Certain breast cancers spread to the bones using an enzyme that drills “seed holes” for planting new tumours, research has shown.



The discovery could lead to treatments aimed at preventing secondary breast cancers in patients with non-hormone sensitive disease.

The enzyme lysyl oxidase (Lox) is released from the primary tumour in the breast. Scientists found that it produces holes in bone that provide fertile ground for the growth of spreading, or metastatic, cancer cells.

But the process could be blocked, at least in mice, with bisphosphonate drugs that prevent bone loss and are used to treat osteoporosis.

The drugs are already prescribed to men with advanced prostate cancer that has spread to the bones, to prevent pain and fractures.

Dr Alison Gartland, from the University of Sheffield, who led the research, said: “This is important progress in the fight against breast cancer metastasis and these findings could lead to new treatments to stop secondary breast tumours growing in the bone, increasing the chances of survival for thousands of patients.

“We are really excited about our results that show breast cancer tumours send out signals to destroy the bone before cancer cells get there in order to prepare the bone for the cancer cells’ arrival.

“The next step is to find out exactly how the tumour secreted Lox interacts with bone cells to be able to develop new drugs to stop the formation of the bone lesions and cancer metastasis. This could also have implications for how we treat other bone diseases too.”

Most breast cancers are hormone sensitive, meaning they are fuelled by the female hormone oestrogen. But it was non-oestrogen sensitive (oestrogen receptor negative, or ER negative) breast cancers that used the Lox mechanism to spread to the bones, the scientists found. Why this should be the case remains unanswered, but Lox production was linked to low-oxygen conditions in the primary tumour.

Secondary breast cancer that has spread to the bones or vital organs such as the liver is the primary cause of the 12,000 deaths caused by the disease each year in the UK.

An estimated 85% of secondary breast cancers involve bone metastasis.

The findings are reported in the journal Nature. Study co-author Dr Janine Erler, from the University of Copenhagen, said: “Once cancer spreads to the bone it is very difficult to treat. Our research has shed light on the way breast cancer cells prime the bone so it is ready for their arrival.

“If we were able to block this process and translate our work to the clinic, we could stop breast cancer in its tracks thereby extending patients’ lives.”

Katherine Woods, from Breast Cancer Campaign and Breakthrough Breast Cancer, a new organisation formed from the merger of two leading breast cancer charities, said: “By unveiling the role that the protein Lox is playing, these results open up a whole new avenue for research and treatments that could stop breast cancer spreading to the bone. The research also adds weight to the growing body of evidence supporting the role of bisphosphonates in stopping secondary breast cancer in its tracks.

“The reality of living with secondary breast cancer in the bone is a stark one, which leaves many women with bone pain and fractures that need extensive surgery just when they need to be making the most of the time they have left with friends and family.

“Secondary breast cancer kills 1,000 women each and every month in the UK alone and yet we still don’t know enough about how and why breast cancer spreads to stop it.”

Breast Cancer Campaign contributed funding to the research.