Sign up Calendar Latest Topics
 
 
 


Note: This topic is locked. No new replies will be accepted.


Reply
  Author   Comment  
kareylou

Seeker
Registered:
Posts: 27
Reply with quote  #1 
Hello Edge,
You don't know me, but you have provided me with so much valuable information, inspiration, and confidence over the five years I have been dealing with breast cancer. Thank you!
Now--here's my question. Have you refined your opinion regarding the advisability of axillary node dissection when micrometastases are found during the sentinel node biopsy, in light of the Dutch MIRROR study?
Here is what you wrote regarding micrometastases in the sentinel lymph node biopsy in 2007:

*********************************************************
The Question of Micrometastases
The phenomenon you describe, apparent migration of a small tumor to the lymph node, is in fact an artifact, namely an artifact of the increasing use SLN biopsy: Danish researcher Deirdre Cronin-Fenton and her colleagues recently showed that sentinel lymph node biopsies often detect small numbers of tumor cells that do not necessarily indicate that the cancer has truly spread or migrated, namely they are micrometastases rather than macrometastases. As the researchers concluded: "Increases in small tumors with micrometastatic lymph node involvement may be attributable to the increased use of the sentinel lymph node biopsy in community practice".

The critical question is what is the clinical significance of such micrometastatic involvement, where the current definition of micrometastatic disease is one or more N1mi tumors, that is, between 0.2 and 2 mm in size? The first clinical implication we know from seminal research just completed and reported last month by Charlex Cox's team at the H Lee Moffitt Cancer Center is that detection of such micrometastatic carcinoma (N1mi) in the SLNs of invasive breast cancer patients is a major indicator of poorer survival, confirming their earlier findings reported out first at SABCS 2006. Furthermore, although trials are still in progress to determine the benefit of ALN dissection in patients with SLN micrometastases , I would agree with the conclusions of a major recent comprehensive review of this issue published this year by Emiel Rutgers that while we are awaiting the results of these determinative trials, it would be prudent to advise patients to have the axilla treated electively, either by axillary dissection or by radiotherapy (viable especially when tumor size is small), especially since we know that between 10% to 20% of patients with such micrometastatic disease will have non-SLN involvement (in keeping also with the conclusions of French researchers Jean-S├ębastien Krauth and colleagues).

*****************************************************

My dear friend has just been diagnosed. She had a 2.4 cm tumor and was initially told that her lymph nodes were negative. The "third level stain" showed micrometastases in one node. She will be doing chemotherapy because of the size of her tumor even if all other factors are favorable, so is there any reason for her to have more lymph nodes removed? Either for the purposes of removing more cancer cells, or for determining which/how much treatment to do? She is 67, excellent health, ER PR +, her2neu-. I'm encouraging her to get a copy of her actual pathology report, so if more information would be helpful I'll probably be able to supply it.

Thanks for so much,

Karen






edge

Chief of Research
Registered:
Posts: 1,129
Reply with quote  #2 

Karen:

 

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.

 


Constantine Kaniklidis

Breast Cancer Watch

edge@evidencewatch.com

kareylou

Seeker
Registered:
Posts: 27
Reply with quote  #3 
Well, you just made me cry. I had just come to the realization that the Conference was going on, or had just finished, and had concluded that you must be way too busy to respond any time soon. I had resigned myself to helping my friend make this decision. I'm a pianist turned self-educated breast cancer expert and she is a secretary who has never been sick a day in her life.
These few paragraphs help us more than you will ever know and I once again thank you, for so much.

added subsequently: Lest anyone think that I really consider myself a "breast cancer expert", and I'm out here dispensing medical advice, "self-educated breast cancer expert" was my way of saying that I've been through it.

edge

Chief of Research
Registered:
Posts: 1,129
Reply with quote  #4 

Karen:

 

You have pretty much stated succinctly precisely the principles involved, and the tradeoff.  What is opaque and apparently confused  here from her oncologist is the sufficiency of chemotherapy to comprehensively eradicate SNL micrometastases, which flies against the large body of consistent evidence that the problem is just that - namely the adverse prognostic significant of residual nodal (and bone) micrometastases after (neoadjuvant) chemotherapy.  This post-therapy residual micrometastatic disease is well-documented and clearly indicates the limited and compromised adequacy of chemotherapy to wholly eradicate residual disease at this level, with the associated entailment of compromised prognostic outcome; if chemotherapy were indeed consistently effective for such eradication, we would not have the problem of residual micrometastatic disease in the first place. And although different regimens may have differential impact on residual disease, (1) we have at present no way to discriminate accurately among agents and regimens, and (2) even if we had, we have not discovered any drug regimen that consistently and verifiably results in comprehensive and significant micrometastatic eradication to negate the adverse prognostic effect.

 

It is indeed disconcerting that important pathological information is not being transmitted to the one person who should have a maximal sense of her status and prognosis, namely the patient herself.  If she is up to it, requesting copies of pathological / biopsy reports and any radiological (scan) results may be able to fill in some critical gaps.  Otherwise, my perspective on this matter is much as before, so the balance hangs between the possibility of lymphedema (which is by no means assured and universal) and the prospect of some non-trivial compromise to recurrence and survival outcome, a difficult choice even with outcome being involved given the highly individual importance of quality-of-life (QoL) to the patient, a consideration never to be dismissed.

 


Constantine Kaniklidis

Breast Cancer Watch

edge@evidencewatch.com

kareylou

Seeker
Registered:
Posts: 27
Reply with quote  #5 
Thanks once again. That clears it up even more. I wanted to be absolutely certain that the recommendation for further treatment by radiation or axillary dissection held fast even when chemotherapy is inevitable. (not just your recommendation, by the way. From the research I have done it seems that once again you are saying what everyone's oncologist will eventually be saying given enough time.) I want to be very careful about telling her anything that would disagree with her oncologist--taking into consideration that I am after all a pianist.
She is going to another oncologist this week for a second opinion, so hopefully this doctor will be more forthcoming with details. I have a feeling that she will not end up pursuing her treatment with the current  oncologist.


nosurrender

Avatar / Picture

Moderator
Registered:
Posts: 7,476
Reply with quote  #6 
(((Karey Lou)))
You are a good friend, and she is so fortunate to have you there. If it were me, I would want more treatment, either by surgery or radiation. That was backed up by what we learned at the conference. I totally understand your "expertise" - heck, just getting through this we practically earn our medical degree!

hugs,
g

PS- please see my note in the surgical section about how they can now perform the axillary dissection and preserve the lymphatic channels.

__________________


WE WILL PREVAIL





kareylou

Seeker
Registered:
Posts: 27
Reply with quote  #7 
Thanks Gina! I'm off to the surgical section--
Previous Topic | Next Topic
Print
Reply

Quick Navigation:

Easily create a Forum Website with Website Toolbox.