40% of lymph node mets are of a different ER positivity/negativity, her2 positivity/n

[Lani]

negativity than the primary tumor

But since patients die of distant mets rather than lymph node mets, determining the ER, PR and her2 status of the lymph node is really not important compared to determining the ER, PR and her2 status of any distal mets or bone marrow infiltrates.

This is why it is so important to biopsy mets in order to be sure they are being treated with the agents most likely to be effective and why it may turn out to be important to do bone marrow sampling (perhaps even early) to determine if any tumor cells there match the primary tumors characteristics or not.

As I mentioned in my review of the recent San Diego meeting, Christoph Klein believes the latter is most important.

Food for thought

Here is the article from the BBC--


Breast cancer changes with spread



Nearly 40% of breast cancer tumours change form when they spread, a UK study shows.
The researchers say this could mean that patients require changes to their treatment regime.
They analysed 211 tumours which had spread to the lymph nodes in the armpit - the place where breast cancer tends to migrate first.
The study, by Breakthrough Breast Cancer scientists in Edinburgh, appears in Annals of Oncology.
Breast cancer is a complex disease with many different types which can be treated in different ways.
Breast cancer spreads to the lymph nodes in about 40% of the 46,000 women diagnosed with breast cancer in the UK each year.
Cancer cells which spread in this way are often more difficult to treat than those in the breast - so it is vital that women receive the most appropriate treatment.

This suggests there is a need to test which type of disease a woman has in the lymph nodes, because it could radically alter the course of treatment she receives

Researchers were surprised to find the disease changed in such a high proportion of patients, and in so many ways, when it had spread.
For example, 20 tumours changed from oestrogen receptor (ER) negative to ER positive.
This change would mean hormone therapies such as tamoxifen, which would not have worked for the original tumour, could help treat the disease if it has spread.
Other tumours changed from ER positive to ER negative, which suggests those patients may be given treatments which will not benefit them - experiencing side-effects unnecessarily.
Surprising result
Lead researcher Dr Dana Faratian said: "We were surprised that such a high proportion of tumours change form when they spread beyond the breast.

[Rich66]

Do you have any marrow sampling info by Klein handy? Since some CSC theories hold that stem cells may be different than the bulk of cells, does he feel marrow is more at stem level? BTW, Tamoxifen seems to have a body of info suggesting it works on ER-. Been compiling them in Articles section.

[Lani]

PLEASE NOTE I NOT ACCESSED THE ABOVE ARTICLE IN ITS ORIGINAL YET AND I COULD NOT EDIT AWAY THE TITLE WHICH MAY END UP ERRONEOUS IN THAT THEY MAY NOT HAVE EVALUATED her2 +ivity vs -ivity. The article only discusses ER+ vs -

Feel free to search PubMed articles under the name Christoph Klein. His ideas are just as revolutionary as the cancer stem cell "hypothesis" and need a little while to get one's Mind "around"

[Midwest Alice]

Thanks guys, I am working on learning about research. I find the two on topic here interesting and hopeful.
Blessings,

[Lani]

The original article ends up being open access and does cover differences in ER , PR and her2!!

OPEN ACCESS: Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases
[Annals of Oncology]
Background: Assessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance.
Patients and methods: A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed.
Results: Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases.
Conclusions: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.

[Lani]

I have read that the Pathways activated and markers, chemicals secreted which make breast cancer cells home to lymph nodes rather than bone, liver, brain and lungs are different and that bone marrow cells are much more indicative of breast cancer stem cells and what they think ultimately kills a patient.

Bone marrow tumor cells do not seem to clear with most chemo--the bone marrow tumorcells seem to divide only rarely (are dormant like mold in a shower stall this makes them return when the environment is right even after using clorox) making them impervious to treatments which kill the most quickly dividing cells-- and
can be followed to see if they disappear with targeted therapy.

How many of you would be willing to accept a test which hurt for under two minutes and left you a bit sore for one to three days in order to perhaps learn whether the treatment you had undergone was working or not?

I think many more than the oncologists think. They seem to think patients would prefer the side effects of weeks chemotherapy that may or may not even providing ANY benefit for all the "unpleasantness" to undergoing a quick test without associated nausea, vomiting, hair loss, anemia, low white counts and infections, mouth sours, cognitive changes, etc which might spare them the wrong treatment and help get them on the right road to one which might benefit them.

Any opinions?

[StephN]

Thanks, Lani -
Do they need a bone MET to biopsy or will these dormant stem cells be found scattered about?

Where is the best place to do the biopsy?

I wonder, since I am no longer taking Herceptin prophylactically, if a bone biopsy would tell me whether I may still have some cancer stem cells that could rise up one of these months/years? That is, if the 7+ years of Herceptin did not search and destroy those stem cells.

And, YES, I am sure most here would want to know if the treatment that is knocking them silly is having any effect against the cancer. Obviously the Adriamycin I endured did nothing for me!

[Lani]

no need to have any met visible on any study CT, MRI or PET

These are individual tumor cells like CTCs

The test is usually called an aspiration because they use a syringe at the end of a core type needle/trochar to create a negative pressure to get the spicules of bone from the marrow to come along with blood from the marrow so it
can be treated w Ficoli preparation(according to Braun and Pantel's articles) and centrifuged and spread on glass slides for staining for cytokeratins and perhaps one other marker (her2) with mechanical and/or manual reading to detect one cell in many hundred thousands

As I understand it, they don't stain for the second marker unless the first is positive as all the reagents (monoclonal antibodies or otherwise) are expensive.

I don't know the difference in caliber between a core needle for a breast biopsy and a Jamshite needle for a bone marrow aspiration but sort of doubt it is that different. The procedure is done after infiltrating the area with local anaesthetic and is done on either the posterior or anterior iliac crest usually.

It is described(protocol) in the articles as being done bilaterally and as they usually do it the first time before starting the breast biopsy with the patient on their back, it is usually described as being done on the anterior iliac crest (thebump one feels if one lies prone on a hard floor if one is not well enough "upholstered")

Steph it would mean more if you had had your bone marrow sampled before, but yes, if you were now positive it might mean more regardlng
need/no need for further treatment than if you were now negative and let's say if you were positive,seeing if a course of
bisphosphonate changed that might be interesting--although I can hear
the oncologists say it would mean nothing without a large randomized prospective trial...

The fact is we don't know and we won't know until they start LOOKING!

[Lani]

Jamshidi needles range from 8-13 Gauge, breast core needle biopsy diameter is 14 gauge (the smaller the gauge, the bigger the diameter of the needle)

[Rich66]

Oh c'mon. Chemo just for the fun of it. Neutropenic fever blackout in a hotel? Good times.

This bone marrow cell/CSC issue seems to keep cropping up. The CTC test seems to be questioned by Klein:

Eur J Cancer. 2008 Dec;44(18):2721-5. Epub 2008 Nov 18.
The direct molecular analysis of metastatic precursor cells in breast cancer: a chance for a better understanding of metastasis and for personalised medicine.

Klein CA.
Division of Oncogenomics, Department of Pathology, University of Regensburg, Regensburg, Germany. christoph.klein@klinik.uni-regensburg.de
The search for disseminated cancer cells has become a routine procedure in many clinical centres since the pioneering work of Riethmüller and Schlimok was published in the mid 1980s. Until today, clinical studies have mostly focused on the prognostic role of disseminated cancer cells that can be detected in bone marrow samples before manifestation of metastasis. As a more recent development, the field is increasingly concentrating on the prognostic information provided by tumour cells circulating in the peripheral blood instead of analysing the nature of disseminated tumour cells that have successfully homed to a new microenvironment and may eventually grow into metastases. This review critically questions that direction and proposes exploiting the unique opportunities provided by the direct molecular analysis of metastatic precursor cells for a better understanding of metastasis, tumour dormancy, therapy target identification, and personalised medicine in an adjuvant therapy setting.

PMID: 19022661 [PubMed - indexed for MEDLINE]