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: At issue are genes called BRCA1 and BRCA2. When they’re mutated, the body can’t repair damaged DNA as well, greatly increasing the chances of breast, ovarian and certain other cancers. Gene testing allows affected women to consider steps to lower their risk, such as when actress Angelina Jolie underwent a preventive mastectomy several years ago. Most cancer isn’t caused by BRCA mutations — they account for 5% to 10% of breast cancers and 15% of ovarian cancers — so the gene tests aren’t for everyone. But mutations cluster in families, and the U.S. Preventive Services Task Force has long recommended that doctors screen women who have relatives with BRCA-related cancers and refer those who might benefit from gene testing to a genetic counselor to help them decide. Tuesday, the task force expanded that advice, telling primary care doctors they should also assess women’s risk if: —they previously were treated for breast or other BRCA-related cancers including ovarian, fallopian tube or peritoneal cancers, and now are considered cancer-free. —their ancestry is prone to BRCA mutations, such as Ashkenazi Jewish women. Why screen breast cancer survivors? After all, they already know there’s a risk of recurrence. Take, for example, someone who had a tumor removed in one breast in their 40s a decade ago, when genetic testing wasn’t as common. Even this many years later, a BRCA test still could reveal if they’re at risk for ovarian cancer — or at higher than usual risk for another tumor in their remaining breast tissue, explained task force member Dr. Carol Mangione of the University of California, Los Angeles. And it could alert their daughters or other relatives to a potential shared risk. “It’s important to test those people now,” Mangione said. “We need to get the word out to primary care doctors to do this assessment and to make the referrals.” Private insurers follow task force recommendations on what preventive care to cover, some at no out-of-pocket cost under rules from former President Barack Obama’s health care law. The recommendations were published in the Journal of the American Medical Association. Cancer groups have similar recommendations for BRCA testing, and increasingly urge that the newly diagnosed be tested, too, because the inherited risk can impact choices about surgery and other treatment. Identifying BRCA mutation carriers “can be lifesaving, and should be a part of routine medical care,” Drs. Susan Domchek of the University of Pennsylvania and Mark Robson of Memorial Sloan Kettering Cancer Center, who weren’t involved with the new guidelines, wrote in an editorial accompanying them. But too few high-risk women ever learn if they harbor BRCA mutations, they wrote. For example, cancer groups have long recommended that all ovarian cancer patients be tested, but several studies have found testing is done in less than a third. Don’t skip the genetic counseling, said the task force’s Mangione. BRCA testing can cause anxiety and sometimes gives confusing results, finding mutations that might not be dangerous — things the counselors are trained to interpret. There’s a shortage of genetic counselors, particularly in rural areas, and she said counseling by phone can work. There’s a wide array of gene tests, some that search just for BRCA mutations and others that test dozens of additional genes at the same time. There’s even a direct-to-consumer kit sold by 23andMe — but Domchek and Robson warned it only detects the three mutations found most in women of Ashkenazi Jewish descent, not dozens of other mutations. ___ The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content. Claim: Guidelines say more women may need breast cancer gene test.
More women may benefit from gene testing for hereditary breast or ovarian cancer, especially if they’ve already survived cancer once, an influential health group recommended Tuesday.

Paragraph: Although the release doesn’t give actual costs of warfarin versus some of the newer drugs, or factor in the cost of the usual monthly blood testing required of those taking the drug, it does note the cost of the gene testing used for the study, and that the $200 price tag is now less than a month’s prescription of one of the newer anti-coagulants on the market. The release gives results in both actual numbers of patients and the percentage of reduction of adverse events in those given the genetic test and a comparison group. Although it does so in general terms, the release covers the essentials: the risk of using blood thinners like warfarin and the risks of not using them. The release offers a good description of the design of the study. It was randomized and enrolled more than 1,600 older patients at high risk of blood clots following surgeries. The release explains that one group received warfarin dosing based on standard factors (age, height and weight) and the second group was dosed using these clinical factors plus their genetic variants. The release also offers a detailed breakdown on how many fewer side effects occurred among patients had genetic testing completed compared to those who didn’t. No mongering here. Nicely done and quite complete. Although the release briefly mentions the availability of a “newer anticoagulant,” it should have included a sentence or two about these newer injectable drugs and their overall risks and benefits in comparison to warfarin. It would also have been helpful to tell readers whether the genetic testing that appears to play a role in safer warfarin dosing would have clinical relevance for informing the use of the new blood thinners as well. The fact is that genetic testing is irrelevant for the newer anti-coagulants because they operate in a completely different manner. But all the blood thinners — old and new — carry the same risk of bleeding. The problem with warfarin is the variability in blood levels which requires frequent monitoring, hence the genetic tests to guide dosing. The careful reader will get it: testing for these genetic variants is still an experimental practice for the most part, and further testing of how the mutations affect warfarin is needed. But the release could have been more explicit in saying that no one is yet recommending genetic testing for millions of warfarin users. While the genetic tests are “available” in the sense that anyone can order them for the most part, they are not routinely used clinically and probably wouldn’t be covered by insurance so in that sense they are not widely available to most people. The release describes how the genetic test used in the new study differs from previous similar studies. Overall the language is careful and contextual. The headline should have been toned back a bit to note that this is early research and more study is needed before concluding that “Genetic testing helps set safe dose of common blood thinner,” as the headline now states. Claim: Genetic testing helps set safe dose of common blood thinner
This news release describes results of a study designed to learn whether testing for the presence of three gene variants could make dosing with the blood thinner warfarin safer for patients given the drug to prevent blood clots after joint replacement surgery. The study found a modest reduction in the risk of bleeding or clots (from over- or under-dosing) in those whose regimens were developed in part by genetic testing for the variants, compared to those whose doses were calculated without the genetic testing. The release does an overall good job in describing the study, its purpose and design; and in quantifying the results. It could have been even stronger if it had included more information about newer alternatives to warfarin that are growing in use and an explicit statement that no one is yet recommending routine genetic testing for the variants based on this study. And although the headline somewhat over promises clinical benefit at this point in time, thoughtful readers will come away with a decent understanding of the context of the research and its potential impact. Some estimates put the number of Americans regularly taking the clot-preventing blood thinner warfarin and several newer anticoagulants at more than six million. Warfarin (sold under the brand name Coumadin) requires frequent blood testing to address risks of overdoses (and potentially lethal bleeding) and under-dosing (ineffective prevention of strokes and other blood clots). Because warfarin is cheap, and its effects are reversible with vitamin K, research designed to make it easier and safer for patients to take is likely to be highly newsworthy for them and their caregivers.

Paragraph: Costs aren’t discussed. The article gives the absolute rates of major adverse cardiac events for each treatment group. Also, while this is likely not a major issue for most readers and not an official strike against the article, as an FYI we point out that there are some interwoven concepts that can be confusing. The article’s headline is that SES won this contest. If you want to get technical, there are two buts. First, while SES did have the fewest cardiac events of the 3 stents, the difference with ZES wasn’t statistically significant. In other words, the apparent superiority of SES may have been do to chance. Or not. We don’t know. Researchers call this a trend but not significant evidence. Second, this contest, the study, wasn’t designed to answer whether SES was the best. The researchers concluded, as quoted in the story, that this study answered two main questions: ZES and SES were similar, and ZES fared better than PES did. Notice it didn’t say SES was the best. There’s overlap between harms and benefits here because stents are designed to prevent harm. However, the study identifies the development of blood clots on the stent as a safety outcome (along with the numbers of heart attacks and death). While the article tells us that the rate of clots was significantly lower with one type of stent, it does not quantify the harms. There are some valuable details about the study in this article, including the number of subjects, the 3 treatment arms, randomization, the follow-up period, a definition of the endpoint—a composite called “major adverse cardiac events”—and what actual events that means. It gets kudos for identifying the key limitation of the one-year follow-up with a nod to important results from a longer ongoing study. There were some aspects of the evidence missing, which is not surprising in a short article about a fantastically complex topic. In a quote the researchers laud their study as a “practical” one. We’re not told what that means. And see our comment under Benefits regarding the explanation of the results. Also, an article of this length doesn’t have the real estate to go into all the nooks and crannies (and limitations) of composite endpoints, like MACE, which are very standard in such trials. But we appreciated that the author unpacked it a bit by noting that rates of death and heart attacks did not differ. We give the article a Satisfactory rating because, in this very focused and balanced review, it doesn’t balloon the target population for drug-coated stents. That said, we would’ve liked to have seen at least some overview of who is a candidate for stents at all, bare or coated. Not everyone with a clogged artery gets stents, or, rather, should get stents based on the evidence. It’s a complex topic, with different guidelines for those having heart attacks and those with stable angina, but it’s also a hot topic these days due to widespread misconceptions about who gets stents and what benefits they actually have. Recent evidence, such as the COURAGE trial, suggests that for most people with stable angina, stents don’t prevent heart attacks or improve survival compared to only taking medicine and leading a heart-healthy lifestyle. One source, Dr. Fonarow, was apparently not affiliated with the study. We appreciated his placing the results in context with prior research and on clinical decision-making. Google tells us that he has a financial relationship with the company that makes zotarolimus-coated stents. But given the fact that his quotes—and the study—are not in favor of zotarolimus, perhaps the lack of this disclosure is excusable. One key conflict of interest, study funding from a stent manufacturer, was identified. However, we fail the article on this criterion because it neglects to mention that the researchers disclosed a web of financial relationships with literally all the stent manufacturers. We count 9 financial relationships with Cordis, who makes the sirolimus-coated stent, which came out “on top” in this article. Taking into account that the article implies availability of the 3 stent types, the study itself was comparing a newer approach with the “old standby.” The article could’ve been more explicit about the availability of these 3 stents, but the last sentence describing the study’s real-world implications, suggests that all 3 are currently available in cath labs. The article explains that the three stents are coated with different drugs, the zotarolimus version is a newer entry, while the sirolimus one is the “old standby”. It would’ve been nice to read how the stent with paclitaxel fits into the big picture. Claim: In Test of Stents, Old Standby Wins Out

Our review names some story elements that we think could’ve been added or removed. To us, the most notable omission was the litany of financial conflicts of interest the researchers had with stent manufactures.