Blood test to spot cancer gets big boost from J&J Handout image provided by PNAS Early Edition

shows the HB-Chip for cancer blood testing in Boston, Massachusetts. The inset shows the uniform blood flow through the device. The test works by identifying rare circulating tumor cells (CTCs) present in the bloodstream of patients with cancer. CANCER THROUGH TIME *2625 BC*: The Egyptian surgeon Imhotep describes a case of breast cancer. Under "therapy," he lists "there is none." *440 BC*: Greek historian Herodotus writes of a Persian queen, Atossa, who underwent perhaps the first mastectomy, when she asked Greek slave to cut out her breast tumor. *400 BC*: Hippocrates, the "father of medicine," coins the term "karkinos" crab to describe cancer. *160 AD*: Greek scientist Galen proposes that cancer is the result of trapped black bile, a hypothesis that would hold sway until the 17th century. *1761*: John Hill publishes /Cautions on the Immoderate Use of Snuff,/ proposing a link between snuff inhaled tobacco and lip cancer. *1775*: English surgeon Percival Pott notices a link between chimney sweeping and scrotal cancer. *1778*: English doctor John Hunter assigns stages to cancer. For early cancer, he recommends surgery; for late stages, "remote sympathy." *1811*: English novelist Fanny Burney undergoes a mastectomy without anesthesia or antisepsis and lives to write about it. *1847*: German doctor Rudolf Virchow coins the term "leukemia" to describe an overgrowth of white cells in the blood. *1860*: Austrian monk Gregor Mendel discovers genes units of inheritance in pea plants. *1867*: English doctor Joseph Lister invents the use of antiseptic methods in surgery. *1890-1900*: American surgeon William Halsted invents the "radical" mastectomy, removing not only the breast, but nearby lymph nodes and muscle. Some radical mastectomies even removed bone. *1903*: Polish scientist Marie Curie wins the first of two Nobel prizes for her discoveries about radiation. *1913*: Berlin surgeon Abraham Salomon uses mammograms to see breast cancer using X-rays. *1915*: American Thomas Morgan uses fruit flies to demonstrate that genes are carried on chromosomes *1928*: Herman Muller, Morgan's student, uses fruit flies to show that

X-rays increase the rate of mutations. *1929*: American biochemist Edward Doisy discovers the female hormone estrogen, which will later be found to play a major role in breast cancer. *1940-1945*: Saul Hertz, at Massachusetts General Hospital, uses radioactive iodine to kill thyroid cancer cells. *1945*: Activist and philanthropist Mary Lasker, the "fairy godmother of medical research," takes over the American Society for Cancer Control, turning it into a fundraising and lobbying machine. *1946*: Doctors use variants of mustard gas to kill malignant white cells. *1947-1948*: Boston doctor Sidney Farber uses successfully uses chemotherapy on children with leukemia, obtaining brief remissions. *1948-1950*: American and British researchers link smoking to lung cancer. *1952-1954*: George Papanicolaou finds a way to diagnose cervical cancer, leading the way to screenings that reduce deaths dramatically. *1955*: Philip Morris introduces the Marlboro Man, its most successful smoking icon to date, and sales of the brand shoot up by 5,000%. *1963-1968*: Americans Paul Carbone and Vince DeVita treat breast cancer with chemotherapy after surgery, increasing survival. DeVita and others go on to cure advanced Hodgkin's disease. *1964*: U.S. Surgeon General releases a landmark report on smoking and lung cancer. *1967*: British nurse Cicely Saunders founds the first hospice program to care for the terminally ill. *1968*: St. Jude's Children's Research Center reports a 60%-to-80% cure rate for acute lymphoblastic leukemia. *1971*: President Nixon launches the "War on Cancer" by signing the National Cancer Act. *1971*: Last cigarette commercial is broadcast on TV. *1971*: Di-ethyl-stilbestrol, or DES, a drug given to pregnant women to delay preterm delivery, is found to cause uterine cancer in their daughters. *1973*: While examining chronic myeloid leukemia cells, American scientist Janet Rowley discovers a new gene created by the fusing of chromosomes 9 and 22. This discovery paves the way for the creation of the drug Gleevec. *1976-1980*: American scientists Michael Bishop and Harold Varmus propose that cancer-causing genes are created through the distortion of normal genes found inside cells. *1977*: Doctor Bernard Fisher shows that tamoxifen treatment after breast cancer surgery increases survival for women with estrogen-sensitive cancer. *1979-1982*: American Robert Weinberg and others isolate cancer-causing

genes from cancer cells. *1981*: A landmark study shows that radical mastectomy performed on an estimated 500,000 women over the past 90 years, offers no benefit to the less invasive, "simple mastectomy." *1982-1984*: Australian researchers Barry Marshall and Robin Warren demonstrate that Helicobacter pylori, a bacterium, causes stomach ulcers and cancer. Marshall helped prove H. pylori's link to ulcers by swallowing a glass of it. *1988*: American scientist Bert Vogelstein proposes that cancer cells are created as the result of multiple genetic alterations. *1990*: Mary Claire-King identifies a genetic region that confers increased risk for breast cancer. This is eventually found to be the gene BRCA1. *1991 to 2003*: Doctors use an unproven and highly toxic combination of high-dose chemotherapy with bone-marrow transplants to treat breast cancer. More than 40,000 patients later, research eventually shows the therapy doesn't save lives. *1998*: The Food and Drug Administration approves Herceptin for breast cancer, the first man-made antibody to treat cancer, widely seen as the beginning of the new field of "targeted therapies." *2001*: FDA approves Gleevec, a drug based on Rowley's discovery, to treat chronic myeloid leukemia. Gleevec becomes a new ideal in cancer therapy, allowing patients to live symptom-free for years without major side effects. *2003*: Scientists complete the Human Genome Project, sequencing all the genes in the human chromosome. *2006-2009*: Scientists working on the "cancer genome" sequence nearly all the genes of multiple samples of breast, colon, ovarian and brain cancers. BOSTON (AP) A blood test so sensitive that it can spot a single cancer cell lurking among a billion healthy ones is moving one step closer to being available at your doctor's office. Boston scientists who invented the test and health care giant Johnson & Johnson announced Monday that they are joining forces to bring it to market. Four big cancer centers also will start studies using the experimental test this year. Stray cancer cells in the blood mean that a tumor has spread or is likely to, many doctors believe. A test that can capture such cells has the potential to transform care for many types of cancer, especially breast, prostate, colon and lung. Initially, doctors want to use the test to try to predict what treatments would be best for each patient's tumor and find out quickly if they are working. "This is like a liquid biopsy" that avoids painful tissue sampling and may give a better way to monitor patients than periodic imaging scans,

said Dr. Daniel Haber, chief of Massachusetts General Hospital's cancer center and one of the test's inventors. Ultimately, the test may offer a way to screen for cancer besides the mammograms, colonoscopies and other less-than-ideal methods used now. "There's a lot of potential here, and that's why there's a lot of excitement," said Dr. Mark Kris, lung cancer chief at Memorial Sloan-Kettering Cancer Center in New York. He had no role in developing the test, but Sloan-Kettering is one of the sites that will study it this year. Many people have their cancers diagnosed through needle biopsies. These often do not provide enough of a sample to determine what genes or pathways control a tumor's growth. Or the sample may no longer be available by the time the patient gets sent to a specialist to decide what treatment to prescribe. Doctors typically give a drug or radiation treatment and then do a CT scan two months later to look for tumor shrinkage. Some patients only live long enough to try one or two treatments, so a test that can gauge success sooner, by looking at cancer cells in the blood, could give patients more options. "If you could find out quickly, 'this drug is working, stay on it,' or 'this drug is not working, try something else,' that would be huge," Haber said. The only test on the market now to find tumor cells in blood ? CellSearch, made by J&J's Veridex unit ? just gives a cell count. It doesn't capture whole cells that doctors can analyze to choose treatments. Interest in trying to collect these cells soared in 2007, after Haber and his colleagues published a study of Mass General's test. It is far more powerful than CellSearch and traps cells intact. It requires only a couple of teaspoons of blood and can be done repeatedly to monitor treatment or determine why a drug has stopped working and what to try next. "That's what got the scientific community's interest," Kris said. Doctors can give a drug one day and sample blood the next day to see if the circulating tumor cells are gone, he explained. The test uses a microchip that resembles a lab slide covered in 78,000 tiny posts, like bristles on a hairbrush. The posts are coated with antibodies that bind to tumor cells. When blood is forced across the chip, cells ping off the posts like balls in a pinball machine. The cancer cells stick, and stains make them glow so researchers can count and capture them for study. The test can find one cancer cell in a billion or more healthy cells, said Mehmet Toner, a Harvard University bioengineer who helped design it. Researchers know this because they spiked blood samples with cancer cells and then searched for them with the chip. Studies of the chip have been published in the journals Nature, the New England Journal of Medicine and Science Translational Medicine. It is the most promising of several dozen that companies and universities are rushing to develop to capture circulating tumor cells, said Bob McCormack, technology chief for Veridex. The agreement announced Monday calls for Veridex and J&J's Ortho Biotech

Oncology unit to work on improving the microchip, including trying different designs and a cheaper plastic to make it practical for mass production. No price goal has been set, a company official said, but the current CellSearch test costs several hundred dollars. The companies will start a research center at Mass General and will have rights to license the test from the hospital, which holds the patents. In a separate effort, Mass General, Sloan-Kettering, University of Texas M.D. Anderson Cancer Center in Houston and Dana-Farber Cancer Institute in Boston will start using the test this year. They are one of the "dream teams" sharing a $15 million grant from the Stand Up to Cancer telethon, run by the American Association for Cancer Research Already, scientists have been surprised to find that more cancer patients harbor these stray cells than has been believed. In one study, the test was used on men thought to have cancer confined to the prostate, "but we found these cells in two-thirds of patients," Toner said. This might mean that cancer cells enter the blood soon after a tumor starts, or that more cancers have already spread but are unseen by doctors. Or it could mean something else entirely, because researchers have much to learn about these cells, said Dr. Minetta Liu, a breast cancer specialist at Georgetown University Lombardi Comprehensive Cancer Center. She led a session on them at the recent San Antonio Breast Cancer Symposium and has been a paid speaker for Veridex. She hopes the cells will someday aid cancer screening. "The dream is, a woman comes in for her mammogram and gets a tube of blood drawn," so doctors can look for cancer cells in her blood as well as tumors on the imaging exam, she said. That's still far off, but Mass General's test already is letting doctors monitor patients without painful biopsies. Like Greg Vrettos, who suffered a collapsed lung from a biopsy in 2004, when he was diagnosed with lung cancer. "It had spread to both lungs and they couldn't operate," said Vrettos, 63, a nonsmoker and retired electrical engineer from Durham, N.H. Tests from the biopsy showed that he was a good candidate for the drug Iressa, which he has taken ever since. He goes to Boston every three months for CT scans and the blood test. "They could look at the number of cancer cells and see that it dropped over time. It corresponded with what the scans were showing," Vrettos said of doctors looking at his blood tests. The test also showed when he had a setback last January and needed to have his treatment adjusted. "I think it's going to be revolutionary," he said of the test.