A groundbreaking discovery holds out the hope of taming deadly non-hormone sensitive breast cancers.
In laboratory tests, Swedish scientists have succeeded in transforming the aggressive tumour cells so that they become highly responsive to standard hormone therapy.
They used an experimental drug to block a signalling molecule that transmits information between breast cancer cells and surrounding connective tissue.
Detailed analysis of around 1,400 breast cancers showed that women with high levels of the signalling molecule, PDGF-CC, in their tumours had a poor prognosis.
Lead scientist Professor Kristian Pietras, from Lund University, said: “We have … developed a new treatment strategy for aggressive and difficult-to-treat breast cancers that restores sensitivity to hormone therapy.
“These findings have major implications in the development of more effective treatments for patients with aggressive breast cancer.”
Most breast cancers are fuelled by female hormones, mostly oestrogen. They generally respond to treatments that either block activity of the hormones or cut off their supply.
The 10-15% of breast cancers that do not respond to hormone therapy treatments are known to be more aggressive and likely to recur.
Previously it was thought that different mammary gland cell types gave rise to different types of breast cancer. Hormone sensitivity was therefore “set” at the start of a cancer’s development.
The new research shows that communication between breast cancer cells and connective tissue via PDGF-CC can “switch off” hormone sensitivity.
When the Swedish team used an antibody drug to block the signalling pathway, non-hormone sensitive “basal” cancers were transformed into hormone sensitive “luminal” cancers.
Laboratory mouse studies showed that the altered tumours became “highly responsive” to standard hormone therapy.
The scientists wrote in the journal Nature Medicine: “Out of all breast carcinomas, basal-like tumours have the highest recurrence rate, the shortest time to recurrence and the worst overall survival rate owing to a paucity of therapeutic targets.
“Thus, new treatment approaches for patients with basal-like breast cancer are urgently required.”
The promising lab results justified evaluating the new treatment approach in clinical trials, they added.
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