her2 positivity changes everything--tumor cells can disseminate from earliest stages

[Lani]

Cancer Cell. 2008 Jan;13(1):58-68.
Systemic spread is an early step in breast cancer.

Hüsemann Y, Geigl JB, Schubert F, Musiani P, Meyer M, Burghart E, Forni G, Eils R, Fehm T, Riethmüller G, Klein CA.
Department of Pathology, Division of Oncogenomics, University of Regensburg, Regensburg 93053, Germany.
It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single premalignant HER-2 transgenic glands displayed disseminated tumor cells and micrometastasis in bone marrow and lungs. The number of disseminated cancer cells and their karyotypic abnormalities were similar for small and large tumors in patients and mouse models. When activated by bone marrow transplantation into wild-type recipients, 80 early-disseminated cancer cells sufficed to induce lethal carcinosis. Therefore, release from dormancy of early-disseminated cancer cells may frequently account for metachronous metastasis.
PMID: 18167340 [PubMed - in process]

[mts]

This topic is what onc's and patients dwell on quite a bit. To chemo or not to chemo in Stage 1...especially with tumors smaller than 1cm.

Maria

[Lani]

Before it was just a "judgement/guess" that perhaps breast cancer behaved differently than many other cancers because cutting it out and radiating it did not cure as many people as other cancers.

Now we have the technology to discover if that is true, machines to test for circulating tumor cells and better techniques to look for individual cells in bone marrow samples--yet those aren't hardly being used.

Here they showed in mice that they could see disssemination of tumor cells even from DCIS when her2 was present. To me, that means looking for signs of micrometasis when staging the breast cancer would make sense.

Also, many drugs languish for years being used for those with macrometastasis only, which could be tried at an earlier stage with the understanding if micrometastasis were looked for and found to see if that would impact the disease. That is just beginning with trials of herceptin with avastin in the adjuvant setting, but perhaps highrisk patients should no longer be defined by the number of lymph nodes positive, but by whether there are isolated tumor cells in their bone marrow.

I don't want to annoy people who will say, yes, but I could never get my oncologist to look for that, only to make people aware that evidence has been found for what oncologist only suspected and perhaps this knowledge should be used to look freshly upon how cancer is staged, clinical trials run and patients treated

[penelope]

almost all DCIS is her2+. I believe this is written in Susan Love's book as well as other papers.

If this is the case doesn't it make sense that more women would get mets with a diagnosis of DCIS only, but this does not seem the case.

[Lani]

Her2/neu overexpression in DCIS
is common and is associated with higher grade and
comedo necrosis; these pathologic features are associ-
ated with a higher risk of local recurrence.
Almost half of ER-negative DCIS lesions express
Her2/neu, and a majority of Her2/neu-positive DCIS
lesions are ER negative and there are few effect-
ive medical treatments for ER-negative DCIS...
About 12% of ER-positive DCIS cases overexpress Her2/neu,
and there is some concern that ER expression may pro-
vide some resistance to tamoxifen.

Also keep in mind:

--THERE ARE DCIS THAT NEVER DEVELOP INTO IDC--WITHOUT KNOWING HOW many of these THERE ARE, HOW DO WE KNOW WE ARE NOT MISSING A WHOLE LOT OF DATA FROM PEOPLE WHO NEVER HAVE MAMMOGRAMS WHICH COULD BE USED TO ALLAY THE CONCERNS OF THOSE WHO DO AND ARE FOUND TO HAVE DCIS ONLY (ie without invasive component)
AND WHO is TO ASSUME THAT MOST CASES OF DCIS that occur are even discovered--MANY women DIE PROBABLY DIE OF OTHER CAUSES WITHOUT EVER DISCOVERING the DCIS. THIS MAKES IT VERY HARD TO SAY HOW MANY DCIS ARE ER+,HER2+, EVENTUALLY INVADE ETC.

Just pointing this out as it is necessary that periodically those things that are "generally accepted" get questioned.

[Jean]

of a trial of bone biopsey being performed on patients during lumpectomy.
I do know of a trial being done at Cornel NY, I was a bit annoyed at the time (2005) that I was not informed about it prior to my lumpectomy
as I would have been glad to participate in the trial since I fit the profile
small tumor, SNB, ....have not a heard about it in almost three years.

Happy New Year !
jean