Quantitative digital imaging analysis of HER2 immunohistochemistry predicts the response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma

Li, Aidan C; Zhao, Jing; Zhao, Chao; Hartage, Ramon; Zhang, Yunxiang; Li, Xiaoxian; Parwani, Anil V.

doi:10.1007/s10549-020-05546-0

Cited by 23 publications

(22 citation statements)

References 30 publications

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“…Regardless of ASCO/ CAP FISH groups, IHC 2+/HER2 amplified tumours showed significantly lower rates of pCR than IHC 3+ tumours. Consistent with previous studies, our data highlight that HER2 IHC 3+ and histological grade 3 are independent predictors of pCR following treatment with anti-HER2 therapy [9,29]. Although a higher rate of pCR in HER2 IHC 3+ tumours was reported in the Table 5 Correlation between HER2 categories in pre-treatment core biopsy and the post-treatment excision specimen.…”

Section: Discussionsupporting

confidence: 90%

Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer

et al. 2021

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The response of human epidermal growth factor receptor2 (HER2)- positive breast cancer (BC) patients to anti-HER2 targeted therapy is significant. However, the response is not uniform and a proportion of HER2-positive patients do not respond. This study aims to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive BC patients. The study group comprised 500 BC patients treated with neoadjuvant chemotherapy (NACT) and/or neoadjuvant anti-HER2 therapy and surgery who had tumours that were 3+ or 2+ with HER2 immunohistochemistry (IHC). HER2 IHC 2+ tumours were classified into five groups by fluorescence in situ hybridisation (FISH) according to the 2018 ASCO/CAP guidelines of which Groups 1, 2 and 3 were considered HER2 amplified. Pathological complete response (pCR) was more frequent in HER2 IHC 3+ tumours than in HER2 IHC 2+/HER2 amplified tumours, when either in receipt of NACT alone (38% versus 13%; p = 0.22) or neoadjuvant anti-HER2 therapy (52% versus 20%; p < 0.001). Multivariate logistic regression analysis showed that HER2 IHC 3+ and histological grade 3 were independent predictors of pCR following neoadjuvant anti-HER2 therapy. In the HER2 IHC 2+/HER2 amplified tumours or ASCO/CAP FISH Group 1 alone, ER-negativity was an independent predictor of pCR following NACT and/or neoadjuvant anti-HER2 therapy. In the current study, 22% of HER2-positive tumours became HER2-negative by IHC and FISH following neoadjuvant treatment, the majority (74%) HER2 IHC 2+/HER2 amplified tumours. Repeat HER2 testing after neoadjuvant treatment should therefore be considered.

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Section: Discussionsupporting

confidence: 90%

Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer

et al. 2021

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“…While it exerts a limited effect on dimerization inhibition, this incomplete inhibition of the HER2 enabling sustained signaling from uninhibited HER2 protein [ [43] , [44] , [45] , [46] ]. The overexpression of HER2 is mainly driven by HER2 amplification, and they show a positive correlation [ 47 ]. Hence, we can speculate that HER2 amplification leads to HER2 overexpression and subsequent overactivation of HER2 signaling, thus resulting in a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

HER2 copy number quantification in primary tumor and cell-free DNA provides additional prognostic information in HER2 positive early breast cancer

et al. 2022

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“… 27 IHC 3+ cases almost always show high level gene amplification, whereas the IHC 2+ cases often show low level amplification and/or heterogeneity. 6 , 27 – 30 Response to NACT plus anti-HER2 targeted therapy occurs more frequently in tumours with HER2/CEP17 ratios >3.7 and HER2 gene copy number >11.5. 28 In a study of HER2-targeted therapy without chemotherapy, none of the 11 patients with HER2/CEP17 ratio <4.0 and/or HER2 gene copy number <10.0 achieved pCR, compared to 29% of patients with ratios >4 and/or HER2 copy number >10.…”

Section: Discussionmentioning

confidence: 99%

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

et al. 2021

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Background The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT). Methods 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed. Results 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017). Conclusion No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.

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Quantitative digital imaging analysis of HER2 immunohistochemistry predicts the response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma

Cited by 23 publications

References 30 publications

Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer

Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer

HER2 copy number quantification in primary tumor and cell-free DNA provides additional prognostic information in HER2 positive early breast cancer

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

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