Breast cancer therapy success rates drop sharply for overweight people

Being overweight can lead to several health issues and now a new study is revealing it can even hinder the treatment of breast cancer, according to a press release by the University of Southampton published on Tuesday. Researchers from the institution found that patients with a high body mass index had an environment around their breasts that could lead to the growth of tumors in that area.

'Crown-like structures' that engulf fat cells

More specifically, the researchers discovered that increased body fat surrounding the breast can cause inflammatory immune cells, called macrophages, to collect and accumulate in the breast's fat tissue. These macrophages can then develop into what the researchers call 'crown-like structures' that engulf the body's fat cells. This creates an environment conducive to the onset and growth of tumors.

To reach this conclusion, the researchers assessed samples from a group of HER2+ breast cancer patients and examined the link between high body mass index and the development of crown-like structures. They concluded patients who were overweight or obese had significantly more crown-like structures in the fat tissue surrounding their tumors and they were more prone to faster development of metastatic disease.

They even pinpointed a potential molecular biomarker called CD32B that when found on the surface of the macrophages in these crown-like structures resulted in a decreased response to therapy. The type of therapy used in the study was a drug called trastuzumab (Herceptin®).

Improved treatment options for overweight and obese patients

Stephen Beers, Professor of Immunology and Immunotherapy at the University of Southampton and lead author of the new research, said in the statement, "These findings will be of interest to clinicians and researchers involved in breast cancer treatment as they could potentially be used to develop personalized treatment in patients with HER2 positive overexpressed breast cancer."

"For example, doctors would know that patients with a high body mass index and the marker on their crown-like structures are likely to have a poor response to trastuzumab therapy. They may therefore benefit from more intensive anti-HER2 therapy earlier in their treatment."

Beers continued, "On the other hand, this study highlights how effective trastuzumab treatment is in patients that do not have the marker. So these patients could benefit from a lower dose of anti-HER2 therapy which may minimize the side effects they experience. Further studies with more patients will be needed to help confirm these initial findings."

The results were published in the journal Scientific Reports. The findings could be used to come up with improved treatments for overweight and obese patients. It should be noted that a high body mass index is associated with an increased risk of developing breast cancer and worse survival rates when the disease is present.

Study abstract:

Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer, the presence of CLS has been correlated to high body mass index (BMI), larger mammary adipocyte size and postmenopausal status. However, the prognostic significance of CLS in HER2 + breast cancer is still unknown. We investigated the prognostic significance of CLS in a cohort of 69 trastuzumab-naïve and 117 adjuvant trastuzumab-treated patients with primary HER2 + breast cancer. Immunohistochemistry of tumour blocks was performed for CLS and correlated to clinical outcomes. CLS were more commonly found at the adipose-tumour border (B-CLS) (64.8% of patients). The presence of multiple B-CLS was associated with reduced time to metastatic disease (TMD) in trastuzumab treated patients with BMI ≥ 25 kg/m² but not those with BMI < 25 kg/m². Phenotypic analysis showed the presence of CD32B + B-CLS was strongly correlated to BMI ≥ 25 kg/m² and reduced TMD in trastuzumab treated patients. Multivariable analysis suggested that CD32B + B-CLS positive tumours are associated with shorter TMD in trastuzumab-treated patients (HR 4.2 [95%CI, (1.01–17.4). This study indicates adipose-tumour border crown-like structures that are CD32B + potentially represent a biomarker for improved personalisation of treatment in HER2-overexpressed breast cancer patients.