Weekly paclitaxel plus carboplatin with or without trastuzumab as neoadjuvant chemotherapy for HER2-positive breast cancer: loss of HER2 amplification and its impact on response and prognosis

Wang, Ruo Xi; Chen, Sheng; Jin, Xi; Chen, Can Ming; Shao, Zhi Ming

doi:10.1007/s10549-016-4064-9

Cited by 38 publications

(49 citation statements)

References 28 publications

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“…To date, phase II and III trials have not been conducted to explore trastuzumab use following trastuzumab plus NAC administration preoperatively in cases who did not achieve pCR. The efficacy of anti-HER2 agents in non-pCR responders also remained controversial [42]. The present study results revealed that these patients gained benefits from using trastuzumab maintenance, although they are less likely to respond to trastuzumab plus NAC.…”

Section: Biomed Research Internationalmentioning

confidence: 60%

[Retracted] Efficacy of Neoadjuvant Chemotherapy with Epirubicin and Cyclophosphamide and Weekly Paclitaxel and Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Carcinoma: A Real‐World Study

Zhang

et al. 2020

BioMed Research International

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Background. Trastuzumab has been introduced a decade ago and demonstrated improvement in the prognosis in patients with human epidermal growth factor receptor 2- (HER2-) positive (+) breast carcinoma (BC). This study is aimed at evaluating the efficacy of epirubicin/cyclophosphamide with weekly paclitaxel-trastuzumab as neoadjuvant chemotherapies in HER2+ BC patients. Methods. A total of 234 HER2+ BC patients were given neoadjuvant chemotherapy (NAC) between 2010 and 2016. The primary endpoints were pathologic complete response (pCR) and disease-free survival (DFS). Univariate and multivariate analyses of clinical and pathological factors associated with pCR and DFS were conducted. Results. The pCR (30.4% vs. 14.8%; P=0.004) and DFS (P=0.036) showed significant differences between patients administered with neoadjuvant trastuzumab therapy and those who did not. Multivariate logistic regression analysis showed that neoadjuvant trastuzumab treatment was regarded as an independent predictor of pCR. Patients with pCR had prolonged DFS (P=0.025). In patients who did not achieve pCR (non-pCR), those who received trastuzumab had more prolonged DFS (P=0.046). The luminal B/HER2+ subtypes had prolonged DFS when compared with nonluminal B/HER2+ subtypes (P=0.010). The luminal B/HER2+ subgroup also showed improved DFS in non-pCR patients (P=0.010). In the subgroup of non-pCR, the luminal B/HER2+ subgroup administered with trastuzumab showed no superior DFS (P=0.168). However, a positive result was observed in patients without trastuzumab (P=0.039). Multivariate analysis showed cT stage (P=0.006) and tumor grade (P=0.041), considering them as significant prognostic factors of DFS. Conclusions. HER2+ BC patients showed improvement in pCR and DFS after neoadjuvant trastuzumab treatment. Patients without pCR had prolonged DFS after trastuzumab maintenance. Although the prognosis of luminal B/HER2+ BC showed favorable outcomes in the non-pCR subgroup, those receiving trastuzumab showed no survival advantage.

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Section: Biomed Research Internationalmentioning

confidence: 60%

[Retracted] Efficacy of Neoadjuvant Chemotherapy with Epirubicin and Cyclophosphamide and Weekly Paclitaxel and Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Carcinoma: A Real‐World Study

Zhang

et al. 2020

BioMed Research International

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“…Secondly, the number of HER2 negative tumor cells may increase after trastuzumab-based chemotherapy. Recent studies in breast cancer patients have indicated that trastuzumab-based chemotherapy has a significant impact on loss of HER2 positivity, and have suggested that treatment-induced clonal selection, biological modification, and tumor heterogeneity could explain this impact (25,26). HER2-positive gastric tumor cells have been shown to have higher chemosensitivity compared with HER2-negative gastric tumor cells (27).…”

Section: Discussionmentioning

confidence: 99%

Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

et al. 2019

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Background/Aim: The aim of the present study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with advanced HER2-positive gastric cancer. Materials and Methods: We assessed HER2 expression using immunohistochemistry and/or fluorescence in situ hybridization in pre-treatment biopsied specimens and post-treatment resected specimens obtained from seven patients with advanced HER2-positive gastric cancer receiving trastuzumab-based chemotherapy. Results: Four patients maintained the HER2-positive status and three patients had a change in HER2 expression from positive to negative. In patients showing the loss of HER2 expression after treatments, HER2-positive tumor cells with a dominant histological type disappeared, and HER2-negative tumor cells with another dominant histological type were identified. Conclusion: HER2 expression can change after trastuzumabbased chemotherapy in patients with advanced HER2positive gastric cancer. Continuous monitoring of HER2 expression after treatments may be utilized to determine whether the continued use of trastuzumab is advisable.

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“…In the setting of neoadjuvant chemotherapy (NAC), some studies indicate insufficient concordance rates for HER2 between pre-NAC CNB and post-NAC surgical specimens, which indicates that HER2 should be re-tested after NAC [ 18 , 19 ]. The loss of HER2 positivity in the surgical specimen after NAC is associated with poor recurrence-free or disease-free survival and could potentially indicate the need for further systemic therapy [ 18 , 20 , 21 ]. Data on the conversion of biomarkers such as HER2 among Swedish breast cancer patients are largely lacking but an evaluation is highly relevant since laboratory methods can vary between countries and routines for re-testing differ.…”

Section: Introductionmentioning

confidence: 99%

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

Robertson

Rönnlund

Boniface

et al. 2019

Breast Cancer Res Treat

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Purpose The accuracy of predictive and prognostic biomarker assessment in breast cancer is paramount since these guide therapy decisions. The aim was to investigate the concordance of biomarkers and immunohistochemical (IHC)-based surrogate tumor subtypes between core needle biopsies (CNB) and consecutive paired breast cancer surgical resections. Methods This retrospective study comprised two cohorts of patients with primary breast cancer diagnosed between 2016 and 2017: one treated with primary surgery ( n = 526) and one with neoadjuvant chemotherapy (NAC) ( n = 216). The agreement between preoperative CNB and paired tumor specimens regarding the assessment of biomarkers and surrogate tumor subtypes was evaluated in both cohorts. Results In the primary surgery cohort, the concordance rates and kappa values for estrogen receptor (ER), progesterone receptor (PR) and Ki67 were 98.6% ( κ = 0.917), 89.3% ( κ = 0.725) and 78.8% ( κ = 0.529), respectively. Importantly, human epidermal growth factor receptor 2 (HER2) IHC assessment showed only moderate agreement ( κ = 0.462). HER2 status combining IHC and in situ hybridization was discordant in 3.6% of cases, potentially impacting on indications for HER2-targeted therapy. The concordance rate for IHC-based surrogate tumor subtypes was only 73.2–78.3%. Generally lower concordance rates for ER, PR and HER2 were observed in the NAC cohort. Here, HER2 status was discordant in 7.4%. Conclusions The agreement of HER2 and Ki67 between CNB and paired surgical specimen in primary breast cancer is insufficient. Limited agreement of surrogate tumor subtypes indicates a significant clinical value of biomarker re-testing on surgical specimens.

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Weekly paclitaxel plus carboplatin with or without trastuzumab as neoadjuvant chemotherapy for HER2-positive breast cancer: loss of HER2 amplification and its impact on response and prognosis

Abstract: Our study has provided new evidence that anti-HER2 treatment has a significant impact on HER2 loss. Far more importantly, the loss of HER2 amplification could identify non-pCR patients with high risk of disease relapse, which might help in tailoring following systemic treatment.

Cited by 38 publications

References 28 publications

[Retracted] Efficacy of Neoadjuvant Chemotherapy with Epirubicin and Cyclophosphamide and Weekly Paclitaxel and Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Carcinoma: A Real‐World Study

[Retracted] Efficacy of Neoadjuvant Chemotherapy with Epirubicin and Cyclophosphamide and Weekly Paclitaxel and Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Carcinoma: A Real‐World Study

Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

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