scholarly journals STAT3 activation confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive breast cancer

2018 ◽  
Vol 109 (10) ◽  
pp. 3305-3315 ◽  
Author(s):  
Lei Wang ◽  
Quanren Wang ◽  
Mingzhao Gao ◽  
Li Fu ◽  
Yun Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takahiro Nakayama ◽  
Tetsuhiro Yoshinami ◽  
Hiroyuki Yasojima ◽  
Nobuyoshi Kittaka ◽  
Masato Takahashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Observational Study ◽  
Real World ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
The Real ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract Background Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post–T-DM1 treatments is currently lacking. We evaluated the effectiveness of post–T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. Methods In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post–T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken. Results Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8–6.9) months, 5.6 (4.6–6.4) months, and 22.8 (18.2–32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8–56.7) and 23% (15.1–31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months. Conclusions In the real-world setting in Japan, several post–T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings. Trial registration UMIN000038296; registered on 15 October 2019.

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.

scholarly journals CLINICAL CASE OF SUCCESFUL APPLICATION OF KADSYLA APPLICATION IN METASTATIC HER2 POSITIVE BREAST CANCER

2017 ◽  
pp. 56-58
Author(s):  
D. D. Sakaeva
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Clinical Case ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Pet Ct ◽  
Positive Breast Cancer

A clinical case of trastuzumab emtansine in therapy line 4 in patient with metastatic HER2positive breast cancer is provided. After 10  courses of targeted therapy by the drug a complete  response to the therapy was obtained. By results of PET CT conducted in the period from December 2015  to September 2017 the complete response is preserved.

scholarly journals Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

2019 ◽  
Vol 380 (7) ◽  
pp. 617-628 ◽  
Author(s):  
Gunter von Minckwitz ◽  
Chiun-Sheng Huang ◽  
Max S. Mano ◽  
Sibylle Loibl ◽  
Eleftherios P. Mamounas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer

2019 ◽  
Vol 122 (5) ◽  
pp. 603-612 ◽  
Author(s):  
Francis W. Hunter ◽  
Hilary R. Barker ◽  
Barbara Lipert ◽  
Françoise Rothé ◽  
Géraldine Gebhart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Experimental Studies ◽  
Resistance Mechanisms ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Egfr Expression ◽  
The Impact ◽  
Antibody Drug ◽  
Positive Breast Cancer

AbstractThe HER2-targeted antibody–drug conjugate trastuzumab emtansine (T-DM1) is approved for the treatment of metastatic, HER2-positive breast cancer after prior trastuzumab and taxane therapy, and has also demonstrated efficacy in the adjuvant setting in incomplete responders to neoadjuvant therapy. Despite its objective activity, intrinsic and acquired resistance to T-DM1 remains a major clinical challenge. T-DM1 mediates its activity in a number of ways, encompassing HER2 signalling blockade, Fc-mediated immune response and payload-mediated microtubule poisoning. Resistance mechanisms relating to each of these features have been demonstrated, and we outline the findings of these studies in this review. In our overview of the substantial literature on T-DM1 activity and resistance, we conclude that the T-DM1 resistance mechanisms most strongly supported by the experimental data relate to dysfunctional intracellular metabolism of the construct and subversion of DM1-mediated cell killing. Loss of dependence on signalling initiated by HER2–HER2 homodimers is not substantiated as a resistance mechanism by clinical or experimental studies, and the impact of EGFR expression and tumour immunological status requires further investigation. These findings are instructive with respect to strategies that might overcome T-DM1 resistance, including the use of second-generation anti-HER2 antibody–drug conjugates that deploy alternative linker-payload chemistries.

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