scholarly journals Comparing Biomarkers for Predicting Pathological Responses to Neoadjuvant Therapy in HER2-Positive Breast Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Fuxing Zhao ◽  
Xingfa Huo ◽  
Miaozhou Wang ◽  
Zhen Liu ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diagnostic Accuracy ◽  
Neoadjuvant Therapy ◽  
Her2 Positive ◽  
Summary Receiver Operating Characteristic ◽  
Ki 67 ◽  
Predictive Values ◽  
Pik3ca Mutations ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

IntroductionThe predictive strength and accuracy of some biomarkers for the pathological complete response (pCR) to neoadjuvant therapy for HER2-positive breast cancer remain unclear. This study aimed to compare the accuracy of the HER2-enriched subtype and the presence of PIK3CA mutations, namely, TILs, HRs, and Ki-67, in predicting the pCR to HER2-positive breast cancer therapy.MethodsWe screened studies that included pCR predicted by one of the following biomarkers: the HER2-enriched subtype and the presence of PIK3CA mutations, TILs, HRs, or Ki-67. We then calculated the pooled sensitivity, specificity, positive and negative predictive values (PPVs and NPVs, respectively), and positive and negative likelihood ratios (LRs). Summary receiver operating characteristic (SROC) curves and areas under the curve (AUCs) were used to estimate the diagnostic accuracy.ResultsThe pooled estimates of sensitivity and specificity for the HER2-enriched subtype and the presence of PIK3CA mutations, namely, TILs, HRs, and Ki-67, were 0.66 and 0.62, 0.85 and 0.27, 0.49 and 0.61, 0.54 and 0.64, and 0.68 and 0.51, respectively. The AUC of the HER2-enriched subtype was significantly higher (0.71) than those for the presence of TILs (0.59, p = 0.003), HRs (0.65, p = 0.003), and Ki-67 (0.62, p = 0.005). The AUC of the HER2-enriched subtype had a tendency to be higher than that of the presence of PIK3CA mutations (0.58, p = 0.220). Moreover, it had relatively high PPV (0.58) and LR+ (1.77), similar NPV (0.73), and low LR− (0.54) compared with the other four biomarkers.ConclusionsThe HER2-enriched subtype has a moderate breast cancer diagnostic accuracy, which is better than those of the presence of PIK3CA mutations, TILs, HRs, and Ki-67.

scholarly journals UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells

2021 ◽  
Author(s):  
Jun Hua ◽  
Zhe Zhang ◽  
Lili Zhang ◽  
Yan Sun ◽  
Yuan Yuan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Needle Biopsy ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer

Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.

scholarly journals The role of the neoadjuvant approach in the treatment of primary operable HER2 positive breast cancer

2020 ◽  
Vol 10 (2) ◽  
pp. 45-52
Author(s):  
M. A. Frolova ◽  
Е. V. Glazkova ◽  
A. V. Petrovsky ◽  
О. V. Krokhina ◽  
M. В. Stenina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Response ◽  
Residual Tumor ◽  
Response To Treatment ◽  
Comprehensive Treatment ◽  
Her2 Positive ◽  
Ki 67 ◽  
Her2 Positive Breast Cancer ◽  
Neoadjuvant Systemic Therapy ◽  
Positive Breast Cancer

Neoadjuvant systemic therapy is an essential component of the comprehensive treatment of primary operable HER2‑positive breast cancer. Therefore, it is extremely important to search for treatment efficacy predictors and optimal system for assessing tumor response to treatment. The study analyzed factors predicting pathological complete response (pCR) in patients with luminal and non‑luminal HER2‑positive tumor subtypes. The morphological assessment of the tumor response to treatment was carried out using the RCB system; additional characteristics of the residual tumor were studied as well. It was shown that a comprehensive assessment involving the use of the RCB system and determination of the Ki ‑ 67 level helps to divide patients into prognostic groups and individualize the adjuvant therapy plan.

scholarly journals Role of Post-Neoadjuvant therapy with trastuzumab emtansine in HER2-positive breast cancer

2021 ◽  
pp. 68-74
Author(s):  
E. V. Lubennikova ◽  
Ya. V. Vishnevskaya
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Residual Tumor ◽  
Long Term Results ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

The widespread introduction of anti-HER2 agents has changed the natural course of Her2-positive breast cancer. The use of trastuzumab, and later dual anti-HER2 blockade with pertuzumab, in neoadjuvant regimens significantly increased the chances of complete cure. However, among patients with early and locally advanced forms of Her2-positive cancer, there is a cohort with an extremely unfavorable prognosis – tumors that have not achieved complete pathomorphological regression after neoadjuvant chemotherapy.The presence of a residual tumor in Her2-positive breast cancer has long been only a prognostically unfavorable factor without the potential to influence disease outcome. The results of the international phase III study KATHERINE, which demonstrated the high efficacy of post-adjuvant therapy with trastuzumab emtansine (T-DM1) in this patient cohort, have established a new standard of care. Due to T-DM1 adjuvant therapy, the possibility to significantly improve long-term results determined the predictive characteristics of the morphological response to the choice of treatment tactics, which became an important argument in favor of neoadjuvant therapy in patients with not only locally advanced but also primarily resectable Her2-positive breast cancer, followed by personalization of therapy.This article presents our own experience with post-neoadjuvant therapy with trastuzumab emtansine in a young patient with a residual tumor. The data of the main studies in early Her2-positive breast cancer are summarized.

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