Why is chemo effective for more advanced low oncotype cancer?

JustMeM

I have been offered some treatment options, and I am trying to decide on a plan. My doctor had previously said with my oncotype (I believe it was 5), we would absolutely not do chemo because it would have no effect, but my pathology came back with 12 of 14 nodes positive (all macromets) and surprised everyone. It seems that with the extent of what they found chemo is automatic. (Regimens are AC-T or TC)

Not sure if this is crazy, but I'm questioning if chemo is the right choice. I am not at all against doing it if it has a benefit for me, but I'm trying to understand why it would be more effective just because there's more of a type of disease that doesn't respond anyway. I'm wondering about delaying radiation for 5-6 months on breast and nodes, especially because I had a lumpectomy and there were a few tiny calcifications they decided not to worry about after additional imaging, reassuring me that radiation would get them just in case. They had a lot of trouble detecting the size of the original tumor even with multiple imaging modes (2.8 cm after surgery), maybe a combination of lobular type and dense breast tissue, so I thought if there happened to be more breast involvement radiation would be key. Also apparently my predicted low response to chemo is balanced by a predicted good response to hormonal and targeted therapies, so I'd like to get started on what should be most helpful. (Not sure of the exact names of other therapeutics except that we'd be adding a cdk4/6 inhibitor)

My doctor is on the forefront of the movement toward no chemo for women with low oncotype and I get the sense he's not confident it's going to be all that helpful but doesn't want to out and out give me advice that flies in the face of industry standard. Based on some of the research apparently coming out I'm wondering if we're on the cusp of change with this, even with more advanced disease.

All this to ask what my husband put much more succinctly: “If they missed something, is the chemo going to do better than radiation and hormonal therapy?"

I know nobody can absolutely advise me, but interested in thoughts or info I can consider as I make this decision.

moth

JustMeM - I don't want to be a Debbie Downer but... have they done chest & abdomen CT with contrast, MRI and nuclear bone scans? Blood tumor markers? ILC pts on this board frequently report it's hard to find on imaging and scans, hence multiple modalities need to be used. Honestly I would push for all these first if you haven't got them yet.

I think the Oncotype predictions go out the window once this many lymph nodes are affected. "the group with ≥4 positive lymph nodes had a markedly elevated risk of recurrence, even if the RS was classified as low-risk (~50% 9-year risk of distal recurrence at an RS score of 18).15 This supports the consensus that RS testing is not of value in patients with >3 positive axillary lymph nodes." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC58274...

I think it just turns Oncotype into something that you end up needing to ignore. I had Oncotype because we thought I was weakly ER+. Oncotype came back classifying me as triple neg and with a recurrence score....which my MO said it shouldn't have even reported the # because it's not validated for tnbc at all. (but it turns out it was right as I did recur)

If it were me, I'd do the chemo but I've always been a "throw what it takes at it" person so I don't have any regrets later.

best wishes

Spookiesmom

Agree with Moth. While I have a different cancer, IDC, and didn’t do Onco test, I wanted to throw everything at it I was stage 3, grade 3, high risk for reoccurrence. It wasn’t fun, but I did it. I had 7 free years before I found another lump. I don’t regret any of it, and would do it all again.

It’s a personal decision, only you can decide what you can live with.

Best wishes.

LillyIsHere

JustMe, I was told ILC has low Oncotype in general. In my case, BS and MO didn't even ask to have it checked. I was also told that chemo works for fast dividing cells and ILC tends to grow slow (and sneaky) so chemo is not much effective. However, I know people with ILC who have done chemo and it has shrunk their tumor. I agree with Moth, be as aggressive as you can early on to reduce the recurrence. In the end, it is your body and your decision.

ElaineTherese

Hi!

Both hormonal therapy and chemo are systemic -- chemo kills cancer cells that have escaped from the original tumor that are circulating in your body through your bloodstream and/or lymph system. Since your cancer made it into your lymph nodes, your medical team has good reason to believe that it may be circulating in your lymph system. Hormonal therapy either starves the cancer cells of estrogen or prevents the cancer cells from using estrogen as fuel to grow. They are both useful tools.

According to your signature, your cancer was Grade 2, which means that it wasn't THAT slow growing. Plenty of breast cancer patients have success with chemo with Grade 2 cancer. (Grade 1 is another story.) I was Grade 3, so chemo did wipe out my active cancer in my breast and compromised lymph node.

If I were you, I'd consider doing both, but only you can decide what you want to do. Hormonal therapy is a very powerful tool; however, you need to be committed to it for years and it's not always well-tolerated. (I'm finishing year six.) Chemo is five, maybe six months and then it's over. I did six months of AC+T, and it was doable.

Good luck! ((Hugs))

JustMeM

Thanks for the helpful responses. I am not sure I'm understanding the oncotype correctly, and also if I'm explaining myself correctly. Forgive me, I've had a lot of info come at me and my brain is limited as it it, lol.

I can see that oncotype is no longer a good predictor of recurrence risk with so many positive nodes, but the way my doctor explained it to me it also was a predictor of the effectiveness of chemo on that particular cancer. My oncologist refers to it as the "personality." I took away the understanding that it would basically laugh at chemo. So I’ve been wondering why chemo would help just because there's more of it, if that makes sense. To use a bad analogy, if you had a patch of rash and it was highly responsive to cream A (hormonal/targeted/radiation) and barely if at all to cream B (chemo), why would it be more responsive to cream B if it turned into a larger rash? That's where I feel like I'm misunderstanding something.

I'm guessing it's not that simple, but that was the premise I was using. I absolutely would do whatever it takes, just seemed I was told the effectiveness of chemo was likely to be almost nonexistent. I also read that time to treatment for radiation matters in lumpectomy and should be inside of 8 weeks at longest, so 5-6 months seems a lot longer. Really just trying to pick the best scenario for my particular circumstances based on the info I've been given.

Moth, thanks for the link, great info. I have had CT of chest to pelvis with contrast and abdominal MRI with contrast. Also bone scan with contrast.

ElaineTherese, I didn’t know grade affected response to chemo. It’s hard to incorporate all the info quickly, so thank goodness for the people here. My oncologist used the oncotype thing so much, maybe I just got hung up on it. I believe it’s truly his focus.

Beesie

"I am not at all against doing it if it has a benefit for me, but I'm trying to understand why it would be more effective just because there's more of a type of disease that doesn't respond anyway."

To my understanding, chemo isn't recommended for low Oncotype cancers not because these cancers don't respond to chemo but because the risk from the disease is lower than the risk of serious side effects from the chemo itself. It's a risk vs. benefit assessment. For example, if someone has an Oncotype score that suggests only a 3% risk of metastatic recurrence, the risk reduction benefit from chemo would be 1%. The risk of serious side effects from chemo is greater than 1%. Therefore it is better for this patient to not have chemo. Or if someone has an Oncotype score that indicates a 10% risk of mets, and if this risk can be reduced to 6% with endocrine therapy alone, with the addition of chemo reducing the risk only by another 2%, then based on the risks and side effects of chemo, chemo usually would not be recommended. So it's not that chemo doesn't work - it's that the risk of mets isn't high enough to warrant chemo.

You may have had a 5 Oncotype score, but as moth said, that prediction is out the window. The genetic make-up of your cancer might be favorable, but the genetics just provide directional guidance and nothing more. With 12 positive nodes, your cancer is not behaving favorably. The reason Oncotype tests are usually run after surgery is because cancer is unpredictable, and if the pathology is unfavorable, the genetics of the cancer (as assessed by the Oncotype test) no longer count. As per the information moth provided, Oncotype tests are not supposed to be done when there are more than 3 positive nodes; the Oncotype results are meaningless as compared to aggressive pathology. So whatever the genetics, your cancer has shown itself to be a spreader. This puts your risk of mets at much more than whatever an Oncotype 5 would suggest. And this completely changes the risk vs. benefit equation for chemo. For example, if your risk of mets is 20% (I pulled that out of the air), chemo might be able to reduce your risk to approx. 14%. That benefit significantly outweighs any risks from the chemo itself.

To get an general ideal of the benefit you would get from chemo, you can complete these two on-line models:

http://www.lifemath.net/cancer/breastcancer/therapy/ Choose "Display As" pictogram, for the easiest interpretation of the results.

https://breast.predict.nhs.uk/tool After you input your diagnosis information, a new section will appear that allows you to select different treatment options. Choose Icons to view the results for the easiest interpretation.

ShetlandPony

All those nodes with macromets suggest a more aggressive cancer than an oncotype score of 5. Tumor heterogeneity could account for this; that is, the sample sent to oncotype did not represent the whole tumor well. But I will throw out another thought: What if Oncotype is not actually very accurate for ILC??? See the discussions of LobSig, a test being researched as a better test for ILC.

ShetlandPony

I want to say that I understand your question and the cream analogy. If the cream is not effective on a little bit of rash why would it be effective on a lot of rash? Well, in this case the rash is not the kind of rash we thought it was at first. It is a different kind of rash. Your pathology report gives you more information. Beesie of course explained the risk-benefit assessment well.

I believe the usual order is chemo, then radiation, then hormonal therapy. Remember chemo is systemic (including the breast and nodes), and radiation is a local treatment (just breast and nodes). Hormonal therapy is systemic treatment that is usually given for five to ten years.

MinusTwo

Seems clear to me - throw out the oncotype & consider the lymph nodes. Maybe someone has already suggested this, but if you're still not sure - what about getting a second opinion?

LeesaD

I so get why you’re asking. I always wondered the same thing. My Oncotype was a low 3 with 2 sentinel nodes micromets and 2 axillary nodes with macromets. My MO said Oncotype not valid for more than 3 involved nodes but he said research maybe in a few years will show otherwise. On my Oncotype results on the 1-3 node results it showed survival with chemo less than without so chemo was more detrimental. That one extra node threw all of that away I guess. I was OK with it as I always wanted to be as aggressive as possible so I did not have a problem doing the chemo. Although my chemo regime was changed from AC-T to TC as my MO thought the heart risk associated with the Adriamyacin outweighed any benefit with the low Oncotype. During my chemo he even voiced to me that he thought he might be over treating me but said he had to give it. I understood. I wanted to throw all I could at it. I knew the hormone therapy was what my cancer would respond to most and couldn’t wait to begin that. I didn’t want to regret not doing all I could so I did chemo, radiation, and oopherectomy so I could go right to AI’s. Everything that gave me percentages I did. With your amount of nodal involvement I don’t think you’d find an MO who wouldn’t recommend chemo but you have to be comfortable with your decisions.

ShetlandPony

JustMeM, are you pre- or post-menopausal?

cathy67

Hi JustMeM,

I had almost same situation last November. My oncotype score is 6, which is very low, with 11% recurrence in 9 years, and no chemo benefit. So doctor said, no chemo. My lump is 2.1 cm, grade 2, one node positive. I just wonder why they got 14 nodes, lumpectomy plus sentinel node biopsy is the standard right now. For me, since my sentinel code is only one, so I only got 1 positive node, no possible 2 nodes, 3 nodes or more. Also you said, low oncotype score let your MO suggest no chemo, then pathology report back so many positive nodes, but we got pathology report first, then tissue sent out for oncotype test.

Reading your experience, I don't know how many positive nodes I have if also removed so many during surgery. My MO and my radiation oncologist all said no chemo, I will react to hormone very well, no chemo benefit. I understand it is so tough to decide, I really don't know the answer, either of us, I just followed doctor's suggestion.

I think one key point here is node, how to understand the number of nodes for oncotype test? Right now, lots of patients only have sentinel node data, I believe a lot of only have 1, 2 or 3 sentinel nodes in total, won't have 4 or 5 positive nodes in that case. My node is 3mm, a bit bigger than micromet. My radiation group talked to me about this positive node, they think that is minor, compared to lots of patients they met. Both doctors said no chemo, however they were very conservative on my radiation treatment and hormone treatment, especially hormone.

Pray for you.

Salamandra

Even though this doesn't apply to me personally at this point, I'm so glad you asked, JustMeM, because this thread has been really helpful and clarifying.

I guess the last piece is about the impact of delayed radiation.

My understanding is that radiation helps to clear up and kill remaining floating cancer cells before they can escape/grow again. I wonder whether delaying it less of a concern with chemo, because the presumption is that the chemo will either destroy or keep those under control while a person is having chemo, and then whatever's left, even though more time has passed, is something that the radiation will still be able to take care of?

BCat40

JustMeM, I recommend trying to get a telemed 2nd opinion with Otto Metzger at DanFarber. He specializes in ILC research and might be able to help clarify things for you.

Shetland Pony, was your ILC originally Her2- and came back Her2+?

JustMeM

I appreciate all the responses to this, I feel like I have a better understanding of the chemo benefits. It seems it will be a good choice.

Beesie, thanks for taking the time to explain that, it makes sense. I basically understood chemo with low oncotype as akin to using an antibiotic for a virus. No real effect.

ShetlandPony, thanks for the info and seeing what I was saying. Yes, that is the order they gave me for the different treatments. I might ask if it’s possible to layer some hormonal therapy toward the end of the radiation as I think I saw where that has happened, I am post-menopausal.

Cathy67, the reason they took so many nodes is because they knew I was node positive, I had a palpable node under my arm and others that showed on some imaging.

Salamandra, the delayed radiation is a concern for me, but I guess you have to just try to choose the best path and timeline available.

BCat40, going to send you a PM about that.

Thanks again to everyone who posted, it helped me get a sense of what I wanted to do.

ShetlandPony

BCat40, no, it was and still is typical ILC with ER+ Her2- . But it developed a mutation in Her2, and my arm of the phase II clinical trial is aimed at showing that this combo that includes neratinib is effective for ER+ Her2 mutated bc as it is for Her2+ bc.

(It was also highly PR+ to begin with but last biopsy did not have enough to evaluate the PR, so I don't know if it is currently PR+ or PR-.)

Salamandra, I believe you are correct. The idea is that chemo can go after any escaped cancer cells that could take up residence in other parts of the body — which is the most worrisome thing — and of course at the same time it would also go after any cells in the breast. So that's why chemo is commonly first.

BCat40

Thanks for the info Shetland--I hadn't thought about a mutation in the HER2 gene as opposed to HER2 positivity.

Also, your sig says your ILC was grade 1. I was under the impression that ILC always registered as at least grade 2 because it gets the highest score on the tubule formation element of the scoring system. Have you heard this before?

*****

Tubule formation, mitotic count and nuclear pleomorphism – three headers, each generating 1 to 3 points. When the 3 scores are added, Grade 1 totals 3-5, Grade 2 is 6-7. Grade 3 is 8-9.

Left out in the cold, however, with the adoption of the Nottingham system was invasive lobular carcinoma (ILC). By definition, the histology of ILC does not allow tubule formation as a feature. So, a low grade ILC gets penalized with 3 points before one ever gets to the true distinguishing features – mitoses and nuclear pleomorphism. This creates the bizarre situation wherein invasive ductal grading starts with a minimum total of 3 points, whereas an ILC (a slightly more favorable histology) starts with a minimum of 5 points, ready to leap into the Grade 2 category. One simple, subjective, slip-up here (a 2 for either mitoses or pleomorphism), and you've turned a truly Grade 1 cancer into Grade 2 with a total score of 6.

https://alanhollingsworth.wordpress.com/2018/10/07...:~:text=Tubule%20formation%2C%20mitotic%20count%20and%20nuclear%20pleomorphism%20%E2%80%93,the%20Nottingham%20system%20was%20invasive%20lobular%20carcinoma%20%28ILC%29.

****

I guess in your case you must have had a 1 mitotic score and a 1 on pleomorphism. What horrible luck for a small grade 1 to come back like that. Best wishes for ongoing useful treatments for you.

cathy67

Hi JustMeM,

So your doctor knew it was node positive clinically before surgery, but still ordered oncotype test (before pathology report came out). I think this means the oncotype score influenced the treatment consideration more or less, and you got super low score, it is good to know hormone will work very effectively, no matter how chemo will perform. I hope you can get a second opinion soon, even you already decided to go for chemo, I think yuo'd better study chemo regimen, so you can discuss with your doctor about that. When I was waiting for oncotype score, I studied chemo regimen. Everybody's treatment plan is unique, I hope we all pick the most effective option.

Best wishes.