Loss of Tumor Suppressor Improves Breast Cancer Response to Neoadjuvant Therapy

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(ChemotherapyAdvisor) – Loss of retinoblastoma (RB) protein expression is associated with the complete pathologic response of breast cancer patients to neoadjuvant chemotherapy, according to a team of the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. This conclusion is based on a study entitled “RB-pathway Disruption is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer,” which was published online in Clinical Cancer Research on July 18.

In this study, the researchers sought to determine if dysregulation of the RB tumor suppressor pathway is associated with improved response to neoadjuvant chemotherapy in breast cancer. Using an RB-loss gene expression signature, the investigators were able to analyze the association between pathway status and pathological complete response for 3 different neoadjuvant regimens. Pretreatment tumor biopsies were assayed for RB-pathway status by parallel immunohistochemical analysis to determine this association as well.

The investigators reported the following results. Loss of RB expression signature was associated with increased pathological complete response of breast cancer patients (N=1,000) to treatment with neoadjuvant therapy. A similarly improved response was found in both ER-positive and ER-negative breast cancer. Other breast cancer-associated genes, including p16ink4a, positively correlated with the RB-loss signature (R=0.493–0.5982) and pathological complete response. More importantly, RB-deficient tumors experienced an overall improved response to neoadjuvant chemotherapy.

Based on these data, the researchers concluded that RB-status is associated with the response to neoadjuvant chemotherapy in breast cancer and could be employed to inform treatment.

Abstract

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