Mastitis: massively common and poorly understood

Lactation mastitis is an inflammatory breast disease that causes pain, fever, and low milk supply. It’s one of the most common problems faced by people who are breastfeeding – about 1 in 5 will experience mastitis within the first 6 months after giving birth.

“[Mastitis is] incredibly painful in the breast, but it can also be associated with flu-like symptoms. So, the whole body becomes affected – there’s temperature, chills, aches,” Associate Professor Wendy Ingman, a breast biologist at the University of Adelaide, told Cosmos.

“Some women have described it as ‘the day I thought I was [going to] die’, because it’s just so debilitating.

“Sometimes, women end up being hospitalised […] and it can lead to a breast abscess as well.”

She recently spoke at the Cosmos Science City: Meet the Midwife event about her work in understanding the biological causes of mastitis, which may lead to improved prevention and treatment of the disease.

The challenges of mastitis can cause many women to turn to supplementary formula, or stop breastfeeding altogether, so this could allow more people to breastfeed for longer.

“We don’t currently have great ways of treating [mastitis] because we don’t understand enough about the biology of how mastitis occurs,” said Ingman, who is research leader of the Breast Biology and Cancer Unit at the Basil Hetzel Institute, at the Queen Elizabeth Hospital.

“We’ve based our approach to treating mastitis on what worked in the dairy industry 40 years ago.”

Mastitis treatment should be based on clinical evidence in women, not dairy cows

Mastitis in dairy cows is driven by infectious bacterial pathogens, which trigger inflammation in the mammary glands.

“So, there was an assumption that humans have the same relationship between pathogenic bacteria and mastitis, [which] hasn’t really been supported by clinical evidence,” Ingman says.

“What’s evolved is the idea that there’s a blockage in the breast, so there’s a build-up of milk which isn’t being secreted, and that’s causing bacteria to grow.”

She says that current treatments focus on trying to alleviate that blockage through gentle massage, regular feedings, warm showers, and rest. Then, if symptoms don’t resolve within 12-24 hours, antibiotics.

A photograph of a woman wearing a grey dress, outside
Professor Wendy Ingman. Credit: University of Adelaide

However, says Ingman: “There are women where you can find really high levels of pathogenic Staphylococcus aureus in their breast milk, and they have no symptoms whatsoever. And then there are some women who have mastitis, that are in the hospital with it, and they have no detectable bacteria at all.”

Clearly, pathogenic bacteria play a role in mastitis, but they aren’t the only culprit in humans.

In 2021, Ingman received a National Health and Medical Research Council (NHMRC) of Australia Ideas Grant to address these key gaps in our understanding.

Targeting the mediators of inflammation in the breast

Ingman and colleagues are researching the inflammatory triggers of mastitis and specifically inflammation in the absence of infection – known as sterile inflammation.

“The body’s immune system isn’t just looking for incoming danger, but it can also be looking for danger in our bodies. [Because] if there’s something going wrong, that needs attention,” she explains.

Specifically, they’re looking at certain proteins in breast milk that mediate this inflammation, called Danger Associated Molecular Patterns (DAMPs), which Ingman says may be more common in some women than others.

“When there’s a build-up of milk if there’s a blocked duct, there can be changes in the proteins,” says Ingman.

“Or, because there’s a build-up [of milk], stress signals put out by the breast then trigger the inflammatory process – irrespective of whether or not there’s bacteria there.”

Their research focuses on a receptor found on the surface of breast cells, called ‘toll-like receptor 4 (TLR4)’, which is activated by a range of different inflammatory triggers to kick-start an inflammatory response.

“If we know that mastitis is associated with these inflammatory triggers that are acting through this receptor, we could potentially detect those triggers in breast milk,” says Ingman.

Ultimately, this could lead to a new treatment for mastitis that works by targeting TLR4.

“So, a new treatment based on a better understanding of what is actually the underlying biology that’s causing [mastitis] specifically in humans,” she concludes.

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