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Breast Cancer Genomic Recurrence Signature Influenced by BMI in Young Patients

NEW YORK – Body mass index (BMI) appears to influence an established gene expression-based breast cancer recurrence score in young women with a history of estrogen receptor (ER)-positive, HER2/ERBB2-negative breast cancer, according to new research by a Korean team.

"The findings of this study suggest that increasing BMI might be associated with a higher genomic risk in younger patients with ER-positive, ERBB2-negative breast cancer," co-corresponding authors Sung Gwe Ahn, with Gangnam Severance Hospital, and Sae Byul Lee, at the University of Ulsan College of Medicine's Asan Medical Center, and their colleagues wrote.

As they reported in JAMA Network Open on Monday, the researchers brought together data for nearly 2,300 Korean women diagnosed with stage I to stage III ER-positive, HER2/ERBB2-negative breast. The participants included women diagnosed between the ages of 22 and 81 years old who had undergone multigene panel testing with the Oncotype Dx 21-gene expression panel between the spring of 2010 and late 2020.

The team did not consider breast cancer cases diagnosed at stage IV, those classified as HER2-positive, or cases that involved neoadjuvant chemotherapy treatment prior to surgery.

In the subset of 776 women who were 45 years old or younger, the team saw differences in genetic recurrence score and related treatment patterns in the 101 women with a BMI of 25 or higher relative to the 675 women with a BMI below 25.

In particular, young women from the higher BMI group tended to have higher Oncotype Dx scores and were, consequently, more likely to receive post-surgical chemotherapy. Compared to the leaner patients under 45, they also had slightly higher rates of breast-conserving surgery rather than mastectomy surgery, along with increased rates of subsequent radiation or endocrine therapy.

The five-year recurrence-free survival reached nearly 97 percent for the women studied, the team reported, noting that 33 cancer recurrence cases occurred over an average of 45 months of follow-up time.

While BMI itself did not show ties to cancer recurrence, the researchers explained, the expression-based risk score was significantly linked to recurrence. Specifically, the 33 cases of cancer recurrence included just over 3 percent of the 546 individuals with low-risk scores and 7 percent of the 230 individuals with high-risk scores.

The results contrast with prior studies describing decreased Oncotype Dx recurrence scores in postmenopausal women from higher BMI groups, the researchers noted, highlighting the need for further research to interpret and expand on the current results in the younger, mainly pre-menopausal women.

"Taken together, further studies are warranted to understand the complexity of the mechanism by which enriched adipose tissues affects the genomic profiles of young patients with ER-positive breast cancer with obesity," the authors wrote.

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