interesting article about cancer - catastrophic burst

minxie

http://www.nytimes.com/2011/01/11/health/11cancer.html?_r=1&ref=health 

last paragraph sure sounds like triple negative

Titan

minxie..I can't seem to access that?  basically, what does it say?

squidwitch42

minxie,

 Very interesting article.

Titan, I googled NYT cancer catastrophic burst and it brought up the article and other publications carrying it. The end of the article mentions this theory could give an explanation as to why one might have a normal mammogram and then shortly thereafter have abnormal/cancer.

Thanks for keeping the info flowing!

LRM216

Wow, thanks, Minxie.  Sure would also explain why we get so many new members every single dang day.  It truly is like breast cancer has just burst wide open and it attacking so many females, no matter what their age in life.  Thanks for sharing.

minxie

Here's the whole article, hope it is allowed to post it in its entirety here:

Cancer Can Develop in Catastrophic Burst
By NICHOLAS WADE
Published: January 10, 2011
NY Times

New rapid methods of decoding DNA have brought to light a catastrophe that can strike human cells: a whole chromosome may suddenly shatter into pieces.

If the cell survives this disaster, something worse may ensue: the cell becomes cancerous.

The finding marks a striking exception to the current theory of how cancer develops. Cells are thought to become cancerous over many years as they collect, one by one, the mutations required to override the many genetic restraints on a cell's growth. It now seems that a cell can gain all or most of these cancerous mutations in a single event.

The discovery is reported in the current issue of Cell by a team led by Peter J. Campbell of the Sanger Institute near Cambridge, England.

The institute is part of a consortium with the National Institutes of Health in the United States to study the genomes of different types of cancer cells, a task now brought within reach because of fast and cheap methods for decoding DNA. The hope is to identify the causative mutations that drive each type of cancer.

As part of this project Dr. Campbell, a hematologist, was scanning the genome of 10 patients with a certain kind of leukemia. Cancer cells lose control of their chromosomes, and their genomes are often a chaotic hodgepodge in which the chromosomes are rearranged, with some segments duplicated and others lost. In one of his patients, Dr. Campbell noticed an unusual feature: almost all of the damage was confined to a single chromosome.

By reconstructing the exact pattern of chromosomal rearrangements, he and colleagues found it could not be explained by the standard process in which one mutation is acquired after another in a protracted series. Rather, the chromosome must have shattered into pieces in a single event; the cell then knitted them together as best it could, but in the wrong order.

Usually a cell that suffers this much damage will destroy itself, either immediately or after it has tried unsuccessfully to repair its chromosomes. But in certain cases, the self-destruct mechanism evidently fails, leaving a cell like Frankenstein's monster, with badly patched-up chromosomes but a survival advantage that leads to unrestrained growth.

Dr. Campbell's group reports that about 2 percent to 3 percent of all cancers, and 25 percent of bone cancers, originate in this kind of chromosome-shattering crisis.

"It's very hard to explain why the damage is so catastrophic but so localized," Dr. Campbell said, referring to the fact that almost all the damage occurs in a single chromosome or chromosome region. His best guess is that the damage is caused by a pulse of radiation.

Bone cancer is sometimes treated with radioactive isotopes that home in on the bone, which might explain why so many cases of bone cancer arise this way.

But Matthew Meyerson and David Pellman, two cancer biologists at the Harvard Medical School, say in a commentary that the chromosomes could shatter accidentally when they condense, a process that happens before the cell divides. Whatever the cause of the shattering, the finding "reveals a new way that cancer genomes can evolve," they write.

The discovery has no immediate implications for therapy. But it could explain why a few cancers, contrary to the usual rule, appear very suddenly. "There are clearly examples where someone has had a normal mammogram, then presents shortly after with an aggressive tumor," Dr. Campbell said.

Titan

Thanks Minxie!  Curious about the bone cancer/rads thing..did you read it? Why wouldn't you have rads after the bone cancer is discovered..or am I missing something?

That's scary stuff about the Frankenstien thing..what causes the cell to mend itself incorrectly..is it our immune system?  It just freaks me out that our cells may be doing this and we don't know what to do to stop it.

minxie

Titan - the bone cancer thing confused me too. I think they're saying radiation affect bone in a worse way? I know when I started my rads, they did say a possible SE was cancer in muscles/bone 20 years or so down the road.

I had a clear mammo, and 20 months laters, a 1.2 cm tumor. My BS looked over the old mammo quite thoroughly and said there was not a single sign of cancer, no calcifications, nothing. Very scary how it just came out of nowhere.

LRM216

Minxie -

Same here - only difference between your stats and mine is that I had no node involvement.  I have had mammos every year since 40 (for no reason other than we were "supposed" to).  No cancer whatsoever in either side of my family.  I missed my 2008 mammo due to my daughter's being seriously ill and hospitalized, and with never even a call back, decided I'd be ok to just wait until Feb of 2009.  Viola!  1.2 cm IDC triple neg. They checked all my mammos back to 2005 and saw absolutely nothing.  I guess in the 24 months in between mammos, this grew and seeing how fast some gals grow (TN) in a way I'm surprised it was only 1.2 cms.  Some gals had mammos and 3 months later had a TN 3.0 cms!  This is just such scarey stuff.

forgot to add that at diagnose I was just 62 by two days (nice birthday gift!) so I didn't even have the "youthful" factor to deal with.

lrr4993

I don't see how this explains sudden appearing cancers.  The exploding gene would still have to replicate and grow into a tumor.  They are not saying that millions of cells do this at the same time are they?

This is my theory on the clear mammo/sudden tumor phenomenon:  High grade, fast growing tumors can double in size as quickly as every 30 days . . . on average every 60 from what I have read.  Thus, it can go from .25 cm to 2 cm in 4 - 8 months.  The former is probably easily missed by mammo.  Not to mention that, from what I am learning, mammos are not terribly reliable, generally speaking.  I do not think these things can possibly grow from a single mutated cell to 1-2 or more cm tumors in a matter of months.  I think it is just physically impossible from what I have read.

My tumor popped up out of no where.  I was 39 so had not yet had a mammo.  It had a 98% proliferation rating, meaning that almost every cell was duplicating.  This makes me think that mine probably doubled in size almost overnight, which is when I noticed it.  It went from an undetectable 1 cm to a very palpable 2 cm.  So glad they got it out of me before it doubled again.  

Titan

I had a clear mammo in Aug. 08..found the lump in January..09. We are talking 6 mos...had the lumpectomy in March and it was a 1.8 cm tumor..oh yeah..these things grow quickly..I still wonder if I would have moved a little more quickly on the mammo/ultrasound instead of waiting if it would have been smaller..guess I will never know.

Linda..I was 49 at diagnosis...so not exactly youthful either...my co-worker was in her early 50's and she is tn...(7 years out and doing great by the way)...

I know that triple negative is predominately asian, Jewish, young (as in 30's, early 40's) and African American...but it sure seems to me that alot are in the late 40's and 50's and 60's and Caucasian.

lrr4993

Titan - I wonder the same thing.  I found my lump in mid June.  I immediately called to make an appt with my gyno, but could not get in until late july.  I had to cancel the late july appt due to work.  Instead of waiting another month to see my gyno, I asked them who they would send me to for a suspicious lump and they gave me the name of the woman who was eventually my surgeon.  I was able to get an appt with her within a week, had an ultrasound that day, and my first mammo and biopsy within a week.  So, that was a delay of approximately 1 1/2 months between finding it and confirming by ultrasound that it was not a cyst (which is what I thought and my BS thought from touch).  

I was convinced that it grew during that time because I could find it much easier than I could at first.  But it is hard to say.  It may have been that I just knew it was there and so it was easier to find.  I often wonder if it would have been a slightly less scary 1 cm tumor (it was 2 cm by ultrasound and the same post op) if I had pushed for a quicker appointment in the beginning.  But I was so young (39) and no family history of BC, I had no reason to really be overly concerned . . . kind of odd to say that looking back now.  

LRM216

I wish there was a way to stop wondering just "when" the tumor began.  I will never know whether or not my 1.2 cm would have been found earlier had I not missed that 2008 mammo, and might just have been only DCIS back then (since I had a small amount of that in two magins, which were reexcised and came back clean after first lumpectomy).  Mine was 5 cms. below my nipple, so it was never palable.  I thank God I went in 2009 for that mammo, since that was how they found it.   Also, in August of 2008, I fell down a set of bleachers (they were wet and I had sneakers on) and the only thing that stopped by fall was the metal fencing separating the bleachers from the football field. I landed so hard on my chest, but the right breast took most of the impact, and I fractured two ribs at the same time.  I will ALWAYS wonder if that had anything to do with this "out of the blue" cancer that was diagnosed.  Again, another thing I will never really know.

lrr4993

I know LRM - there are so many questions with no answers.  How long has it been there?  What made it start?  What caused it to grow so quickly?  Why is it so high grade?  It drives me nuts.  I am a problem-solver by nature.  I absolutely hate any situation that I cannot rationalize and solve through reason.  Grrrr.

It is hard to understand how to prevent it from happening again when no one can give you in any information on why it happened to begin with. 

thenewme

Wow, this is a really interesting find - thanks for sharing, Minxie!

Here's a link to the Cell article - very technical, but it's also fascinating!  

http://download.cell.com/mmcs/journals/0092-8674/PIIS0092867410013772.mmc7.pdf

My tumor appeared overnight too, and noticeably grew to 5-cm between diagnosis and surgery!  My ki-67 was 100%, so that explained the fast growth.  LRR493 - yours was 98%?  It sounds like your course was a lot like mine - I always sort of thought of it as a "big bang theory,"and this article seems to confirm the possibility!  Yikes! 

LRR493, if your tumor was literally exploding like mine was, I'm curious why you think it would be impossible to grow from a single catastrophically shattered cell into a measurable tumor within a few months? I was diagnosed at 39 also, before my first mammogram, so I have no confirmation that there was no tumor present earlier, but I know how fast I felt it growing, despite my doctors assuring me "oh no, it's probably been growing for years...they don't grow fast enough to feel them...it's probably swelling from the biopsy that you're feeling...etc" 

When I first felt it, it felt round, hard, and flat like a thick nickel or something.  I felt it growing bigger and bigger.  A sinus infection delayed my surgery, but it was a 5-cm ball of exploding cancerous gunk just 6 weeks later!   Ugh. 

I wonder if the proliferation rate has to do with how jumbled up the pieces are when the body frantically tries to fix it and gets into a frenzy trying to repair/duplicate it.  I guess mine was all mixed up, backwards, sideways, inside out, and probably even spinning, LOL!  

They theorize that this only happens in approximatel 2-3% of all cancers, but triple negative seems to fit the characteristics, and TN accounts for 15% of all breast cancers.  So, who's a math whiz?  Does 15% of all breast cancers correlate to 2-3% of all cancers?  

When I read studies like this, I wish I could donate my tumor, blood samples, tissue samples, whatever - to them to study me - now!  I'd gladly contribute some of my anomalous self to research!  Where do I sign up?

lrr4993

thenewme -  I am not basing my theory on any science, just very basic math and few bits of info I have read here and there.  I could be completely way off base, trust me.

However, if a 2 cm tumor (mine was just under that) has 2 billion cancer cells in it, which is what I have read, then it it takes a mathematically certain number of doublings to get from a single cell to a 2 cm tumor.  I have read that the fastest growing cancers replicate about every 30 days, with the average for high grade, fast cancers being about every 60 days (slower ones can take over a year to double). Just dividing by 2 (for the doubling of the cells by replication) backward each month, it would take 4 months to go from approx. 1/2 cm to 2 cm.  I am guessing (but don't know) that tumors under .5 cm are easily missed on mammos.  Indeed, it seems that mammo often miss tumors larger than that. 

I seem to remember reading somewhere that to go from a single cell to either 1 cm or 2 cm (can't remember which) takes about 30 doublings. . . or 30 months at a minimum for the fastest of tumors. 

Even with my very high Ki67, my tumor did not grow between my ultrasound and surgery, which was about 20 days.   

This also explains why you can have clear scans following treatment but then suddenly find yourself at stage 4 three or four years later. . . that one rouge cell takes that long to develop into a detectable and/or symptomatic tumor.  

It just makes sense to me, but again, I could be completely wrong. The specialists have no idea on these sorts of details - Lord knows I don't either.