Cancer Can Spread Even Before a Tumor Develops

cp418

http://www.mountsinai.org/about-us/newsroom/press-...

Researchers Reveal How Cancer Can Spread Even Before a Tumor Develops

ElaineTherese

Interesting about DCIS.... We normally think about DCIS as non-invasive and unlikely to coincide with metastasis. Thanks for posting!

KathyL624

I found this study really scary, but I guess that is why even us early stagers do systemic treatments like tamoxifen or AI's, to take care of any of these early, microscopic metastasis. In the end, though, does it come down to the biology of the cancer? The statistics show that many many people with early stage disease go on to live normal lifespans, so is it that in those people those traveling cells never get turned on at their distant sites?

Everytime I start to feel better about my situation, I read something like this study that makes me feel hopeless.

ElaineTherese

Kathy,

I'm assuming that it comes down to the biology of the particular tumor. I would also assume that since most women with early stage breast cancer have high survival rates, that this situation is pretty rare. Moreover, few of us develop cancer with an occult primary tumor. I see this article saying, yes, this can happen rather than yes, this is widespread.

CCS648

This happened with my father. He had bone and lung mets. They diagnosed cancer after his spine started collapsing, lung mets killed him, but they never found the primary.

wallycat

And I have to think our immune system plays some role. Decades before I got cancer, there were studies and stories about how all of us have cancer cells floating here and there and that our immune system can usually "clean up" any rogue cells. Maybe it is the same with this.

BarredOwl

I believe the studies profiled are (sadly, with full text behind a paywall):

(1) Harper (2016), "Mechanism of early dissemination and metastasis in Her2+ mammary cancer"

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature20609.html

(2) Hosseini (2016), "Early dissemination seeds metastasis in breast cancer"

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature20785.html

BarredOwl

lintrollerderby

Kathy, it shouldn't make you feel hopeless. Cautiously optimistic...maybe. Vigilant...perhaps. Hopeless...why?

MTwoman

Well it was scary to me too. Having had DCIS, completed active treatment phase and moved into life after . . . I guess I consoled myself with the data saying that my MX would (with 98-99% certainty) mean that I am in the clear (for the most part).

BarredOwl

I think these findings do not negate known statistical information about distant recurrence risk (e.g., the percentage that do not suffer a distant recurrence; the percentage that does).

These findings appear to speak to an underlying mechanism of metastasis that could explain some of the observed cases of distant metastasis, which we already knew about.

To say, "it can happen like this" (how) or to say, "this can happen earlier than we expected" (when), is NOT to say that the incidence of recurrent distant metastatic disease is greater than it has been shown to be in various clinical studies.

BarredOwl

MTwoman

Thanks, BarredOwl, I do understand where this information fits into the current literature. And I think it helps medical providers better understand where metastises can come from when there doesn't appear to have been a primary invasive cancer.

I was just speaking about my own emotional response when I finished the article and letting KathyL624 know that she isn't alone in hers. I was younger when I was diagnosed and treated, and so have had years to come to terms with it all. I do, however, go through times when I read something that stirs up my anxiety. I guess that it is my cancerversary may also be a factor.

KBeee

MT, I think that 98-99% of the women with DCIS are in the clear. This explains a mechanism for that 1-2% who see metastasis

marijen

Kathy I have/had an occult tumor also. I can understand how you feel, but I don't feel hopeless. I'm going to print the article for my oncologist and not worry about it. It is what it is. Forewarned is forearmed.

marijen

Now that I think of it, if cancer cells can stay dormant that this new information applies to everyone, right?

Kkubsky

this absolutely terrified me too. It's been a rough year since DCIS dx in January. Finally starting to get on with life after dealing with anxiety which morphed into food disorder, and then I read this. I already have been obsessive about recurrence rates but was able to deal with some of my fear by telling myself it is dcis-non invasive. Thankfully some of the above explanations have helped settle me down a bit but I kind of wish I never read the article.

zpw

Agree.

ChiSandy

Note that the article mentions the formation of the ductal system within the breast, using the word “embryogenesis.” So the very process that causes our breasts to develop (as early as pre-natally, and certainly as early as puberty) by turning those “stop & go switches” on & off to burrow into our breast tissues and form the milk ducts (the breasts’ raison d’etre) can also cause some of those cells to “go off the reservation” and travel elsewhere in the body—where they lay dormant for decades and may or may not wake up, regardless of whether tumors form. In other words, it truly is what it is and we need to realize that although our bodies are amazing machines and science is growing ever more sophisticated…we can’t control everything, whether by surgery, conventional treatments or unproven “alternative” therapies. Life is, and I suspect will continue to be, a mystery.

Could this also be that while they are both “carcinomas in situ,” DCIS is generally considered a cancer, whereas LCIS is not (and probably is a risk coequal with “atypical hyperplasia”)? Lobes are different in shape and function and are constructed by a different process than are ducts, and therefore the potential for going rogue is less? (And is it possible that because bronchioles, blood and lymph vessels are also hollow tubes and might be built in utero via the same "on-off" process as are mammary ducts, might we all have lymphoma or blood dyscrasia cells lying dormant in “distant outposts” from “day one,” even though we will probably never develop lung cancer, lymphoma or leukemia)?

Just because a cancer is “in situ” doesn’t mean it isn’t “cancer:” the earliest stage of malignant melanoma is “in situ,” confined to the mole itself without having penetrated beyond the skin. But the cytology of the in situ melanoma is exactly the same as one that’s penetrated below the dermis and to the sentinel nodes. It’s still malignant melanoma.

Beesie

ChiSandy, the National Cancer Institute doesn't agree with you.

What Is Cancer?

"An even more serious condition is carcinoma in situ. Although it is sometimes called cancer, carcinoma in situ is not cancer because the abnormal cells do not spread beyond the original tissue. That is, they do not invade nearby tissue the way that cancer cells do. But, because some carcinomas in situ may become cancer, they are usually treated."

From what I've read, the same "is it or is it not cancer?" debate that we have about DCIS is also going on with in-situ melanoma and other in-situ cancers.

Personally, while I was certain that DCIS was cancer (and outraged that anyone would suggest otherwise) 11 years ago when I was first diagnosed, the more I've read about it, and the further I get from my own diagnosis (and therefore as I become more objective and take it less personally), the less certain I am. It's not that I agree with the NCI and would say that DCIS isn't cancer, it's just that I now understand and appreciate the arguments on both sides of the debate.

wallycat

Just to hear myself think, I wonder if combining these thoughts could mean that any "invasive" breast cancer should really be called metastasis since it has left the original Dcis or Lcis location. Kidney cancer is kidney cancer unless it spreads elsewhere, same for lung cancer, brain cancer, etc...once it leaves the "origin" of development, don't we call it mets? So maybe my invasive lobular was really a mets from the lobule of my breast...?

solfeo

One thing that has stuck in my mind from my early research, was a doctor who was quoted in an article about mets as saying that all breast cancer is likely to be systemic at diagnosis, and should be treated as such. I wish I could remember who said it and where I saw it, but I know it was in a reputable place. What prevents it from turning on in some of us and not others is the great mystery.

BarredOwl

Hi ChiSandy:

I saw in another thread (link) that you mentioned that early embryonal ductal cells can spread to distant sites even before we are born, and "when they wake up [many years later] in distant organs and have the same biology as the original tumors they are metastases."

https://community.breastcancer.org/forum/96/topics/854009?page=1#post_4941145

I read the Mt. Sinai feature in this thread quite differently. I understood it to say that tumor cells are reactivating an embryonic gene program so they too can migrate.

I may be missing something completely (and it is frustrating that the original papers are behind a paywall), but I understand it to say that in a preclinical breast cancer model the activation of HER2 plus the inactivation of tumor suppressor p38 resulted in the aberrant transcription of a block of genes that conferred migratory capacity on the tumor cells. This migratory capacity can be used by the tumor cells to move through tissue into and out of blood vessels or lymph vessels, enabling distant metastasis, as seen by high resolution imaging in their animal model of adult breast cancer. In this context, cellular migration is abnormal.

Coincidentally, this same block of genes is normally transcriptionally active in normal embryonal breast cells, because migratory capacity is required for "movement of cells during embryogenesis and tissue development." In this context, cellular migration is a normal part of embryonal development of breast tissue. In my understanding, normal embryonal cells form ducts where none existed before in the extraordinarily choreographed and orderly process of human development. The cells are not moving to distant pastures. Then, as these embryonal cells differentiate into mature ductal cells in the breast, this block of genes is normally inactivated. Sadly, this block of genes, so useful in embryonic development, can be later reactivated for nefarious purposes.

During tumorigenesis, formerly mature normal differentiated breast cells acquire more and more genetic and cellular alterations over time, that can alter gene expression patterns and release the cells from controls on growth, confer migratory capacity, etcetera. The dogma had been that only "highly mutated" tumor cells that had accumulated many changes and new skills, relatively far along the continuum of tumor formation, were capable of distant spread. But based on their results in this model system, this group posits that only a limited number of genetic changes may be needed to confer migratory capacity on early tumor cells, suggesting that "dissemination and metastasis" might occur much earlier along the continuum of tumor formation than had previously been believed.

BarredOwl

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Edited to add:

It has been known for some time that tumor cells co-opt this embryonic "EMT" gene program.

Hanahan (2011): http://www.cell.com/cell/pdf/S0092-8674(11)00127-9.pdf

"The EMT Program Broadly Regulates Invasion and Metastasis

A developmental regulatory program, referred to as the ''epithelial-mesenchymal transition'' (EMT), has become prominently implicated as a means by which transformed epithelial cells can acquire the abilities to invade, to resist apoptosis, and to disseminate (Klymkowsky and Savagner, 2009; Polyak and Weinberg, 2009; Thiery et al., 2009; Yilmaz and Christofori, 2009; Barrallo-Gimeno and Nieto, 2005). By co-opting a process involved in various steps of embryonic morphogenesis and wound healing, carcinoma cells can concomitantly acquire multiple attributes that enable invasion and metastasis. This multifaceted EMT program can be activated transiently or stably, and to differing degrees, by carcinoma cells during the course of invasion and metastasis."

marijen

bump

illimae

Makes sense to me and would help explain why I felt a large lump that appeared out of nowhere and within 2 weeks of PCP check, mammo, US, biopsy, cancer was confirmed. 2 weeks after that bony scans revealed a bone met, so I went from perfectly normal to stage IV in less than a month.

marijen

Thanks for your comments Illimae, makes sense to me too.

Bright55

hi everyone yes this is a rare occurance some of us do develop mbc ..bad luck