Abstract
BackgroundAPOBEC3B was recently identified as a gain-of-function enzymatic source of mutagenesis, which may offer novel therapeutic options with molecules that specifically target this enzyme. In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. However, its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated.Patients and methodsRNA was isolated from 55 primary breast cancers and paired metastases, including regional lymph node (N = 20) and distant metastases (N = 35). APOBEC3B mRNA levels were measured by RT-qPCR. Expression levels of the primary tumors and corresponding metastases were compared, including subgroup analysis by estrogen receptor (ER/ESR1) status.ResultsOverall, APOBEC3B mRNA levels of distant metastases were significantly higher as compared to the corresponding primary breast tumor (P = 0.0015), an effect that was not seen for loco-regional lymph node metastases (P = 0.23). Subgroup analysis by ER-status showed that increased APOBEC3B levels in distant metastases were restricted to metastases arising from ER-positive primary breast cancers (P = 0.002). However, regarding ER-negative primary tumors, only loco-regional lymph node metastases showed increased APOBEC3B expression when compared to the corresponding primary tumor (P = 0.028).ConclusionAPOBEC3B mRNA levels are significantly higher in breast cancer metastases as compared to the corresponding ER-positive primary tumors. This suggests a potential role for APOBEC3B in luminal breast cancer progression, and consequently, a promising role for anti-APOBEC3B therapies in advanced stages of this frequent form of breast cancer.
Highlights
Breast cancer is the fifth cause of overall cancer related death [1] and this mortality is largely caused by progression of metastatic disease [2]
APOBEC3B mRNA levels of distant metastases were significantly higher as compared to the corresponding primary breast tumor (P = 0.0015), an effect that was not seen for loco-regional lymph node metastases (P = 0.23)
APOBEC3B mRNA levels are significantly higher in breast cancer metastases as compared to the corresponding ER-positive primary tumors
Summary
Breast cancer is the fifth cause of overall cancer related death [1] and this mortality is largely caused by progression of metastatic disease [2]. The generally accepted hypothesis is that metastases are caused by multiple intricate steps that arise in the primary tumor site [3]. The study of molecular differences between matched primary tumors and metastatic lesions may improve our understanding of disease progression and has the potential to reveal novel, potentially targetable drivers of metastatic progression. APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. Its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated
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