NYT article--divide and conquer breast cancer--more than one type of her2+ bc(sound

[Lani]

famiiar?)


Genetic Study Divides Breast Cancer Into 4 Distinct Types
By GINA KOLATA
Published: September 23, 2012


In findings that are fundamentally reshaping the scientific understanding of breast cancer, researchers have identified four genetically distinct types of the cancer. And within those types, they found hallmark genetic changes that are driving many cancers.

These discoveries are expected to lead to new treatments with drugs already approved for cancers in other parts of the body and new ideas for more precise treatments aimed at genetic aberrations that now have no known treatment.

The study, published online on Sunday in the journal Nature, is the first comprehensive genetic analysis of breast cancer, which kills more than 35,000 women a year in the United States. The new paper, and several smaller recent studies, are electrifying the field.

“This is the road map for how we might cure breast cancer in the future,” said Dr. Matthew Ellis of Washington University, a researcher for the study.

Researchers and patient advocates caution that it will still take years to translate the new insights into transformative new treatments. Even within the four major types of breast cancer, individual tumors appear to be driven by their own sets of genetic changes. A wide variety of drugs will most likely need to be developed to tailor medicines to individual tumors.

“There are a lot of steps that turn basic science into clinically meaningful results,” said Karuna Jaggar, executive director of Breast Cancer Action, an advocacy group. “It is the ‘stay tuned’ story.”

The study is part of a large federal project, the Cancer Genome Atlas, to build maps of genetic changes in common cancers. Reports on similar studies of lung and colon cancer have been published recently. The breast cancer study was based on an analysis of tumors from 825 patients.

“There has never been a breast cancer genomics project on this scale,” said the atlas’s program director, Brad Ozenberger of the National Institutes of Health.

The investigators identified at least 40 genetic alterations that might be attacked by drugs. Many of them are already being developed for other types of cancer that have the same mutations. “We now have a good view of what goes wrong in breast cancer,” said Joe Gray, a genetic expert at Oregon Health & Science University, who was not involved in the study. “We haven’t had that before.”

The study focused on the most common types of breast cancer that are thought to arise in the milk duct. It concentrated on early breast cancers that had not yet spread to other parts of the body in order to find genetic changes that could be attacked, stopping a cancer before it metastasized.

The study’s biggest surprise involved a particularly deadly breast cancer whose tumor cells resemble basal cells of the skin and sweat glands, which are present in the deepest layer of the skin. These breast basal cells form a scaffolding for milk duct cells. Such cancers are often called triple negative but the study researchers call them basal-like.

Basal-like cancers are most frequent in younger women, in African-Americans and in women with breast cancer genes BRCA1 and BRCA2.

And, the researchers report, their genetic derangements make these cancers a much closer kin of ovarian cancers than of other breast cancers. Basal-like breast cancers also resemble squamous cell cancer of the lung.

“It’s incredible,” said Dr. James Ingle of the Mayo Clinic, one of the study’s 348 authors, of the ovarian cancer connection. “It raises the possibility that there may be a common cause.”

The study gives a biologic reason to try routine treatments for ovarian cancer — platinum drugs, for example — in basal-like breast cancer, the investigators said. And a common class of drug used in breast cancer, anthracyclines (adriamycin or epirubicin), might be dropped from the basal-like cancer treatment regimen because they do not increase help in ovarian cancer.

Anthracyclines, Dr. Ellis said, “are the drugs most breast cancer patients dread because they are associated with heart damage and leukemia.”

A new type of drug, PARP inhibitors, that seems to help squelch ovarian cancers, should also be tried in basal-like breast cancer, Dr. Ellis said.

Two other types of breast cancer, accounting for most cases of the disease, arise from the luminal cells that line milk ducts. These cancers have proteins on their surfaces that grab estrogen, fueling their growth. Just about everyone with estrogen-fueled cancer gets the same treatment. Some do well. Others do not.

The genetic analysis divided luminal cancers into two distinct subtypes. The luminal A subtype had good prognoses while luminal B did not, suggesting that perhaps patients with luminal A tumors might do well with just hormonal therapy to block estrogen from spurring their cancers while luminal B patients might do better with chemotherapy in addition to hormonal therapy.

In some cases, genetic aberrations were so strongly associated with one or the other luminal subtype that they appeared to be the actual cause of the cancer, said Dr. Charles Perou of the University of North Carolina, who is the lead author of the study. And he called that “a stunning finding.”

“We are really getting at the roots of these cancers,” he said.

After basal-like cancers, and luminal A and B cancers, the fourth type of breast cancer is what the researchers called HER2-enriched. Breast cancers often have extra copies of a gene, HER2, that drives their growth. A drug, Herceptin, can block the gene and has changed the prognosis for these patients from one of the worst in breast cancer to one of the best.

Yet although Herceptin is approved for every breast cancer patient whose tumor makes too much HER2, the new analysis finds that not all of these tumors are alike. The HER2-enriched should respond readily to Herceptin; the other type might not.

The only way to know is to do a clinical trial, and one is already being planned. Herceptin is expensive and can occasionally damage the heart. “We absolutely only want to give it to patients who can benefit,” Dr. Perou said.

For now, despite the tantalizing possibilities, patients will have to wait for clinical trials to see whether drugs that block the genetic aberrations can stop the cancers. And it could be a massive undertaking to get all the drug testing done. Because there are so many different ways a breast cancer cell can go awry, there may have to be dozens of drug studies, each focusing on a different genetic change.

One of Dr. Ellis’s patients, Elizabeth Stark, 48, has a basal-type breast cancer. She has gone through three rounds of chemotherapy, surgery and radiation over the past four years. Her disease is stable now and Dr. Stark, a biochemist at Pfizer, says she knows it will take time for the explosion of genetic data to produce new treatments that might help her.

“In 10 years it will be different,” she said, adding emphatically, “I know I will be here in 10 years.”

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About the Cancer Genome Atlas

The field of genomics is caught in a data deluge, as reported by Andrew Pollack of the New York Times (DNA Sequencing Caught in Deluge of Data, December 1, 2011). DNA sequencing is becoming faster and cheaper, but the result is that the ability to determine DNA sequences is starting to outrun the ability of researchers to store, transmit and especially to analyze the data.

“Data handling is now the bottleneck,” said David Haussler, director of the center for biomolecular science and engineering at the University of California, Santa Cruz. “It costs more to analyze a genome than to sequence a genome.”

That could delay the day when DNA sequencing is routinely used in medicine. The cost of determining a person’s complete DNA blueprint is expected to fall below $1,000, but that long-awaited threshold excludes the cost of making sense of that data, which is becoming a bigger part of the total cost.

“The real cost in the sequencing is more than just running the sequencing machine,” said Mark Gerstein, professor of biomedical informatics at Yale. “And now that is becoming more apparent.”

The lower cost, along with increasing speed, has led to a huge increase in how much sequencing data is being produced. There will probably be 30,000 human genomes sequenced by the end of this year alone, up from a handful a few years ago, according to the journal Nature.

In a few cases, human genomes are being sequenced to help diagnose mysterious rare diseases and treat patients. But most are being sequenced as part of studies. The federally financed Cancer Genome Atlas is sequencing the genomes of thousands of tumors and of healthy tissue from the same people, looking for genetic causes of cancer.

And DNA is just part of the story. To truly understand biology, researchers are gathering data on the RNA, proteins and chemicals in cells. That data can be even more voluminous than data on genes. And those different types of data have to be integrated. There are giant piles of data and no way to connect them.

There is now so much raw data that it is becoming not feasible to re-analyze it. So researchers will increasingly store just the final results. In the case of human genomes, they might store even less, only the difference between a particular genome and some reference genome.

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Dr. Len Lichtenfeld of the American Cancer Society wrote:

“It is important to recall that despite the fact this is incredibly sophisticated and difficult work, it is still reasonably early in our ability to perform the analyses, interpret the data, and determine the best way to apply it to the clinic. We still have a long way to go, and we must always remember that cancer has a way of being more complicated at every turn that we might otherwise anticipate as our research and our knowledge advances. But research such as this also puts more of the pieces of the puzzle of breast cancer together in a way that a solution to the dilemma of understanding breast cancer and how we can apply the best treatment does appear to be more readily at hand.

What is the most important message from this research?

Unfortunately, it is not going to change lives immediately. Your doctor isn’t going to give you a different treatment for your breast cancer today, tomorrow, or next week because of this research. There is no question that doctors involved in breast cancer treatment are going to take a very careful look at this research and determine the best way to apply this information to new approaches to breast cancer as quickly as they can, but that will still take time.

To me, the most important message from this research is to confirm what many of us have been thinking for some time now: we are seeing the fruits of decades—yes, decades—of hard work in the laboratory taking us to a point we are going to have a significant impact on patient care and the outcomes of treatment for cancer. At the same time, the very support for that research is in jeopardy due to decreases in government funding, business investment, and private philanthropy.”

http://acspressroom.wordpress.com/20...ncertypes2012/

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Mandy Stahre, PhD.
Breast Cancer Survivor

I sit here rolling my eyes as I hear the latest round of news stories touting a “breakthrough” or “cure” for breast cancer based on a recent Nature article. I’m not saying research isn’t important, but the media grasps onto any sort of advancement in basic science as the next sure thing for curing cancer. For many breast cancer advocates, myself included, the information contained in the recent Nature article is not new. Many of us have been attending conferences (alongside health journalists) in the past year in which these results have been presented. Missing from the media hype is the caution that an advancement in the knowledge or basic science does not translate into a change in treatment. Treatment for breast cancer will not change today, tomorrow, and possibly won’t change at all based on the recent findings.

Clinical trials, pharmaceutical companies, academic institutions, government agencies, these are just some of the players that must work together to test, approve, create, and market any sort of new treatment. It takes time, and unfortunately, reporting that new cures are just around the corner does nothing but give false hope to many cancer patients. Frankly, using the word “cure” with regards to cancer in health journalism should be a clear sign that the writer of the article doesn’t even possess a simple understanding of what it takes to develop new cancer treatments.

This recent media hype causes my cynical side to show. I can’t help it, this is what happens when you are diagnosed with cancer at a young age. October is fast approaching and with it, the “pink washing” of America. I can’t help but think the Nature study results splashed all over the media will be used as “proof” that consumers can make a difference in the fight against breast cancer, not by lobbying their congressmen to increase funding for breast cancer research, but by buying some awful Pepto Bismol-colored hand mixer. Frankly, if companies were interested in donating to help fight breast cancer, then why don’t they just donate the money anyway instead of making consumers buy a pink product? And in reality, did any pink product really help fund the current study described in Nature, probably not.

http://www.healthnewsreview.org/2012...news-coverage/