Blood work with DCIS?

coastalaggie

I spoke with a friend of mine who has stage 4 BC. She was initially diagnosed with mutifocal lcis given a lumpectomy, rads, and tamoxifen. She got a second opinion by a MO and he asked if she had blood work done. She said no. Well he did it and found circulating cancer cells. Did a PET and found mets in her bones. So basically she had mets that were not discovered with the lumpectomy alone (which included biopsy of sentinel nodes). This freaks me out as none of my docs have mentioned or suggested bloodwork. I don't understand why they don't do at least the blood work just to rule out mets because there is a possibility you have mets but it slipped under the radar? Thoughts anyone? Has anyone else had blood work done with just a DCIS dx

MelissaDallas

coastalaggie, your friend must have had something in addition to LCIS (IDC or ILC) because LCIS is just an increased risk marker - it is not considered cancer and you would not receive radiation for it, nor would you have metastatic cancer from it.

I believe CTC tests are not considered reliable and are not widely used

SiameseX2

Coastalaggie,

I sure wish there was a blood test that would detect bc. Curious as to the timing of all this - why would it be considered a second opinion after she already sought treatment (lumpectomy, etc?)

The only bloodwork I had done were a basic CBC and Chemistry to prepare for surgery. And the only thing out of whack was that red count was slightly low (that was never the case before).

MTwoman

I'm with SiameseX2, the only blood work I had was in preparation for surgeries. (had to re-run the same ones prior to each)

I'm also with MelissaDallas, radiation isn't done for LCIS, so she must have had something in addition to her LCIS (just like some women have DCIS + IDC get treatment focused on the most aggressive of the 2, the IDC).

coastalaggie

I will have to ask her what motivated her to go to the other dr. Supposedly he is world renowned in stage IV cancer treatment and trained/practiced at MD Anderson. I have also asked if I could see her pathology report from the lumpectomy. She is a nurse though and seemed pretty educated on what she had or at least what the dr told her at the first place she went o. I also dug into the literature on CTCs. There are studies that have shown that you can have tumor cells escape from pure DCIS:

http://www.nature.com/bjc/journal/v108/n12/full/bj...

"According to the prevailing model for systemic cancer progression, metastasis is a late event, and cancer progresses within the primary tumour before metastatic dissemination of fully malignant cells. However, Braunet al (2000) showed many years ago that tumour cells can disseminate early during tumour progression, whereas Pantel and Brakenhoff (2004) claimed that 'immature' tumour cells can leave the primary tumour early during tumour progression. Klein (2009) proposed a second model that draws together data from disease courses, tumour growth rates, autopsy studies, clinical trials and molecular genetic analyses of primary and DTCs. This model posits a parallel, independent progression of metastases arising from early DTCs (Klein, 2009).

Only invasive cancers are assumed to shed isolated tumour cells into the bloodstream and infiltrate lymph nodes. However, latest studies indicate that tumour cell dissemination may occur before stroma invasion, that is, in ductal carcinoma in situ (DCIS). Either these cells have already started to disseminate from pre-invasive mammary lesions or from occult invasive tumours, or represent the earliest step of microinvasion in a pre-invasive lesion (Banys et al, 2012; Sänger et al, 2011). The clinical relevance of these cells has to be further evaluated."

From what I am reading, just because you have CTCs in your blood does not guarantee that they will "settle down" in a new place in the body as mets. The right microniche for mets has to also occur. It certainly raises your risk if they are there though. There is no 100% guarantee with BC but that said many women get DCIS get treated by the standard procedures (surger, rad etc) and go on to live happy lives. it seems that there are a certain percentage of DCIS patients who have more going on.. question is how much are you willing to do to verify that you do not fall into that unlucky percent? Science still can not predict with 100% accuracy whose DCIS will progress to invasive cancer and whose will not. Statistics are generally on the side of most DCIS patients and most of us will likely roll the dice and know that the odds are in our favor.

All I am saying is that if is possible to have a CTC test done, I would do it for the piece of mind that there is not something that has been missed.

MTwoman

But the CTC test aren't considered reliable. So you'd be doing it for peace of mind that isn't really based on anything scientific, not truly knowing if "something has been missed" or not.

I've read those same journal articles that you posted. And they are disconcerting - to say the least. But they basically raise theoretical questions and only provide answers to why (a very few) women who've only been diagnosed previously with DCIS can have a later mets without another primary occurring. This isn't happening to large numbers of women, but an infinitely small number. The standard of care, that is based on current scientific knowledge, for Stage 0 pure DCIS is lx +rads vs mx, and then (for ER+) endocrine therapy. If there are micro-invasive components, then depending on their number and size, you become essentially Stage 1 IDC, NOT Stage 0 pure DCIS.

coastalaggie

Could you direct me to the published literature that conclusively says that the tests are unreliable?

Beesie

"It seems there are a certain percentage of DCIS patients who have more going on"

Yes, but only a very tiny percentage.

The long-term survival rate for women initially diagnosed with DCIS ranges from 97% to 99%, depending on the study. In the vast majority of cases where someone with DCIS is subsequently diagnosed with mets, what comes first is a localized invasive recurrence - and of course once invasive cancer is present, the diagnosis is no longer considered to be DCIS and there is a risk of mets. Even the most pessimistic study I've seen showed that only a fraction of a percent of women initially diagnosed with pure Stage 0 DCIS end up with mets without first having either an invasive recurrence or the development of a new primary invasive breast cancer. In this study, the small percent who did end up with mets without first having an in-breast invasive cancer (I believe the study put the figure at 0.4% but I'm going by memory) could well have had an occult invasive cancer, or there may have been errors in recording (cases of DCIS-Mi are often erroneously recorded to be DCIS - we see that on this board all the time).

As far as I know, up to now there has been no definitive scientific proof that pure DCIS (on it's own, without a microinvasion or occult invasion) can metastasize. There are hypotheses and Petri dish studies, and yes some women with DCIS have CTCs (but the studies I've seen have not associated this with the development of mets). If at some point it is definitely shown that DCIS can in fact metastasize, what will also be shown is that the percent of women affected is very very small. This is unquestionably the case, given the very high long-term survival rate and the fact that almost all cases of mets are preceded by an in-breast invasive event.

What is critical for anyone with DCIS, particularly high grade aggressive DCIS, is ensuring that recurrence risk is minimized. 50% of DCIS recurrences are not found until invasive cancer has already developed - and that's where the risk lies for DCIS patients. So appropriate and adequate treatment at the time of the initial DCIS diagnosis is the best way to avoid a more serious diagnosis - a localized invasive recurrence, which can lead to a metastatic recurrence -in the future.

GAMomma

In my opinion,I think anything can always lead to something else. I have 5 kids,out of those kids 1 of them has always had adverse reactions to immunizations. He had chicken pox,measles,meningitis..not all at the same time and very mild reaction,but still there. Everyone is different. He is not immuno suppressed,just a odd duck. So with that I would think anyone who has either a history,fam history , or past cancer really just needs to be proactive in self care and preventative measures. I have an alpha protein deficiency leaving me at Rick for lung disorders. My.mother died from COPD. I get a chest X-Ray or low dose CT yearly,to watch. Now I do prevent as much as possible. No smoking..ever..keep away from strong fumes,use a mask when needed.. all simply proactive. I am the last person on here to ever link a literature anything,this is just my opinion 💖

MTwoman

coastalaggie,

you wanted citations about problems with CTC testing? here are a few:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175647 (april 2017)

Summary of their results, " We found greater numbers of putative CTCs by this approach than by the cytokeratin-based CellSearch technology, but a high number of CTC false positives were identified in healthy volunteer samples which were not reduced in successive blood draws."

https://www.ncbi.nlm.nih.gov/pubmed/28373442 (april 2017)

summary of conclusions, " Even though the blood coagulation pathway may be activated in more aggressive disease related to an elevated CTC count, in this study, we did not find any association between CTCs and plasma concentrations of tPA."

https://www.ncbi.nlm.nih.gov/pubmed/28361862 (march 2017)

this one says, " Indeed, data on prognostic or predictive value of CTC are rather contradictory, because there is still no standard method of CTC identification, represented by different populations manifesting various biological behavior as well as different potency to metastasis."

Currently, there is quite a bit of research going on to figure out how to best measure CTCs and what their implication is. One of the articles suggested that clasters of CTCs have a greater ability to metastesize than single CTCs, so even finding single CTCs doesn't necessarily have drastic implications. A recent meta-analysis https://www.ncbi.nlm.nih.gov/pubmed/28337998 was suggestive of CTCs being useful in determining if a treatment protocol was working by monitoring a woman's CTC levels during treatment (not using the levels themselves, but comparing them over time) but that it wasn't helpful in certain subgroups of tumor types (TNBC).

Hope this helps!

coastalaggie

not trying to be argumentative but the paradigms of how cancer works have been flipped upside down.. it is not a always a linear progression like what was once thought. it has been shown in mouse models and corroborated with cellular and molecular data in humans that tumor cells can shed well before any tumor formation. These cells can enter the blood stream and lay "dormant" for an indefinite amount of time. Depending on a multitude of factors they can be turned back on and met to another area of the body or back to the breast. I read one article that suggested that the cancerous tissue in the breast may influence these dormant cells in circulation. This blew my mind.

https://www.sciencedaily.com/releases/2016/12/1612...

Even before tumors develop, breast cancer cells with a few defined molecular alterations can spread to organs, remain quiet for long periods of time, and then awaken to form aggressive, deadly breast cancer metastasis, says a team of investigators led by researchers at Icahn School of Medicine at Mount Sinai and the University of Regensburg in Germany. They say their finding, published in two papers in the journal Nature, and conducted in animal models and tested in human samples, now solves the mystery of how breast cancer metastasis forms without a primary tumor in this new model of early dissemination and metastasis. Furthermore, a clinical primary tumor may never develop, investigators say.

The University of Regensburg team had discovered that cancer cells could spread not only from a highly mutated, overtly evolved and pathologically-defined invasive tumors, but also from early stage cancers commonly considered incapable of spreading cells. However, how these early cancer lesions could spawn cells with traits of malignant tumors was unknown.

In two papers published in the journal Nature, and conducted in animal models and tested in human samples, the two teams now have identified the first mechanisms that allow cells to spread early in cancer progression and contribute to metastasis.

In the study from Mount Sinai, two changes in mammary cancer cells -- a switched-on oncogene and a turned-off tumor suppressor -- motivated cells to travel from breast tissue to the lungs and other parts of the body. There, the cells stayed quiet until a growth switch was activated and metastases developed in lungs.

"This research provides insight into the mechanisms of early cancer spread and may shed light into unexplained phenomena -- among them, why as many as 5 percent of cancer patients worldwide have cancer metastases but no original tumor, and most importantly, why it is so difficult to treat cancer that has spread," says the study's senior investigators, Julio A. Aguirre-Ghiso, PhD, Professor of Medicine, Hematology and Medical Oncology, Maria Soledad Sosa, PhD, Assistant Professor of Pharmacological Sciences, and graduate student Kathryn Harper of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

http://www.nature.com/nature/journal/v540/n7634/fu...

And..

http://www.sciencedirect.com/science/article/pii/S...

Though the finding of microinvasion at the stage of ADH may not apply to all patients with breast cancer, the detection itself of disseminated cancer cells in DCIS suggests that conventional histopathological analysis may miss tumor spread in human cancer as well. Although very rare, metastasis in DCIS patients has been observed despite complete resection of their mammary tissue (Cutuli et al., 2001). Other well-known clinical findings, such as cancer of unknown primary (van de Wouw et al., 2002) as well as inadvertent transfer of cancer with organ transplants from donors with small undiagnosed malignant lesions (Riethmuller and Klein, 2001), are equally consistent with early dissemination and potential metastatic outgrowth.

These findings may also explain why people have recurrences down the roadeven after a masectomy.

Beesie

Manipulations in a Petri dish and with mouse models are a long way from definitive science. These scientists are testing out hypotheses. They are many years and many tests away from proving that any of this actually happens in the same way within the human body. The rate of successful translation from mouse models to human clinical cancer trials is less than 8%.

The fact remains that anywhere from 97% to 99% of women diagnosed with DCIS survive long-term and of those who don't, almost all have an in-breast invasive cancer event prior to the discovery of mets. All the studies and hypotheses in the world won't change these facts. Are there some unexplained cases of mets? Yes, but these are extremely rare, representing a fraction of a percent.

coastalaggie, I don't mean to be rude, but at this point I have to ask... why are you so intent on making your diagnosis of DCIS out to be worse than it is? It's not that a diagnosis of DCIS isn't scary and concerning - of course it is - but DCIS, when properly treated, has the best possible prognosis. From reading many of your posts, it seems that you have been putting a lot of time and effort into finding every possible worst case scenario. A diagnosis of DCIS comes with a lot of unknowns. But so does life. And as a woman, and yes, even a woman diagnosed with DCIS, you are actually about 4 times more likely to die of heart disease than to die of breast cancer. The good news however is that a recent study showed that woman diagnosed with DCIS actually have a lower overall mortality rate (over a median timeframe of 10 years) than women never diagnosed - this may be because a diagnosis of DCIS is highly survivable and leads to a greater awareness of good health and the development of healthy habits.

BarredOwl

Hi Coastalaggie:

Your source noted: "The clinical relevance of these cells has to be further evaluated." However, you then remarked: "It certainly raises your risk if they are there though." Did you find any publications that demonstrated that the identification of CTCs is associated with a statistically significant increase in the risk of metastatic recurrence in patients with a final diagnosis of Stage 0 disease (pTis(DCIS))?

From your original post, it seems like you would like to "rule out mets" in the setting of DCIS (assuming that will be your final pathologic diagnosis). Current metastatic disease is diagnosed by imaging and biopsy (where feasible).

Others have noted issues regarding the clinical validation of CTC tests in the diagnosis of current metastatic disease. For example, per this late 2015 article, the CellSearch test (Janssen Diagnostics) "can detect one or more CTCs per 7.5mL in most (~70%) but not all patients with overt metastatic disease. . . " In other words, a "negative" test result does "rule out" overt metastatic disease. In addition, the most sensitive circulating tumor DNA detection tests "remain currently unable to detect a micrometastatic dissemination . . ." So, a negative test result does not rule out disseminated tumor cells either, which can reportedly be found elsewhere (e.g., bone marrow) per the Sänger et al. (2011) reference cited in the text you posted above.

In the case of a positive CTC test result (the clinical relevance of which is not clear), presumably you would pursue additional diagnostic scans and tests.

Given the above limitations of either a positive or negative result by CTC testing, should an asymptomatic DCIS patient seeking to rule out mets request whole-body scans?

The chance of detectable distant metastases in such cases is remote. Yet as is often the case when you scan someone, possible areas of concern are found, necessitating biopsy (if feasible) of potentially benign lesions.

Nor do clearly negative scans eliminate the possibility of future distant metastatic recurrence. While whole-body scans are used in the diagnosis of metastatic disease, they are NOT currently capable of detecting micrometastases at distant sites, which if present (e.g., due to misdiagnosis of in situ disease; due to occult invasive disease) could lead to later distant relapse.

Re: "I don't understand why they don't do at least the blood work just to rule out mets because there is a possibility you have mets but it slipped under the radar?"

Neither CTC testing nor scans are performed as a matter of routine, primarily because the possibility of finding detectable distant metastases in an asymptomatic person recently diagnosed with pathologic Stage 0 disease (pTis(DCIS), Nx or N0) is pretty remote. Secondly, with CTC testing, negative results may not rule out mets or any dissemination of tumor cells, and positive results could lead to unnecessary whole-body scans and biopsies (with attendant risks). With over 50,000 cases of DCIS diagnosed annually in the US, neither CTC testing nor whole-body scans are recommended under current clinical consensus guidelines in asymptomatic individuals.

The odds are in one's favor. One observational study of 108,196 women with DCIS (diagnosed from 1988 to 2011) in the SEER18 database (which covers approximately 28% of the US population (based on the 2010 Census)), there were 956 women who died of breast cancer in the follow-up period (with and without documented invasive diagnosis of recurrent or new ipsilateral or contralateral disease). The mean (range) duration of follow-up was 7.5 years (Range: 0 to 23.9 years).

BarredOwl

[Edited in several places]

Susug

I will have to say what is concerning to me is the conception that DCIS is not cancer. Ductal CARCINOMA (cancer) in situ Is treated with radiation. Why would any doctor treat a patient with radiation if it isn't cancer?i don't think coastlaggie is trying to make it more that it is. She is being realistic. All this malarkey about telling someone DCIS isn't cancer is misleading haven't updated my DX DCIS r breast treated with radiation

candles1

DCIS is, in my opinion, a very serious disease that nobody should take lightly. But I'm not sure that radiation is only used to treat cancer. I think radiation is used to treat many types of tumors and conditions, including benign ones. So, you can't call something "cancer" just because it's treated with radiation.

Not saying DCIS is - or isn't - cancer. Just saying I don't think radiation treatment is the deciding factor.

MelissaDallas

I was referring to the fact she said her friend had stage 4 mets with her LCIS. LCIS is not cancer and she didn't get mets from LCIS.

Nobody said DCIS wasn't cancer. There is a big difference between the conditions.

Bright55

hi everyone ..i have been following your posts...there are a few of us who were diagonsed with DCIS and have gone on to develop Mets. Most medico say this is rare ..just bad luck..

For me ..There was no lymph node involvement so this the mystery as it wasnot thought to be of mets concern.

just read some medical papers that also considered the presence of comedo necrosis as a maybe cause for micro mets tranference and time given was 4/12 years...this was the time lapse for mine being picked up on CT scan the lung biopsy showed development of mets

Generally protocol herein australia did not have test for Her status or octoype score when i was first diagonised

All i can say is that Dcis is a gray area for predicting its reoccurance at mets

I could recommend that ct scan be done after 3 yers

generally only followup mammograms are done on remaining breast

Different maybe if i had had been on AI if i had a lumpectomy..but i had a mastectomy

As the name says ductal carcinoma it is a cancer but is usually O labelled as a stage

Susug

I would NEVER agree to radiation to a "pre-cancer" this is SO MISLEADING!!! I have never heard of anyone having radiation to treat a benign tumor. So many patients have MX with DCIS. My BS told me patients are told this isn't cancer and it's wrong. I think some doc will keep an eye on some stage 0 but not with the most aggressive one.

Susug

I would NEVER agree to radiation to a "pre-cancer" this is SO MISLEADING!!! I have never heard of anyone having radiation to treat a benign tumor. So many patients have MX with DCIS. My BS told me patients are told this isn't cancer and it's wrong. I think some doc will keep an eye on some stage 0 but not with the most aggressive one.

Bluebirdgirl

Bright55, that is scary as hell. I'm so sorry that has happened to you!! I had grade 3 with comedonecrosis and it scares me that somehow maybe some cells traveled! I had a recent scare with a lesion found accidentally on my liver. 3 cat scans later and 1 PET scan and 1 ultrasound and they are "pretty sure" it is a benign hemangioma. I retest in 6 months to a year. It really bothers me to think what if they are wrong and it is NOT a hemangioma? I try not to obsess about it.

Good luck to you. Hugs.

MinusTwo

I had DCIS. I had biopsies, blood work, CT scans & a PET. Diagnosed ER/PR negative. Then I had a BMX. Obviously no other treatment since it was DCIS for crying out loud. Then more CT's & more blood work including cancer antigen tests for the next two years.

Exactly two years later there was a lump under my collar bone. It was not called METS. It was called a "local recurrence". Well, whatever, the BS and MO were astounded since I originally had clear margins & SNB on both sides with everything clean during surgery. They don't test for HER2 with DCIS, but now they found not only was it HER2+, but it had morphed to IDC. So chemo with no pCR, then ALND surgery, then more chemo, then rads.

It doesn't really matter to me what the new label is for DCIS. II still believe it's cancer. And it still came back. The docs think maybe a stray cell escaped before the original surgery. WTH . Again... it's still cancer whatever they want to call it this year.

Susug

MinusTwo - so sorry you had to go through this. I agree with you about what they want to call it. I had IDC in left Brest in 2014. I'm more worried about the DCIS that I had in my right breast in 2016.