Breast cancer risk. Is Mammography Helpful or Mythical?

                                  

Conventional wisdom has long dictated that routine mammography can detect early breast cancers and save lives. A recent report, however, from Canada§ ignited a torrent of controversy about the validity of this premise. In summary, researchers followed almost 90,000 women, aged 40-59. Half were randomly assigned to receive regular mammograms plus physical breast exams, and the other half received only breast exams by trained medical personnel abetted by self examination. Both groups were followed for up to 25 years. Overall, 7.1% of all subjects developed cancer, and 1.1% succumbed from this disease.  But importantly, mortality was the same in both groups. Of those who received mammography, 1 in 424 (representing 22% of those diagnosed with cancer) was considered “over diagnosed”. Over-diagnosis was estimated in this type of screening trial when they failed to progress after a sufficiently long period has elapsed from the cessation of screening—that is, when all cancers should have become clinically apparent. Over diagnosis generally leads to unnecessary cancer treatment, including surgery, chemotherapy and radiation.  This latter figure is probably an underestimation, because earlier studies had estimated that approximately 25% to 30% of small cancers detectable by X-ray only (without a palpable lump) will not progress to invasive, or life threatening, disease, at any time during one’s lifetime.

Let’s look a bit further into this problem. If a woman tests positive on a mammogram, the likelihood she has cancer is clearly higher than those testing negative, but, within that group there are numerous “false positives”. This means that although these individuals are harboring “densities” in X-ray images, only a minority will be found to actually have cancer. On the other hand, a negative mammogram provides more reassurance, for this reduces the likelihood of not having cancer to nearly 100%, virtually eliminating one’s chance of having this disease. Given these underlying numbers, a negative result is far more useful and reassuring than is a positive result.

These numbers help to explain why so much controversy had previously surrounded the issue whether widespread screening of women at any age with mammography should be undertaken. Since the vast majority of positive responders will have no disease, this often leads to considerable anxiety and further testing (additional imaging and/or biopsies) that entails significant expense and sometimes even risk.

Previous research had already provided important data that, at least in women under the age of 50, there was insufficient evidence to support a mortality benefit stemming from regular mammography screening. Even in those beyond this age, there was little convincing evidence to indicate that very early detection of subtle abnormalities—when found in individuals without palpable breast “lumps”—added any benefit in lowering ultimate mortality. But finding palpable lump(s), especially with a positive mammogram, dramatically increases the odds that invasive, life threatening, cancer will be found. This latter group would more likely be improved—with reduced mortality—when receiving active treatment. Other factors such as a strong family history or results of genetic testing will help to increase the odds of invasive breast cancer, and this would also justify a more aggressive approach to diagnosis and treatment.

What can the individual woman conclude from this apparently conflicting information? In general the results of one study generally cannot be used to alter universal management, but, in this case, they add to an already growing body of information that questions the value of routine mammography screening. No matter how one elects to respond, however, careful breast examinations by one’s self and/or by trained medical personnel, becomes more important than ever! Mammography may eventually be relegated to a secondary role in screening.



§ BMJ 2014;348:g366, Feb 11, 2014

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Marijuana: What Can Science Teach Us?

      With all the current hype, it’s time to take a reasoned look at the subject of Marijuana, now enjoying much publicity because of its recent acceptance in Colorado and Washington for recreational use. The marijuana (cannabis) plant contains over 60 cannabinoid substances, and the primary component of this group that accounts for its psychic effects is delta-9-tetrahydrocannabinol (THC). When the plant is smoked, about 20% of the THC is absorbed into the blood through the lungs. Herbal cannabis can also be eaten, but less THC reaches the circulation because it is partially inactivated by the liver. Whether smoked or eaten, the recipient usually experiences a “high”, i.e., a relaxed euphoric sense as anxiety recedes, but alertness also decreases. Exceptionally, users can experience increased fear or panic. Those high on marijuana usually experience an increased sense of sociability with an altered perception of time, with imagined time faster than real time. Spatial perceptions may change, and colors may seem brighter and music more resonant. Although high doses may cause hallucinations, dangerous or fatal outcomes have been virtually nonexistent. Mild or distressing withdrawal symptoms may occur after chronic use, they are also not generally serious or life threatening, and whether this agent is truly addictive remains controversial. These effects might be contrasted with alcohol, which, if given abruptly in large quantities, can be fatal, and if continuously imbibed for several weeks, can result, upon sudden withdrawal, in serious physical manifestations, and even death.

    Because of long-standing legal prohibitions against marijuana, reliable scientific data have been scarce. Two recent reviews, however, examine results from approximately one hundred randomized placebo-controlled trials involving over 6,100 patients with a variety of medical conditions. The results show that marijuana is useful in treating anorexia, nausea and vomiting, glaucoma, irritable bowed disease, muscle spasticity, multiple sclerosis, symptoms of amyotropic lateral sclerosis (Lou Gehrig’s Disease), and Tourette’s syndrome. It is also useful in providing modest relief of pain. In this latter regard, it seems to reduce chronic pain by about 30 percent, a benefit achieved with fewer serious side effects than encountered with commonly used opiates (codeine, morphine, etc). Thus there is ample evidence to support the legalization of marijuana for medicinal purposes. Notwithstanding this information, medicinal use is now authorized in only 20 states and remains proscribed at the federal level. One exception, however, is provided by Nabilone (CesametR), which represents an oral form of cannabis that is currently available and approved for use specifically against nausea and vomiting.

    But what about marijuana for recreational use? As noted, the psychic effects are basically euphoric, providing its chief rationale for use. But risks include the impairment of cognition and muscular responses, a decrease of one’s reaction time, attention, concentration, short-term memory, and assessment of risks. These impairments of psychomotor performance can last longer than the feeling of being high for as long as twenty four hours. This clearly impairs ability to drive vehicles, for several studies show that, in comparison to those who are drug and alcohol free, drivers who use marijuana are two to seven times more likely to be responsible for accidents.

    The effects of marijuana on overall behavior are controversial. Although chronic users have a repeated pattern of poor performance such as inability to fulfill responsibilities in the workplace and persistent social problems at home, this may result primarily from emotional disorders that cause one to use marijuana rather than this latter agent per se.      

     Scientific study has thus far not supported the common belief that initial use of marijuana will “lead” to subsequent use of hard drugs such as heroin, but further scrutiny of this subject is warranted. Many also believe that legalization of marijuana will lead to increased crime rates. This latter assertion has been refuted by a nationwide study recently published in a scientific journal. Researchers at the University of Texas at Dallas looked at the FBI’s Uniform Crime Report data across the country between 1990 and 2006, a span during which 11 states legalized medical marijuana. Although during this time period crime was broadly falling throughout the United States, those states that legalized the drug before and after the law’s passage demonstrated no relative increase across an entire spectrum of crimes: homicide, rape, robbery, assault, burglary, larceny, and auto theft. The robbery and burglary findings are particularly interesting, as those are the crimes we’d most likely expect to see outside of medical dispensaries.

   Interestingly, despite its common use through smoking, marijuana’s effects on the lungs appear far less than those of tobacco. According to a new study, habitual use of marijuana alone doesn’t appear to lead to significant abnormalities in lung function or chronic lung disease.

    So what can we conclude at this time? Legalizing marijuana for medicinal purposes is clearly justified. Allowing its use for recreational purposes remains clouded, but its effects appear similar—but less dangerous—than those of alcohol.

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