Would you offer RNI for young patient with cT3N0 triple negative breast cancer that had progression of disease during neoadjuvant chemotherapy, followed by mastectomy and sentinel node biopsy?

Yes, without hesitation. The primary randomized data suggesting an improvement in overall survival (OS) with PMRT in the T3N0 setting included RNI (e.g. Overgaard et al., PMID 9395428). There is also a study of +/- PMRT (including regional nodes) in T3 patients (about 40% of which were T3N0), that also reported improvements in OS (Klefström et al., PMID 3300953). 

There is mounting interest in using response to chemotherapy as a parameter to decide if we should deliver PMRT. The hypothesis is that responders to chemo perhaps do not derive a benefit from PMRT. It is important to emphasize that this is a presently unproven hypothesis, and one can logically argue against this hypothesis (see Marks and Prosnitz, PMID 24378409). In either case, as this patient was a non-responder to chemo, one cannot invoke this argument in this case. 

Now, the SLNBx result is perhaps informative. But, I am unaware of randomized data showing OS benefits with PMRT to the chest wall alone (i.e. w/o the nodes). 

I usually favor PMRT with RNI for clinical T3 No treated with NACT unless pCR then discuss the pros and cons.

I would offer PMRT (including RNI) in this case for multiple reasons, primarily due to the large size/T3 (citations above). But combined with progression during chemo in a premenopausal patient with triple negative disease…no question. 

Short answer: Yes. Progression through chemotherapy is a poor prognostic indicator and therefore, PMRT + RNI should be given. 

Long answer: T3N0 represents a spectrum of disease in breast cancer and unfortunately, there will never be clinical evidence that specifically addresses every risk factor permutation. Fortunately, we do have knowledge of the clinical outcomes of both “bookends” – that is T3N0 patients without any risk factors vs. T3N0 patients that have many of the most concerning risk factors.

On one hand, T3N0 patients without risk factors have classically < 10% risk of recurrence without PMRT + RNI (Metaanalysis Clarke et al., PMID 16360786 and Retrospective Taghian et al., PMID 16921044). PMRT is not indicated for these patients due to low risk of LR, and potential/higher risk of DM as the first site of recurrence.  

On the other hand, we have good evidence even from very early studies that the common BCa risk factors impact LR (e.g., ECOG Pooled Analysis, Fowble et al., PMID 3292711: Large Size, LN+, ER-, Necrosis, Pre-Fascia Involvement. Retrospective Jagsi et al., PMID 15990006: ≥ 2 cm size, margin < 2 mm, premenopausal, LVI).

We also expect that triple-negative breast cancer should be quite chemosensitive and potentially result in a pCR. In general, rates of pCR (for breast and axilla) based on tumor markers are as follows (Mougalian et al., PMID 26720612):

ER+/Her2-       7%       Mnemonic 7x1

ER+/Her2+      28%     Mnemonic 7x4

ER-/Her2-        28%

ER-/Her2+       40%    

Those without pCR (and those even further subdivided by RCB metrics) fare considerably worse in all survival outcomes than those achieving pCR.

Therefore, a triple negative tumor not only failing to respond but instead growing through chemo makes a good argument to strongly consider PMRT + RNI.