Generate an explanation for the given claim using the provided supporting material from the paragraph. Please consider the following points while generating an output. 1) The claim will always have supporting proof in the paragraph, and the paragraph will have a clear point of view supporting the claim. 2) There can be instances where direct correlation to the claim is not available. Make use of the sentences in the paragraph to provide a corresponding output supporting the claim. 3) The explanation should be at least one and at most twelve sentences long.

Paragraph: The analysis suggests the potentially harmful effect of Celebrex dosage is most pronounced in higher-risk patients, researchers said at the American College of Cardiology scientific meeting. “Patients at low cardiovascular risk should take some level of comfort,” said Dr. Scott Solomon, lead researcher of the National Cancer Institute-sponsored analysis. “That wasn’t so clear previously.”   Doctors should exercise caution in prescribing the drug, generally known as celecoxib, in high-risk patients, said Solomon, whose analysis was also published online in the journal Circulation. Celebrex belongs to a class of pain drugs known as cox-2 inhibitors and is the only such drug still on the market in the United States. Merck and Co Inc withdrew its widely used cox-2 drug, Vioxx, from the market in 2004 after a study showed it doubled the risk of heart attack and stroke in long- term users. Another cox-2 inhibitor from Pfizer called Bextra was also pulled from the U.S. market due to safety concerns. While the analysis sheds light on how the drug should be used, Solomon said he could not judge whether the data lift the cloud over this class of drugs. The six trials involving a total of 7,950 patients all studied Celebrex against a placebo for uses other than arthritis. Patients received either 400 milligrams once a day, 200 mg twice a day, or 400 mg twice a day. The primary goal of the pooled analysis was an assessment of the combined risk of cardiovascular death, heart attack, stroke, heart failure or events involving blood clots. Researchers found the heart risk was lowest at the 400 mg daily dose. They found nearly a two-fold risk of adverse heart events with the 200 mg twice daily dose and that jumped to about a three-fold risk at the 400 mg twice daily dose. “Even 400 mg once a day showed elevated risk” in the high-risk population, Solomon said, adding he could not extrapolate whether doses lower than 400 mg cut risk further. The increased risk was not affected by aspirin use, researchers said. “Most of the data used in this pooled analysis have previously been published and are consistent with what we already know about the cardiovascular risks of Celebrex and other prescription arthritis pain relievers,” said Gail Cawkwell, Pfizer’s executive medical director. “The analysis doesn’t provide any new conclusions on the FDA-approved doses of Celebrex, including the most commonly prescribed dose of 200 mg daily,” she said. Dr. Steven Nissen of the Cleveland Clinic, who has a study on lower doses underway, added: “There aren’t long-term randomized placebo-controlled trials for that dose, The only way we’re ever going to answer these questions is with good randomized prospective data,” he said. “We’ll tell it like it is when the data is in.” Claim: Celebrex risky in high-risk patients, study finds.
Doctors should prescribe the lowest doses of Celebrex possible in patients at high risk of heart problems, researchers who did a combined analysis of six studies of the Pfizer Inc pain drug said on Monday.

Paragraph: The story does not mention the cost of mammography (or of follow up tests and treatments) to the individual, or, collectively, to society. And these costs are substantial. Based on the results of this study, 2,500 women would have to be screened every other year for a decade in order to prevent one death from breast cancer. As the story points out, during that same time 1,000 of those women would have at least one false alarm and 500 would undergo an unnecessary biopsy, thus adding to the price tag. On balance, this story does a fair job of describing the benefits of screening mammography as seen in this study. It reports the apparent 10 percent reduction in breast cancer deaths, while also pointing out that because relatively few women in the 50-69 age group die of breast cancer, that reduction can also be described as cutting the 10-year risk of death from 4.4 per 1,000 women to 4 per 1,000. The second statistic helps counteract popular assumptions about how many middle-aged women die from breast cancer. However, the framing of a story – and who gets the last word – sometimes overwhelms evidence-based explanations earlier in the story. That almost happened with this story, which gives the final word to an advocate of annual breast cancer screening for all women beginning by age 40, which is just the sort of blanket recommendation this latest study calls into question. The story includes a comment that because mammograms detect lumps that would not have become life-threatening, five to 15 women may be treated for every one whose life is saved by treatment. The story oversimplifies the methods used by researchers, saying they compared “women who were similar in most ways, except that one group received mammograms and the other didn’t,” without explaining that this was not a randomized trial where some women were assigned to screening and others weren’t, but rather an observational study that looked at data on women during a 9-year period when Norway phased in mammography region by region. The story does alert readers to some of the limitations of the study: one, that a longer follow-up period might have shown more benefit to screening and, two, that the researchers had no information on whether any of the women received mammograms outside of the national screening program. It’s a tossup for us to grade and, as we do in most such cases, we’ll give the story the benefit of the doubt. Claim: Mammogram benefits more modest than doctors thought
However, it does not explain to readers what is new or different about this study compared to earlier reports. Also, the final word in the story goes to an expert who touts benefits of mammography screening that clash with what was seen in this study. By comparing this story with, for example, the Philadelphia Inquirer and WebMD stories, you see how some of the gaps we’ve identified were addressed by competitors, giving readers a more complete and helpful story.

Paragraph: That’s the premise behind the recent approval of a landmark drug, the first cancer therapy ever cleared based on a tumor’s genetics instead of the body part it struck first. Now thousands of patients with worsening cancer despite standard treatment can try this immunotherapy — as long as genetic testing of the tumor shows they’re a candidate. “It’s like having a lottery ticket,” said Johns Hopkins oncologist Dr. Dung Le, who helped prove the new use for the immunotherapy Keytruda. “We’ve got to figure out how to find these patients, because it’s such a great opportunity for them.” Today, doctors diagnose tumors by where they originate — breast cancer in the breast, colon cancer in the colon — and use therapies specifically tested for that organ. In contrast, the Food and Drug Administration labeled Keytruda the first “tissue-agnostic” treatment, for adults and children. The reason: Seemingly unrelated cancers occasionally carry a common genetic flaw called a mismatch repair defect. Despite small studies,  FDA found the evidence convincing that for a subset of patients, that flaw can make solid tumors susceptible to immunotherapy doctors otherwise wouldn’t have tried. “We thought these would be the hardest tumors to treat. But it’s like an Achilles heel,” said Hopkins cancer geneticist Bert Vogelstein. And last month FDA Commissioner Scott Gottlieb told a Senate subcommittee his agency will simplify drug development for diseases that “all have a similar genetic fingerprint even if they have a slightly different clinical expression.” It’s too early to know if what’s being dubbed precision immunotherapy will have lasting benefits, but here’s a look at the science. WHO’S A CANDIDATE? Hopkins estimates about 4 percent of cancers are mismatch repair-deficient, potentially adding up to 60,000 patients a year. Widely available tests that cost $300 to $600 can tell who’s eligible. The FDA said the flaw is more common in colon, endometrial and gastrointestinal cancers but occasionally occurs in a list of others. “Say, ‘have I been tested for this?’” is Le’s advice for patients. MUTATIONS AND MORE MUTATIONS Most tumors bear 50 or so mutations in various genes, Vogelstein said. Melanomas and lung cancers, spurred by sunlight and tobacco smoke, may have twice as many. But tumors with a mismatch repair defect can harbor 1,500 mutations. Why? When DNA copies itself, sometimes the strands pair up wrong to leave a typo — a mismatch. Normally the body spell checks and repairs those typos. Without that proofreading, mutations build up, not necessarily the kind that trigger cancer but bystanders in a growing tumor. THE PLOT THICKENS Your immune system could be a potent cancer fighter except that too often, tumors shield themselves. Merck’s Keytruda and other so-called checkpoint inhibitors can block one of those shields, allowing immune cells to recognize a tumor as a foreign invader and attack. Until now, those immunotherapies were approved only for a few select cancers — Keytruda hit the market for melanoma in 2014 — and they work incredibly well for some patients but fail in many others. Learning who’s a good candidate is critical for drugs that can cost $150,000 a year and sometimes cause serious side effects. In 2012, Hopkins doctors testing various immunotherapies found the approach failed in all but one of 20 colon cancer patients. When perplexed oncologists told Vogelstein, “a light bulb went off.” Sure enough, the one patient who fared well had a mismatch repair defect and a “mind-boggling” number of tumor mutations. The more mutations, the greater the chance that at least one produces a foreign-looking protein that is a beacon for immune cells, Vogelstein explained. It was time to see if other kinds of cancer might respond, too. WHAT’S THE DATA? The strongest study, published in the journal Science, tested 86 such patients with a dozen different cancers, including some who had entered hospice. Half had their tumors at least shrink significantly, and 18 saw their cancer become undetectable. It’s not clear why the other half didn’t respond. Researchers found a hint, in three patients, that new mutations might form that could resist treatment. But after two years of Keytruda infusions, 11 of the “complete responders” have stopped the drug and remain cancer-free for a median of eight months and counting. Catherine “Katie” Rosenbaum, 67, is one of those successes. The retired teacher had her uterus removed when endometrial cancer first struck, but five years later tumors returned, scattered through her pelvis and colon. She tried treatment after treatment until in 2014, her doctor urged the Hopkins study. Rosenbaum took a train from Richmond, Virginia, to Baltimore for infusions every two weeks and then, after some fatigue and diarrhea side effects, once a month. Then the side effects eased and her tumors started disappearing. A year into the study she was well enough to swim a mile for a Swim Across America cancer fundraiser. “Nothing else had worked, so I guess we could say it was a last hope,” said Rosenbaum, who now wants other patients to know about the option. ___ This Associated Press series was produced in partnership with the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content. Claim: Tumor gene testing urged to tell if drug targets your cancer.

Colon cancer. Uterine cancer. Pancreatic cancer. Whatever the tumor, the more gene mutations lurking inside, the better chance your immune system has to fight back.