Higher lignan levels improve breast cancer survival
In an article published online on September 6, 2011 in the Journal of Clinical Oncology, German researchers report that high serum levels of enterolactone, a biomarker of lignan intake, are associated with a significantly greater chance of surviving postmenopausal breast cancer in comparison with having low levels. Lignans are phytoestrogen compounds found in flax and other seeds, in addition to vegetables and wheat. These compounds are converted in the colon to enterolactone, which is then absorbed into the bloodstream.
Serum enterolactone levels were measured in blood samples obtained between 2002 to 2005 from 1,140 postmenopausal women with breast cancer. Incidences of tumor metastasis or patient death were documented over a 6.1 median follow-up period.
One hundred sixty-two deaths occurred over follow-up. The median enterolactone level for survivors was 21.4 nanomoles per liter (nmol/L), compared to 17.0 nmol/L for those who did not survive. Women whose enterolactone levels were among the top 25 percent of participants had a 42 percent lower risk of dying over follow-up compared to those whose levels were among the lowest fourth. Subjects whose lignan intake was highest experienced a similarly reduced risk of undergoing metastasis. Further analysis determined a protective effect for enterolactone on estrogen receptor-negative tumors as opposed to those which were receptor-positive.
"We now have first clear evidence showing that lignans lower not only the risk of developing postmenopausal breast cancer, but also the mortality risk," stated lead researcher Jenny Chang-Claude of the German Cancer Research Center in Heidelberg. "The result was significant only for the group of tumors that have no receptor for the estrogen hormone. This gives reason to suspect that enterolactone protects from cancer not only by its hormone-like effect … In order to find out whether enterolactone also inhibits the aggressiveness of estrogen receptors in estrogen-positive tumors, we would need to expand this study to include much larger groups of women."
"By eating a diet that is rich in wholemeal products, seeds and vegetables, which is considered to be health-promoting anyway, everybody can take in enough lignans," she recommended.
Breast cancer cells frequently metastasize to the bone, where they cause severe degradation of bone tissue. Metastatic cancer affects more than half of all women during the course of their disease. Bone metastases are a significant cause of morbidity due to pain, pathological fractures, hypercalcemia (abnormally high levels of calcium in blood plasma), and spinal cord compression. The bisphosphonates, including alendronate (Fosamax), tiludronate (Skelid), pamidronate (Aredia), etidronate (Didronel), risedronate (Actonel), ibandronate, and zoledronic acid (Zometa), are a class of drugs that protect against the degradation of bone, primarily by inhibiting osteoclast-mediated bone resorption (bone breakdown).
Bisphosphonates are analogs of a naturally occurring compound, called pyrophosphate, which serves to regulate calcium and prevent bone breakdown. Bisphosphonates are a major class of drugs used for the treatment of bone diseases as they have a marked ability to inhibit bone resorption. Bisphosphonates are considered standard care for tumor-associated hypercalcemia and have been shown to reduce bone pain, improve quality of life, and to delay and reduce skeletal events (Hortobagyi 1996; Roemer-Becuwe et al. 2003).
The renewal of bone is responsible for bone strength throughout our life. Old bone is removed (resorption) and new bone is created (formation). This process is called bone remodeling. Healthy bone is continually being remodeled. Two main types of cells are responsible for bone renewal: the osteoblasts involved in bone formation and the osteoclasts involved in bone resorption. There are several stages involved in bone remodeling. The first is activation. This process involves preosteoclasts that are stimulated and differentiated under the influence of cytokine and growth factors to mature into active osteoclasts. The next step is resorption, in which osteoclasts digest mineral matrix (old bone). The third step is reversal, which ends resorption and signals for the final phase, formation. During this stage, osteoblasts are responsible for bone matrix synthesis (collagen production). Two other noncollagenous proteins are also formed: osteocalcin and osteonectin, together they form new bone.
In patients with bone metastases, bone resorption by the osteoclasts is increased and exceeds bone reformation. Calcium lost from the bones appears in increased amounts in the patient's blood serum and urine. This increase in bone resorption may result in pain, bone fractures, spinal cord compression, and hypercalcemia.
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