Interesting Breast Case (DCIS Recurrence)

[meddoc2011]

52 y/o woman(now) presents with history of right breast DCIS (ER+/PR+) in 2007 - treated with lumpectomy alone. Patient declined Tamoxifen at that time (49 y/o then) and Rad Onc that she met said "she didn't need RT").

In 10/09, she finds a RUOQ lump and MMG showed a 2 x 1.8 x 1.4 cm mass and right axillary lymphadenopathy. Biopsies show Grade 3 IDCa (ER+/PR+/H2N+) in the mass and axilla. She received 6 cycles of Taxotere/Carboplatin along with Herceptin. Recent Mastectomy showed only minimal focus of residual DCIS and 0/12 positive lymph nodes. The DCIS focus is less than 0.5 cm and has widely negative margins. She will finish out her year of Herceptin.

Patient now here for RT consideration.

Would you treat?

What would you include in your fields if you treated?

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[Brim]

I would treat chest wall and supraclav nodes.

52 y/o woman(now) presents with history of right breast DCIS (ER+/PR+) in 2007 - treated with lumpectomy alone. Patient declined Tamoxifen at that time (49 y/o then) and Rad Onc that she met said "she didn't need RT").

In 10/09, she finds a RUOQ lump and MMG showed a 2 x 1.8 x 1.4 cm mass and right axillary lymphadenopathy. Biopsies show Grade 3 IDCa (ER+/PR+/H2N+) in the mass and axilla. She received 6 cycles of Taxotere/Carboplatin along with Herceptin. Recent Mastectomy showed only minimal focus of residual DCIS and 0/12 positive lymph nodes. The DCIS focus is less than 0.5 cm and has widely negative margins. She will finish out her year of Herceptin.

Patient now here for RT consideration.

Would you treat?

What would you include in your fields if you treated?

 

[deleted4401]

I'd look at the recurrence as a new event, and disregard the fact she had DCIS in the past. So...

Not much data other than MDACC for predictors of LRR after NAC and mastectomy. Both prechemo factors - high clinical stage (tumors >5cm, T4 or any stage III) and postchemo factors - number of path positive nodes (4 or greater), amount of residual disease, pathologic size of primary after chemo.

Was the lymph node mobile in the axilla? If so, then she is clinical stage II/T1N1 with an excellent response (complete, as residual DCIS wasn't counted as residual disease). She has a low risk of recurrence, and wouldn't offer her PMRT based on MDACC series.

I wonder if there are any other series... There is a need for more data
-S

 

[G'ville Nole]

I would treat chest wall and supraclav nodes.

This.

To expand a bit, despite a bit controversy over treatment of post-mastectomy N1 patients, I routinely offer it to younger women, and even to older women with high risk features. In my mind, Peto's update of the EBCTCG at San Antonio in 2007 offers the most compelling evidence of benefit for PMRT in the N1 subset (LC benefit of 15% at 5 yrs, CSS benefit of 7% at 15 yrs). The only other issue would then be comprehensive lymphatic coverage, and I'd agree with Brim to add a SCV field, although I would consider levels 1&2 to have been adequately addressed with her surgery, so I wouldn't add a PAB or use high tangents.

 

[meddoc2011]

The lymph node(s) were mobile and there were none larger than 1cm on the pre-chemo imaging.

I have offered CW and S'clav RT to her for three reasons:
1. Young age (I know not <40, but...).
2. It is a recurrence.
3. It is slightly more aggressive with H2N+.

I don't know how much the H2N+ would add in percentage points, but I feel that the RT would add to local control. I tend to follow the San Antonio data now for Post-Mast RT.

I thought this is an interesting situation and that it truly could go either way.

 

[deleted4401]

I think the Peto update didn't break down patients who received NAC?

If the same woman presents after mastectomy without chemotherapy with the same features, would more strongly consider RT. But, NAC complicates things. The patients with clinical stage I-II disease that had CR at surgery had recurrence rates of <5% in the series, and so it is hard to ignore that. These are the exact women who may get the negative effects of the RT without the benefits. No one else has any other data regarding patients treated with NAC followed by mastectomy (as far as I know), as far as I know. I think it is challenging - had quite a few NAC cases the last rotation, and we relied on that to guide decision-making.

Her-2-Neu used to be prognostic and predictive in pre-Herceptin era, but I don't think it's prognostic any more - i.e. with Herceptin, they actually do very well compared to other subtypes.

These cases are tough, though! Not much evidence to rely on
S

 

[clintpark]

My takes, in no particular order:

1. Offer post-lumpectomy XRT to women with DCIS, especially if young and not going to take tamoxifen, regardless of what Silverstein said, we got Wong et al. to back us up.

2. Why was this patient given neoadjuvant TCH when they were going to take her for mastectomy anyway? Was it more locally advanced than her clinical T1cN1 would imply? Was there an attempt to convert her to lumpectomy candidate (that is, was her remaining breast after the first lumpectomy really small?) Unless the answer to either question is yes, I would have requested that they do upfront surgery.

3. In general, I offer postmastectomy chestwall + SCLN XRT based on patient's pre-mastectomy clinical stage. Tumor response, including pCR, does not change my decision. It's a prognostic factor. I see the patients before they start any treatment, lay out the plan and try to stick to it regardless of mid-course response. In other words, I do not practice response adaptive XRT for breast cancer like some pediatric protocols.

4. In this patient particular, I would also offer XRT for all the reasons others mentioned. We collectively should really try to dispell the formula "postmastectomy XRT for T3+ or N2+" and treat individual patients based on her multiple factors.

 

[medgator]

4. In this patient particular, I would also offer XRT for all the reasons others mentioned. We collectively should really try to dispell the formula "postmastectomy XRT for T3+ or N2+" and treat individual patients based on her multiple factors.

Agreed. Things like LVI, Grade, menstrual status etc. would all play a role in my ultimate decision. Especially in a pt. with G3, H2N+ disease and a clinically positive axilla upfront who's premenopausal (although not sure now at age 52), i'd rather err on the side of treating than not.

Excluding things like the full axilla/PAB and the IMs should spare a lot of the toxicity without compromising the efficacy IMO. We've already got the negative (although well-criticized) RCT presented at ASTRO recently regarding radiation of the IMs (even though that was part of the danish techique in the PMRT trials).

 

[G'ville Nole]

I think the Peto update didn't break down patients who received NAC?

If the same woman presents after mastectomy without chemotherapy with the same features, would more strongly consider RT. But, NAC complicates things. The patients with clinical stage I-II disease that had CR at surgery had recurrence rates of <5% in the series, and so it is hard to ignore that. These are the exact women who may get the negative effects of the RT without the benefits. No one else has any other data regarding patients treated with NAC followed by mastectomy (as far as I know), as far as I know. I think it is challenging - had quite a few NAC cases the last rotation, and we relied on that to guide decision-making.


S

Simul, you're correct that Peto's analysis doesn't segregate NAC, and I'm honestly not sure if any of the included trials utilized it. Given that the neoadjuvant approach in this population is a more recent trend, I doubt it. However, a fair number of the PMRT trials included adjuvant chemo, especially for node positive patients, and the N of this group was about 8500. This begs the question: If adjusted for potential stage migration, would the sequencing of chemo and surgery be expected to have a meaningful impact on LR/DFS? I don't profess to have the answer, but intuitively I wouldn't think it would. My view and approach to this is as Clint desribed, with the primary indication for PMRT in this case the patient's cN1 disease.

Regarding the MDACC study, I don't recall how many of the cohort were node-negative, but this group certainly would have positively contributed to the low recurrence rates. I'd never argue that a T1-2 N0 patient needs PMRT, actually I'd argue that they don't need chemo.

I agree that these cases are challenging, and the ongoing discussion here reflects the lack of a strong consensus. Dad-gum med oncs!

 

[deleted4401]

I think that's the new challenge. Because with adjuvant chemo, we can't see the effect of the therapy since it is all microscopic disease, witth NAC we are faced with the opportunity/challenge to select those patients with favorable disease (i.e. that melts away with chemo that has a low risk of locoregional recurrence). It's a new paradigm, and from B18 and B27 we know that the response to chemo plays a large role in how women will do, both for recurrence and survival.

I think that even an Oncotype would be helpful in this scenario, as it also predicts for LRR, but I'm uncertain that an insurer would pay for it knowing that the patient will definitely be getting systemic treatment.

In the sister paper to the MDACC series, in patients with cT1-T2 w pCR after chemo, they compared those that got PMRT and those that didn't, and there was no difference in recurrence rates (i.e. both less than 10%), so that's another interesting result.

I agree that the primary role of NAC was to increase probability of lumpectomy, but there are other benefits. A pCR is highly prognostic, and for some women, it might be nice to know that you are going to do very well. Also, other theoretical biologic reasons that everyone always mentions (better bloodflow/oxygenation prior to surgery, can see if she is resistant to a specific chemo regimen, etc. etc.). Regardless of what we think is the "right" reason for NAC, the medoncs are testing/utilizing in more and more situations, and we need to figure out RT's role using outcomes data.

As for not giving RT after lumpectomy for DCIS, I agree that's not what I would have recommended. However, it is still an option based on NCCN guidelines and something that happens with great frequency regionally (particularly on the West Coast.) We don't have any evidence that it improves survival, and even though I would offer RT to all women with DCIS, I don't blink if a patient with widely negative margins declines. It's a valid choice.

Simul, you're correct that Peto's analysis doesn't segregate NAC, and I'm honestly not sure if any of the included trials utilized it. Given that the neoadjuvant approach in this population is a more recent trend, I doubt it. However, a fair number of the PMRT trials included adjuvant chemo, especially for node positive patients, and the N of this group was about 8500. This begs the question: If adjusted for potential stage migration, would the sequencing of chemo and surgery be expected to have a meaningful impact on LR/DFS? I don't profess to have the answer, but intuitively I wouldn't think it would. My view and approach to this is as Clint desribed, with the primary indication for PMRT in this case the patient's cN1 disease.

Regarding the MDACC study, I don't recall how many of the cohort were node-negative, but this group certainly would have positively contributed to the low recurrence rates. I'd never argue that a T1-2 N0 patient needs PMRT, actually I'd argue that they don't need chemo.

I agree that these cases are challenging, and the ongoing discussion here reflects the lack of a strong consensus. Dad-gum med oncs!

 

[napoleondynamite]

I tend to think that NAC buys you PMRT. There are too many what-if's and unknowns, particularly in a young pt with other aggressive features like G3, HER+, etc. But at my institution, we typically offer PMRT to all women (regardless of complete vs incomplete response) who were clinically concerning enough to be treated with NAC.

 

[meddoc2011]

The Med Onc's here in the Southeast have offered a few patients with NAC but this specific situation is a new one for me. The MO here did the chemo upfront because of the recurrence and felt it was important to get systemic therapy started as soon as possible.

I would have offered RT back in 2007 to her when it was "just DCIS". I cannot speak to what the prior Rad Onc was thinking since his notes are not available. He was part of a group who is busy "curing prostate cancer (.com)".

I think the fact that this is an invasive recurrence and she responded so well to the NAC is great. I have still offered her further treatment with PMRT.

Thanks for the lively discussion!

 

[deleted4401]

I get everyone's feelings about things ...

Anyone mind sharing evidence relevant with the case rather than telling me how they feel about it?

I gotta say - every single person that responded disagreed with me, but none of the answers were based on evidence. I feel like a rad onc in a room of med oncs. Here is my evidence below (the PMIDs will refer you to the neoaduvant data). You all are making me feel like I don't know what I'm doing. Please show me an evidence based answer to why I should have recommended RT, other than how you feel about it.

PMID 11773149

PMID 12095553

PMID 17418973

 

[TarHeelRadOnc]

I get everyone's feelings about things ...

Anyone mind sharing evidence relevant with the case rather than telling me how they feel about it?

I gotta say - every single person that responded disagreed with me, but none of the answers were based on evidence. I feel like a rad onc in a room of med oncs. Here is my evidence below (the PMIDs will refer you to the neoaduvant data). You all are making me feel like I don't know what I'm doing. Please show me an evidence based answer to why I should have recommended RT, other than how you feel about it.

PMID 11773149

PMID 12095553

PMID 17418973

Simul- I will back you up on this, as I agree that the available data with regarding locoregional recurrence after neoadjuvant chemotherapy with pCR at mastectomy managed without PMRT for stage II disease supports your case. The MDACC group- who have, by far, the largest prospective and retrospective experience using NAC- have reported a 0% incidence of locoregional recurrence after NAC and mastectomy without PMRT for patients stage II disease with pCR. By contrast, in the aforementioned McGuire study, patients with stage III disease with pCR to NAC who did not receive PMRT had a 33% incidence of LRR. In addition to the studies you reference, the 2004 JCO paper by Huang et al also supports the low rate of LRR in stage II patients with pCR.

I think that it is important to understand how pCR was determined in the MDACC experience when applying this data. In their experience, patients did not have SLN Bx prior to NAC. These patients had an FNA or axillary core biopsy of any suspicious LN detected on clinical exam, mammo, US and more recently, MRI. Patients only had SLN Bx performed after NAC, and only had completion ALN Dx if SLN Bx was positive. Since only 40% of patients with positive SLN Bx will have additional involved LNs detected on completion ALN Dx (data from NSABP B-32), performing SLN Bx prior to NAC results in the loss of information regarding the response of axillary disease to NAC in the majority of patients. pCR rates in NSABP B-27 with TAC chemotherapy in the breast primary was 40%, whereas pCR rates in the primary + axilla was only 27%. As such, the pCRs in the MDACC experience represent a potentially more profound response to NAC than pCRs from other series, and I would only apply this data to patients managed in this way.

Given that the patient presented above had stage II disease at presentation with palpable axillary adenopathy, but did not (at least in the summary presented) have a SLN Bx prior to NAC, the MDACC data applies to her and could be used to justify withholding PMRT. In addition to the MDACC data, there is unpublished data from NSABP B-18 and B-27 demonstrating LRR rates of less than 10% in patients with stage II disease who had pCR to NAC (I believe that the rates of LRR were 7.5% and 5%, respectively). It is important to note that PMRT was not permitted in either of these trials.

The low rate of LRR after NAC and mastectomy for stage II patients with path CR really shouldn't be terribly surprising. LRR rates for patients with pN1 disease treated with upfront mastectomy and adjuvant chemotherapy (without PMRT) in the large series from ECOG (Recht et al.), NSABP (Taghian et al.) and MDACC (Katz et al.) are in the 10-14% range. Moreover, we know that DFS (and OS) is substantially improved in patients with pCR compared to those with less than a pCR to NAC, with a hazard ratio for DFS in the range of 0.35-0.5 for those with pCR. Applying these same hazard ratios to the previously mentioned LRR rates for pN1 disease in the ECOG/NSABP/MDACC series, we would expect LRR to be in the 3.5-7% range. Using the ratio of 1 additional survivor at 15 years for every 4 additional patients with loco-regional control at 5 years (from the EBCTCG 2005 meta-analysis of locoregional therapy), then the survival benefit from PMRT in patients with stage II disease with pCR to NAC, if it confers the expected 65-70% reduction in locoregional recurrence, would be expected to be in the 1% range, and would not likely be significant in any clinical trial due to sample size restrictions.

Whether the history of inadequately treated ipsilateral breast DCIS in this patient influences the decision to treat is unknown. DCIS is known to progress to invasive breast cancer if untreated in ~33% of cases and approximately 50% of ipsilateral recurrences of DCIS are invasive. That being said, DCIS is also a marker of increased contralateral breast cancer risk and increased risk of distant ipsilateral breast cancer occurring remote from the original lumpectomy cavity. I'm not sure that we can take the history of DCIS and call the current breast cancer a true local recurrence that warrants more aggressive local therapy (ie PMRT) based on the information presented. No real data available either way on this, but just my gut feeling&#8230;

 

[medgator]

These cases are tough, though! Not much evidence to rely on
S

I get everyone's feelings about things ...

Anyone mind sharing evidence relevant with the case rather than telling me how they feel about it?

I gotta say - every single person that responded disagreed with me, but none of the answers were based on evidence. I feel like a rad onc in a room of med oncs. Here is my evidence below (the PMIDs will refer you to the neoaduvant data). You all are making me feel like I don't know what I'm doing. Please show me an evidence based answer to why I should have recommended RT, other than how you feel about it.

The data is there. I think G'ville Nole said it best:

However, a fair number of the PMRT trials included adjuvant chemo, especially for node positive patients, and the N of this group was about 8500. This begs the question: If adjusted for potential stage migration, would the sequencing of chemo and surgery be expected to have a meaningful impact on LR/DFS? I don't profess to have the answer, but intuitively I wouldn't think it would. My view and approach to this is as Clint desribed, with the primary indication for PMRT in this case the patient's cN1 disease.

The sequence is what we are questioning, and perhaps one day, we'll have the large multi-institional prospective data to answer this question, but for now, the stronger multi-center data supports PMRT in pts with node-positive disease.

Is a subset analysis from the NSABP and single-institution data from MDACC regarding adaptive therapy after NAC enough to counteract the data from several randomized trials regarding PMRT (2 Dutch studies, BC etc.) along with the EBCTCG analysis showing a local control benefit in these patients? I think this is where one's clinical judgment comes in.

There will always be clinical situations where EBM is lacking, and that's why we have to use individualized patient factors along with our clinical judgment to come up with an appropriate management strategy when an evidence-based approach doesn't give us a clear answer. My clinical non-EBM gut feeling sees the data but still gets worried about a 52-y/o peri-menopausal pt with G3, H2N+ disease who had an IDC a few years after DCIS. How does MDACC's data apply to patients who have LVSI, G3 disease, H2N+ etc? It's certainly a consideration to treat these patients, something the folks from MDACC have affirmed. My understanding is that H2N+ is still a negative prognostic factor compared to a garden variety hormone-receptor positive CA, despite the use of herceptin, but a better actor than the triple-negative phenotype.

Interestingly, I found a review article from MDACC from 2002, and this was their flowchart as to how to manage these patients:

Interestingly, a number of factors we would consider important are not mentioned on that chart (LVSI, Grade, H2N status, age/menopausal status etc.)

 

[TarHeelRadOnc]

I think that most Rad Oncs now agree that PMRT should be given for patients with pN1 disease. Despite the ASCO consensus statement and the holdouts at Dana Farber, etc, I think that the majority of available data supports PMRT for pN1 disease. As you pointed out, these patients benefited in the two Danish studies and the BC study. Further, in the re-analysis of the Danish studies limited to patients with >8LN removed, the magnitude of benefit was equivalent to the benefit observed in patients with pN2-3 disease. Moreover, the IBCSG patterns of failure analysis of over 5000 women (Wallgren et al.) also shows a comparably higher rate of LRR in patients with pN1 disease (16-25% for premenopausal and 13-19% for postmenopausal) compared to the NSABP/ECOG/MDACC studies even with a median 15 LN dissected, suggesting a potential benefit of PMRT. I completely agree that PMRT should be given in patients with pN1 disease managed with up-front mastectomy.

This data, however, does not specifically apply to patients treated with neoadjuvant chemo. Patients with pCR to neoadjuvant chemotherapy have far better survival and event-free survival compared to those with less than a complete response. As such, it makes sense that the 9-10% survival benefit observed in the Danish/BC studies and the 4.4% survival benefit in the Oxford meta-analysis may not apply to these patients. If the local recurrence rate is <7.5% in these patients (as all of the available data suggests), I think that withholding PMRT in this subset of patients (representing only 25-30%, and a little higher in Her2Neu+) is reasonable.

Breast cancer is moving toward individualized patient care with regards to systemic therapy (oncotype Dx, tam/AI, Hereceptin, Zometa, etc), but to this point individualized radiation therapy recommendations based on molecular factors, protein expression or response to other therapies has lagged behind. A re-analysis of LRR according to recurrence score (Mamounas et al. JCO) in NSABP B14 and B20, shows that recurrence (Oncotype) score is highly predictive of LRR, just as it was predictive of distant metastases in th original Paik study. Similar to Oncotype, pCR to NAC is a marker of tumor biology, and more favorable biology is going to be associated with better DFS, DMFS and LRC.

Like you said, this is an "art of medicine" question, but I think that withholding PMRT is very defensible in this situation.

 

[medgator]

Like you said, this is an "art of medicine" question, but I think that withholding PMRT is very defensible in this situation.

Oh I agree. There is definitely data on both sides of the controversy. It's tough when you see a patient with bad prognostic factors and the evidence is less than clear cut.

If this patient was post-menopausal with a 2 cm, Grade 1, -LVSI, ER+/H2N- tumor with a similar situation, I think that would sway a lot of people over to the "don't treat" camp (including myself).

 

[TarHeelRadOnc]

Oh I agree. There is definitely data on both sides of the controversy. It's tough when you see a patient with bad prognostic factors and the evidence is less than clear cut.

If this patient was post-menopausal with a 2 cm, Grade 1, -LVSI, ER+/H2N- tumor with a similar situation, I think that would sway a lot of people over to the "don't treat" camp (including myself).

It is paradoxical in a way:

younger age, Her2+ and high grade disease are associated with increased locoregional recurrence

younger age, Her2+ and high grade disease are associated with increased likelihood of pCR with optimal neoadjuvant therapy and pCR is associated with improved outcomes

Difficult to reconcile these seemingly conflicting data. Of these, I would argue that the presence of pCR at mastectomy is by far the most important predictor of outcome. Pathologic response to therapy is the most important prognostic factor, for both local control and disease-specific survival, in virtually every site we treat. As such, I would argue that PMRT could be avoided in the setting of pCR for stage II disease even in the setting of the otherwise adverse factors you listed above...

 

[Ursus Martimus]

I think all the data presented so far is in an extension of disease in the primary setting, which is to be taken with a grain of salt. I think it reasonable to have the pathologist look at the DCIS and new IDC to see if they have a similar phenotype. If he can't do that morphologically, there are tests to look at molecular clonality by loss of heterozygosity. Non the less I would treat CW + SCV. I would be pretty concerned about her contralateral breast, any additional w/u requested there? Regarding Her2 and prognosis, I believe there was a ASCO abstract in 2008 suggesting that, at least in stage IV disease that being HER2+ (in this age of herceptin) is actually better than being Her2-

 

[Palex80]

Here's the European view to this:

I would treat chest wall and paraclavicular nodes, not axilla and not mammaria interna.

Our current (institutional) guidelines for post mastectomy irradiation are:

1. R1/R2 resection
2. T3-T4
3. N+

or

a combination of 2 of the following factors:

a) T2 >3cm
b) Her2+ and no Herceptin/Lapatinib (for example due to heart problems)
c) premenopausal patient
d) L1
e) V1
f) R0 with a margin closer than 4mm
g) ER-, PR-, Her2-
h) extensive in-situ component


The DEGRO (german radiation oncology society) guidelines state:
"In the case of neoadjuvant chemotherapy the indication for postoperative radiation therapy should be based on tumor characteristics BEFORE neoadjuvant chemotherapy".

As far as this being a patient, that may only feel the negative and not positive effects of radiation therapy, I think this statement needs rethinking.

We only have clinical information on the initial axillary status, not surgical axillary staging. Therefore I would be cautious in using figures from studies which included postsurgical pN1-status. For all we know, this patient may have been pN2, had she received a pre-chemo surgical axillary staging.

The risk of the patient developing a locoregional recurrence without radiation therapy is IMHO above 10%, the chance of her suffering major sequlae from radiation therapy below 2% with modern techniques. What would you prefer? A rib fracture or a chest wall recurrence?


Radiation therapy may indeed in this case not have a significant impact on overall survival, but preventing a recurrence is also a legitimate reason to treat.
We do this every day, look at neoadjuvant rectal cancer (with modern TME) or soft tissue sarcoma.
I still do not understand, why we have to reach this "magical" 5% goal in overall survival benefit, in order to be able to justify postoperative radiation therapy in breast cancer. The medical oncologists regularly do adjuvant chemotherapy with 2-3% survival benefits according to adjuvantonline.com.

Medgator noted that there is a negative RCT on mammaria interna irradiation. The study showed that mammaria interna irradiation added to chest wall, axilla, paraclavicular irradiation only led to a 3% overall survival benefit after 10 years, which was statistically insignificant.
However look at what the study was looking for: 10% extra survival benefit through mammaria interna irradiation! That was the goal.
Don't you think that was a goal set a bit too high? 10% absolute survival benefit just by including the mammaria interna chain? We only get 5-7% overall survival benefit at 10 years by adding radiation therapy after mastectomy at all according to the EBCTCG-data (PMID: 16360786). Did anyone really expect that by adding mammaria interna irradiation to chest wall, paraclavicular and axilla irradiation we would simply get another 10%?
We are lucky to see 3% difference in the RCT IMHO and 3% may indeed even be worth irradiating the mammaria interna chain. This RCT could even not be negative, it could be positive after all, it's just not powered enough to show it. We probably need 10,000 patients for that, which we will never get.

 

[Winged Scapula]

2. Why was this patient given neoadjuvant TCH when they were going to take her for mastectomy anyway? Was it more locally advanced than her clinical T1cN1 would imply? Was there an attempt to convert her to lumpectomy candidate (that is, was her remaining breast after the first lumpectomy really small?) Unless the answer to either question is yes, I would have requested that they do upfront surgery.

From a breast surgeons' standpoint:

1) you don't know whether they were "planning" a mastectomy anyway. Perhaps the patient wanted breast conservation *again* (although IMHO she did not receive SOC of care the first time. Despite Silverstein's teachings, many of us trained by him still send patients for RT, regardless of margin width or VNPI. In this particular case we don't know whether or she was a recurrence or, as I suspect, an inadequately treated primary.) but didn't have an adequate CR after NAC to allow for breast conservation without cosmetic distortion.

2) NAC isn't just for reducing in breast tumor burden. I frankly prefer it if a patient is going to be a candidate for adjuvant chemotherapy anyway.

Patients with post-operative complications end up having their adjuvant treatment delayed. The rate of infection for patients with tissue expanders/implants can be as high as 40%; the rate without may be as high as 15-20%. Infections delay chemotherapy and other adjuvant treatments. Wound breakdown delays treatments. Post-operative MI/CVA/CHF, etc delay treatment. Patients who need a plastic surgery consultation have their treatments delayed (over 90% of the members of the American Society of Breast Surgeons offer immediate recon to their patients and patients want it). Scheduling 2 surgeons takes time and may take weeks before we can coordinate our schedules. If a patient needs systemic treatment, I don't want to be the one delaying it while scheduling their surgery, waiting for a post-operative wound to heal, while we treat an infection, etc. The medical oncologists are on the phone weekly asking if they can start chemo because they don't want to be responsible for delay in treatment either.

Additionally, the widespread use of Neulasta in our patients make the decision about whether or not the fever and increased WBC are due to an implant infection or reaction to the medication very difficult - I have yet to find any clinical or microbiological evidence of infection in such patients when we remove their implants (at the urging of ID and Med Onc who insist the WBC is due to an infected device).

I understand that the post NAC axilla is difficult to assess in terms of whether or not the nodes were positive but from a surgical standpoint there are good reasons to delay definitive surgery until after NAC.

Finally, and perhaps I missed something but there appears to be a lot of talk in this thread about the OP's patient being a pN1. Looks like to me she had some lymphadenopathy on imaging but that there is no pathological evidence that she ever had positive nodes (I don't see any biopsy results) either before or after NAC. That's a shame because if she had clinical lymphadenopathy she should have had a biopsy, if only to document axillary disease.

 

[medgator]

Finally, and perhaps I missed something but there appears to be a lot of talk in this thread about the OP's patient being a pN1. Looks like to me she had some lymphadenopathy on imaging but that there is no pathological evidence that she ever had positive nodes (I don't see any biopsy results) either before or after NAC. That's a shame because if she had clinical lymphadenopathy she should have had a biopsy, if only to document axillary disease.

That doesn't happen nearly enough.

 

[Winged Scapula]

That doesn't happen nearly enough.

I agree.

In fellowship, we often did sentinel node biopsies on patients prior to NAC.

That doesn't appear to be in favor here where I am currently practicing and I am not sure if the med and rad onc community doesn't prefer it, or if it is patient driven (ie, avoiding a second operation - which I could believe because these patients act like I'm suggesting we do their surgery without anesthesia when I float the idea of checking nodes before their definitive surgery.) When I first arrived, I was told, "it won't change what we do" so stopped doing it.

That being said, if I have a patient in my office with clinical adenopathy, its easy for me to biopsy the node right then and there, with image guidance if needed so as to have more information regardless of what path they are going down (ie, NAC vs adjuvant).

 

[TarHeelRadOnc]

Palex- you make a very nice argument for PMRT. Again, there can be reasonable arguments made on both sides of this issue

I have four specific responses to your comments above:

"We only have clinical information on the initial axillary status, not surgical axillary staging. Therefore I would be cautious in using figures from studies which included postsurgical pN1-status. For all we know, this patient may have been pN2, had she received a pre-chemo surgical axillary staging."

I definitely agree that pathologic staging is more valuable and accurate than clinical staging. That being said, the two reported NSABP trials of NAC (B18 and B27) and the entire MDACC experience with NAC is based on clinical staging (none of the patients had full axillary dissection prior to NAC to determine true pathologic stage). As such, all of the available data showing low rates of local recurrence for stage II patients with pCR to NAC is based on clinical staging and, therefore, the data is applicable

"The risk of the patient developing a locoregional recurrence without radiation therapy is IMHO above 10%, the chance of her suffering major sequlae from radiation therapy below 2% with modern techniques. What would you prefer? A rib fracture or a chest wall recurrence?"

You contend that the risk of locoregional recurrence in this patient would be above 10%? Unfortunately, that estimate is not at all supported by the available data in clinical stage II patients with pCR to NAC (0-7.5%).

"I still do not understand, why we have to reach this "magical" 5% goal in overall survival benefit, in order to be able to justify postoperative radiation therapy in breast cancer. The medical oncologists regularly do adjuvant chemotherapy with 2-3% survival benefits according to adjuvantonline.com."

The issue here is not a "magical" 5% survival benefit.... rather, the issue is that randomized trials of adjuvant radiotherapy are almost always underpowered to demonstrate a survival benefit <5%, thereby making survival differences of 5% or greater the necessary threshold to demonstrate a statistically significant survival benefit with adjuvant RT.

By contrast, trials of chemotherapy/hormonal therapy are often much larger (ATAC trial had ~10,000 patients) and are thereby powered to demonstrate significant survival benefits in the 2-3% range. Even the comparably large Danish studies of PMRT only included ~1700 and ~1300 patients, respectively.

"The study showed that mammaria interna irradiation added to chest wall, axilla, paraclavicular irradiation only led to a 3% overall survival benefit after 10 years, which was statistically insignificant. However look at what the study was looking for: 10% extra survival benefit through mammaria interna irradiation! That was the goal.
Don't you think that was a goal set a bit too high? 10% absolute survival benefit just by including the mammaria interna chain? We only get 5-7% overall survival benefit at 10 years by adding radiation therapy after mastectomy at all according to the EBCTCG-data (PMID: 16360786). Did anyone really expect that by adding mammaria interna irradiation to chest wall, paraclavicular and axilla irradiation we would simply get another 10%?
We are lucky to see 3% difference in the RCT IMHO and 3% may indeed even be worth irradiating the mammaria interna chain. This RCT could even not be negative, it could be positive after all, it's just not powered enough to show it. We probably need 10,000 patients for that, which we will never get"

I would be very careful saying this. The statement above is very misleading. The 3% difference was a point estimate only. The curves, which were shown at the plenary talk, overlapped at multiple time points. If the curves never overlapped and the IMN RT arm was always above the no IMN RT arm and the problem was an underpowered study, as you suggest, then the p value would be much lower than the p statistic observed. By contrast, the overlapping survival estimates over time lead to a p value of 0.88... ie nowhere near significant. To say to a patient or colleague that there is a 3% survival benefit with IMN RT which may have been statistically significant with a larger sample size is not supported by the actuarial survival curves from the French trial and would be a misleading statement.

 

[TarHeelRadOnc]

That doesn't happen nearly enough.

Totally agree. FNA of suspicious nodes under US guidance is simple enough with negligible risk of complications

 

[clintpark]

I love the lively discussion!

Don't you think this is way better than "will I match?" or "how many away rotations?" threads?

Thanks for posting the case, OP.

 

[clintpark]

Another retrospectively study, this one from British Columbia, trying to answer the question of PMRT with 1-3 LN (in conventional sequence)

Pauline Troung, et.al. IJROBP 2005, 61:1337

SELECTING BREAST CANCER PATIENTS WITH T1-T2 TUMORS AND ONE TO THREE POSITIVE AXILLARY NODES AT HIGH POSTMASTECTOMY LOCOREGIONAL RECURRENCE RISK FOR ADJUVANT RADIOTHERAPY

Clinical and pathologic factors can identify women with T1-T2 breast cancer and one to three positive nodes at high LRR risk after mastectomy. Age <45 years, >25% of nodes positive, a medial tumor location, and ER-negative status were statistically significant independent factors associated with greater LRR, meriting consideration and discussion of PMRT. Combinations of these factors further augmented the LRR risk, warranting recommendation of PMRT to optimize locoregional control and potentially improve survival. The absence of high-risk factors identifies women who may reasonably be spared the morbidity of PMRT.

 

[clintpark]

Without being able to come up with reference, I seem to remember there was a paper that compared two different historic periods of MDACC neoadjuvant chemo experience. During one period, patients with pCR received XRT and during the other period, XRT was omitted. I thought there was a higher risk of failure during the period that omitted XRT. Am I dreaming this up?

 

[TarHeelRadOnc]

Without being able to come up with reference, I seem to remember there was a paper that compared two different historic periods of MDACC neoadjuvant chemo experience. During one period, patients with pCR received XRT and during the other period, XRT was omitted. I thought there was a higher risk of failure during the period that omitted XRT. Am I dreaming this up?

I suspect that you are thinking of Eugene Huang's paper published in JCO. In this study, PMRT after NAC/mastectomy was associated with improved LRC and associated with improved LRC/DFS/BCSS in patients with clinical IIIB/IIIC disease. Important to remember that this data was for all patients receiving NAC/mastectomy, both with pCR and without pCR. Subsequent publications looking specifically at patients with pCR showed no potential for benefit with PMRT in patients with stage II disease, in whom the risk of LRR without PMRT was 0%.

 

[meddoc2011]

Sorry, I was "away" for the weekend with my son's 1st birthday party. Which, as we mostly know and can understand, was for my wife.

When the patient in question was diagnosed with the recurrence, she was biopsied at the breast and axilla and they both were similar. I do not think those path specimens were compared with the original DCIS from 2007.

Since there is evidence to support PMRT and evidence to withhold it, I posted. This has lead to a great thread and I appreciate all of your thoughts, input, and the references.

I spoke with the patient this morning and she has declined therapy. Originally, I was gung ho for PMRT, but after this thread, I told her that with very close follow-up and exams, we could go forward without RT. She was ecstatic and thanked me (and I thank all of you!).

Let's keep this going if you'd like. It definitely is better than the "where did you rank" type of post.

 

[Palex80]

Finally, and perhaps I missed something but there appears to be a lot of talk in this thread about the OP's patient being a pN1. Looks like to me she had some lymphadenopathy on imaging but that there is no pathological evidence that she ever had positive nodes (I don't see any biopsy results) either before or after NAC.

To me it seems she had histologic confirmation of lymph node metastasis in the axilla.
Meddoc2011 wrote:

Biopsies show Grade 3 IDCa (ER+/PR+/H2N+) in the mass and axilla.

 

[Palex80]

I definitely agree that pathologic staging is more valuable and accurate than clinical staging. That being said, the two reported NSABP trials of NAC (B18 and B27) and the entire MDACC experience with NAC is based on clinical staging (none of the patients had full axillary dissection prior to NAC to determine true pathologic stage). As such, all of the available data showing low rates of local recurrence for stage II patients with pCR to NAC is based on clinical staging and, therefore, the data is applicable

I was actually referring to this statement of yours:

LRR rates for patients with pN1 disease treated with upfront mastectomy and adjuvant chemotherapy (without PMRT) in the large series from ECOG (Recht et al.), NSABP (Taghian et al.) and MDACC (Katz et al.) are in the 10-14% range.

Those are upfront pN1-patients.

You contend that the risk of locoregional recurrence in this patient would be above 10%? Unfortunately, that estimate is not at all supported by the available data in clinical stage II patients with pCR to NAC (0-7.5%).

The problem here is that we are basing all of our "evidence" on M.D. Anderson data for quite a few patients. PMID 17418973 provides data on 22(!) patients with Stage I+II breast cancer, achieving pCR after neoadjuvant chemotherapy, not receiving post mastectomy irradiation and all of them developing no recurrence. The rest of the quoted articles do not provide a breakdown according to stage and pCR reached.
Can we really say that it's safe to ommit radiation therapy (although we do have numerous indications for it) simply because there is a single, single-arm study out there with 22(!) patients, which all had no recurrence?
IMHO: I don't think so.

The issue here is not a "magical" 5% survival benefit.... rather, the issue is that randomized trials of adjuvant radiotherapy are almost always underpowered to demonstrate a survival benefit <5%, thereby making survival differences of 5% or greater the necessary threshold to demonstrate a statistically significant survival benefit with adjuvant RT.

I fully agree with you on this.
But in every day work the argument of medical oncologists is:
"Local recurrence risk is 10%, so radiation therapy provides about 2-3% survival benefit, thus we don't need it."
Bollocks!

I would be very careful saying this. The statement above is very misleading. The 3% difference was a point estimate only. The curves, which were shown at the plenary talk, overlapped at multiple time points. If the curves never overlapped and the IMN RT arm was always above the no IMN RT arm and the problem was an underpowered study, as you suggest, then the p value would be much lower than the p statistic observed. By contrast, the overlapping survival estimates over time lead to a p value of 0.88... ie nowhere near significant. To say to a patient or colleague that there is a 3% survival benefit with IMN RT which may have been statistically significant with a larger sample size is not supported by the actuarial survival curves from the French trial and would be a misleading statement.

Ok, thank you for making this point, since I never saw the Kaplan-Meier-curves.
They are not available on the online version of the abstract.
Good to know that. So I agree with you, according to this trial we can not see a benefit for mammaria interna irradiation.
However, I think you too would agree with me, that the design of this trial had major flaws. Noone really expected mammaria interna irradiation to show an absolute survival benefit of >10% over standard irradiation in post mastectomy patients. Right?
Which brings up the point: Who designed this trial, what has she/he thinking of when presuming that mammaria interna irradiation would raise survival by 10% and what's the bottom line of this trial.
If you look at it from a very "statistical point of view" then all you can say by this trial, is that it failed to detect a survival benefit through mammaria interna irradiation which would be greater than 10%. For every other statement this trial was not powered enough to give more information. Perhaps we should look into other endpoints of the trial like recurrence free survival. Maybe there we will find (retrospectively) some more info if mammaria interna irradiation changed patterns of failure.

 

[deleted4401]

Wow. Step away for a few days, and damn the thread grew...

Interesting that it seems that there are such regional differences. Tarheel, didn't realize that most rad-oncs were going in that direction. We still evaluate each 1-3 LN+ patient individually using ECOG, Vancouver, MDACC data. I saw the subset analyses from the Overgaard studies, some of the editorials in JCO, but something just doesn't feel right with how high the recurrence rates were in those patients that were not treated with RT, even in the 1-3 LN+ patients with >=8 nodes assessed (27% vs 4%, 2x as high as our series). I just don't think the American data compares to the Danish data. There is a disconnect, and based on those numbers, the weak axillary dissection just doesn't fully explain it - even those patients with good dissections had such a high recurrence rate. But yes, if taken as a whole and with the Wallgren dataset, any LN + patient post-mastectomy could get RT, based on those studies, and that I don't really refudiate.

Another thing that isn't discussed is that the chemo is completely different. For one, CMF is not used any more. For another, taxanes and Herceptin are used selectively to improve both distant and LRR outcomes. Finally, molecular diagnostics like Oncotype are completely changing the game. I think our estimates of LRR may be off. Now, the other point can be that as systemic therapies have improved, LRR will be of greater importance. Case in point: there is that paper that explains that the 4:1 ratio for LRR:Survival is more like 2:1 when you consider the ER+/Her2 Negative molecular subtype, b/c distant recurrences << LRR, and that PMRT/LRC is far more important, and that those with worse prognoses (ER-) may not get the survival benefit at all, b/c their distant risk is so high.

I'm definitely surprised, though, that patients treated with NAC aren't looked at differently by most of the community (on this board, at least). They way we are trained is that you just can't ignore a pCR response - these women do terrifically well, based on data and anecdote. I'm certain the future will have trials that will allow us to select out those patients that we may not have to treat further. You've got to love the de-escalation of therapies for Hodgkins for low risk patients that have great responses - super high cure rates with 2 cycles of ABVD and only 20 Gy! Clearly different disease and outcomes, but again, very interesting and offers an opportunity to make things easier on the patient.

Anyway, really good discussion
S

 

[Palex80]

I don't want to distract attention from the ongoing discussion, but here's a similar case I would like to report to you.

55 year old patient with a cT2 cN0 cM0 invasive breast cancer.
On diagnosis the tumor was 25 mm big, G3-invasive ductal, ER negative, PR negative, Her2 negative.

During the staging sentinel lymph node biopsy the surgeon found macroscopically suspicious lymph nodes so he completed the axillary staging without waiting for pathologic confirmation in the axilla. 16 nodes were removed, all of them tumor free as it later turned out.

The patient received 4 cycles of TEC and demonstrated very good clinical response in the breast tumor.

BCS was then performed which showed a pCR.

The patient was sent to us for adjuvant radiation therapy after BCS.

We gave 50 Gy to the whole breast, but did not give a boost because during the BCS a rotation plastic was performed in order to cover the relatively large defect in the breast. Therefore we were not really sure "where" to safely apply the boost. Unfortunately no clips were placed during the operation and the surgeon was not all that helpful in target volume defintion for a boost. We thought about increasing total dose to 54-56 Gy to the whole breast, but the patient had still quite a large breast and developed focal °III skin reaction during the 5th week, so we stopped at 50 Gy.
After all (we all thought) she did have a pCR.

1 year later she had a local recurrence, 16 mm big and underwent mastectomy.

I don't know if the boost would have prevented that and surely this is a patient with BCS not mastectomy like in the case we discuss.
The current discussion of pCR and possible ommission of radiation therapy because of it, reminded me of this special patient and some discussions we had in our clinic.

 

[TarHeelRadOnc]

i was actually referring to this statement of yours:

Those are upfront pn1-patients.


"the problem here is that we are basing all of our "evidence" on m.d. Anderson data for quite a few patients. Pmid 17418973 provides data on 22(!) patients with stage i+ii breast cancer, achieving pcr after neoadjuvant chemotherapy, not receiving post mastectomy irradiation and all of them developing no recurrence. The rest of the quoted articles do not provide a breakdown according to stage and pcr reached.
can we really say that it's safe to ommit radiation therapy (although we do have numerous indications for it) simply because there is a single, single-arm study out there with 22(!) patients, which all had no recurrence?
imho: I don't think so."

there is additional data supporting the point i was making: Pmid: 17602071. This is another mdacc study describing outcomes in 277 patients with pcr or pcr with residual dcis only. Among them 152 (55%)had clinical stage ii disease and 76 (27%) had stage iii-iv disease. Patients with stage ii disease with pcr did not receive pmrt. In this study, lrr was only 5% for patients with pcr and 6% for patients with pcr with residual dcis, and i suspect that many of these recurrences occurred in patients with stage iii-iv disease. The number of patients with pcr from nsabp b18/b27 is also much larger than the aforementioned mcguire study.

"i fully agree with you on this.
but in every day work the argument of medical oncologists is:
"local recurrence risk is 10%, so radiation therapy provides about 2-3% survival benefit, thus we don't need it."
bollocks! "

agreed


"ok, thank you for making this point, since i never saw the kaplan-meier-curves.
they are not available on the online version of the abstract.
good to know that. So i agree with you, according to this trial we can not see a benefit for mammaria interna irradiation.
however, i think you too would agree with me, that the design of this trial had major flaws. Noone really expected mammaria interna irradiation to show an absolute survival benefit of >10% over standard irradiation in post mastectomy patients. Right?
which brings up the point: Who designed this trial, what has she/he thinking of when presuming that mammaria interna irradiation would raise survival by 10% and what's the bottom line of this trial.
if you look at it from a very "statistical point of view" then all you can say by this trial, is that it failed to detect a survival benefit through mammaria interna irradiation which would be greater than 10%. For every other statement this trial was not powered enough to give more information. Perhaps we should look into other endpoints of the trial like recurrence free survival. Maybe there we will find (retrospectively) some more info if mammaria interna irradiation changed patterns of failure."

i completely agree, the power calculations and expected survival advantage of imn rt in this study made almost no sense when taking into account the observed survival benefts with chest wall and comprehensive nodal rt in the danish and bc studies and in the oxford meta-analysis. Additionally, it would have been informative for the trial investigators to define local control and metastases-free survival as endpoints in the trial. Unfortunately, only overall survival was reported at astro.

th

 

[TarHeelRadOnc]

Wow. Step away for a few days, and damn the thread grew...

Interesting that it seems that there are such regional differences. Tarheel, didn't realize that most rad-oncs were going in that direction. We still evaluate each 1-3 LN+ patient individually using ECOG, Vancouver, MDACC data. I saw the subset analyses from the Overgaard studies, some of the editorials in JCO, but something just doesn't feel right with how high the recurrence rates were in those patients that were not treated with RT, even in the 1-3 LN+ patients with >=8 nodes assessed (27% vs 4%, 2x as high as our series). I just don't think the American data compares to the Danish data. There is a disconnect, and based on those numbers, the weak axillary dissection just doesn't fully explain it - even those patients with good dissections had such a high recurrence rate. But yes, if taken as a whole and with the Wallgren dataset, any LN + patient post-mastectomy could get RT, based on those studies, and that I don't really refudiate.

Maybe that was an overstatement... hard to say without a modern patterns of care study. I do feel, however, that those breast cancer academics who were previously staunch opponents of PMRT for patients with pT1-2N1 disease have softened their tone at recent ASTRO meetings. IMHO, the lion's share of evidence is in favor of PMRT for pN1 patients with up-front mastectomy (Danish x2, re-analysis of Danish with 8+ LN, British Columbia, Wallgren). Moreover, a recent Red J study from Mass General supports a local control, DFS and trend toward overall survival benefit with PMRT in a relatively small study of 238 patients with pT1-2N1 disease at mastectomy (McDonald et al. Red J 2009).

The main criticism of the Danish studies has always been the higher than expected rate of local recurrence in patients with pN1 disease and the inadequate number of LN dissected at surgery (med 7). Many have argued that the majority of patients with pN1 disease in the Danish trials would have hd pN2+ disease with more complete LN dissectoon. That said, there are studies using models based on surgical data of axillary dissection showing that approximately 64-71% of patients with pN1 disease in the Danish studies would have remained pN1 even after complete axillary dissection (med 15-18 LN removed). Moreover, the British Columbia study showed a significant improvement in survival with PMRT, with no apparent variation in treatment effect for patients with 1-3 vs 4 or more positive LN. The median number of nodes dissected in this trial was 11.

The arguments against PMRT for pN1 disease has traditionally been based on the patterns of failure after mastectomy and adjuvant chemotherapy without PMRT observed in large North American experiences with more extensive LN dissections (NSABP/ECOG/MDACC; median number of nodes dissected 16-18). The largest of these is the NSABP experience with ~4000 patients (Taghian et al.) The problem that I have with this patterns of failure analysis is that locoregional failure was not defined as a primary endpoint in any of these trials and was not even defined as a secondary endpoint is some of them. Similar criticisms of trial design can be made of the trial comprising the ECOG patterns of failure analysis (Recht et al). The NSABP, as an organization, does not consider locoregional failure to influence the natural history of breast cancer (see disease-free survival definitions in NSABP B4 and B6!), and Bernie Fisher vehemently argues that the Danish and British Columbia studies and the 2005 Oxford analysis do not prove that adjuvant radiotherapy improves survival in breast cancer (PMID: 20008611). As such, I find it hard to base treatment decisions entirely on a locoregional patterns of failure analysis performed by a cooperative group who firmly believes that locoregional recurrence has no impact on the natural history of the disase.

 

[deleted4401]

That is, in American scientific parlance, a "bummer".
In B-27, with similar chemo, the rate of IBTR were 5-7%. Boosts drop the rate by half.... Can never get it down to zero.
S

I don't want to distract attention from the ongoing discussion, but here's a similar case I would like to report to you.

55 year old patient with a cT2 cN0 cM0 invasive breast cancer.
On diagnosis the tumor was 25 mm big, G3-invasive ductal, ER negative, PR negative, Her2 negative.

During the staging sentinel lymph node biopsy the surgeon found macroscopically suspicious lymph nodes so he completed the axillary staging without waiting for pathologic confirmation in the axilla. 16 nodes were removed, all of them tumor free as it later turned out.

The patient received 4 cycles of TEC and demonstrated very good clinical response in the breast tumor.

BCS was then performed which showed a pCR.

The patient was sent to us for adjuvant radiation therapy after BCS.

We gave 50 Gy to the whole breast, but did not give a boost because during the BCS a rotation plastic was performed in order to cover the relatively large defect in the breast. Therefore we were not really sure "where" to safely apply the boost. Unfortunately no clips were placed during the operation and the surgeon was not all that helpful in target volume defintion for a boost. We thought about increasing total dose to 54-56 Gy to the whole breast, but the patient had still quite a large breast and developed focal °III skin reaction during the 5th week, so we stopped at 50 Gy.
After all (we all thought) she did have a pCR.

1 year later she had a local recurrence, 16 mm big and underwent mastectomy.

I don't know if the boost would have prevented that and surely this is a patient with BCS not mastectomy like in the case we discuss.
The current discussion of pCR and possible ommission of radiation therapy because of it, reminded me of this special patient and some discussions we had in our clinic.

 

[Brim]

1 year later she had a local recurrence, 16 mm big and underwent mastectomy.

I wonder in a case like that, where neoadj chemo was used and then there was a pCR at lumpectomy, was there a chance of surgical geographic miss?

It's always reassuring to excise a tumor and have it safely in the pathologist's bucket. But if you excise something and there's nothing seen by the pathologist, then either there was truly a pCR and you successfully excised all of the tumor bed (and you'd expect good local control), or you just missed the damn thing. With an initially small tumor and a good response to chemo, #2 is a real possibility, and if that were the case, then a local recurrence at 1 year wouldn't be surprising. But hopefully that wasn't the case.

Were clips used to mark the tumor prior to chemo?

Of course, there's always the tumor that's going to recur no matter what, and that could simply be the case here.

I agree with your radiation plan in this case. In similar situations, I'd give 50 Gy to the whole breast with no boost.

 

[clintpark]

I wonder in a case like that, where neoadj chemo was used and then there was a pCR at lumpectomy, was there a chance of surgical geographic miss?

I believe the lady in this case had neoadj chemo then mastectomy for recurrent breast cancer. [r,yp T0 N0 cM0]

 

[Brim]

I believe the lady in this case had neoadj chemo then mastectomy for recurrent breast cancer. [r,yp T0 N0 cM0]

Yes, in the original case that's true.
But I was referencing Palex's side comment (see below) which was about a different case treated with BCS.
I should have been more skillful with my quoting.

I don't want to distract attention from the ongoing discussion, but here's a similar case I would like to report to you.

55 year old patient with a cT2 cN0 cM0 invasive breast cancer.
On diagnosis the tumor was 25 mm big, G3-invasive ductal, ER negative, PR negative, Her2 negative.
...
The patient received 4 cycles of TEC and demonstrated very good clinical response in the breast tumor.
...
BCS was then performed which showed a pCR.
I don't know if the boost would have prevented that and surely this is a patient with BCS not mastectomy like in the case we discuss.
The current discussion of pCR and possible ommission of radiation therapy because of it, reminded me of this special patient and some discussions we had in our clinic.

 

[Palex80]

I wonder in a case like that, where neoadj chemo was used and then there was a pCR at lumpectomy, was there a chance of surgical geographic miss?

It's good that you bring up this point.
The pathologic report after the BCS reported a fibrosis zone in the middle of the removed specimen, which dimensions matched the initial size of the primary tumor (as measured on ultrasound). The margins around that fibrosis zone were over 6 mm, so I presumed they managed to get the whole thing out.

It's important to watch out that such "fibrosis zones" in pCR after neoadjuvant chemotherapy are completely removed during the BCS and that there is a clear margin with normal breast tissue around them. We have had cases, where the surgeon tried his best to achieve a good cosmetic result and cut marginally along such a fibrosis zone.
We see this patients are R1-patients and ask the surgeon to obtain a larger margin at the involved site, where the BCS was close and if he declines to do that out of fear of disturbing his cosmetic result, we offer the patients 20 Gy boost. You never know if the pCR would still be a pCR on the other side of the close margin.

 

[Winged Scapula]

While an area denoting scar is a helpful finding on post-operative pathology after NAC, surgical standard of care mandates placement of a titanium marking clip in the middle of a lesion and then documenting removal of that clip in your surgical specimen mammogram and pathology. IMHO, both imaging and pathology documentation are needed because sometimes the clip falls out/off or is lost during pathological processes, so I use an intraoperative mammogram to document removal of the clip.