Update From the Medical Journals: December 2012

What's the latest news in the medical journals this month? Find out what your doctor is reading.

Longer Tamoxifen Use Reduces Breast Cancer Deaths

Breast cancer is divided into types based on whether the cells have receptors for the female hormone estrogen. Receptors are proteins on the surface of cells. If the cancer has estrogen receptors, estrogen can stimulate the cells to grow and divide, resulting in more cancer. These cancers are known as ER-positive. Tamoxifen is a common breast-cancer drug that blocks estrogen receptors on cells. It prevents breast cancer from growing or spreading.

Women who take tamoxifen for 10 years instead of 5 years can further reduce their chance of dying from breast cancer, a new study says.

Researchers focused on a group of 6,846 women with ER-positive breast cancer. When the study began, they already had taken the drug tamoxifen for 5 years. This is the standard length of treatment. In the study, the women were randomly assigned to the standard treatment or to take tamoxifen for 5 more years.

By the end of the study, cancer had returned in 25% of women who took the drug for 5 years and 21% of those who took it for 10 years. About 12% of the women who took the drug for 10 years died of breast cancer, compared with 15% of the women who stopped taking tamoxifen after 5 years. These were important differences. The journal Lancet published the study online on December 6.

Another drug that is used for ER-positive cancer is letrozole (Femara). It is only effective after menopause. Compared to tamoxifen, letrozole is more effective against breast cancer. Taking both drugs is no better than taking letrozole alone. Letrozole is commonly chosen over tamoxifen for women after menopause. This study did not look at whether longer treatment with letrozole lowered cancer deaths; it only looked at tamoxifen.

Breast cancer treatment involves some complicated decisions. If you have ER-positive cancer, you need to decide whether tamoxifen or letrozole is the appropriate drug to take. If you choose tamoxifen, then you have to decide for how long to take it. It is likely that 10 years will become the new standard treatment plan. But tamoxifen does cause serious side effects that women need to consider. For example, tamoxifen triples the risk of blood clots and doubles the risk for uterine cancer. Tamoxifen also increases stroke risk by about 50%. Other side effects are hot flashes, night sweats and vaginal discharge.

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Weight May Affect Drug Treatment for High Blood Pressure

Your weight may predict the best combination of drugs for treating your high blood pressure, according to a study published online in the Lancet December 6.

Researchers looked at data from more than 11,000 people who needed two drugs to treat their high blood pressure. They were randomly divided into 2 groups. Both groups took benazepril (Lotensin). This is a type of blood pressure drug known as an ACE inhibitor. Half of the people also took hydrochlorothiazide, a diuretic. The other half took amlodipine (Norvasc) in addition to the benazepril. Amlodipine is a calcium channel blocker.

People in the diuretic group whose weight was normal had worse health outcomes compared with overweight people in the same group. They were 68% more likely to die or have a heart attack or stroke than obese people taking a diuretic. People with normal weight did just fine in the calcium channel blocker group. Compared with similarly thin people in the diuretic group, those who took a calcium channel blocker had a 43% lower rate of death, stroke and heart attack. For people who were obese, both drug combinations worked equally well.

Doctors are going to have to carefully think about this study. Diuretics are trusted drugs for treating high blood pressure. They are often used alone. They are also the most commonly used medicine when a person needs more than one drug to treat high blood pressure. This study raises specific concerns about combining diuretics with ace inhibitors for people with normal body mass index ("BMI," calculated from weight and height). Based on this study, doctors should advise thin people that calcium channel blockers, like amlodipine, work better when combined with ace inhibitors, and are preferred.

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Patients with Deep Vein Thrombosis May Benefit from Longer Treatment

It's common for blood clots to form in the deep veins of the legs. This is called a deep venous thrombosis or DVT. Doctors treat DVT with blood-thinning drugs (anticoagulants). They make the clot stop growing. The most commonly used drug is warfarin (Coumadin). Normally, people take it for three to six months, sometimes longer. Bleeding can be a frequent complication.

A DVT can cause pain, leg swelling and complications. The most dangerous complication is a pulmonary embolus. This is a blockage of blood flow to one or more areas of your lungs. It occurs when a clot in the leg breaks off or dislodges, sending solid debris through your bloodstream and into the lung arteries.

A new study suggests that people with a DVT might benefit from taking a blood-thinning drug for longer than usual. And we may soon have a new drug called apixaban (Eliquis) to use. The New England Journal of Medicine published the study December 8.

The study included nearly 2,500 people who had completed standard treatment with warfarin after having a clot. There was no obvious reason for the clot, so doctors suspected they had a hereditary tendency to form clots. The people were randomly assigned to receive either apixaban or placebo pills twice a day. During the next year, 9% of those taking the placebo had a new blood clot. But only 1.7% of those taking apixaban had one. People taking the drug also had lower rates of stroke and death. There was no increase of major bleeding for people who took apixaban.

Is it important to extend the treatment time for DVT? I would say, stay tuned. Do not draw conclusions from this study. It suggests that new blood clots are quite common after treatment stops. But the study was designed to identify as many clots as possible — even clots that had slight symptoms. Patients were interviewed monthly, and they received ultrasound tests for even minor symptoms. We don't know what risk, if any, they carried relative to large, symptomatic clots.

If it turns out that longer treatment is beneficial, new drugs like apixaban may be a good choice. Warfarin is a tricky drug to use. It requires close monitoring with blood tests at least every three weeks to make sure the dose is correct. Certain drugs and foods can interact with it, which can hinder its effectiveness, or be dangerous.

Unlike warfarin, patients taking apixaban do not need frequent blood tests for monitoring. But it is not clear that it will be a better therapy. And doctors will need to consider drug costs before deciding whether long-term treatment with this drug is appropriate. Apixaban is likely to be a very expensive drug — about $10 per day — judging from the cost of two similar drugs, rivaroxaban (Xarelto) and dabigatran (Pradaxa).

Also, we still need to make sure it's a safe drug. This current study was designed and funded by the makers of the drug. They were careful to include people in the study who had a low risk for complications. This could make the drug look more safe than is fair. A related drug, dabigatran, has recently been linked to higher heart attack rates. Some patients who were at high risk for heart attack, including people who had daily full-dose aspirin on their medication list, were not allowed to participate in the apixaban study.

More News in Brief

• Kids Should Limit Milk to Two Cups a Day. Cow's milk can irritate an infant's intestines before age one year. After this age, it can prevent children from eating foods with more complete nutrition. What is the result? Iron deficiency. But milk also has vitamin D, which is an important nutrient. A new study tried to find out how much milk should children drink.

  Researchers surveyed parents about how many cups of milk their young children drank in an average day. Then they did blood tests to measure vitamin D and iron levels. The study included more than 1,300 healthy children between the ages of 2 years and 5 years. The study's conclusion was that 2 cups a day was the best amount of milk for a child to drink. The study results were published online in the journal Pediatrics on December 17.

  Kids who drank more than 2 cups were at risk for iron deficiency. For each additional cup of milk that a child drank in a typical day, iron levels were about 4% lower than those of children who drank 2 cups. Kids who drank less milk than this were at risk for vitamin D deficiency: If 1 cup was consumed in a typical day instead of 2, vitamin D levels were about 7% lower.) The exception was children with darker skin. In the winter, they needed to drink 3 to 4 cups of milk to get enough vitamin D.

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Mary Pickett, M.D. is an Associate professor at Oregon Health & Science University where she is a primary care doctor for adults. She supervises and educates residents in the field of Internal Medicine, for outpatient and hospital care. She is a Lecturer for Harvard Medical School and a Senior Medical Editor for Harvard Health Publications.

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