Dealing with residual tumor after neoadjuvant therapy
To my fellow community members diagnosed with HER2 positive breast cancer and who underwent neoadjuvant therapy, I think it is important for the individuals dealing with residual tumors (NOT pathological complete response) to share our post surgical thoughts and plans. What was your next step? Let's learn from each other.
Giveityourall
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On July 23, 2018, I had my cancerous lump surgically removed. Undergoing an ultrasound at the end of June 2018, I knew my taxotere, carboplatin, Herceptin, and Perjeta had shrunk my tumor, but did not annihilate it. So, I scheduled my surgery as quickly as possible - three weeks later (July 23).
My tumor was covered by white blood cells (lymphocytes) and measured 1.5 x 1.2 x 1.9 cm. My first ultrasound reported my measurements as 1.9 cm x 1.9 cm x 1.9 cm. I have continued my Herceptin and Perjeta infusions (completed round 11 of the recommended 18). A few weeks ago, my PET scan reported no evidence of disease. However, I am worried about recurrence. Thinking about taking Xeloda, oral chemo pill. Any suggestions? I need your help.
Giveityourall
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Hi Giveityourall: Did your residual tumor contain active cancer cells? (sorry if this is a dumb question, but I don't know what it means to have lymphocytes)
Anyway, I did not achieve PCR. During chemo my tumor was no longer palpable, but surgery showed a residual tumor that looked like swiss cheese. My SNB was negative and I did not have LVI. I finished Herceptin in 10/2017. My MO did not recommend any additional treatment. She isn't recommending Nerlynx because she says that hormone negatives don't seem to really benefit from it.
So I've been off treatment for over a year. I get annual mammograms (of my remaining breast) along with US of my remaining breast and MX scar, and see my BS afterwards. I see my MO about every 3 - 4 months. I've had mixed feelings about not having any treatment, but at the same time I'm glad to be finished with treatment.
I fear recurrence, but I don't want to take treatment just to take treatment. KWIM?
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Bellasmomto,
I do know what you mean. Big time. I don’t want to take more chemo medicine... just because this did not work entirely. I am scared to take more meds. I did the toxic chemo thing.
As for my residual tumor, it was cancerous. It was not holy or hole-y. My tumor did not look like it was attacked by an M-16 - it did not look like Swiss cheese. However, it was blanketed and filled with white lymphocytes. Lymphocytes are a type of white blood cells. There are two types: T cells and B cells. T cells are usually your first responders. So, although my tumor still existed... a lot of its mass was due to an abundance of lymphocytes. That make sense?
So, your turn to educate me... Nerlynx is an oral chemo drug for hormone positive - not HER2...right?
My best. Glad you are doing well. YEAH!!
Giveityoural
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Hi there, I was diagnosed with HER2 BC in February 2017, a 4.5 cm mass with node involvement.
I had the standard treatment offered by our public health care system: Neoadjuvant treatment - 3 cycles of EC and 3 cycles of Taxol (9 weekly) plus Herceptin and Perjeta. I had ultrasound after the first 2 cycles of EC, and was switched to Taxol/Herceptin/Perjeta due to no effect. My tumor shrunk by 1 cm only, and I still had micromets in one node at the time of surgery.
I recurred shortly after surgery, i.e. while I was still on Herceptin, and my cancer is rapidly spreading.
So please, please, no matter how beat up you feel after neoadjuvant treatment, if you have extensive residual disease go for everything you can get! I myself did not have this option, since the public health care system in DK operates with standard treatments according to the principle of "one size fits all".
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Thanks for starting this thread.
My tumor started out with largest dimension at 5.7cm prior to neoadjuvant TCHP. The tumor had softened and shrunk and felt like a tiny pea from the outside by the end of my 6 rounds of chemo. At the time of surgery, the mass showed "marked impact" from treatment, but there was still 1.7cm (20%) of residual cancer present. My two SNs were negative. My MO said my tumor response was typical for triple-positive and that is why the anti-hormonal medication treatment is so important. I had rads due to that remaining 20% and I have done 6/13 HP infusions so far.
If I didn't have the HP infusions and AI meds ongoing I would be very nervous about recurrence and/or mets.
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Giveityourall: Nerlynx is a oral drug for Her2+. It's supposed to be taken within 2 years of finishing Herceptin. Its common SE is severe diarrhea. My MO says that it seems to benefit hormone +, but not so much the hormone -. There are some BCO discussions on Nerylnx.
ADDK: So sorry standard treatments (so far) haven't worked on your tumor.
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I was diagnosed triple positive after originally being diagnosed ER+/PR+/Her2-. I had multicentric tumors, the primary being 3.3cm with several satellite nodes - one right behind the nipple, an area of "non-mass enhancement" and at least one involved lymph node, but probably more than one. My MO had started me on zoladex, anastrozole, and Ibrance as neoadjuvant therapy. They biopsied after a month to see if the Ibrance was working (since it's experimental for neoadjuvant therapy), and it was, but that's when I was found to be Her2+. In the interval between the biopsy and when the FISH test for Her2 came back, the extremely unscientific measurement that my MO's nurse practicioner does showed the tumor was growing so she sent me for a mammogram and ultrasound, which showed my tumor had shrunk by about 25% after one cycle of Ibrance. This is relevant, I promise.
At that point I was quickly started on six cycles of TCHP. The tumor seemed to shrink a lot the first two rounds, but not much after that. Mammo at 5 rounds showed nothing but MRI picked up a 1.8cm tumor and 2 lymph nodes. Surgery found a tumor that was 2.1cm at its largest dimension and three positive lymph nodes, but the satellite tumors and area of non-mass enhancement were gone. The remaining tumor showed impact from the chemotherapy, which I guess means some of the cancer cells had died and the tumor was less dense. Path also showed lymphovascular involvement.
I met with my MO after surgery and asked to have the tumor re-tested for receptors. He sent it straight for FISH and it came back Her2-. I have continued on Herceptin, but not Perjeta as that is indicated more for hormone negatives as adjuvant therapy. He mentioned that I would go on hormone supressors after radiation, and that I could go on Nerlynx after Herceptin is finished. We also discussed putting me back on the Ibrance, as it had shown benefit before I went on chemo, but it remains to be seen if insurance will pay for it. If they won't, I don't know that I'll do it. Maybe I'll do a shorter course, but that stuff is about $10k/month so even six months of it will be a huge chunk of change if I have to pay out of pocket.
I am currently having comprehensive radiation: chest wall, scar, skin, inframammary and supraclavical lymph nodes, and axilla. I meet with my MO a week after radiation is finished and I will see what his final recommendation is then. My vote is for going back on the zoladex, anastrozole, and Ibrance in addition to finishing out the Herceptin. I'm not too hot about the Nerlynx because looking at the study data it seems like they just sliced up the patients into ever smaller groups until they found a group who showed benefit. I work with statistics a lot in my job and I know that you can find whatever result you want if you slice the data up enough, but that result is often a false positive. I suspect this is what happened with the Nerlynx study.
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Hapa,
Very interesting story. All of our stories are interesting because it shows that the universal solution does not universally work. Is it because cancer tumors are like snowflakes - inherently different? Or is it due to cancer cells mutating - for survival purposes, a HER2+ tumor bathed in Herceptin and/or Perjeta learns to shed its HER2 characteristics. With less HER2+ receptors, the drugs will be less effective and allow the adapting tumor to thrive. Are tumors like chameleons? Can they learn to change their characteristics for survival purposes?
Hapa, like you, I understand statistics and read a lot of the new research articles. Unfortunately, some of the studies discussing the ErbB (human epidermal growth factor receptors) components are too complicated. I am not familiar with all of the verbiage, but I do know there are different types of ErbB's also known as HER's. There is HER1, HER2, HER3, HER4 https://www.hindawi.com/journals/mbi/2014/852748/). These HER types can also be written as ErbB1, ErbB2, ErbB3, ErbB4. Each HER/ErbB has dedicated responsibilities regarding a cell's survival and growth through signaling pathways. I know this is getting into the nitty gritty, but if we want to understand why our tumor did not achieve pCR (pathological complete response), we should try to understand our tumors' differentiation from the tumors that did have pCR. For instance, becoming more educated, I have learned to request different tests for my surgically removed tumor. Like Hapa and many others, I stand tall and am often the guide for some of my treatments and exams.
Hapa, great to hear that u achieved results and am glad you shared your triumphs and struggles. I, and I hope others, are learning new things. I particularly like learning about viable medical options.
I find it interesting that your neoadjuvant therapy was oral chemotherapy. I am familiar with Xeloda (a new study touts it as an annihilator of residual HER2+ tumors resistant to TCHP) and Ibrance (see it on the tv A LOT - hormone positive drug, I think), but I am not familiar with anastrozole. Educate me, please.
Giveityourall
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Bellasmom,
Wow- Nerlynx has been shown to be effective as long as it is taken within two years of last Herceptin infusion? That is interesting. I never knew. I gotta read this stuff. I need to know my future options and perhaps use one of them now to prevent a recurrence. I don't know what to do.
Giveityourall
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Anastrozole is just an aromatase inhibitor. I was taking it to treat the ER/PR+ tumor. AIs are given along with Ibrance.
For the record, I don't think my tumor mutated under treatment so much as it was two different cancers at dx. The biopsy that came back Her2+ was taken from a different place than the other biopsies, close to the nipple and near one the satellite tumors that disappeared. And at surgery, my closest margin was at the chest wall, so it seems like most of the shrinkage was on the other side, near the nipple. The remaining tumor was grade 1, compared with grade 2 or 3 at dx. So I think the tumor had mutated recently to Her2+ and those cells were aggressive and growing quickly, while the Her2- stuff was rather indolent. Additionally, Her2 testing looks at things like ratios and percentages, so it's likely that once the Ibrance and hormone suppressors killed off a fraction of the ER/PR+ stuff, what was left was more Her2+ than it started. Your hypothesis, that the tumor is mutating in reaction to different treatments is also something I've considered, and it worries me the most.
I think a lot more study is needed to differentiate between subtypes of Her2+ tumors. I imagine a lot of highly ER+/PR+, low Her2+ women like myself actually have two different cancer types.
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Sidalee,
Thank you for participating. I have learned so much from everyone's responses.
I believe “marked impact" means the tumor displays “scars." The scars represent the places where the medications destroyed the cells. However, in Bellamom's scenario, the resulting holes represented the treatment's efficacy. I would assume Bellasmom's tumor had scars as well.
I am incredibly grateful to read that your tumor was affected. Simultaneously, ADDK's story weighs heavily on my heart.
Did they biopsy a section of the surgically removed tumor measuring 1.7 cm? If so, do u mind sharing the results?
Thanks,
GIVEITYOURALL
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ADDK, Thank you for joining our topic and sharing your trials and tribulations. Familiar with the pitfalls of a public health system, I was wondering if there are any viable clinical trials in neighboring countries?
Also, I do not understand what you mean by nine weekly cycles. I understand that your initial treatment included EC - the infused chemotherapy agents, and Herceptin along with Perjeta as targeted therapies. Deciding that your chosen treatment was only providing minimal results, your medical team switched you to Taxol, Herceptin, and Perjeta. So, my question is the following- did u receive your infusion on a weekly basis... but only for nine weeks?
I noted that your surgery was in August and you were diagnosed in February. I had some questions about your treatment, but I understand the sensitivity of the situation. Therefore, I understand if you do not want to answer my questions.
After your Feb 2017 diagnosis, how many weeks transpired before you received chemotherapy? When did you finish your nine cycles? Once you finished your chemotherapy treatment (neoadjuvant therapy), how many weeks passed before you underwent the removal of your tumor?
In addition, I read and reread your advice - “get everything you can get.” I will follow your advice.
Giveityourall
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Hapa, So, you are stating that the top of the tumor (by nipple) and the satellite tumors had more HER2 on their individual cells than the bottom of your tumor. In other words, the base of your tumor contained more ER and PR.
Have you or anyone else reading this post come across medical articles discussing HER2 subsets? I have seen it a few times,but am not sure what HER2 subsets entail. However, scientists/researchers feel the HER2 subsets are more difficult to treat and as such, are often portrayed as HER2 drug resistant. In other words, rather than it being drug resistant, the HER2 subset does not have a cure. Maybe our harder to treat cancer cells contained HER2 subsets?
Giveityourall
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Hapa,
Regarding tumors ability to mutate, it can happen. I am including an article from BCO that discusses and substantiates a tumor’s mutation properties.
According to Utthara Nayar, PhD (April 2018), “ in cases where the ER-positive tumors had developed activating HER2 mutations in response to ER suppression, if we inhibited only the HER2 mutation with Nerlynx, we would eventually provide an avenue for the tumor to revert back to ER dependence. That's why, to achieve maximum tumor suppression, we hypothesized that we'd need to simultaneously inhibit both ER and HER2 with the Faslodex plus Nerlynx combination. And indeed, as you mentioned, this was the most effective -- and the only effective -- combination against ER-positive tumor cells with the HER2 mutations (https://www.breastcancer.org/community/podcasts/evolving-mutations-in-mets-20180416).
Wild stuff.. isn’t it? And scary... but I would rather know the scary stuff so that I can make sound treatment decisions.... but that is just me. Others don’t want to know and I respect their choices.
Giveityourall
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Here is some info on my final pathology:
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Giveit, Please feel free to ask anything you would like to know. I´m happy to share. I received my Taxol infusions on a weekly basis for 12 weeks. The standard treatment offered is six cycles of chemotherapy, so I had 2 x EC and 4 x Taxol (in 12 weekly doses), in addition Perjeta concurrent with Taxol every third week l (i,e. four doses in total), and one year of Herceptin every third week. The last eight doses of Herceptin as adjuvant treatment, of course.
I started chemotherapy (EC) exactly two weeks after diagnosis, and had surgery five weeks and two days after completing neoadjuvant treatment. Originally, the procedure was scheduled ten days after end of neoadjuvant treatment, but was postponed: I had mastectomy and tissue expander placement in one procedure, which required the presence of two surgeons (breast cancer and plastic) at the same time and place. This, I learned, is extremely difficult to coordinate - even if both surgeons work in the same building :-). From Dr. Google I knew that my only option for reconstruction would be concurrent tissue expander placement, and after a consultation with the same doctor (Mr. Google), I concluded that my acceptable limit should be six weeks, and hence accepted the additional waiting time.
I think my case is rather a case of Herceptin resistance than timing of treatment/surgery, and the fact that with no hormonal involvement HER2-pos. cancer is simply more aggressive (everything based on my consultations with Dr. Google, of course :-))
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ADDK,
If you think that your tumor has become resistant to Herceptin, then wouldn't you suspect that the migrated cancer cells possess this same characteristic - resistance to Herceptin? If that is the case, why would you take Kadcyla, which is a combination of Herceptin and chemo drugs? Are Kadcyla's chemotherapy drugs more effective than Xeloda's for your particular case? Just wondering. Something to research or ask your oncologist.
Out of curiosity, do your February and June 2018 biopsy FISH tests show similar HER2/CEP17 ratios? Did they perform a FISH for the August 2018 surgically removed tumor or tumors? If so, are the August 2018 results similar to the other FISH results?
Am I reading your profile correctly? Both tumors were in the left breast? Also, you selected to have a single mastectomy , correct?
Giveityourall
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Giveit, My treatment is the standard treatment that my hospital offers, and is not subject to discussion ("take it or leave it").
I recurred about 6 months into Herceptin treatment, which my hospital has afterwards (reluctantly) admitted. As 1st line metastatic treatment I was offered Herceptin (again), Perjeta (again) and Navelbine. After 5 cycles, during which my cancer spread, I was switched to Kadcyla (another Herceptin drug), have had two cycles, and my cancer is still spreading.
I have had two FISH tests - February 2017, and May 2018. The first one showed 3,66 (estimated Ki67: 35%), the second one 3,17 (no Ki67 entry), "CEP17" does not appear from the reports.
I had one cancerous tumor in my left breast (mastectomy side), and did not have a choice regarding surgery (single/double mastectomy). My recurrence is not a solid tumor, but inflammatory skin mets, so any effect of treatment will be visible.0 -
Sidalee,
Diagnosed at 40 must be tough. You have gone through a lot and appear to be hanging in there. You are a tough cookie. You must also have a strong support system.
I don't know if you experienced anxiety, but I did. Although meditation and exercise have alleviated my anxiety levels, I occasionally have scary cancer thoughts. Do you ever get them? If so, how do you squash them?
Giveityourall
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Hi everyone, the tumor in my breast had a complete response but I had cancer cells remaining in 2 lymph nodes. I'm currently on HP. My MO mentioned at my appointment last week that Kadcyla is about to be recommended for early stage HER2 positives who did not get a complete response instead of the HP I'm currently on. I may be able to switch over after the new year. The final trial results (KATHERINE III) are being announced in December. It does say it shows significantly (whatever that means) better results than HP adjuvant for people who did not get a complete response. I'm hoping to get a couple months on it before my adjuvant treatment ends in March. I can't get the link to post, but you can google based on the information below:
Media Release
Basel, 15 October 2018
Roche's Kadcyla reduced the risk of disease recurring in people with HER2-positive early breast cancer with residual disease after neoadjuvant treaatment.
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Hi Giveityourall,
I have my ups and downs for sure, but my husband and kids help me stay positive and busy. I had a really hard time mentally with radiation and got very sad about the potential SE's of endocrine which I will be starting in a couple of weeks. I did my research, though, and I know how important the AI is for my long-term survival so I am determined to give it my best shot.
I have had a couple of bad dreams about recurrence lately and it scares me a lot. I go for daily walks each morning near my office and sometimes I go out again after lunch just to take some deep breaths, get a little fresh air and sunshine, etc. It helps.
I'm sitting at the clinic getting my HP 7/13 as I type this. My big SE from Perjeta is the big D and it is getting pretty bad again. The PA told me that they would have to pull the Perjeta again if I get to the point of needing hydration like I did during chemo. I'm supposed to start every morning with an Imodium now to see if we can get things under control. I want to stay on the meds as long as possible.
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Giveityourall - Thank you so much for posting that link about tumor mutation. I mean, it scared the crap out of me but it's good to know. I'll be going on AIs or tamoxifen as soon as I'm done with rads, while I'm still on herceptin. Hopefully this will give the cancer cells nowhere to hide.
ADDK - I'm sorry. Your situation really sucks. A lot of people wonder how Americans can tolerate our exorbitantly expensive health system that doesn't even cover everyone, but I've come the conclusion that socialized medicine works best for healthy people who are have minor, temporary health issues. If you're seriously ill in America and you have good health insurance and/or a decent chunk of money you have a lot of options for treatment.
AbbyPuff - thanks for the info on Kadcycla. I see my MO on the 12th, I'm wondering if he'll suggest a switch from herceptin.
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ADDK,
Now your profile makes sense to me. I was having one heck of a time deciphering your June 10, 2018 “metastasized to other." Your Stage IV involves skin mets. I know many of our sisters diagnosed with an overexpression of HER2 proteins also deal with skin cancer or an overproduction of their epidermis (outermost skin layer). For instance, one patient diagnosed with HER2+ has excessive skin on her feet and hands - primarily around the nails.
Occasionally, I try to read and understand scientific research articles. I have read a few articles discussing PLK-1 as our next targeted site to kill cancer. Are you familiar with it?
Thanks, Elizabeth
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Hapa, As the weeks progress, our understanding of cancer cells exponentially increases. Therefore, I am hoping new drugs become available to us - ones that work differently than Herceptin and Perjeta. If I am understanding their pharmokinetics correctly, then HP works on extra cellular receptors. In other words, these receptors, which are special doors that only open to special invitees, sit on the outside of the cell's membranes. Knowing that 40% of us will become resistant to HP, I am hoping that the scientific community finds weaker points along Her2's signalling pathway. I am thrilled with some of their new prospects - like PLK-1.
(https://www.researchgate.net/publication/310775709_PLK1_A_Potential_Target_for_Cancer_Therapy
Happy Turkey Day!!
Giveityourall
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Jumping in for a moment to point out an important distinction. Regarding Giveit's Nov 15 post above: a Her2 mutation is different from a Her2 amplification/overexpression. Neratinib (Nerlynx) can work on a mutation that would not respond to Herceptin. While standard FISH etc can determine Her2 positive aka overexpressed, a Her2 mutation would only be found by genomic testing Of the tumor, such as Foundation One, or liquid biopsy such as Guardant 360. It would be called a mutation in ERBB. This is my understanding.
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ShetlandPony,
I am not a cancer specialist by any means and I am plodding through literature to learn what all of this means. So, if I explained something incorrectly or used incorrect terminology, I am thankful for your clarifications and deeper insights. I read about the liquid biopsies and found it to be a revolutionary idea. Limited in my knowledge, I do not believe any of my local Tampa, Florida breast cancer peers have been offered the choice of a liquid biopsy versus biopsy/tissue sample of cancerous tumor. If I am understanding liquid biopsies properly, it uses bodily fluid, such as blood, to find and analyze tumor's circulating free DNA. By examining the circulating free DNA, lab technicians will be able to detect cancerous tumors at very early stages - earlier stages than an MRI or CT/PET scan could detect; determine neoadjuvant treatment's efficacy; and note tumor mutations that normally coincide with greater heterogeneity and drug resistance (https://www.cancer.gov/news-events/cancer-currents...). That sound right?
Liquid biopsies will certainly aid in the detection of cancer; ascertain cancer patients' need for a different drug; and ultimately increase our overall survival rates. Although the United State's FDA approved this unique testing, I read that liquid biopsies are in their infancies and not deemed as reliable. Hopefully, in the near future, scientists will resolve liquid biopsies' inherent issues. Have you had a liquid biopsy? Giveityourall
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Sidalee,
I am thrilled to read about your strong support team - your family. I always think of love and exercise as two of the most under utilized, underrated medicines in the world. Glad you take spoonfuls of each - love from your husband and kids and walks during your work breaks. Sidalee, you are pretty amazing!! How do you manage tough days with kids and work? I guess you plow through. I think I would fall to the ground, curl up in a ball, and cry.
In a few days, I will undergo my 12/18 HP treatments. I can relate to the big "D" and will share one of our fellow online member's tricks. To prevent hydration, she would sip her favorite smoothie and eat frozen grapes during her HP infusions. I don't know why, but frozen seedless grapes taste sooooooooo good during my infusions. Maybe it is the cold, unusual frozen grape texture that I like. I am not sure.
Thanks for telling me about your fears. This is scary, terrifying stuff. I am worried about my tomorrows and am very scared of dying. Simultaneously, I am worried, like you, about side effects from our post-surgery/radiation drug. In your case and as you noted, your Aromatase Inhibitors are an integral part of a your medication regimen. I am glad they are available to you.
Giveityourall
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Giveityourall,
Thanks, you are very sweet. Some days I feel tough and brave and other days I seriously consider crawling under the covers and staying there. Yesterday was one of those rollercoaster days. I listened to Christmas music on the way to the clinic for my Zoladex Injection #2 and I was feeling it. I was a half-hour early for my appointment so I walked all over the beautiful campus and was just feeling all positive. For some reason I was scheduled in the ambulatory infusion center instead of the chemo building for my shot so my nurse said we had to wait for the drug to be brought over from the other building. In the meantime, she decided to do my Lidocaine shot to numb me up and when she asked what they did before I told her that my chemo nurse had sort of gone around in a circle...so this lady gives me TEN separate shots in a circle on my stomach! Not sure how that was even sanitary to stick me 10 times with the same needle. Then it takes almost an hour after that before the drug finally shows up and I get the big shot. I was almost 2 hours late for work and I have a hematoma the size of a 50-cent piece with 11 total injection sites. Needless to say, my good mood was over and I called to make sure all further injections are scheduled in the chemo building.
Today is a better day. Next week I will take my first Letrozole. I keep telling myself how much I need to take it.
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Sidalee,
That is crazy. Ten sticks? Unfortunately, I am unfamiliar with the proper administration of Zoladex. I guarantee a BCO member knows the correct methodology. Have u verified its proper administration with your doctor and, for your own peace of mind, with Zoladex's pamphlet (must be online). As you know, those pamphlets ALWAYS discuss the administration and route (I.e. oral, subcutaneous injection, intravenously).
I often feel that the world of oncology, which advances quickly, is simultaneously bombarded with newly diagnosed patients. As such, oncology waiting rooms are becoming more crowded; and the doctors and nurses, who are taxed with higher number of patients, must set aside hours for continuing education. The obvious solution is to hire more staff, but our medical facilities' (some of them) priority is to save money not lives. I know that is a harsh statement, but healthcare is a business. What dictates a business' practices? Money. I also know most of the healthcare practitioners are doing their best to provide great medical care, but it's tough. Nevertheless, it has to occur. With that being said, what is the correct way to administer Zoladex?
GIVEITYourAll
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ADDK,
How are you? What is the latest news on your treatment?
Out of curiosity, do your pathology reports discuss the color of your tumor or tumor sample? Does it use words like “white” or “tan?” I ask because white indicates white blood cells.
Giveityourall.
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