Big bang theory of cancer development

[Joan M]

From The New York Times, January 11:

Cancer Can Develop in Catastrophic Burst

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.

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This theory does make me wonder. One year my mammogram was okay. The following year I had two tumors in one breast (DCIS and infiltrating) that were HER2+ and 7 positive lymph nodes.

Joan

[Nancy L]

Very interesting and thanks for posting. Sounds like me too. They never did see my 7cm tumor on a mammogram. I had a clear mammogram at Stanford 8 mos before I was diagnosed.

[krisvell]

Joan,
This is a good article. Hope it doesn't take 20 years to do something with the new found knowledge. I too had a 5 cm tumor that come out of nowhere with a sh** load of positive lymph nodes just 10 months after getting my happy mamo letter saying all is good.
Kris....

[Rich66]

Mammos themselves don't seem to be enough in many cases. I think I read somewhere about a 30% false negative rate. Maybe the newer digital ones are better...

[Joan M]

Rich,

My mammo was digital, but I wonder whether a breast MRI would have shown the tumor sooner. I've never had that test.

Joan

[Hopeful]

Joan,

I posted this over in the articles forum when it was published, along with another article about Her2+ bc that made me think it was a "big bang" cancer:

http://her2support.org/vbulletin/sho...eferrerid=1173

Hopeful

[Becky]

I join your club with a clear mammo 7 months prior. HOWEVER, in my case (an unbeknowst to me) many of my mammogram full doctor versions said, "this patient has extremely dense breasts that are difficult to read", although there is no change in last year, we recommend MRI to rule out any unseen changes". This is not what you, the patient, gets from the mammo center. We get "no changes" and perhaps a birads reading. Prior to cancer, I did not ask or receive the full blown out version the prescribing doctor did. I get them now and don't go to that family practioner either as she should have sent me for follow up MRIs for 5 years running (as I got all my reports after bc and this density issue was always mentioned but no one ever told me)! So maybe there was something there 7 months prior that just couldn't be seen because of dense tissue - or it was a big bang. I too had a positive node.

[Jean]

Joan,
Great article! I had been having digital mammo's for five years prior to having been dx. with bc. I too had always had dense breasts and no one ever mentioned having an MRI (?) why not...six months after my mammo I had a pain deep in my arm pit and insisted on another digital mammo...6MM tumor was found.

Remember hearing firmly "Cancer does not hurt"
I wonder if this was the bang theory in my case? Will never know. I tell every woman today who has dense breasts to have a base line MRI done.

I now have MRI done every other mammo.

jean

[Joan M]

Jean,

Good advice about the MRI. I too have dense breasts (or now only one dense breast since the DIEP flap reconstruction), and perhaps my tumors were also missed due to density. The larger infiltrating tumor was 2.5 cm. I'm going to mention the MRI to my onc the next time I see her.

Joan

[Jackie07]

The theory affirmed my suspecion that I was 'poisoned' by the 'tar' used for roof repair in the college library where I worked.

My 'stable' brain tumors suddently enlarged 10 months later and breast cancer was found 2 1/2 year later - exactly the time frame my surgical oncologist estimated how long the cancer had been growing.

Reports on the cancer incidents of World Trade Center survivors and first responders seem to also confirm this 'Big bang' theory.

[caya]

Many of you know my story - I had a "clean" mammogram and breast ultrasound in July 2006 - 3 months later, Oct. 2006, I had a breast reduction, my plastic surgeon found my 1.7 cm. tumour - I have very dense breasts, apparently this was noted on previous mammos, unbeknownst to me.
I have a breast MRI every January on my remaining breast and a digtial mammo every June. As far as I am concerned, mammos are pretty useless for premenopausal, dense breasted women. The breast MRI is the ONLY way to go, IMHO - go straight to the breast MRI, and bypass the mammo. I know there can be false positives, but better than a false negative.
All the docs say that breast reduction saved my life...

all the best
caya

[StephN]

“There are clearly examples where someone has had a normal mammogram, then presents shortly after with an aggressive tumor,”

The above quote from the article makes my case quite clearly. Three months after a "normal" mammogram I found my lump.

My letters for 2 or 3 years citing my negative mammogram ALSO did include a mention of my dense breasts, thus my doc was ordering the mammos yearly. And I was occasionally doing my self checks ...

My primary tumor was quite small, but cancer was moving rapidly through my lymph nodes.

I always thought something happened other than a slow progression taking years for my cancer to develop.

[Trish]

I've always thought my lump ocurred very suddenly and grew rapidly. I'd had a thorough and unremarkable breast exam by my local doc in April and in May found a very hard, obtrusive lump. Pathologist reported a 3cm infiltrating ductal carcinoma with 16 of 18 lymph nodes containing metastatic ductal carcinoma with extracapsular spread to distance of 2mm . I still can't believe I hadn't noticed it before that fateful evening! I suspect a "big bang" occurred at some point. I still feel like an idiot for not noticing it earlier though.

[harrie]

Interesting article Joan. Thanks for posting.

[Chelee]

When first dx with bc I constantly heard that my tumor had been growing for yrs before we found it. I never once believed that...even if I'm wrong. Just as that article said, "mine appear very suddenly." Mammo's never picked anything up and I did BSE's often. It seemed like my tumor showed up over night...that fast. (I'm sure it wasn't quite that quick...but it sure seems like it.)

Thanks for sharing this article Joan...it's very interesting. I sure believe in this BB theory.

Chelee

[michka]

Same for me. I had a mammo less than a year before and a long exam by a doctor 3 months before without talking about my self exams. And my breast are Not dense. It was stated at every mammo. They use to tell me as a positive thing: "your breasts are very readable". This could also add to the big bang theory. And nobody ever suggested I do a MRI although I have a very bad family history. Michka

[StephN]

Regarding breast MRI.

This was a new technology and just in trial at the end of 2000, when I had my first ones. It was called Rodeo MRI and the software was brand spanking new.

I only got the MRI here as Dr. Connie Lehman was one of the few investigators.

They are not routine for me, but I have had one since to get a better look at something, which turned out to be a benign node.

My friend who lives on the outskirts of Paris started getting breast MRI around 2004 or 05. Don't know if she still has them.

It is a special table and you don't go into a tube like normal MRI.

[StephN]

Bringing this back up in case anyone else is interested or has comments.