Nodal ITC after neoadjuvant chemotherapy

[Treat]

Dear colleagues,

I would greatly appreciate your input on this situation.

cT2N0 triple positive breast cancer.
Mastectomy and axillary clearance after neoadjuvant chemotherapy shows pCR in the breast and sentinel node biopsy shows ITC.

RT? Leave alone?

Thanks

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[Palex80]

The standard answer would be: Leave alone.

However, it would be nice to know a few more things about this patient:
a) age / menopausal status
b) size of primary tumor at diagnosis
c) differentiation
d) how many nodes removed
e) any scars in the nodes

 

[scarbrtj]

The age and menstruation status of patient doesn't matter. Whether the tumor was 2.0001 cm or 5.0000 cm in size doesn't matter. The grade doesn't matter. The number of nodes removed doesn't matter. Nodal scarring doesn't matter. All those things as useful as Nostradamus to predict her outcome in regards to what can or can't be helped by RT. The biologics are changing our older understanding of breast cancer biology. What matters? She's essentially pN0 and by virtue of having a ~pCR in the setting of Her2+ disease can easily have a 1% chance of local failure (maybe less, "I have not seen one [local recurrence in 2000 women with Her2+ disease]"). And if you were to treat, since ENI has no OS advantage, the risk/benefit of ENI would be skewed toward more risk than benefit with ENI (since her LR recurrence risk is so low) leaving CW only RT as the more reasonable approach. And wouldn't it feel a tad weird/counterintuitive to do CW-only RT given the ITCs in the axillary node? (It would feel weird to some but not me heh.) ENI is even more risky nowadays. TL;DR... no RT.

 

[evilbooyaa]

ITC in LNs means that if patient had undergone upfront surgery you would have (most likely given pCR in breast) seen at least N1mi, if not N1 disease if patient underwent upfront surgery. ITC after NAC is not the same as ITC at upfront surgery. If this patient had undergone upfront surgery, PMRT would have benefitted per EBCTCG meta-analyses and more recently in Her2+ disease, the HERA trial (Post-Mastectomy Radiation Therapy in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Patients: Analysis of the HERA Trial)

While omitting RT after a discussion with patient would not be completely, SOC would still be to treat.

I'm assuming there was treatment effect in the LN removed. We know that 2,000 women without Her2+ disease may not have recurred, but all of them were likely treated with SOC RT (if indicated). Until it has been proven that omitting RT is oncologically safe in this scenario (we don't know how mamounas analysis incorporated ypITC) I would not recommend it off-trial.

 

[scarbrtj]

ITC in LNs means that if patient had undergone upfront surgery you would have (most likely given pCR in breast) seen at least N1mi, if not N1 disease if patient underwent upfront surgery. ITC after NAC is not the same as ITC at upfront surgery. If this patient had undergone upfront surgery, PMRT would have benefitted per EBCTCG meta-analyses and more recently in Her2+ disease, the HERA trial (Post-Mastectomy Radiation Therapy in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Patients: Analysis of the HERA Trial)

While omitting RT after a discussion with patient would not be completely, SOC would still be to treat.

I'm assuming there was treatment effect in the LN removed. We know that 2,000 women without Her2+ disease may not have recurred, but all of them were likely treated with SOC RT (if indicated). Until it has been proven that omitting RT is oncologically safe in this scenario (we don't know how mamounas analysis incorporated ypITC) I would not recommend it off-trial.

“Standard of care” is to treat cT2N0/pT0N0(i+) with PMRT? Under what guideline?

 

[evilbooyaa]

My argument is that pre-chemo the patient would have, if she had undergone upfront surgery, she would have had N1 disease. Currently, SOC is to treat based on pre-therapy stage of disease.

ypN0(I+) and ypN1mi both have similar outcomes, and both are worse than being ypN0: Prognostic Significance of Residual Axillary Nodal Micrometastases and Isolated Tumor Cells After Neoadjuvant Chemotherapy for Breast Cancer - PubMed

Increasing residual nodal disease was associated with higher rates of breast cancer recurrence, with 5-year DFS estimates decreasing from 88.4% in ypN0 disease to 73.5% in ypN0[i+], 74.7% in ypN1mi, 69.5% in ypN1, and 57.4% in residual ypN2–3 disease (Table 1). On adjusted analyses controlling for breast pCR, biologic subtype, and adjuvant radiation, patients with ITCs had significantly poorer DFS relative to those with ypN0 disease (hazard ratio 2.36, 95% CI 1.01–5.51) (Table 2). Similar findings were demonstrated in those with residual micrometastases (hazard ratio 2.14, 95% CI 1.20–3.81), whose clinical behavior was more similar to those with ypN1 disease (hazard ratio 3.13, 95% CI 2.15–4.57). This did not translate into significantly worse 5-year OS relative to those with ypN0 or ypN1 disease given the low number of events (Table 2). As expected, patients with ypN2–3 disease had inferior outcomes.

Although data does seem to be what somewhat conflicting on oncologic importance of ypN0(I+): Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases - PubMed

 

[scarbrtj]

My argument is that pre-chemo the patient would have, if she had undergone upfront surgery, she would have had N1 disease. Currently, SOC is to treat based on pre-therapy stage of disease.

ypN0(I+) and ypN1mi both have similar outcomes, and both are worse than being ypN0: Prognostic Significance of Residual Axillary Nodal Micrometastases and Isolated Tumor Cells After Neoadjuvant Chemotherapy for Breast Cancer - PubMed



Although data does seem to be what somewhat conflicting on oncologic importance of ypN0(I+): Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases - PubMed

I get your point. But it’s a bit woulda coulda shoulda. Not that that’s wrong. But you can’t make woulda coulda be standard of care; standard of care is strong throwdown. It’s your opinion man. It’s not totally unheard of to find that triple positive cT2N0 patients are SN pN0 without NAC. And I would not give a pT2N0(i+) woman sans NAC PMRT and I sure won’t for cN0/ypT0N0. I say it all the time but you go to war with the army you have not the army you want.

 

[evilbooyaa]

Fair enough on avoiding the phrase 'SOC' for a nuanced discussion. I think the likelihood that this patient would've been, with upfront surgery, pT2N0(I+) is essentially 0%. If she had minimal response in the breast, then maybe I would consider it. But with pCR in the breast and ITC in the nodes, I don't think she had ITC prior to chemo.

 

[Palex80]

My argument is that pre-chemo the patient would have, if she had undergone upfront surgery, she would have had N1 disease. Currently, SOC is to treat based on pre-therapy stage of disease.

This is correct.
And this is why I would like to have had some more information about the patient and her tumor, so I can put that all into a calculator which would then give me the risk of pN1 in the sentinel.

 

[Treat]

Thanks for all the replies! This was a question posed to me by a colleague, so I don't have all the clinical information. Tumor was 30+mm initially FWIW.

My concerns are exactly what evilbooya has mentioned... Any other opinions?

 

[DebtRising]

Question is based on what axillary clearance is defined as.

if patient had complete response, I doubt she had an axillary nodal dissectioN (maybe she did but why, was the node clinically / rad positive up front? Was there imaging after chemo that suggested residual disease? Was it just whatever nodes they felt like because they couldn’t do a sentinel? Did they biopsy and clip any of the nodes up front and verify those were removed?)

if clearance is 5 nodes or less, I would, with rationale that there may be more itcs and more itcs after chemo to me means likely more nodes upfront. If 10 nodes of more, I wouldn’t, and I can’t justify why I wouldn’t treat the supraclav in her more than likely low volume node disease at diagnosis. IMN is dealer choice on primary location, how you spare the heart, and her current and projected cardiotoxic Med doses and age

 

[Treat]

There was only a sentinel node biopsy. So treat?

 

[scarbrtj]

So we are treating all cN0 women with pN0 isolated tumor cells post-NAC in a node w/ PMRT now because ITCs post-NAC equal N1 disease pre-NAC 100% of the time? If this is logically true, thinking about the number of lymph nodes dissected or not would be illogical because the binary breakpoint is "N1 yes/no?" pre-chemo. I think SDN just invented a new PMRT indication (pN0i+ after NAC ~CR)... I kid, I kid. The psychiatrists say "always keep a dirty mind." We've got a very dirty mind about the state of this lady's pre-NAC nodes. If one is not treating all cN0 women with pN0 isolated tumor cells post-NAC in a node, all's I'm saying is there's a very wide avenue in which to drive relatively unproven opinions around re: when/when not to treat in that situation. It's almost like if the lady hadn't had a CR in the tumor and had ITCs post-NAC, by the above logic there'd be less indication to treat. Her CR "doomed" her to PMRT.

 

[DebtRising]

Listen, you’re the one with all the graphs showing our declining future. Can’t you give me a break for trying? Also we should do online tumor board on sdn. This is the best distraction from my poor choice of this field.

My rationale is that there exists randomized data showing breast cancer specific survival with ENI. ypN0itc really could equal anything pN - from the same designation to pN1. It would be reasonable to not treat, but also reasonable to infer that triple positive has pretty good chemo/her response rates and thus ITC post chemo is suspicious for more up front. Sentinel after pCR is also Easy in some but difficult in others to technically perform (or the surgeons I work with seem to think so). I would also like to know if any axillary sampling was done pre surgery.

So if your practice is to treat on the pre chemo characteristics, which may or may not have been fully evaluated in this case, and a post chemo sentinel biopsy with ITC is all you have to make decisions, can assume there was a higher N stage previously, or assume there wasn’t, discuss the benefits, put in context of B51, but if younger and healthy would offer. I wouldn’t push for CW coverage and accept what I get (another hole in my logic).

 

[ramsesthenice]

This thread is making me so happy I don’t treat breast cancer anymore. Is there a disease site with more minutia? I found keeping track of all the axillary studies about as hard as anything when I was a resident.

 

[Palex80]

Let's presume she had a 34mm, G2 invasive ductal primary tumor and was 65 years old

Here's the MSKCC-nomogram: 52% chance of being pN1 with an upfront sentinel procedure.

And I didn't put in any high risk features. Put a G3 or an L1 in there, make her a a little younger and you are easily in the 70-80% range.


Now if she had been pN1 and received chemo only afterwards, most of us would have treated her. But it's the fact that we do not know all the facts about her initial disease and her favorable response to the neoadjuvant treatment that may alter our decision.

 

[scarbrtj]

Let's presume she had a 34mm, G2 invasive ductal primary tumor and was 65 years old

Here's the MSKCC-nomogram: 52% chance of being pN1 with an upfront sentinel procedure.

View attachment 319882

And I didn't put in any high risk features. Put a G3 or an L1 in there, make her a a little younger and you are easily in the 70-80% range.


Now if she had been pN1 and received chemo only afterwards, most of us would have treated her. But it's the fact that we do not know all the facts about her initial disease and her favorable response to the neoadjuvant treatment that may alter our decision.

Yes, there's a significant chance she was N1 pre-NAC. I haven't been disputing that at all. (I do dispute that her pre-NAC N1 probability was 100%.) What I've been disputing is the wisdom of: "Because I can't be sure of her pre-NAC nodal status, I have to treat." The only things I'm sure of in this case are she was cT2N0. And pT0N0i+ after chemo. (And that ITCs in nodes post-NAC portend a worse prognosis than not.) Neither of those are in and of themselves indications to treat, as we all know. It is impossible to quote a benefit from PMRT in this case. It has to be guessed.

 

[Ray D. Ayshun]

This thread is making me so happy I don’t treat breast cancer anymore. Is there a disease site with more minutia? I found keeping track of all the axillary studies about as hard as anything when I was a resident.

We're still treating breast cancer?

 

[Ray D. Ayshun]

In all seriousness, if this were me, I'd want treatment.

 

[evilbooyaa]

If one is not treating all cN0 women with pN0 isolated tumor cells post-NAC in a node, all's I'm saying is there's a very wide avenue in which to drive relatively unproven opinions around re: when/when not to treat in that situation. It's almost like if the lady hadn't had a CR in the tumor and had ITCs post-NAC, by the above logic there'd be less indication to treat. Her CR "doomed" her to PMRT.

I'd be OK treating all patients with the bolded, FWIW. cN0, s/p NAC, with ITC in LNs, if there was any (not necessarily pCR) response in the breast. For me doesn't matter if it was Her2+ or not.

 

[scarbrtj]

I'd be OK treating all patients with the bolded, FWIW. cN0, s/p NAC, with ITC in LNs, if there was any (not necessarily pCR) response in the breast. For me doesn't matter if it was Her2+ or not.

Exactly what I'm saying: the cT2N0 woman who gets NAC and is (without any chemo response in the primary) pT2N0i+... this is one we seem to all be agreeing no indication to treat. Which is odd because more of a chemo response might indicate less indication to treat, at least in "borderline" cases. It's like a "chemo biopsy" is "proving" to you guys that when that "biopsy" is negative (ie lack of primary response to chemo) we can more readily believe a pre-NAC pN0 (or pN0i+) in cN0. And I'm just completely unaware of the data that let's me pontificate about that. And when I can't cogently pontificate, I just go with what I got. I don't have the data to argue your viewpoint is incorrect 🙂

 

[Mandelin Rain]

I'd treat nodes only.

























(not actually, but assuming scarb's head exploded)