Micrometasteses and lymph node biopsy

[harrie]

Breast Cancer Lymph Node Biopsy May Need Closer Look: Stray 'micrometastases' could be missed, harming long-term survival, study suggests (http://health.usnews.com/usnews/health/healthday/080409/breast-cancer-lymph-node-biopsy-may-need-closer-look.htm) [U.S. News & World Report Online (http://www.usnews.com/)]

WEDNESDAY, April 9 (HealthDay News) — A new long-term analysis of breast cancer patient survival suggests it might be time to update the way pathologists test lymph node biopsies.

A team of New York City physicians found about one in four patients originally declared to be free of cancerous cells in their sentinel lymph nodes were actually not cancer-free, and that tiny cancer remnants called micrometastases reduced the women's survival over a 20-year period.

These findings address a long-standing question among breast cancer researchers: Are such micrometastases prognostically significant?

"This is the first study to show that there is a survival impact for the detection of micrometastases," said Dr. Stephen F. Sener, a professor of surgery at Northwestern University Feinberg School of Medicine in Chicago.

The results are published in the April 10 issue of the Journal of Clinical Oncology.

In the study, a team led by Dr. Hiram S. Cody III, a professor of clinical surgery at Memorial Sloan-Kettering Cancer Center in New York City, analyzed a population of 368 patients who were originally diagnosed with breast cancer in the 1970s. At the time, these patients were judged to be free of cancerous cells on the basis of a single tissue slice (standard procedure at that time). As a result of that diagnosis, these patients received no follow-up treatment for their disease.

Each of these patients was then monitored over the following 20 years or so. Cody and his team retrospectively reanalyzed the decades-old tissue samples using modern techniques. They then assessed how many of the slices did, in fact, contain cancerous cells, and whether those stray cancerous cells had affected the women's survival.

"What we found was that among these patients, 23 percent were converted to node-positive [cancer status], and among those who were converted, their survival was worse than among patients who remained node-negative," said Cody.

"The 23 percent number is very significant, because it argues that if pathologists just do one section, you may want to ask them to do more," he explained. "We think the information you get by doing more is significant."

According to Cody, 30 years ago the standard of care for breast cancer patients was complete dissection of the axillary lymph nodes (those found under the armpit) followed by cell-shape analysis using a single tissue slice from each node. Such a surgery would typically collect 15 to 20 nodes, on average. Today, however, a different, less traumatic approach called sentinel node biopsy is used.

In sentinel lymph node (SLN) biopsy, a patient's tumor is injected with a combination of dye and radioactive tracer molecules. The following day, only those lymph nodes to which the tracer molecules migrated (the SLNs) are biopsied and analyzed. So, instead of harvesting 15 to 20 nodes, on average only two are three are collected using the new technique.

That reduction in work per node has a real payoff, because pathologists can delve much deeper into each sample, Cody explained.

"Because you remove fewer nodes, you can study them more carefully, and we argue that the information you get by doing that is prognostically significant," he said.

Current guidelines from the College of American Pathologists recommend analyzing one tissue slice per biopsied lymph node, Cody noted. Yet for years, he said, physicians have known that the more carefully one looks, the more cancerous cells one can find. The problem has always been one of balancing the additional work and expense required against the likelihood of success — some studies have suggested a pathologist would need to analyze as many as 1,600 additional sections to find a single additional node-positive case.

In the current study, Cody's team took four sections per node, analyzing two each for cell shape (morphology) and the presence of a molecular marker of cancer. Nine percent of patients were found to be node-positive using morphological criteria alone; the other 14 percent were detected using molecular markers. In both cases, survival was poorer than in patients who remained node-negative.

"What we are suggesting is that perhaps the staging system for lymph node metastases should be reevaluated in the next edition of the AJCC [American Joint Committee on Cancer] staging," he said.

[Sheila]

Harrie
First of all, Love the new Picture...you look gorgeous!
This article is very interesting, there was alot of discussion in San Antonio concerning node dissection...basically it is only as good as the lab/pathologist that does it...so many are not accredited like one would think. There is work being done to get this accomplished. I think of it like taking a grape and slicing it and chopping it into as many pieces as possible, when they analyze it, if they miss the one little fragment, what good is it...they really need to get this to a science so all are done the same with more uniform results. Our lives depend on it.

[Jean]

Sheila,
Remember this well in S.A.
Back in 2005 Lani was serching articles for me reltating to node neg.
dx. and the results of those studies. The news was not uplifting. This is another issue to be addressed.
Cells that can/or may/pass through, can remain dormant for years.

Test vary from lab to lab. Also a tiny micro met can pass through and never be detected. I would much rather have a dr. say that a neg. node result is a favorable situation. But, certainly not a guarantee, leaving the patient with a "false sense of security." 20 years ago it was thought that the cancer cells only pass via the nodes., which is the usually course of travel, but we also now know that the a cell/or/cells can travel via the blood system.

What is the point of being dx. with early stage cancer and the dr. saying how "lucky you are to have caught it early" base a trt decsions on that and not consider the type of cancer, the gene make up of the person's cancer....order additonal assasys.

How many newly dx people know to ask those questions to the dr.
It is only when you must travel down the road and research do you discover all the branches that are on the tree.

I spoke with Lily Shockney from John Hopkins regarding nodes...she offered the following analogy:
Think of a cancer cell as a tiny tomato seed. Then consider your node as the catch basket in your sink. Is it possible for that tiny tomato seed to pass through the grating of the basket and go down the drain?

While it is favorable to have node neg. it is not a guarantee.

Thank you Harriecarnie for this great article.
PS I told you that you looked liked a teenager!
Hugs,
Jean

[AlaskaAngel]

Hi Harrie,

The article had been posted in the "Articles Forum" too. Use of the best technique can even help some who didn't have the opportunity in the past to get the best technique and ended up with recurrence to know what might have been the reason for their recurrence. It can also help some who are not sure if they want to do hormonal therapy, or stay on it, to have better info when they are making those decisions.

AlaskaAngel

[Jean]

While I was in S.A. Dr. Love posted daily blogs: She wrote the following:

"This new thinking was also highlighted by the Genomic Health presentations, which showed that their Oncotype DX Recurrence Score was as accurate in women with ER-positive tumors and positive nodes as it had been in the women with negative nodes. This does not just mean we have a new test. Instead, it means that nodes are much less important than we thought in dictating which treatment is indicated! It’s the tumor biology that matters most and should determine treatment strategies"

"As Genomic Health reported, the women with a low recurrence score who were node positive benefited from hormonal therapy but not from chemotherapy, whereas the women with a high recurrence score did better with chemotherapy. This means using node status to decide whether a woman should have chemotherapy or hormone therapy is probably not relevant. Whether the cancer has spread to the nodes may be helpful in determining a woman’s prognosis, but it does not appear that it’s an appropriate way to determine treatment. This means that our hypothesis, which had been that if the cancer has spread to the nodes, the more aggressive the treatment has to be, is probably not true."

By the time we get the answer, will it really matter? If the biology determines which treatment is indicated, will nodes be as important as they once were? The great thing is that we continue to question, explore, and challenge our assumptions in an attempt to make more progress in breast cancer, and that is the fun of San Antonio!

Jean


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[Becky]

I am not so certain that the nodes are not important. The example being a woman who is highly ER+/PR+ (but not Her2+). Let's say this woman is diagnosed Stage 2B - has a tumor 2.5cm and 2 positive nodes.

This woman may not need chemo - even with Oncotype DX (as they may start testing this type of patient for the need for chemo. Let's say she scores low. In order to avoid chemo, this woman would also have to be postmenopausal (it is a criteria now). So - do they give this woman an AI for 5 years or do they give her Tamoxifen for 5 years and follow by Femara for 5 years. You CAN'T say they will give her an AI for 10 years. Just because we (or in some cases our oncs) want us to take an AI 10 years, it does not mean that will be done generally as it is not standard of care and there have been no trials that it works and no upcoming trials to test this.

As everyone may have gathered from other "conversations" here on the timing of recurrence, a woman such as this is more likely to recur later (in the 6-8 yrs past surgery) than a woman with a more aggressive cancer (such as a Her2+ or triple negative where the rate of recurrence is highest in the first few years). However, this 6-8 yrs is based on looking at this type of woman over time and when 5 yrs of Tamoxifen (only Tamoxifen) was used. It has just recently been (re)posted on how following 5 yrs of Tam with 5 yrs of Femara reduces recurrence (which was typically in this range). However, STILL, some of these women recur after the Femara as well. This is because the slow growing cell(s) (as this type of cancer is slow growing) are still there in dormancy in the hip bone or in the liver, slowed to a crawl by Tamoxifen and then Femara - but not killed by a robust immune system (as is the hope). This woman would typically get chemo upfront first. For some, it may have killed that cell in the hip bone. Even node negative women, if the tumor is 2cm or larger, that tumor sheds and the larger it is, the more it sheds. Cancer travels via the bloodstream just as much as through the nodes. The only good thing about a positive node is that you know the cancer has traveled.

I am a micromet girl myself - negative nodes at surgery and one positive node with 2 micromets a couple of days later (upon close inspection). The good thing was that it got me 4 Taxol as well as the 4 AC and made it easier to fight for Herceptin when it became available.

This is a mute point for Her2+ women who are node positive but I hope they do alot of testing on node positive women who are highly ER+/PR+ before cutting off chemo because they will need anti hormonals for a long time (and what does a long time really mean and will that be better for their uteruses and bones than a short round of chemo - just thinking out loud here).

[Jean]

Hi Becky,
I hear you loud and clear...

Have a question for you...
When I was seeing all the dr. (I was postmenopausal) they all suggested trt with AI...I thought that if a woman was PostM she would not be given tamoxifen.

Many women worry that when they stop taking tamoxifen or an AI that their cancer will just take off. The data is showing the opposite. The benefits of tamoxifen are long lasting. After 5 yrs. and then stopping there is a continuing improvement of survival over the next five yrs. and the curves are still changing. The ATAC trial shows a similar effect with the AI.

Or maybe, women will take a break from the hormonal therapy, (time out) to resume HT? This will be an interesting factor at next BCS as there
are no clearly defined trt decisions on this. My onc. recently said,
that it appears that I will be taking AI longer.

From Dr. Susan Love: reported.
Thea Tlsty, PhD, a pathologist at the University of California, San Francisco (UCSF) Comprehensive Cancer Center, gave a late-breaking presentation on her work with ductal carcinoma in situ (DCIS). Dr. Tlsty conducted a large, retrospective study of 1460 women who had been diagnosed with DCIS. Of this group of women, 1102 had no subsequent tumors while 358 had a recurrence. Of those, 194 were diagnosed with more DCIS while 164 were diagnosed with an invasive tumor. All of the women had been diagnosed in the 1980s, and the only treatment they had was surgery. Dr. Tlsty tried to figure out if she could identify a group of biomarkers that could predict who had the kind of DCIS that recurred as invasive and who did not.
Ultimately, she was able to identify markers that did pretty well at predicting which DCIS would come back as invasive cancer. But even more interesting was that the biomarkers predicted a subset of breast cancers that we refer to as basal-like tumors, and which are known to be very aggressive. Why is this so exciting? Not only because it would be wonderful to be able to figure out which DCIS needs aggressive treatment and which does not, but also because it says that the different kinds of cancers start way earlier in the precancerous stage. If you are a shy kid you grow up to become a shy adult not an aggressive adult. Similarly, if you are an aggressive DCIS you grow up to be an aggressive tumor! This , in turn, may mean that targeted therapies are as important for treating DCIS as they are for treating invasive cancer!

Interesting question you raise on the subject of a woman who is ER+ PR+ 2.5 CM tumor...2 Nodes positive/and showing a low score...Yikes.
I would be hard pressed to say what I would do. If the score came back
low - less than 11....I would have to think hard about it. (meaning chemo) with such a low score... But to be honest in my heart I would be feeling much better having that low score/verses....let's say 46....

I remember faintly when we were attending one of the lectures the numbers coming up of cut off with patients and what the dr. were relating to Dr. Hudis was using 30...another 24...do you remember...this was verses...moderate to high....I know I do remember feeling uncomfortable with the 24/and/30 score...for decision making on chemo.

Interesting Becky....look forward to what you think.
Hugs to you,
Jean

[harrie]

Jean, that was very interesting what you wrote in regards to Thea Tisty's presentation on DCIS breakthroughs. How encouraging that they are taking DCIS much more seriously and analyzing the biomarkers within those tumors. In the 1990s when I had my episodes of DCIS, it was not even considered a "real" cancer and an aggresive form of tx was never considered. But technically speaking, the cancer cells in DCIS are not different then the invasive cancer cells in breast tissue. Therefore, it would make a lot of sense to study the biomarkers in the DCIS for the prediction of a future invasion and base a tx accordingly. When I had my DCIS, the most aggresive adjuvant therapy was tamoxifen and radiation preceeded by a lumpectomy or a mastectomy for those who were paranoid. Even then a mastectomy was considered overly aggresive, at least in my case. But then again, back in the 90s, no one suggested I be tested genetically either.
It would be very beneficial if the studies would include the significance of being genetically positive to the biology of the cancer cell.

Jean, when you mentioned at Dr. Hudis lecture with the Oncotype numbers, and being uncomfortable with the 24 - 30 scores for the decision on chemo.....Are you saying that with those numbers, you would be hard-pressed to make the decision to go for the chemo tx?
I was just wondering. My score was in the low-intermediate range score of 12.

I thought in order to qualify for an Oncotype dx testing, you needed to be stage 1 with no lymph node involvement.

Maryanne

[harrie]

Jean, I just went up and re-read your post on Dr. Love's blog on the Genomic Health presentation. Very interesting information on what GH had to say. I had always believed that if the node status is positive, chemotherapy would be a given.

It is so exciting to see that as the understanding of the biology of the tumor cells unfold, the changes and strategy of treatment become much more targeted and refined.

[juanita]

Love the new picture! I was told by one onc that I was node negative but my surgeon said I had microcells there, but I had to have chemo anyway because I was grade 3 and can't think of the word for it but 53% of the cells were active.

[Mary Jo]

I too was told after surgery the 2 sent. nodes were negative. Then when we went in for the pathology reading were told that the 1st node had 1 microscopic cell of invasion (.085 - a pinhead my doc said but I'm not sure now if that's cm. or mm. but whatever it was tiny) Anyway, in my case as well chemo was a definite....grade 3, her2 positive and 4 cm tumor. I opted out of any more nodes to be removed though when told of the micromet invasion. I did receive 28 days of radiation however after chemo had ended and that I wouldn't have had to do if I had let them remove more nodes to see if those would have been negative. Radiation sounded much better to me than more nodes removed and the risk that goes a long with that.

Dang micromets - those nasty little buggers.

Mary Jo

[sarah]

very interesting, thanks for posting this
sarah

[Jean]

Yes,
Much is unfolding at a rapid rate...often times we do not have the data,
just articles to reference (we have much to thank Lani for) as survivors
we need to glean through all articles and see what is worthy.

When one considers the medical advances just in the last three years,
it is amazing...and certainly not fast enough...we all want a cure, an answer..

"Each day we get a little bit closer"
Kind Regards,
Jean

[CLTann]

I have difficulty in accepting the term micromet. A metastasis is a metastasis, regardless of the the size. Of course, if the metastasis is not a sustaining growth, then it should not have been classified as metastasis. All of us have cancer cells in our body but most of them are not able to sustain living and growth. We were just told that AI medication does not kill cancer cells although the AI discourages cancer propoagation and growth. Just because our microscope cannot see the tumor cells does not mean the micro sized cancer cells are not there. If an electronic microscope is used, I am sure it can detect the cancer cells clearly.