Posted by on December 21, 2011 - 8:34am

Why do so many postmenopausal women who are treated for estrogen-sensitive breast cancer quit using drugs that help prevent the disease from recurring?

The first study to actually ask the women themselves -- as well as the largest, most scientifically rigorous study to examine the question -- reports 36 percent of women quit early because of the medications’ side effects, which are more severe and widespread than previously known. The Northwestern Medicine research also reveals a big gap between what women tell their doctors about side effects and what they actually experience.

“Clinicians consistently underestimate the side effects associated with treatment,” said lead investigator Lynne Wagner, an associate professor in medical social sciences at Northwestern University Feinberg School of Medicine and a clinical psychologist at Robert H. Lurie Comprehensive Cancer Center. “They give patients a drug they hope will help them, so they have a motivation to underrate the negative effects. Patients don’t want to be complainers and don’t want their doctor to discontinue treatment. So no one knew how bad it really was for patients.”

The symptom most likely to cause women to stop using the drugs was joint pain. Other side effects women reported as compromising their quality of life were hot flashes, decreased libido, weight gain, feeling bloated, breast sensitivity, mood swings, irritability and nausea.  The drugs, aromatase inhibitors, stop the production of estrogen in postmenopausal women, whose breast cancer cells are stimulated by estrogen. About two-thirds of breast cancers are estrogen sensitive, and aromatase inhibitors reduce the recurrence of cancer in postmenopausal women.

The women at highest risk for quitting the medications before the recommended five years are those who still are experiencing residual side effects from recent chemotherapy or radiation therapy when they start the aromatase therapy, according to the study. Women who had surgery for breast cancer but not chemotherapy or radiation therapy, or who weren’t taking many other medications, were more likely to keep taking the aromatase medication.

“The more miserable they were before they started, the more likely they were to quit,” Wagner said. “By the time they get through chemotherapy or radiation, they have to face five more years of another medication that will make them feel lousy. They feel like they already lost enough time to cancer and have reached their threshold for feeling bad.”

“This is a wake-up call to physicians that says if your patient is feeling really beaten up by treatment, the risk of her quitting early is high,” Wagner said. “We need to be better at managing the symptoms of our patients to improve their quality of life.”

The new research exposes the disparity between clinicians’ reporting of side effects and women’s actual experiences. In a previous study, clinicians reported 5 percent of their patients experienced moderate to severe symptoms as a result of taking aromatase inhibitors. The new Northwestern study surveyed 686 women with a detailed questionnaire about their symptoms before treatment and at three, six, 12 and 24 months after starting treatment. The researchers found after three months of treatment that 33 to 35 percent of women had severe joint pain, 28 to 29 percent had hot flashes, 24 percent had decreased libido, 15 to 24 percent had fatigue, 16 to 17 percent had night sweats and 14 to 17 percent had anxiety. These numbers increased as women were on treatment longer.

Earlier studies also asked women to recall their symptoms after treatment ended, which is less accurate than reporting them at regular intervals while taking the drugs.

As a result of the side effects, 36 percent of women ended treatment before an average of 4.1 years. After two years, 10 percent had quit; the remainder quit between 25 months and the 4.1 years.

“These findings can help us identify women at risk for quitting the therapy, counsel them about the importance of staying on it and provide treatment for troubling side effects,” Wagner noted.

Weight gain can be addressed with nutritional counseling, while mood swings and irritability can be treated with cognitive behavioral therapy or mind-body techniques, Wagner said. Joint pain can be tempered with nonsteroidal anti-inflammatory drugs, or women may be switched to a different hormonal medication. Nausea can be reduced with medication.

This multi-site trial was conducted by the Eastern Cooperative Oncology Group, a national clinical cancer research organization funded by the National Cancer Institute.  Wagner’s research was presented Dec. 9 at the 34th Annual San Antonio Breast Cancer Symposium.

Posted by on August 22, 2011 - 6:35am

High-dose vitamin D relieves joint and muscle pain for many breast cancer patients taking estrogen-lowering drugs, according to a new study from Washington University School of Medicine in St. Louis.

The drugs, known as aromatase inhibitors, are commonly prescribed to shrink breast tumors fueled by the hormone estrogen and help prevent cancer recurrence. They are less toxic than chemotherapy, but for many patients, the drugs may cause severe musculoskeletal discomfort, including pain and stiffness in the hands, wrists, knees, hips, lower back, shoulders and feet.

"About half of patients can experience these symptoms," says Antonella L. Rastelli, MD, assistant professor of medicine and first author of the study published online in the journal Breast Cancer Research and Treatment. "We don't know exactly why the pain occurs, but it can be very debilitating to the point that patients decide to stop taking aromatase inhibitors."

Because the drugs reduce cancer recurrence, finding a way to help patients stay on them is important for long-term, relapse-free survival, according to Rastelli. Aromatase inhibitors are prescribed to post-menopausal women for at least five years and often longer after a breast cancer diagnosis. There is some evidence that patients who experience the drugs' side effects are less likely to see their cancer return, providing even more incentive to help these patients continue taking them.

It was Rastelli's colleague, Marie E. Taylor, MD, assistant professor of radiation oncology, who first noticed that patients on aromatase inhibitors who experienced this pain found some relief from high doses of vitamin D.

So Rastelli's group recruited 60 patients who reported pain and discomfort associated with anastrozole, one of three FDA-approved aromatase inhibitors. The patients they studied also had low vitamin D levels. Half the group was randomly assigned to receive the recommended daily dose of vitamin D (400 international units) plus a 50,000-unit vitamin D capsule once a week. The other half received the daily dose of 400 units of vitamin D plus a weekly placebo. All subjects received 1,000 milligrams of calcium daily throughout the study.

Patients in the study reported any pain they experienced through three different questionnaires. They were asked to quantify their pain intensity, as well as report how much the pain altered their mood, affected their work and interfered with relationships and daily activities. The results show that patients receiving high-dose vitamin D every week reported significantly less musculoskeletal pain and also were less likely to experience pain that interfered with daily living.

"High-dose vitamin D seems to be really effective in reducing the musculoskeletal pain caused by aromatase inhibitors," Rastelli says. "Patients who get the vitamin D weekly feel better because their pain is reduced and sometimes goes away completely. This makes the drugs much more tolerable. Millions of women worldwide take aromatase inhibitor therapy, and we may have another 'tool' to help them remain on it longer."

Like anastrozole used in this study, the other two FDA-approved aromatase inhibitors, letrozole and exemestane, also cause musculoskeletal pain. Given the similar side effects, Rastelli says patients on these drugs may also benefit from high-dose vitamin D.

The vitamin used in this study is a plant-derived type called vitamin D2. Rastelli says it achieves the best results when given weekly because the body metabolizes it within seven to 10 days. Rastelli and her colleagues did not use high-dose vitamin D3, which remains in the body longer.

"This was a very carefully conducted study, and the placebo control makes the findings quite compelling," says Matthew J. Ellis, MD, PhD, the study's senior author and director of the Breast Cancer Program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis. "We should follow up these findings further to determine the most efficacious and safe approach to vitamin D supplementation in our breast cancer patients."

Since vitamin D helps the body absorb calcium, too much of it can cause high levels of calcium in the urine, which may increase the risk of kidney stones. Such possible side effects emphasize the importance of tracking patients' urine calcium levels while taking high-dose vitamin D.

"It's important to monitor the patients, but overall it appears to be very safe," Rastelli says. "Because vitamin D2 is eliminated from the body so quickly, it's very hard to overdose."

In addition to relieving pain, the group wanted to examine whether vitamin D could protect against the bone loss often seen in patients taking aromatase inhibitors. The researchers measured each patient's bone density at the beginning of the study and again after six months.

Perhaps because of its role in calcium absorption, high-dose vitamin D did appear to help maintain bone density at the neck of the femur, the top of the thighbone near the hip joint. Although the result did not reach statistical significance, Rastelli calls the result promising and worth further studies.

"It's great that we have something as simple as vitamin D to help patients alleviate some of this pain," Rastelli says. "It's not toxic it doesn't cause major side effects. And if it is actually protecting against bone loss, that's even better."

Rastelli AL, Taylor ME, Gao F, Armamento-Villareal R, Jamalabadi-Majidi S, Napoli N, Ellis MJ. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. Online June 2011.

Source: Washington University in St. Louis

 

 

 

Posted by on February 23, 2011 - 7:10am

Painful Hip Fractures Strike Breast Cancer Survivors

A hip fracture is not common in a 54-year-old woman, unless she is a 54-year-old breast cancer survivor, according to a new Northwestern Medicine study. Researchers found that a combination of early menopause due to breast cancer treatment and common drugs used to treat breast cancer, could be weakening the bones of breast cancer survivors once they hit middle age, leading to hip fractures.

Results of the study are published in the February 2011 issue of Clinical Cancer Research.

Hip fractures are rare in people under 70. Yet, Northwestern Medicine physician Beatrice Edwards, M.D., found that several breast cancer survivors in their early 50s were coming to her for treatment of hip fractures.  Edwards is director of the Bone Health and Osteoporosis program and associate professor of medicine and of orthopaedic surgery at Northwestern University Feinberg School of Medicine.

Researchers studied six of these women over one year and assessed the type of breast cancer they had, the treatment they underwent and a hip fracture’s effect on quality of life, said Edwards, lead author of the study.

“One year after the fracture the women still reported difficulty with climbing stairs, shopping and heavy housekeeping,” Edwards said. “Their health care costs may increase and their fractures contribute to losing some independence.”

Edwards was surprised to find that the majority of the women did not have osteoporosis, but did have lower than normal bone mineral density (osteopenia). This suggests that rapid change in bone architecture from chemotherapy, early menopause and adjuvant therapy may not be evident on bone mineral density test, Edwards said.

The women had early-stage breast cancer and received treatment including lumpectomy, radiation therapy and chemotherapy with cytoxan and adriamycin one to four years before the fracture occurred. They were all perimenopausal at the time of the fracture.

Four of the six women had breast cancer that grew in response to estrogen and received aromatase inhibitors (AIs) as part of their cancer therapy to block their bodies from making estrogen. Recent studies have linked AIs with possible bone loss in women.   Edwards’ team also reviewed reports from the FDA’s adverse event reporting system and other databases and found that AIs were the most common drug class associated with hip fractures.

“Although the majority of women with breast cancer can expect to be fully cured from the disease, the prevention of cancer treatment-induced bone loss is important to consider in cancer survival,” Edwards said. “More research needs to be done before treatment guidelines are changed, but greater awareness of the adverse effects of certain breast cancer drugs is needed.”

Edwards said the next step is for researchers to conduct a clinical trial and give bone density screenings to women before they enter breast cancer chemotherapy. High-risk patients would be flagged and given preventive bone loss therapy and monitored for premature hip fractures.

“The pain and suffering and hospital stays and higher health costs associated with these hip fractures might be prevented through early intervention,” Edwards said.

The title of the paper is “Cancer therapy associated bone loss: Implications for hip fractures in mid-life women with breast cancer.”

By Erin White, Northwestern Newscenter