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New Biomarker Discovery Could Help Personalize Breast Cancer Treatment

Credit: The University of Southampton.

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Researchers from the University of Southampton have identified specific structures surrounding breast tumors in overweight cancer patients that may limit their response to therapy.

Breast tissue, tumors and macrophages

A healthy human breast consists of different types of fatty, glandular, supportive and connective tissues. Over recent years, a growing amount of research has explored whether any associations exist between body mass index (BMI) and breast cancer risk. Some evidence suggests that a larger BMI – and therefore higher fat content – is associated with an increased risk of developing breast cancer.


In breast cancer patients with a higher BMI, there is an increased amount of body fat surrounding the breast tissue. This has been shown to lead to an inflammatory immune response, whereby macrophages – a specific type of immune cell – can accumulate in the fat tissue of the breast.


What is a macrophage?


A macrophage is a form of white blood cell. These cells are responsible for surrounding and killing microorganisms, the removal of dead cells and the stimulation of other immune cells.

The formation of crown-like structures

When macrophages accumulate, they can cluster and form structures often referred to as “crown-like structures of the breast”, or CLS-Bs.


The influence of CLS-B formation on a patient’s cancer prognosis, and response to different treatment types, has remained largely unknown. University of Southampton researchers, including Dr. Stephen Beers, professor of immunology and immunotherapy, Dr. Ramsey Cutress, professor of breast cancer surgery and Dr. Charles Birts, principle investigator in breast cancer research, made this the focal point of their new study.


In a clinical cohort of HER2+ breast cancer patients, the researchers collected tissue samples to explore any associations that may exist between BMI and CLS-Bs, and how this may be linked to treatment response using the drug trastuzumab (Herceptin®).


What is HER2+ breast cancer?


HER2 is a type of protein. Breast cancer patients found to express increased HER2 levels are referred to as HER2+. This type of cancer often spreads faster than other types of breast cancer, but can respond well to treatments targeting the HER2 protein specifically. Trastuzumab is an example of anti-HER2 therapy.

Overweight HER2+ patients express CD32B biomarker

In HER2+ patients that were classified as overweight – or obese – a higher number of CLS-Bs were detected in the fat tissue surrounding the tumor. These patients were also found to progress to metastatic disease faster.


“These findings will be of interest to clinicians and researchers involved in breast cancer treatment as they could potentially be used to develop personalised treatment in patients with HER2 positive overexpressed breast cancer,” – Beers.


A biomarker, CD32B – an inhibitory receptor for the antibody IgG – was detected on the surface of macrophages that had formed CLS-Bs. When analyzing samples from obese and overweight patients, the research team found that the presence of this marker was associated with a poorer response to trastuzumab.


Beers and colleagues hope that the findings from this study could contribute to a targeted, personalized approach for treating HER2+ breast cancer patients: “For example, doctors would know that patients with a high BMI and the marker on their crown-like structures are likely to have a poor response to trastuzumab therapy,” says Beers in a news release published by the University of Southampton. “They may therefore benefit from more intensive anti-HER2 therapy earlier in their treatment.”

The observational data could also be used to support trastuzumab’s use in patients that do not possess the CD32B biomarker, Beers explains: “These patients could benefit from a lower dose of anti-HER2 therapy which may minimize the side-effects they experience.” He emphasizes that more studies are needed, with larger patient samples, to confirm these preliminary findings.


Reference: Beers S, Cutress R, Birts C. Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2+ breast carcinoma. Sci. Rep. 2022. doi: 10.1038/s41598-022-11696-6.


This article is a rework of a press release issued by The University of Southampton. Material has been edited for length and content.

Meet the Author
Molly Campbell
Molly Campbell
Senior Science Writer
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