not doing as much as others. However, since I was 100% ER, they all told me that hormonal meds are my strongest weapon.
Btw, the micromets was found in the 2nd sentinel node and there was no mention of axillary dissection.

Optimist52

Cliffyw, sorry that your wife is going through all this. I had ITC in two nodes found in the ALND during my second diagnosis of ILC. My MO has told me that they aren't considered clinically significant although they note them as (I+). I assume your wife will be having the Oncotype DX test? This will help to determine the need for chemo or not. The biology of the tumours is now being considered more important than the size. Are you able to add her diagnosis details below which can make it a bit easier for us to respond? She is lucky to have such a caring husband who is researching so much, there's so much to learn when first diagnosed.

dtad

Cliffyw...so sorry you are both going through this. Your wife is very lucky to have such a supportive husband. I don't know where you live but just want to make sure she is being treated at a major university teaching hospital. IMO where you get treated is a huge factor. So if by some chance you are not close to one, I think it would be a good idea to at least get a second opinion at one. I'm in the medical profession and you would not believe the difference it can make! Good luck and keep us posted.

Cliffyw

Thank you all for the responses. It really helps me to see that others have had similar experiences and received similar answers from their doctors. We did receive confirmation yesterday that the surgeon doesn't want to do further axillary dissection and based on what you all have said, and what I have heard from some others, I will not push it. However, before we see the oncologist next week, they do now want to do a CT and bone scan. So we are now afraid about that, although knowing of course is better.

As of now, they do not think genotype testing is necessary. As far as we have been told, it is already certain that my wife will be receiving chemo based on tumor size however we won't know for certain until we see the onco next week (and a 2nd opinion onco the following week). They also believe that radiation is likely given the tumor size and proximity to the chest wall. I was reading through the NCCN guidelines and it says to "consider radiation therapy" in this case, including "any part of the axillary bed at risk" so I may need to explore that if they do deem radiation makes sense.

Optimist52, I will add my wife's diagnosis to my profile, so hopefully when I do, it will be included in the signature of my previous posts as well.

dtad, yes we are currently going to Georgetown for treatment. While I think the surgeon did a great job with the surgery itself, I do have to say it is a little frustrating how little we actually interact with her instead of just her NP. We will also see a medical oncologist and radiation oncologist at Georgetown, and will be driving up to NY in a couple of weeks for a second opinion from an oncologist at MSK.

Also, I managed to access the full document (I downloaded it, and here is a link to it on google drive for those interested, https://drive.google.com/open?id=0B6cAA6YtixHbRkVr...) . Having now read the full article, it no longer seems as clear cut as the abstract makes it seem. It is a fairly limited sample, and the amount of cases with ITC identified via IHC stain (the more accurate but newer method which was done post-op but not during surgery) was especially small and in those cases where ITC was only seen in that stain (only 3 cases where axillary dissection was performed), none of the axillary nodes had further tumors.

Cliffyw

one small follow-up question regarding the site's profile and ITC. When I added the diagnosis in the profile, it asks "How many lymph nodes tested positive for cancer cells"

That would seem to include ITC, so should I put 4 (the number of nodes with ITC) or 0 (since that is the clinical amount of positive nodes)?

Luckynumber47

Although somewhat concerning, ITCs are considered node negative so put 0. In the signature line where you put "husband" you could also note that 4 of 5 nodes had ITCs

Cliffyw

Thanks luckynumber. Made that change to my signature

Lab-girl

Cliffyw,

Just my 2 cents-I would ask for the oncotype dx testing anyway because if it is quite low, chemotherapy may not be very beneficial and even if both drs you see recommend chemotherapy no matter what the score, it will give you some perspective on the cancer and another data point. Best of Luck.

jgio2960

I am so sorry your wife is going through this. My mom just finished radiation August 30th, it was one of the best days of my lives. It was without a doubt the most stressful depression 5 months of our lives.

Similar to your wife my mom was originally "clinically node negative". Until a week after surgery her doctor found not only a ITC in one node but a micromet in the other... yikes right ? This was the most devastating part for us. She was bumped for stage 1a to 1b and her doctor assured us it would not change outcome just treatment. We were told treatment would not be determined until oncotype score came back....please get that before any decision making. Her oncotype Came back 11 we checked without 3 major hospitals in NYC none of which would even consider chemo

Cliffyw

Thank you. We see the surgeon (or her NP) again today and I'll ask if we can get the oncotype anyway. They had already told us that the oncologist (who we don't meet until next week) does not want the oncotype since she thinks it will not add anything, but I'l see if they can do it anyway. I need to try to think of how to argue for it.

letsgogolf

I would insist on the Oncotype. I had 2 micromets in the first sentinel node only of 8 taken. My Onotype came back with a score of 3. The report shows that chemo would actually decrease my 10 year survival, from 96% to 93%. I wasn't really expecting that.

muska

Cliff, how old is your wife and does she have any serious health issues other than BC?

If chemo and radiation are in her plan anyway, I am not sure Oncotype is really worth pushing for. One thing I learned since BC diagnosis, is always ask what a particular test would change in the treatment plan. With a large tumor that is close to chest wall they will probably recommend chemo and whole breast radiation during which they will radiate axillary area anyway.

Good luck and I recommend your wife create an account on this board!

jgio2960

prayers for your wife. I will say a few different opinions at different hospitals help. Get second opinions and ask for your wife's case to be presented to the tumor board. Also a major help for me was the John Hopkins breast center Q&A, any question you have you can type and Lillie a breast oncology nurse and 2 time be survivor will answer questions us in the medical field just can't answer

Cliffyw

Muska- my wife is 44 which I think factors into the desire to treat it aggressively. They have said that chemo will be needed and radiation is most likely as well.

ShetlandPony

Hello, cliff. I also had ILC with ITCs in the sentinel node, and wondered whether it should be considered a micromet because of the ILC histology. If they are already recommending chemo, they will not want to do oncotype, since the purpose of it is to decide about chemo. But I do think that more information could be useful for determining hormonal therapy. At this point, my main question for you and your wife is, what hormonal therapy is the oncologist planning? Is your wife premenopausal? If so, I would ask about a genomic test or at least ki67 to see whether this ILC is luminal A or luminal B. If luminal B, would they recommend an aromatase inhibitor rather than tamoxifen? See link below to a post I made after the ILC symposium.

In my case, I am glad they did not do axillary dissection because I would not want the increased risk of lymphedema. ALND is only a local treatement, not a systemic one. Since I had a lumpectomy, I got the radiologist to assure me that the level 1 and level 2 nodes would be included in the field. I have had no recurrence in the axilla or that quadrant of the breast. I also understood that systemic therapy was the important thing in case cells had escaped the breast/axilla. I felt that because of the ITCs and we should be more aggressive and use the aromatase inhibitor (with lupron) instead of tamoxifen, but the medical oncologists said that was not necessary. I wish I had listened to my intuition. If we had done a test to determine luminal A vs. luminal B, or at least known the ki67, then maybe we would known more about whether it was likely to be a well-behaved ILC or not, and we may have made a different decision. My oncotype was on the high end of low. No way to know for sure now. Obviously, one does not make decisions based on one person's experience, but my point is that getting more information would be a good idea.

https://community.breastcancer.org/forum/71/topics...

muska

Cliffy, it looks like your wife is in good hands. At her age and apparently no other serious health issues, I would do recommended treatment. You are still in the facts gathering stage, once you meet with the oncologist you will have more questions and options to consider. Good luck!

Cliffyw

ShetlandPony - thank you for that info. I just read the posts you made in the other forum and will make sure to discuss that. We do have Ki-67 on my wife's tumor. It is 25%, so I believe that makes her Luminal B. Your other post there was interesting and relevant too. She is scheduled to have a CT scan and bone scan next week, and from the info you wrote, those may not be as accurate for ILC. However, I need to find out the details on how they are doing the CT scan. I know she will receive some injection, but I don't know if it will be FDG

ShetlandPony

The injection for the CT would be an iodine contrast. FDG is the nuclear injection for PET. Typically a combination PET/CT is done, but the CT you get with PET is a poorer quality CT because there is no contrast agent given. I would just want to know that an expert radiologist is giving input on what scan modalities are best for your wife. How her ILC was detected and imaged may be relevant.

It does sound like her team is doing a good job. And you are, too, on a steep learning curve.

Cliffyw

So they are just doing the CT with iodine contrast for now along with a bone scan. Fingers crossed.

Regarding tamoxifen vs aramatose inhibitor it sounds like the latter would only be given for post menopausal women ( l don't know why). So they may not want to do that for my wife since she is premenopausa. I think sounds like an option may be to combine it with an ovarian suppressant but i don't know if that is a common treatment now or if they are more likely to just give tamoxifen. Maybe find out more Tuesday.

ShetlandPony

Yes, an aromatase inhibitor, combined with a drug to suppress the ovaries, is routinely given to premenopausal bc patients in certain situations. It is considered more aggressive than tamoxifen. Some of the risks and side effects of the two treatments are different. To my mind, the luminal B and the ILC histology are votes for going with OS + AI instead of tamoxifen. But many oncs will go with the standard tamoxifen for a premenopausal woman unless she is very young or her cancer was risky enough to require chemo. (See the results of the SOFT trial). If the oncs confirm the recommendation of chemo for your wife, then they may be planning to offer OS + AI. Typically they recommend lupron or zoladex shots (monthly or sometimes every three months) to suppress the ovaries, as a way of giving the patient a chance to see how they tolerate menopause and the aromatase inhibitor. An oophorectomy can be a later option. Lab-girl makes a good point about considering Oncotype anyway, since tumor biology is more important than tumor size. But then some of us wonder how much to trust Oncotype in the case of ILC.

I think it is very wise of you to get opinions from both Georgetown and from MSK. There are aspects to your wife's case beyond the common diagnosis and treatment, and you want some really expert advice. Hand carry what records you can, just in case.

P.S. The reason the aromatase inhibitor is for naturally or medically post-menopausal women only is this: Since a post-menopausal woman's ovaries no longer pump out estrogen, the majority of estrogen in a post-menopausal woman comes from the aromatase enzyme converting androgens to estrogens, in, for example, the woman's body fat. So the drug inhibits this production of estrogen. Before menopause, the ovaries produce lots of estrogen, so the aromatase inhibitor would be pointless. Tamoxifen is intended to take estrogen's place on the cancer cells' receptors, so they can't "feed" on it. Tamoxifen can also be used in post-menopausal women.

Cliffyw

Thank you again Shetlandpony. That is really useful information. I'll read about the SOFT trial. Do you also know if there are studies regarding differentiated chemo treatment for ILC vs IDC? I've realized I haven't come across info on the decision of different chemo regimens as much as I have on hormonal treatment.

Icietla

Each medicine type has its potential advantages and disadvantages. Tamoxifen treatment increases risks for uterine cancers and abnormal blood clotting. We have some discussion threads -- one is very long -- relating to possible side effects of Aromatase Inhibitors.

Something else you should know -- just for their having cancer, cancer patients are at increased risk for abnormal blood clotting. Some cancers are discovered because of abnormal blood clotting being known as a possible sign of cancer.

https://www.stoptheclot.org/faq_blood_clots_cancer.htm

http://blog.dana-farber.org/insight/2014/04/does-cancer-cause-blood-clots/

https://www.ncbi.nlm.nih.gov/pubmed/12407439

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)10018-6/fulltext

ShetlandPony

Cliff, I personally have not heard about different chemos for ILC vs IDC, but maybe there are some oncs with an opinion on this question. In general, oncs do not distinguish much between ILC and IDC as far as treatment, but hopefully in the future there will be more info. It is hard to get a large enough cohort of ILC people for a trial. I'd like to think that last year's ILC Symposium in Pittsburgh signaled growing interest in the ILC subtype.

Cliffyw

We met with both our local MO and RO for the first time today and I wanted to provide an update. First, the scans did not turn up anything meaningful which was very good news. The CT scan report mentioned some small nodules on the lungs but the pathologist and MO both thought they are not concerning

The MO definitely thinks my wife should receive chemo. She is not in favor of doing the oncotype test since she does not think it will add anything to the decision. The isolated tumor cells are somewhat concerning for her. She mentioned that although she is technically supposed to not consider them, she can't ignore them and especially the fact they are in 4 nodes. She is recommending a dose dense course of AC->T for 8 courses every two weeks. Following that, she may start with some months of tamoxifen before possibly moving to an AI plus ovarian suppression. We are somewhat concerned with that course of chemo given the cardiomyopathy risks associated with the "A" part of AC-T. We mentioned that we are seeking a second opinion from MSK and she mentioned that it is possible they may recommend just TC to avoid potential heart risks. Overall though, we really liked the MO. She seemed to be up to date and tries to tailor the treatment to individual cases.

The RO does think that she should have radiation therapy, and also mentioned that she was a little concerned with the ITC as well. She mentioned the chest wall explicitly but was not sure about the remaining axillary region (which was surprising to me given she mentioned the ITC). She mentioned the possibility of proton radiation but did not think it was necessary. The benefit being that the radiation is on her left chest, so regular photon radiation has increased risk to the heart compared to proton radiation (which isolates its energy at a given depth much better). They reduce the heart risk some with "deep inspiration breath-hold" techniques. Proton radiation seems promising, but the nearest proton radiation device is an hour away from us in Baltimore, and it seems quite possible our insurance would not cover the extra cost. Both of those combined probably rule it out.

ShetlandPony

Thank you for the update. For what it's worth, your onc's thinking about the ITCs makes sense to me. What is her reasoning for starting with tamoxifen then moving to OS + AI? Is the T part of chemo taxol, or taxotere? Are you getting a second opinion from both medical and radiation oncologists?

Cliffyw

Hi Shetland. The T is taxol. As for the course of endocrine treatments, her logic wasn't very clear to me. I believe she said that she wants to see how she responds to the tamoxifen before moving onto ovarian suppression. She also said that even in the studies showing AI plus ovarian suppression is better for ILC, most patients in the studies generally started their endocrine treatment with tamoxifen. I should mention she brought up AI plus ovarian suppression as the better treatment for ILC on her own, which I was happy about, since I had it on my list of things to talk about.

We aren't yet sure whether we will get a second opinion on radiation at MSK. Nothing is scheduled yet. We had asked about it last week and were told the MO's office would try to arrange one. we are going to follow up on it tomorrow.

Also, since my earlier post I found that there are some clinical trials with proton therapy in Baltimore so insurance may not be issue if she is accepted into that. However the distance is still problematic.

LeesaD

Cliff- My MO changed my course of chemo based on the Oncotype score. I had micromets in 2 of 4 sentinal nodes. Met with MO who ordered Oncotype. While waiting for Oncotype I did not feel comfortable not knowing the status of my axillary nodes so I asked my surgeon if we could go back in and he agreed to do ALND athough him and my MO said odds slim they would find anything. Surprise I had 2 of 14 axillary nodes fully positive even more so than sentinal nodes. My MO set me up right away for port placement and A-CT chemo 8 rounds. Week before I was
starting chemo, my Oncotype came back a 3 which is very low. Even though Oncotype is good for 1-3 nodes and I had 4 'involved' my MO said the score of 3 was encouraging enough that now the long term heart risk of the A drug outweighed the benefit and he changed my regime to 4 rounds of TC which is Taxotere/Cytoxin. If your wife's MO mentioned both regimes and not sure which one, the oncotype might sway one way or the other.

Also in reference to the hormone therapy, I had done the research and wanted to go direct to AI's with ovarian suppression even though I was not in menopause yet based on the SOFT study and the AI's having a slightly better track record. When I met with my MO I didn't even have a chance to suggest it as he did first and we were on same page. The suppression is a monthly shot, mine is Zoladex, and I've had two so far. My MO checked my estrogen levels three weeks after first shot and my estrogen was virtually undetectable so I was able to start direct with AI's of which I've been on for six days already. So far so good. Also I'm having ovaries removed so I dont have to get the shots monthly. Having the ovaries removed gives slightly better odds than suppression according to my oncologist so I'm taking all the percentages I can.

Cliffyw

Thank you Leesa. It is possible that MSK will want the oncotype, but they told us not to have it ordered yet, but instead they will decide when we visit next week. I feel like now that if the 2nd opinion recommends TC, I am inclined to go with that. The benefits of AC-T vs. TC do not seem rock solid for moderate risk cases. The studies are ongoing and the current confidence intervals seem pretty high compared to the benefit, except for the obvious high risk cases. Balancing that out with the possible heart issues is difficult, especially when she also will be receiving left breast radiation, which also could cause heart issues. I am worried what the combined impact could be. I wish I knew more about the anthracyclines going into the appointment yesterday so I could ask more detailed questions.

I am trying to do research on what the possible benefit of starting with tamoxifen before AI might be, but so far haven't come up with anything.

ShetlandPony

The only benefit I know of would be that tamoxifen might cause fewer or less-pronounced menopausal symptoms. The onc may be thinking of easing her into it. Personally, I would ask about just starting the OS and then add the aromatase inhibitor, like Leesa.

I'm glad the T is Taxol and not Taxotere, Cliff.

Very interesting information, Leesa.