When breast cancer patients develop metastatic disease — the cancer spreads from the breast to another location in the body — nearly 85 percent of these patients discover it has spread to their bones. Now, researchers from University of Sheffield and University of Copenhagen have identified an enzyme, which enables the spread of disease. The enzyme, LysYl Oxidase (or LOX), is secreted from the primary tumor and from there it causes holes in the bone, thus preparing the way for the spread of disease.

Importantly, the researchers also showed in a series of animal studies that treatment with bisphosphonate, an existing drug used to treat bone diseases, prevented these changes in the bone and so, too, blocked the spread of disease.

"If patients with high LOX levels are selected for the bisphosphonate treatment before the cancer has spread," Dr. Janine Erler, an associate professor at University of Copenhagen and lead co-author of the study, told Medical Daily, it might be possible to stop breast cancer from spreading to the bone.

Global Disease

Breast cancer is the most common cancer in women worldwide. The World Health Organization estimates that, currently, about 508,000 women die each year. Thought to be a lifestyle disease encountered mainly in the developed world, about half of all breast cancer cases and more than half — 58 percent — of all breast cancer deaths occur in less developed countries.

According to the American Cancer Society, a woman living in the United States has a one in eight — or 12.3 percent — lifetime risk of being diagnosed with breast cancer. The risk, though, is not evenly distributed over racial and ethnic groups. Asian/Pacific Islander women have the lowest incidence and death rates, while non-Hispanic white women have the highest. African-American women have lower rates than European American women for most age groups, however, in one age group — younger than 40 — their incidence rate is higher.

While survival rates are quite good when the disease is detected early, "cures are extremely rare when the cancer has spread," Erler told Medical Daily in an email.

For the current study, Erler and her co-researchers retrospectively analyzed a cohort of women whose breast cancer had not spread to their lymph nodes. Though all had their tumors removed, none of these patients had received chemotherapy, radiation, or other systemic treatments. Studying the records, the researchers discovered metastasis occurred within estrogen receptor-negative but not ER-positive patients.

"Estrogen receptor negative breast cancer [patients] have a very poor survival rate," said Erler. Analysis revealed a significant link between breast and metastasis to the bone, in particular. Searching further, the researchers “found LOX was significantly associated with increasing osteotropism” — metastatic spread to the bones.

“Our insight into the very early mechanisms of bone metastases… identifies a new step in bone metastasis and novel opportunities for therapeutic intervention,” the researchers concluded in their published research. If scientists are able to block this process of metastasis with existing treatments, breast cancer might be stopped... and patients' lives extended.

Source: Cox TR, Rumney RMH, Schoof EM, et al. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015.