“This is exploring the landscape of cancer genomics,” said Dr. David P. Steensma, a leukemia researcher at the Dana-Farber Cancer Institute who was not involved with the studies. “Many developments in medicine are about treatments or tests that are only useful for a certain period of time until something better comes by. But this is something that will be useful 200 years from now. This is a landmark that will stand the test of time.” 
 
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 Dr. Douglas Levine of Memorial Sloan Kettering Cancer Center, the principal investigator on the endometrial cancer study, said the group scoured the country for samples of this cancer. 
 
 The cancer has long been evaluated by pathologists who examine thin slices of endometrial tumors under a microscope and put them in one of two broad categories. But the method is not ideal. In general, one category predicts a good prognosis and tumors that could be treated with surgery and radiation, while the other holds a poorer prognosis and requires chemotherapy after surgery. But pathologists often disagree about how to classify the tumors and can find it difficult to distinguish between the two types, Dr. Levine said. 
 
 The new genetic analysis of hundreds of tumors found patterns of genetic aberrations that more precisely classify the tumors, dividing them into four distinct groups. About 10 percent of tumors that had seemed easily treated with the old type of exam now appear to be more deadly according to the genetic analysis and would require chemotherapy. 
 
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 Another finding was that many endometrial cancers had a mutation in a gene that had been seen before only in colon cancers. The mutation disables a system for repairing DNA damage, resulting in 100 times more mutations than typically occur in cancer cells. 
 
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 “That was a complete surprise,” Dr. Levine said. 
 
 It turned out to be good news. Endometrial cancers with the mutation had better outcomes, perhaps because the accumulating DNA damage is devastating to cancer cells. 
 
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 Another surprise was that the worst endometrial tumors were so similar to the most lethal ovarian and breast cancers, raising the tantalizing possibility that the three deadly cancers might respond to the same drugs. 
 
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 Jeff Boyd, executive director of the Cancer Genome Institute at Fox Chase Cancer Center, who was not involved with the new research, said the similarity among breast, ovarian and endometrial tumors was the best example yet of the idea that cancers are more usefully classified by their gene mutations than by where they originate. Though many scientists believe this view is correct, Dr. Boyd said, “It is very rewarding — I can’t overstate it” to see it validated with real data. 
 
 While the genetics of endometrial cancer had gone largely unstudied until now, acute myeloid leukemia has been investigated for decades, in part because leukemia cells are so accessible. They are in the blood and bone marrow. 
 
 Using microscopes and special staining methods, researchers had already discovered, for example, that chromosomes in these leukemia cells are often broken or hooked together in strange ways. They also knew that some chromosomal alterations were associated with a good prognosis, and others with a bad one. Patients with a good prognosis can usually be treated with chemotherapy alone while those with a worse prognosis need the expensive, difficult and risky treatment of last resort: a bone marrow transplant. It comes with a 10 percent death rate. 
 
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 The problem was that the traditional methods for categorizing the leukemia were imprecise, said Dr. Timothy Ley of Washington University in St. Louis, who led the study with Richard Wilson, also of Washington University. Nearly half the acute myeloid leukemias had normal chromosomes. There was no good way to decide which treatment these patients needed. Some did well with chemotherapy; some did poorly. 
 
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 “It was a huge conundrum,” Dr. Ley said. “For patients who cannot be cured with chemotherapy, we have a potentially curative therapy. But picking the right patients for a transplant was very difficult.” 
 
 The new study of 200 acute myeloid leukemias identified at least 260 genes that were mutated in at least 2 of the 200 leukemia samples, finding virtually all of the common genetic malfunctions that occur in it. Now researchers have a new foundation for assessing which cancers will be lethal unless the patient gets a risky bone marrow transplant and which can be treated with chemotherapy alone. 
 
 “We have the basic playbook,” Dr. Ley said. “We finally know what the major pathways are and what all the major mutations look like.” And knowing which genes are mutated also allows researchers to investigate drugs that target those genes. 
 
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 The next step will be for investigators to determine which mutations lead to good or bad outcomes. 
 
 “Within two or three years, risk assessment may be dramatically better,” Dr. Ley said. “It certainly sets the stage for the next era of therapy.” ||||| Photo Advertisement Continue reading the main story 
 
 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, published online on Sunday in the journal Nature, 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 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. 
 
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 “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.” 
 
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 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 in the deepest layer of the skin. These breast cells form a scaffolding for milk duct cells. This type of cancer is often called triple negative and accounts for a small percentage of breast cancer. 
 
 But researchers found that this cancer was entirely different from the other types of breast cancer and much more resembles ovarian cancer and a type of lung cancer. 
 
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 “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.” 
 
 There are immediate therapeutic implications. The study gives a biologic reason to try some routine treatments for ovarian cancer instead of a common class of drugs used in breast cancer known as anthracyclines. 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. 
 
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 Basal-like cancers are most prevalent in younger women, in African-Americans and in women with breast cancer genes BRCA1 and BRCA2. 
 
 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 these cancers into two distinct types. Patients with luminal A cancer had good prognoses while those with luminal B did not, suggesting that perhaps patients with the first kind of tumor might do well with just hormonal therapy to block estrogen from spurring their cancers while those with the second kind 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 vast 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.” ||||| A massive gene-hunting effort involving hundreds of scientists has identified 74 newly discovered regions of DNA that are associated with breast, ovarian and prostate cancers — diseases that strike about half a million Americans every year. 
 
 The international project, known as the Collaborative Oncological Gene-environment Study, or COGS, nearly doubled the number of genetic markers known to be linked with the three cancers, scientists reported Wednesday. Their findings could lead to more effective ways to screen, study and treat these diseases. 
 
 "While these papers may not be what the average person is looking for — e.g., a cure for cancer — they have important near-term value" for medical researchers, said John Witte, an epidemiologist at UC San Francisco and co-author of a commentary on the work that appeared in Nature Genetics, one of five journals that published 13 studies detailing the COGS results. Witte was not a member of the collaboration. 
 
 For the last decade or so, cancer researchers have been working hard to ferret out the DNA changes associated with cancers and other common afflictions. They examine the DNA of large groups of people with and without certain diseases to see if any genetic variations can be linked to particular conditions. 
 
 One hope has been to pinpoint the people at highest risk for developing health problems. Another has been to identify the individual genes that cause illness in the first place so that scientists can better understand how those genes cause harm and use that information to develop better treatments. 
 
 But the work has been difficult because many of the variations linked to diseases are turning out to be more rare than scientists had originally thought, said Harvard Medical School genetics professor Raju Kucherlapati, who was not involved in the COGS group. 
 
 By examining hundreds of thousands of locations on the genome in 250,000 people with and without cancer, the COGS study was able to reveal more associations than smaller studies could. In addition to confirming many genetic markers that had already been found, scientists discovered 41 new regions linked with overall risk for breast cancer, three associated with overall risk for ovarian cancer and 23 tied to overall risk for prostate cancer. 
 
 Researchers also found additional variations linked to subtypes of breast and ovarian cancer, and noted that 16 of the new regions associated with prostate cancer were linked to aggressive forms of the disease. 
 
 Generally, the risks associated with the genetic changes were modest — about 10% to 20% more than the small risks faced in the general population. 
 
 To put that in perspective, Kucherlapati said, more than half of women who have the most dangerous mutations in the BRCA1 and BRCA2 genes will develop breast cancer during their lives. 
 
 But relatively small increases in risk can add up to become significant, said geneticist Rosalind Eeles of the Institute for Cancer Research in Sutton, England, co-author of a study in Nature Genetics that detailed the prostate cancer findings. 
 
 In Eeles' paper, men who fell in the top 1% of risk were nearly five times more likely to develop prostate cancer than the rest of the men in the study. (According to the National Cancer Institute, 16% of American men will be diagnosed with prostate cancer in their lifetime.) Perhaps targeting such men for additional tests could improve screening, Eeles and her co-authors wrote. 
 
 Scientists said that looking for the small genetic changes — known as single nucleotide polymorphisms, or SNPs — in people who are already at high risk for disease could help physicians' early detection efforts. 
 
 "If you have a family history, the SNPs can improve the risk estimate," Eeles said, adding that much more research is needed before SNP screening would be ready for use. 
 
 In the meantime, both Witte and Kucherlapati said the COGS findings could help scientists study the genes that cause cancer, as well as other biological aspects of the disease. 
 
 The new data also underscore how much scientists still haven't figured out about how the genes we inherit contribute to our cancer risk. 
 
 For instance, it is thought that there are more than 1,000 genetic regions associated with breast cancer. Yet only 76 common variants have been identified so far, University of Cambridge cancer researcher Douglas Easton and co-authors wrote in one of the studies published in Nature Genetics. 
 
 In all, the scientists said, about a third of the variants believed to be associated with the three cancers had been discovered. 
 
 What explains the remaining two-thirds is "obviously" the $64-million question, Easton said. 
 
 eryn.brown@latimes.com
– Two major studies of common cancers have zeroed in on the particular gene mutations associated with both, a breakthrough that could lead to better treatment for those with acute myeloid leukemia and endometrial cancer, reports the Boston Globe. But the studies also lend credence to a broader idea: that our traditional way of defining cancer by the organ in which it originates is outdated, reports the New York Times. Instead, it might be time to start thinking of cancer in terms of genetic mutations. In the latest studies, for example, researchers were surprised to discover that the worst endometrial tumors of the uterine were remarkably similar to the worst forms of breast and ovarian cancer. That raises "the tantalizing possibility that the three deadly cancers might respond to the same drugs," writes the Times' Gina Kolata. This emerging approach is called "precision medicine," notes the Wall Street Journal. The theory has been around for a while, but the new research under the sprawling Cancer Genome Atlas project seems to validate it. "It is very rewarding—I can't overstate it," says one expert not affiliated with the work.