pCR after NAC in breast cancer - what to do??

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Gfunk6

Gfunk6

And to think . . . I hesitated
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If you see a breast cancer patient, let's say she is triple negative or HER2/neu amplified, and she opts to undergo neoadjuvant chemo followed by breast conserving surgery then she gets a path CR.

Do you still boost the resection cavity?

I have stopped doing this but don't have any great data to justify - was wondering what others did.
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I treat off the pre-chemotherapy characteristics, just like NCCN tells me to do. The boost question is interesting, hadn't really thought about that in the setting pCR, but if I was going to boost based off of pre-chemo characteristics, I'll still boost regardless of what is seen after chemo
 
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If I was going to boost in the setting of adjuvant chemo, I still boost in the setting of neoadjuvant chemo.
 
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High grade is a known predictive factor for benefit from boost. High grade/triple neg/her2+ patients also tend to have higher pCR rates from chemo. In the absence of new data, I would argue that boost in these patients is highly preferred until proven otherwise.
 
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Yeah, stuck with pre-chemo characteristics to make a decision. I'm certain, non scientifically, that you don't have to boost. In fact, after pCR, the rate of IBTR will be really low overall. But, in the absence of data, reasonable to stick with what you know. I rarely boost unless under 50. Data is only really good for under 40.

I used to be frustrated with NAC. What do you do after a mastectomy!? What do you do after a pCR after a lumpectomy? What to do with the axilla? Right now we follow pre-chemo recs and that's fine....

But, it's really good to know biology, and there is really no better way right now than NAC. We need better trials for what radiation needs to do. I think if patients have an indication for chemo, they should get it up front. I know it's not dogmatic or evidence based, but we need to build that data. That's the future. And, honestly, it's not our choice whether they get the juice first, so we had better start either writing trials or recording outcomes.

I got pressed in breast tumor board about rad onc reluctance to utilize OncoType for DCIS and LR. I was stuck except to say no good prospective data. But they are right. We need prospective data on that, too, to spare most of them additional treatment. However, many of the low risk patients may not even need surgery! That's exciting.
 
Yeah at this point in time I don't know how to reconcile the dueling factors of high grade vs pCR. There is definitely evidence to suggest the higher grade patients get more benefit from boost. There is also evidence that pCR patients have excellent local control above their non pCR counterparts, many of which happen to also be higher grade to begin with. I have trended towards boosting patients when in doubt. My standard is 4256/16 for whole breast only vs 4000/15 + boost for those who qualify, with 5000/25 +/- boost when nodal RT indicated.
 
To pick up on Daniel's point about post mastectomy patients, what would you do for a patient with a cT2 primary and FNA confirming carcinoma in a lymph node, and pCR after a mastectomy?

I'm aware there is some data that suggests rather low rates of locoregional recurrence, but would anyone confidently say no RT is required?
 
The NCCN guidelines are pretty clear about using (or ignoring, rather) post chemo pathology findings when guiding xrt decisions. Until these single institution studies are deemed worthy to enter those guidelines and change recommendations, I'm not using them
 
Treat said:
To pick up on Daniel's point about post mastectomy patients, what would you do for a patient with a cT2 primary and FNA confirming carcinoma in a lymph node, and pCR after a mastectomy?

I'm aware there is some data that suggests rather low rates of locoregional recurrence, but would anyone confidently say no RT is required?
Click to expand...

Isn't this the B51 trial question?
 
Treat said:
To pick up on Daniel's point about post mastectomy patients, what would you do for a patient with a cT2 primary and FNA confirming carcinoma in a lymph node, and pCR after a mastectomy?

I'm aware there is some data that suggests rather low rates of locoregional recurrence, but would anyone confidently say no RT is required?
Click to expand...

My favorite two "go to" papers in this situation are the MD Anderson series and the NSABP B18 and B27 trials.

I try to enroll these patients on B51 when eligible. Off of B-51 I usually do recommend XRT, as it is considered the standard of care arm in B-51...but for a T2N1 with a pCR I really don't sell it really hard if the patient is very motivated to not have XRT (data show local recurrence rates of ~5-7%) in this cohort.
 
BobbyHeenan said:
My favorite two "go to" papers in this situation are the MD Anderson series and the NSABP B18 and B27 trials.

I try to enroll these patients on B51 when eligible. Off of B-51 I usually do recommend XRT, as it is considered the standard of care arm in B-51...but for a T2N1 with a pCR I really don't sell it really hard if the patient is very motivated to not have XRT (data show local recurrence rates of ~5-7%) in this cohort.
Click to expand...

One needs to be very careful with tailoring approaches based on response to neoadjuvant chemo.
Some of the recommendations in the papers to ommit RT in Stage II patients with pCR are based on subgroup patient populations in the trials in the range of 10-20 patients.
 
Palex80 said:
One needs to be very careful with tailoring approaches based on response to neoadjuvant chemo.
Some of the recommendations in the papers to ommit RT in Stage II patients with pCR are based on subgroup patient populations in the trials in the range of 10-20 patients.
Click to expand...

Agreed, we don't have large numbers. I stick to NCCN guidelines, but for the NSABP paper there were 21 patients that had cT2N1 that had mastectomy and achieved a pCR in both the breast and lymph nodes. LR was 0 events at 10 years without adjuvant XRT. In the MD Anderson series I think stage II patients were about n= 30 with again zero local recurrences (but some of them did have XRT, so the numbers that didn't get XRT are even smaller).

You're right, not huge numbers (especially for breast cancer). But there are certainly trends in the data that point to good outcomes for stage II patients that achieve pCR without radiation. Not enough yet for me to confidently observe these patients, but I think the B51 is a great trial to answer this and I encourage enrollment.
 
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I'm seeing a 30 year old with a triple negative 3 cm UOQ tumor and 2 suspicious LNs on initial MRI and PET, one 1.2 cm and one 7 mm, both with low level SUV. The larger node was biopsied and negative. Med Onc staged as a cT2N1. Had neoadjuvant with pCR on mastectomy and 3 node SLNBx only (i.e. no dissection).

What the hell do you do here? There's nothing I can point to definitively to say that she has node positive disease, and I'm loathe to treat a 30 year old with post mastectomy radiation for nothing. What do you think?
 
Mandelin Rain said:
I'm seeing a 30 year old with a triple negative 3 cm UOQ tumor and 2 suspicious LNs on initial MRI and PET, one 1.2 cm and one 7 mm, both with low level SUV. The larger node was biopsied and negative. Med Onc staged as a cT2N1. Had neoadjuvant with pCR on mastectomy and 3 node SLNBx only (i.e. no dissection).

What the hell do you do here? There's nothing I can point to definitively to say that she has node positive disease, and I'm loathe to treat a 30 year old with post mastectomy radiation for nothing. What do you think?
Click to expand...

Damn - now that's a tough case. If that node would have been positive I would have treated, but with a negative path in my mind you've got T2N0 disease. You have that Chinese randomized data (believe at your own risk) that says T2 young triple negatives benefit from XRT after mastectomy (OS benefit), but then you've got the data I posted above showing low recurrence risk with pCR.

In those cases I've thrown a life line to my breast attendings back in residency to get further guidance (one of my attendings did treat a couple of 30 year old females with larger T2N0 triple negative disease that had less than a CR) . I wouldn't blame you either way (treat or not), but I lean toward no treatment.
 
I'd treat her.
The question is WHAT to treat in this patient.

Chest wall is no-brainer if you are going to treat anyway.
But would you treat the lymphatics too? And if yes which ones? All of them?

I'd say chest wall is good. Minimal toxicity, easy therapy.
It's the lymphatics that cause most the toxicity imho...
 
I'd treat that patient. Not only do you have chinese data, there is canadian data as well. Triple-negative breast cancer is nasty not only systemically, but loco-regionally as well.

And if you believe the EBCTCG meta-analysis, local control will impact this lady's OS eventually

http://jco.ascopubs.org/content/early/2011/06/29/JCO.2010.33.4714

Agree with Palex, you'll treat a lot less lung with CW, and still provide some benefit IMO. Hopefully R-sided disease :)
 
Forgot to mention. She was direct implant reconstruction with a +ANA (not yet diagnosed with lupus).

Fun case. Real rock and hard place.
 
anyone mind posting a link (pubmed is fine) to the Chinese RCT for triple negative pts, referenced above?

thanks in advance.
 
Thx.

What are the issues people have with the Chinese and Canadian data on this?
 
Really? We use Canadian data all the time? Whelan?

I figured it was something related to methodology or statistics....
 
havent been treating much breast: Someone who is T2N1 upfront (N1 based on cytology) are all these patients getting neoadjuvant chemo first now even if they are lumpectomy candidate? I presume this can save an ax dissection if they have CR and negative SNLB? Assume they went for surgery first, do all clinically N1's get full ax dissection? If they only had 1 positive on further ax assuming neg margins, 65 yo, no LVI are they still all getting supraclav added? Thanks!
 
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Haybrant said:
havent been treating much breast: Someone who is T2N1 upfront (N1 based on cytology) are all these patients getting neoadjuvant chemo first now even if they are lumpectomy candidate? I presume this can save an ax dissection if they have CR and negative SNLB? Assume they went for surgery first, do all clinically N1's get full ax dissection? If they only had 1 positive on further ax assuming neg margins, 65 yo, no LVI are they still all getting supraclav added? Thanks!
Click to expand...

You're going to get different perspectives, as this is a bit of a moving target. Answers may also depend on biology (ie more extensive nodal coverage in xrt fields for triple negative). Depending upon which surg onc sees the patient, even within my cancer center there will be different axillary management techniques here depending upon which surg onc or breast surgeon sees the patient. A few very general things....

1. If Her 2 + or triple negative it is very common to receive up front chemo for T2N1 disease. Not necessarily for "down staging" to make lumpectomy more feasible, but for other indications (you can have pertuzimab, able to monitor response, etc)
2. If up front node positive, the safest board answer is to complete an axillary dissection at some point in the patients surgical care. However, if only small node and a dramatic neoadj chemo response, some of the surgeons here will just do a post-chemo SLNB (and also make sure the previously biopsy + node is removed (it's clipped at time of biopsy)) and not complete the dissection. I then typically (but not always) cover the axilla in the radiation fields since there was no dissection.
3. If there is still node positivity in spite of neoadjuvant chemo, I would include supraclavicular nodes as part of my target. If a full dissection showed only 1 node, no ECE, then I'd probably cover undissected axilla, supraclav, and breast as my CTV. Some may cover IM nodes here as well, but there's arguments for or against it. I don't have a strong opinion on IM coverage in that scenario.
4. If going for surgery first, I think if clinically/path up front N1 disease, it's most standard to complete a full dissection. So I'd say that's what should happen. If only that one single node positive (with no neoadj chemo) like your example, then you're going to get different answers on radiation field design I bet. I'd probably still cover undissected axilla, breast, and sclv. Others may do breast tangents alone...others would cover everything (see MA20 randomized trial).
5. In the case of a lumpectomy/nodal path CR to neoadj treatment in T2N1, I try to enrolled in the NSABP trial (whole breast versus breast plus nodes). Off study for a path CR I usually cover breast, undissected axilla, and supraclav. I suspect this is overkill though and the trial will show equivalence, but the "standard of care" arm on the trial is nodal coverage.
 
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Haybrant said:
havent been treating much breast: Someone who is T2N1 upfront (N1 based on cytology) are all these patients getting neoadjuvant chemo first now even if they are lumpectomy candidate? I presume this can save an ax dissection if they have CR and negative SNLB? Assume they went for surgery first, do all clinically N1's get full ax dissection? If they only had 1 positive on further ax assuming neg margins, 65 yo, no LVI are they still all getting supraclav added? Thanks!
Click to expand...

For the most part, biopsy proven N1 disease (regardless of receptor status for the most part) gets neoadj. Chemo at my center as well, even if they are lumpectomy candidates. H
And yes, NSABP B-51 is OK with with those who got chemo followed by SLNB alone as surgical staging of the axilla, so people are avoiding Ax Dissections in certain candidates.

I think most cN1s get a full ax dissection.

The answer to your last question is likely a bit more variable. At my institution if we're specifically trying to treat the nodes, then we're generally doing a SCV field as well.

Bobby - How do you treat undissected axilla with or without a SCV field? If there was a ALND (levels I and II) with visible clips and you want to cover level 3? We use half-beam blocks with a single iso to field match our tangential plans with our SCV field, so sparing the dissected axilla in that set-up isn't very feasible. IMRT?

The question of IM nodal coverage is also something that is likely variable. We generally don't cover it except in more medial cancers, but perhaps some of the folks here are covering it for N1 disease with minimal response to chemo.
We had one patient recently with LABC with minimal response to chemo who actually had a node removed at surgery which was from the IMC, so she will obviously get IM coverage.
 
evilbooyaa said:
For the most part, biopsy proven N1 disease (regardless of receptor status for the most part) gets neoadj. Chemo at my center as well, even if they are lumpectomy candidates. H
And yes, NSABP B-51 is OK with with those who got chemo followed by SLNB alone as surgical staging of the axilla, so people are avoiding Ax Dissections in certain candidates.

I think most cN1s get a full ax dissection.


Bobby - How do you treat undissected axilla with or without a SCV field? If there was a ALND (levels I and II) with visible clips and you want to cover level 3? We use half-beam blocks with a single iso to field match our tangential plans with our SCV field, so sparing the dissected axilla in that set-up isn't very feasible. IMRT?

.
Click to expand...

I do it just like you're describing for the majority of patients. I do contour CTV's including breast and undissected axilla (using RTOG guidelines) and try to cover level 3 and supraclav with the MLCs/fields, but yes - usually a single iso technique with tangents/sclv. I rarely do IMRT for intact breast unless something strange with going on with anatomy or excessive lung/heart dose. Post mastectomy i'll look at both 3D and IMRT and see what looks best. I always at least try 3-D (some combo of photon/electrons usually).

You're right though that "sparing" is tough with single iso 3-D. You certainly get some dissected axilla with that arrangement, but I'm not specifically targeting it. But sometimes by contouring you can at least shape your MLC's to not over-cover areas by using the classic blocks. On the contrary if I want to be sure I cover the full axilla in an undissected axilla, I will intentionally contour all levels and make sure the dose is covering it. The plans aren't drastically different though with a single iso technique as you're aware of though.
 
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BobbyHeenan said:
I do it just like you're describing for the majority of patients. I do contour CTV's including breast and undissected axilla (using RTOG guidelines) and try to cover level 3 and supraclav with the MLCs/fields, but yes - usually a single iso technique with tangents/sclv. I rarely do IMRT for intact breast unless something strange with going on with anatomy or excessive lung/heart dose. Post mastectomy i'll look at both 3D and IMRT and see what looks best. I always at least try 3-D (some combo of photon/electrons usually).
Click to expand...

Anything specific you're doing to try and avoid treating the dissected axilla? Or just not including it in the contours at time of sim?
 
evilbooyaa said:
Anything specific you're doing to try and avoid treating the dissected axilla? Or just not including it in the contours at time of sim?
Click to expand...

Sorry, I didn't answer your question well initially - I edited my post.

Basically, the end result is what you're saying - I just don't contour it. It can make for MLC blocks sometimes that don't look like "classic" blocks, but as long as I trust my contours/targets then I think it's a reasonable technique.
 
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Sorry to necro this, but had a related question...
T2N1 biopsy confirmed nodal disease
pCR after neoadjuvant chemo
0/3 sentinel nodes
Would you guys treat the undissected axilla?
The data seems to suggest low false negative rates with 3+ nodes...
 
Treat said:
Sorry to necro this, but had a related question...
T2N1 biopsy confirmed nodal disease
pCR after neoadjuvant chemo
0/3 sentinel nodes
Would you guys treat the undissected axilla?
The data seems to suggest low false negative rates with 3+ nodes...
Click to expand...

This patient would fit into the current running NSABP-trial
Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery - Full Text View - ClinicalTrials.gov

Do you know how many nodes were initially involved? You could try to put the numbers into one of the nomograms (MDACC/MSKCC) to see how high the risk for additional nodes would have been initially.

Treating the axilla or not is one question. Treating Level IV & internal mammary another one...
 
I think going forward I'd like people to just create their own threads if they have a question. It's free. We won't make fun of you. Otherwise we're going to end up with somebody who answers the initial thread question (posted 2 years ago) and not this updated question.

What surgery did patient have (Lumpectomy or Mastectomy + SLNB)? Treatment effect in the lymph nodes (if so, how many)? Was the initially biopsied LN which was positive removed as well? Hormonal/Receptor status?

Off protocol in a non-forefront of academic institution, I would treat this until we have results of B51 saying it's safe. Ideal patient for enrollment to B51.

To answer Palex's question - I'd treat SCV personally. IMC depends on primary location. If UOQ probably wouldn't. If other locations would at least evaluate and if able to do safely within DVH constraints would consider top 3 (or 2 if necessary due to lung DVH) levels.
 
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