Triple-negative breast cancer is an aggressive disease that presents an enormous clinical challenge. Its biology is less well understood compared with many other cancers and there is an urgent need for new prognostic tools and treatments. Now, a new study suggests screening patients for the prolactin receptor may offer a step forward.

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The researchers found that cancer cells in triple-negative tumors that lacked the prolactin receptor were not only more aggressive, they also divided more rapidly and were more invasive.

The study is the work of researchers at McGill University in Canada, who report their findings in the journal Scientific Reports.

A diagnosis of triple-negative breast cancer means the tumor lacks the three most common types of receptor known to drive most breast cancer growth. These receptors are: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2).

Around 15 percent of breast cancer is triple-negative. Unfortunately, it is typically associated with a high rate of recurrence and poor patient outcome.

Suhad Ali, associate professor of medicine and senior author of the new study, explains that triple-negative breast cancer is very difficult to treat. Compared with other types of breast cancer, targeted treatment options are limited and patients often have to undergo invasive chemotherapy and have a poor prognosis.

Studies that have probed the biology of triple-negative breast cancer suggest it is not one disease but a range of diverse cancers that behave differently in different patients.

For example, a study published in 2011 that used gene expression profiles suggested there are at least six subgroups of triple-negative breast cancer.

Prof. Ali and colleagues note that, despite these advances, there is still a need to better understand the biology of triple-negative breast cancer and the molecular pathways involved.

For their study, they examined data on 580 women with triple-negative breast cancer and found survival was prolonged in those whose tumors expressed the prolactin receptor.

They also found that prolactin hormone reduced the cancer cells’ ability to divide and form new tumors – thereby making the cancer less aggressive.

Using a preclinical animal model, they found cancer cells in tumors that lacked the prolactin receptor were not only more aggressive, they also divided more rapidly and were more invasive, compared with those in tumors that expressed the receptor.

Prof. Ali notes that the role of prolactin in breast cancer is still not fully understood and remains controversial. More knowledge about the hormone could affect the advice doctors give patients at high risk for breast cancer – for instance, about using breast-feeding to protect against the disease.

However, Prof. Ali says their findings support those of studies that suggest prolactin has a protective effect against breast cancer and – since breast-feeding is a natural way to produce the hormone in large quantities – it may well reduce women’s risk for the disease.

The results suggest that screening for the prolactin receptor could indicate which patients might benefit from prolactin treatment as a single agent, or in combination with less aggressive chemotherapy. We think this could be a revolutionary path to developing new treatments for breast cancer.”

Prof. Suhad Ali

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