Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine

Abstract

Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

Development and Assessment of a Novel Core Biopsy-Based Prediction Model for Pathological Complete Response to Neoadjuvant Chemotherapy in Women with Breast Cancer

“…Livingston-Rosanoff et al reported a retrospective study that included 38,864 patients who underwent NAC treatment and subsequent surgery for a solitary lesion varying from cT1 to cT3, which revealed that cT3 tumors have a lower probability of achieving pCR irrespective of molecular subtypes [ 22 ], which is consistent with our study. The possible explanation for this finding is that larger tumors have a higher chance of revealing heterogeneity of elevation, which may affect the sensitivity of chemotherapy [ 37 ]. Many prediction models involved clinical tumor staging (tumor size) as a predictive factor [ 38 , 39 , 40 ], which indicates it is a reliable factor for predicting pCR.…”

Development and assessment of a novel core biopsy-based prediction model for pathological complete response to neoadjuvant chemotherapy in breast cancer

“…Livingston-Rosanoff et al reported a retrospective study that included 38,864 patients who underwent NAC treatment and subsequent surgery for a solitary lesion varying from cT1 to cT3, which revealed that cT3 tumors have a lower probability of achieving pCR irrespective of molecular subtypes [20], which is consistent with our study. The possible explanation for this nding is that larger tumors have a higher chance of revealing heterogeneity of elevation, which may affect the sensitivity of chemotherapy [21]. Many prediction models involved clinical tumor staging (tumor size) as a predictive factor [22][23][24], which indicates it is a reliable factor for predicting pCR.…”

Somatic mutations in a multigene panel and impact on prognosis based on TP53 status in Chinese HER2‐positive patients undergoing neoadjuvant therapy: A single‐institution retrospective cohort

“…In recent years, an increasing number of clinical studies have focused on targeted therapies. Neoadjuvant therapy (NAT) has become a standard clinical practice used to downsize the tumor and increase the breast‐conserving surgery rate 4 . The addition of herceptin on top of chemotherapy increased the pathological complete response (pCR) rate to 38%, 5 and after intervention with both herceptin and pertuzumab, the pCR rate increased to approximately 70% 6 .…”