Lymph Node Surgery for Breast Cancer

For decades, the standard treatment for women who have been diagnosed with early-stage breast cancer has been to perform a biopsy on a nearby lymph node, called a “sentinal” lymph node, to see if the cancer has metastasized beyond the breast. If it has, then the usual recommendation is surgery to remove some or most of the thirty axillary (armpit) lymph nodes as well, to try to halt the spread of cancer. The surgery is extensive, and recovery is painful and slow.

A new study published in the Journal of the American Medical Association reports that removal of armpit lymph nodes may not be necessary any more, given the current effectiveness of post-surgical radiation therapy and chemotherapy. In the study, 891 women who had undergone a lumpectomy for early stage breast cancer were randomly assigned to just sentinal node removal, or removal of at least 10 of the axillary lymph nodes. There were no differences in survival rates or disease-free survival rates between the two groups for the entire eight years of the study.

The authors recommend that physicians consider carefully whether more radical axillary node surgery is really necessary in most patients. Some cancer centers are already starting to change their cancer treatment protocols as a result of these new findings.

Does Aspirin Reduce the Risk of Cancer?

In addition to its known blood anticoagulant properties, aspirin might also help prevent cancer, according to an article soon to be published in The Lancet. The authors of the study examined past data from the medical charts of over 25,000 patients in eight different studies who were taking aspirin to reduce their risk of a cardiovascular event. They found that daily doses of at least 75 mg of aspirin for at least five years reduced the overall death rate due to cancer by an astonishing 21%.

So should we all start popping aspirin? Not necessarily, says the Deputy Chief Medical Officer for the national office of the American Cancer Society in his blog post of Dec. 6. Although he finds no fault with the reported results as an interesting observation, he points out that the study was a retrospective (in the past) examination of cancer deaths in studies originally designed for other purposes – far better would be a randomized prospective (looking into the future) trial, in which both the risks and benefits of aspirin could be studied together. But such a study would take another 20 years! Who wants to wait that long?

It’s a quandary often faced in medicine – what to do when there’s tantalizing new information that seems to point in a certain direction, but no way to know for sure. No doubt, some of you will start taking aspirin as a result of this new study. Before you do, consider carefully that taking aspirin may be a double-edged sword; risks associated with taking aspirin include (in some people) gastrointestinal bleeding and bleeding in the brain. It’s your call.

Human Gene Patents Invalidated

Basing his decision on legal arguments that human genes are products of nature and hence cannot be patented, in March of 2010 a U.S. District Court judge invalidated several patents held by a company called Myriad Genetics on the human breast cancer genes, BRCA1 and BRCA2. Myriad Genetics sells a kit used to test for the two genes for about $3,000. The company tried to argue that their method of isolating the genes changed the genes, and thus made them patentable. But the judge ruled that such an argument was just a trick to circumvent the prohibition on the direct patenting of DNA.

About 20% of human genes have already been patented. A number of biotech companies were planning to make a hefty profit by developing and selling patent-protected genetic tests or by selling the patent rights to others. Whether all of those patents could ultimately be invalidated is unclear. With potentially billions of dollars at stake, the decision is likely to be appealed.

Medical and research organizations and patients are pleased by the decision. If it holds up on appeal it should provide wider access to human genes currently under patent protection, and ultimately make genetic tests like those for BRCA1 and BRCA2 less expensive.

Should Older Women be Vaccinated Against HPV?

The U.S. Centers for Disease Control and Prevention (CDC) recommends that all girls and women between the ages of 11 and 26 be vaccinated against the strains of human papillomaviruses (HPVs) that cause cervical cancer. But what about older women; wouldn’t they benefit as well?

The answer appears to be no, or at least not very much. A study of over 9,000 Costa Rican women conducted over a seven-year period found that older women (over 40) tend to get fewer new HPV infections. They also found that HPV infections do not progress towards cancer any faster in older women than in younger women.

Cancer develops in only a small fraction of women who have an HPV infection during their lifetimes, and most HPV infections clear up on their own within a couple of years anyway. Even among women who do develop cervical cancer as a result of an HPV infection, it takes about 25-30 years on average for the cancer to develop fully to the metastatic stage. Therefore, vaccinating older women is not of much use. The ideal time to vaccinate women and girls is before they become sexually active so that they never have an HPV infection in the first place.

Snus - Smokeless Tobacco Made Easy

Now available over the internet and in stores; Snus (rhymes with loose), a smokeless tobacco product containing nicotine that originated in Sweden. Snus comes in colorful tins and is packaged in small tea bag-like packets. It’s real advantage over traditional smokeless chewing tobacco is that no spitting is necessary - the small amount of juice produced can just be swallowed. It’s likely to become popular among teens who want their tobacco use to go undetected, patrons of bars and restaurants where smoking is not permitted, and smokers who want to quit.

The tobacco companies are looking to attract a whole new generation of tobacco users and to shore up profits in the face of declining cigarette sales. R.J. Reynolds launched a nationwide marketing campaign for “Camel Snus” in 2009. As usual, the company denies that it aims its marketing campaign toward underage users.

So far there is no evidence that Snus use may be a risk factor for cancers of the mouth and throat. Nevertheless, it is a tobacco product. It’s worth remembering that there were no clear health risks associated with cigarettes, either, when they first became popular in the 1940s.

Breast Self Examination

Women; have you been feeling guilty because you haven’t been doing regular breast self-examinations to make sure you aren't developing breast cancer? Well, here’s good news for you. The U.S. Preventive Services Task Force (USPSTF), which makes recommendations about preventive care services for people who do not yet have any signs or symptoms of disease, is now recommending against breast self-examination (BSE) as a way to detect breast cancer. (The USPSTF’s previous position on the usefulness of BSE was “insufficient evidence” either for or against).

The USPSTF systematically reviews of the benefits and harms of a preventive care services, and then tries to come up with a net assessment. In the case of BSE, the USPSTF reviewed the latest published data and concluded that; a) regular BSE does not lower the mortality rate from breast cancer, and b) women who perform BSE tend to have more imaging procedures and biopsies than women who don’t. These procedures are expensive and are themselves associated with minor health risks, such as infection and increased exposure to radiation. Overall, the net risk/benefit ratio for BSE is on the side of net risk.

The recommendation against BSE is only for women who are not at increased risk for breast cancer. Women who are at increased risk should consult their physician.

Reference: U.S. Preventive Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann. Int. Med. 151:716-726, 2009.

Breast-Feeding and Breast Cancer

A recent study in the Archives of Internal Medicine raises the possibility (but does not entirely prove) that breast-feeding may lower the risk of breast cancer among women at high risk for the disease. The study gathered data from over 60,000 women who had reported at least one pregnancy by 1997. Among women with close relatives who developed breast cancer, those who breast-fed for a period of time had only 41% as many breast cancers by 2005 as women who had never breast-fed. The lowered cancer incidence was only seen among women at high risk for breast cancer; women with no family history of breast cancer did not benefit from breast-feeding.

Why doesn’t this study prove once and for all that “breast-feeding prevents cancer”? Because it only shows an association between breast-feeding and lowered cancer risk - cause-and-effect has not been proved. Perhaps women who choose to breast-feed are more health-conscious overall. Perhaps they exercise more or have a better diet, and that’s actually what lowered the cancer risk. Further research will be needed to tease out the details.

A DNA test for Cervical Cancer

It was bound to happen eventually. The annual Pap smear, the gold standard for over 40 years for detecting cervical cancer, may soon be replaced by a modern, much more specific DNA test for the human papillomavirus that is responsible for most cervical cancers. The cost of the test is currently around $20-30, but the test is so accurate and specific that women may only need the test once every 5-10 years.

A comparative study of the effectiveness of the new DNA test (HPV test) versus the Pap smear (cytologic test) in preventing cervical cancer deaths was conducted in India with funds provided by the Bill and Belinda Gates Foundation. After just eight years, the study showed that the DNA test reduced cervical cancer deaths by nearly 50% compared to the Pap test. Significantly, not one woman whose DNA test for HPV was negative died of cervical cancer during the study period.

The PSA Test for Prostate Cancer

For over 20 years some health professionals have been recommending that men over 50, and men as young as 45 if they belong to a high-risk group, be screened for prostate cancer by means of a PSA test (see Human Biology 5th ed., table 18.4). The PSA test measures the level of prostate-specific antigen, a protein from prostate cells. An elevated serum PSA indicates that prostate cancer might be present, in which case the next step is a biopsy to determine for sure.

When the PSA test was first introduced in 1987, scientists thought it might lead to as much as a 50% reduction in prostate cancer deaths. But now it seems that it may not save lives after all. In a study of 77,000 U.S. men, the 10-year death rate from prostate cancer was the same in a group who had an annual PSA test for six years plus a digital rectal examination for four years, compared to a control group who were never tested over the same time period. The study may need to be continued out for another decade or so to determine whether the PSA test has any usefulness over the longer term, however.

How can a test that accurately detects prostate tumors not save lives? Apparently the answer is that most prostate cancers are so slow-growing that older men are likely to die of something else first, even if they do have a diagnosis of prostate cancer. For older men, skipping the PSA test altogether may someday be safe option.

By the way, a digital rectal examination is not some sort of digital readout. It's a physician’s gloved digit, or finger.

Using Urine to Diagnose Disease

Your body gets rid of over a thousand different small metabolic waste molecules, called metabolites, by excreting them in the urine. In certain diseases one or more of these metabolites may be elevated in urine. Scientists now believe that through “metabolomics” – the study of metabolites – it may be possible to diagnose certain diseases even before symptoms appear in the patient.

The concept is simple; once you know the normal range of excretion of metabolites in urine, a change in the excretion of one or more metabolites might signal the presence of a specific disease. For example, scientists at the University of Michigan measured 1,126 metabolites in urine and found that one of them in particular, called sarcosine, showed promise as a marker for metastatic prostate cancer. The findings were reported in Nature this month.

Unlike blood, urine is easily collected in large quantities by non-invasive techniques. (Put more bluntly, you just pee into a cup!) As the field of metabolomics comes of age, perhaps some day it will be possible to screen for dozens of diseases at once.

A Screening Test for Ovarian Cancer?

Here’s an ethical dilemma for you:

A promising new screening test for ovarian cancer called OvaSure can correctly identify ovarian cancer 95% of the time. Ovarian cancer is one of the most deadly cancers if it is not detected early. The company marketing the test says that the test has a false-positive rate of only 0.6%. (A false-positive is when the test indicates that cancer is present when in fact it is not.) Should the test be made widely available as a screening test for ovarian cancer?

Let’s see; 95% success rate at detecting ovarian cancer versus a 0.6% false-positive rate – it doesn’t sound like much of a dilemma, does it? You might try it out on your students to see what they think. But it is an interesting dilemma, and the reason is that ovarian cancer is rare; its prevalence is only about 0.06%. So among 100,000 women screened with the new test, 60 (0.06% of 100,000) would have ovarian cancer and 57 of them (95%) would be diagnosed correctly. Many of these 57 might be saved. However, 600 women (0.6%) would be told they had ovarian cancer when they did not. In the absence of any good corroborating tests to confirm the diagnosis, many of those 600 women might choose to have a surgery they actually didn’t need. And almost certainly they'd suffer emotionally from the belief that they had a deadly cancer.

Sometimes you have to run the numbers carefully to see the full effect of what is being said. It pays to be a skeptic.

ADDENDUM: Ovasure was pulled from the market in October, 2008, after the FDA sent the company a letter saying that the kits required FDA approval before they could be marketed and sold.

Your Cell Phone's Radiation Emission

Does the radiation emitted by cell phones cause brain cancers? Although most of the scientific evidence suggests that it doesn’t, the media always seems to find a physician or a patient or even a scientist who is willing to talk about it. The debate has been going on since cell phones first came out, and it’s not likely to go away any time soon.

Are you concerned? How much radiation does your cell phone emit, anyway – a lot, or a little? The Federal Trade Commission sets an upper limit of 1.6 W/kg (watts per kilogram) for certification, but commercial phones on the market vary all the way from 1.6 down to 0.14 – more than a 10-fold difference.

For a complete listing of the radiation output of all current phone models, go to http://reviews.cnet.com, go to “Cell phone reviews”, then click on “Cell phone radiation charts.”

Cell Phones and Brain Cancer

First, someone says (again) that cell phones may cause brain cancer. Then the FDA reports that there is no convincing evidence that cell phones are a health risk. (See “Experts Revive Debate Over Cellphones and Cancer”, The New York Times online, June 3, 2008.) What’s a consumer to believe?

This is a good example of the limitations of the scientific method, and why it is sometimes hard to know the truth. Regarding the first statement, yes, cell phones may cause brain cancer (and then again, they may not.) As for the second statement, it is true that there is still no scientifically convincing evidence that cell phones are a health risk. (but again, that doesn’t mean they aren’t!)

Why is it so hard to find the truth? First, brain cancers are so rare that one would have to study literally hundreds of thousands of people. Second, to do the scientific study properly, a controlled study would need to be done in which the lives of hundreds of thousands of people would have to be strictly controlled. It can’t be done. Third, no one has used cell phones for 50 years, so potential long-term effects won’t show up for awhile. And fourth, modern phones emit much less energy than the older models did.

What can we do? We can study those few patients with brain cancer and ask questions – questions about health habits, including past cell phone use. Self-reports by patients are notoriously unreliable, of course, so it may take hundreds of such studies before we consider the evidence “convincing”. We don’t need to panic, but we need to be watchful of the changing state of knowledge regarding cell phones and cancer.

You might remind your students that a similar question came up in the 1950s when smoking was actively encouraged – does smoking cause lung cancer? Who could have known that nearly sixty years later the rates of lung cancer in persons over 65 would be more than five times the rates of that same age group in 1950?!

Fear of Genetic Testing

Genetic testing to predict the future risk of specific genetic diseases could significantly improve the delivery of health care (see the Current Issue on pp. 458-459 of Human Biology 5th ed., entitled “The Promises and Perils of Genetic Testing”).

And yet, it appears that many people are avoiding DNA tests out of fear that the information could be misused. They worry that if their DNA test reveals a strong likelihood that they might develop a costly or life-threatening genetic disease later in life, they will become uninsurable even though they are currently healthy (see “Fear of Insurance Trouble Leads Many to Shun or Hide DNA Tests”. The New York Times, Feb. 24, 2008). Insurance companies deny it, of course. But even if insurance companies aren’t currently engaged in genetic discrimination, the commonly held perception that they could is enough to cause some people to avoid DNA tests.

Would your students take a DNA test to determine their risk of developing breast cancer or prostate cancer if those diseases ran in their family? You might ask them.

Cancer Therapy

The January issue of Scientific American, now available in electronic form, will have an interesting article about how antiangiogenic drugs (drugs that inhibit blood vessel growth) such as Avastin actually work in cancer therapy. It turns out that it’s not just that they reduce the overall blood supply to a tumor, although that is one of their actions. In fact, they also normalize the remaining vessels, pruning them and improving their permeability properties. As a result, antiangiogenic drugs improve the effectiveness of other cancer treatments such as chemotherapy, because now the chemotherapeutic drugs are better able to reach the tumor cells.

But there is only a window of opportunity in which the combination of antioangiogenic drugs and other therapies is particularly effective, because the antiangiogenic drugs are hard on blood vessels throughout the body and because tumors may eventually lose their responsiveness to the drugs. Nevertheless, our improved understanding of how antiangiogenic drugs actually work is opening new avenues for developing more specific cancer treatment regimens. To learn more, read the original article (“Taming Vessels to Treat Cancer”, by Rakesh K. Jain. Scientific American Jan. 2008, pp. 56-63).

Breast Cancer Around the World

The cover story in this week’s issue of Time magazine (Oct. 15) is about the worldwide incidence of breast cancer. The article discusses how the economic situation in different countries affects the likelihood of screening for breast cancer and the probability that the cancer will be adequately treated once it is detected. The reasons for a failure to detect and treat breast cancers are different in different countries, but they include a shortage of doctors, diagnostic equipment, and x-ray film; the high cost of treatment relative to income; and the inability to reach a medical facility because of the lack of transportation.

Aside from the usual genetic influences, students might be interested to learn that cultural differences also influence the diagnosis and treatment of breast cancer. The article points out that in some countries, women are afraid to admit to having breast cancer out of fear that their husbands will leave them or that their daughters will be shunned by prospective marriage partners. Diet, too, has a significant effect, for reasons pointed out in the article. And finally, there is just plain ignorance about the disease – in one instance, a woman who had an obviously-visible tumor admitted that she had not been diagnosed earlier because it didn’t hurt. Clearly, the fight against breast cancer will need to be fought differently from country to country.

The Immune System and Cancer

The July 2007 issue of Scientific American has an informative article on the role of the immune system in the development and spread of cancer. (A Malignant Flame. Scientific American July 2007, pp. 60-67). The article describes how our thinking has changed over the past decade or so.

It turns out that although the immune system sometimes helps to prevent the development and spread of cancer, at other times the immune system actually contributes to cancer development. This is particularly true of the non-specific immune defense mechanisms (they call it the “innate” immune system). The next generation of anti-cancer drugs may include some anti-inflammatory therapies, as well as traditional chemotherapies. Instructors with a special interest in cancer may wish to incorporate information in the article into their discussion of Chapter 18 – Cancer – in Human Biology, 5th ed.

The article points out that the immune system is also increasingly being implicated as a possible player in a whole host of chronic diseases, including heart disease, diabetes, Alzheimer’s disease, and schizophrenia and depression. More information is likely to be forthcoming on the role of the immune system in these diseases in the years to come.