Thanks much for the kind appreciation! Now as to your excellent query:
SLN Micrometastasis: Where We Stand Today
Time and the associated accumulation of evidence has only served to confirmed my opinion on the advisability of undergoing completion via axillary node dissection in the confirmed presence of SLN (sentinel lymph node) micrometastases (micrometastatic, aka "occult" tumors in the lymph nodal system). Although SLN biopsy has less morbidity (especially as to lymphedema) and can discover approximately 95% of tumor involvement - that is, the absence of metastatic tumor cells in the SLNs accurately predicts the absence of metastasis in the remaining axillary nodes in at least 95% of the cases - this leaves open the possibility of undetected tumor involvement in axillary nodes not inspected by the SLN biopsy.
So although the clinical and prognostic significance of micrometastases continues to be a richly debated and controversial issue, my own critical review of the vast literature including of course the recently reported Dutch MIRROR study (ASCO 2009), is substantially in agreement with the latest review and recommendations of ASCO, and with the conclusions of the just reported review of breast surgical oncology expert Eleftherios Mamounas (Northeastern Ohio Universities), summarized in his presentation at the Annual Controversies in Breast Cancer Conference (NY, Oct. 16 -18, 2009) which Gina and I attended.
In appreciating the clinical significance of SNL micrometastases, it's vital to first understanding the terminology of small-volume tumors. Metastases larger than 2 mm are denoted as macrometastases, while tumors larger than 0. 2 mm up to 2mm in size are denoted micrometastases. Tumor clusters measuring from 0.2 mm and smaller are classified as isolated tumor cells (ITCs) (or occasionally called submicrometastases). In the TNM staging, N categories were recently revised to include as two new substages, (1) pN1mi, indicating the presence of micrometastases and pN0(i+) indicating the presence of ITCs.
Data from a Dutch MIRROR study reported by Vivianne Tjan-Heijnen at ASCO 2009 suggests that the presence of micrometastases - but not isolated tumor cells (ITC) - in sentinel lymph nodes (SLNs) in patients with early-stage breast cancer (EBC) strongly compels additional treatment in order to reduce the risk of axillary recurrence. This study separated microscopic disease into 2 groups: the smaller isolated tumor cells or ITCs (<0.2 mm) and the larger micrometastases (0.2 to 2.0 mm). Hence the MIRROR results show that isolated tumor cells (ITCs) and micrometastases yielded different outcomes and should not be treated the same by clinicians. At the 5 year follow-up, there was a 5% rate of axillary recurrence for the women with micrometastases who only had a SLN biopsy and no follow-up treatment, compared with a 1% rate for those who had either completion axillary lymph node dissection (cALND) or axillary radiation, and note that the 5-year recurrence rare will likely increase with longer follow-up.
I should note, as many professionals have brought up, that findings may appear seemingly at odds with the ASC (American College of Surgeons) study first reported at SABCS 2008 and just published in JCO by David Winchester's team, which found that follow-up treatment with cALND did not improve either axillary recurrence or survival for patients with microscopic disease. This seems directly contradictory and unfortunately has often been misunderstood as such. This is in error, do to methodology as my critical appraisal has found: in the ASC study (1) data were obtained from a cancer registry and (2) did not undergo a central pathology review, and (3) the authors of the American study admitted that their data on axillary recurrence was incomplete, in contrast to the MIRROR study with central pathology review and complete axillary recurrence data for every patient. And note further that the MIRROR findings are furthermore supported by ASCO guidelines, which recommend completion axillary lymph node dissection (cALND) in patients with micrometastases (although again, the cALND procedure can be associated with an increased rate of lymphedema).
Summary of Conclusions
So what this all adds up to is that, whether cALND or axillary radiation, the latest findings (MIRROR trial, ASCO guidelines, Mamounas review, and my own review of the aggregate evidence to date) do suggest clinically significant benefit from some radiotherapy in a cases of nodal micrometastasis, even in EBC (early breast cancer) and that such intervention favors optimal outcome.
On this basis, it appears that even in cases of EBC with prognostically favorable tumor biology (ER+/PR+/HER2-) as with your friend, the current expert view in association with both robust guidelines and the balance of the evidence would support the benefit to clinical outcome of undergoing completion via axillary node dissection (cALND); although naturally this is ultimately a patient decision and one best navigated in consultation with her own oncology team, this is what the best evidence suggests and supports.
Some Guidance on Helping the Decision Process
I can add one practical bit of advise from my own experience: in helping the decision process, I find it is worthwhile to be able to weigh in the balance as comprehensive a risk profile as possible. So, for instance, we would have even greater weight assigned to the decision of completion if the mitotic score (part of the tumor grade index) is high (value of 3), or comparably, the Ki-67 proliferation (as a percentage) index were high, or if there were mammographically confirmed breast density, for instance. These any many other factors, some of which are reported in the histopathology findings can help obtain a finer risk assessment that may color and modulate the decision, one way or the other. Even more decisive would be the Oncotype DX recurrence score (RS), which contrary to popular opinion, can even in prognostically favorable tumor biology (endocrine positive, HER2-negative) show intermediate or high risk of recurrence, so it may also be of value to explore whether this assay, assuming insurance coverage, can be ordered especially in the case of such a difficult decision of SLN micrometastasis with otherwise favorable biology (in the absence of further knowledge from histopathology findings). For me, high mitosis or high Ki-67 or intermediate-to-high Oncotype RS, or one or more adverse histopathological factors, can be suffice to throw the weight decisively towards cALND, so I offer these out as suggestions to help your friend make the most informed determination within the most comprehensive assessment of clinical risk.
Breast Cancer Watch