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DEAR DOCTOR: A friend of mine was recently diagnosed with breast cancer and is terrified of the chemotherapy her doctor is recommending. I read that some women can skip it. Is this true?

DEAR READER: Your friend's fear of chemotherapy is understandable. Its harsh side effects and its risk of toxicity to the body's organs are well-known. However, survival rates significantly improve with chemotherapy. This too is well-known -- and has been shown even in women with breast cancer that hasn't spread to the lymph nodes.

A recent study in The New England Journal of Medicine, however, has called into question the need for chemotherapy in some women who have breast cancer without lymph node metastasis. The trial looked at 9,719 women, ages 18 to 75, with cancer that was hormone receptor-positive and HER2-negative. Such cancer is often treated with hormone therapy, although chemotherapy can be used as well. In this trial, the authors gauged the need for chemotherapy based on a genetic tool called the 21-gene breast cancer assay, which evaluates the risk of recurrence based on 16 cancer-related genes and five other genes. Women who have higher scores in the screening have been shown to have a greater risk of recurrence of breast cancer compared to those with lower scores.

In this study, women with a 21-gene score of 26 or greater received chemotherapy and endocrine therapy (medications that block the estrogen receptor in breast cancer). Those with scores of 11 to 25 received either chemotherapy with endocrine therapy (chemoendocrine therapy) or endocrine therapy alone. Those with a score of 10 or less received only endocrine therapy. The majority of women in the trial (6,711) had scores between 11 and 25. All patients were followed for eight years.

In the group with scores of 11 to 25, no statistically relevant difference was found between those who received chemoendocrine therapy and those who received endocrine therapy alone. Although there was a small non-significant increase in the rate of recurrence at a local or distant site with endocrine therapy, there was no difference in survival rates between those who received chemotherapy and those who didn't. Extrapolating the data to nine years, the rate of invasive-free survival with chemoendocrine therapy would have been 84.7 percent, while it would have been 83.1 with endocrine therapy alone. The small difference suggests that chemotherapy might not be necessary in all patients with a midrange score.

For some, however, it might be. In women younger than 50, those with a 21-gene assay score of 16 to 25 showed a decrease in the rate of recurrence with chemotherapy. Still, no difference was seen in the survival rates.

I can't say what your friend should or shouldn't do. Perhaps -- unlike in this study -- her breast cancer involves lymph nodes and is hormone receptor-negative or HER-2 positive. Further, if she's under 50 and has a gene score of 16 or greater, she would almost certainly benefit from chemotherapy.

But, overall, the study does show that for many women with localized breast cancer, and a 21-gene assay score of 25 or less, chemotherapy may not be necessary.

DEAR DOCTOR: Just how addictive are antidepressants? My doctor thinks I should take one, but I know a lot of people who have had trouble stopping them. Do the drugs even work?

DEAR READER: Your questions land us in the midst of an important and ongoing discussion that has been taking place for some time now. Depression is a serious and sometimes life-threatening disorder that affects people of all ages, races and nationalities. According to the World Health Organization, it was the third-leading cause of disability throughout the world in 2004 and tops the list of disabilities in the developed world. A variety of medications to treat depression have been developed over the decades but have been accompanied by persistent questions about efficacy and long-term viability.

A specific group of symptoms, when experienced over time, mark a diagnosis of depression. These include low mood, low energy, feelings of worthlessness and an inability to experience pleasure, which is known as anhedonia. Additional symptoms can include altered sleep patterns, diminished appetite, an inability to concentrate and thoughts of self-harm. Diagnosis of depression, which can range from mild to moderate to severe, depends on accurate self-reporting of symptoms and of their duration.

When it comes to medications, things get complicated. That's because the causes of depression are poorly understood. Research suggests the condition may arise from certain chemical imbalances in the brain, chronic stress and anxiety, response to life events, temperament and a genetic predisposition. Antidepressants tackle the various chemical pathways that are believed to play a role in the disorder. However, depression medications don't work for everyone. As many as two-thirds of patients don't respond to the first drug they try. But by working with their doctors to fine-tune their treatment regimens -- there are a number of classes of antidepressants, each with its own therapeutic pathway -- many patients living with depression do find relief.

When it comes to stopping pharmaceutical treatment, there's sobering news. Although antidepressants were originally developed for short-term use, six to nine months in most cases, the nature of depression and the scarcity of alternative treatment options meant patients have stayed on the drugs for years at a time.

According to a recent report in The New York Times, which analyzed federal data, more than 15 million people in the U.S. have been taking antidepressants for more than five years. When you look at the two-year mark for antidepressant use, that number jumps to 25 million. It's this long-term use that has been most often associated with adverse effects among patients who stop the drugs. Symptoms of withdrawal may include headache, fatigue, nausea, insomnia, unwanted feelings and unusual physical sensations. Tapering rather than quitting an antidepressant is important, and it should always be done in partnership with the prescribing physician.

While all of this may sound dire, it's important to note that antidepressants, when used properly and as part of a comprehensive treatment program, can be helpful. If you do decide to move forward with a prescription, talk all of this over with your doctor. Make a plan regarding duration, and never make any changes to your drug regimen without medical supervision.

Eve Glazier, M.D., MBA, is an internist and assistant professor of medicine at UCLA Health. Elizabeth Ko, M.D., is an internist and primary care physician at UCLA Health.

Send your questions to, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095. Owing to the volume of mail, personal replies cannot be provided.


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