2019
DOI: 10.3892/ol.2019.9998
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ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab

Abstract: Trastuzumab has markedly improved the treatment and long-term prognosis of patients with HER2-positive breast cancer. A frequent clinical challenge in patients with relapsing and/or metastatic disease is de novo or acquired trastuzumab resistance, and to date no predictive biomarkers for palliative trastuzumab have been established. In the present study, the prognostic values of factors involved in the HER2-associated PI3K/Akt signalling pathway were explored. The first 46 consecutive pa… Show more

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Cited by 6 publications
(7 citation statements)
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“…In addition, a post hoc exploratory analysis in the ToGA study found that patients with high HER2 expression (e.g., IHC 3+ or IHC2+ and FISH positive) had significantly longer OS when treated with trastuzumab plus chemotherapy compared with patients treated with chemotherapy alone [12]. A possible explanation for this finding is that a higher ERBB2 CN may confer increased sensitivity to trastuzumab, as the cancer cell is inherently more 'addicted' to overexpressed HER2 protein, with the assumption that gene CN correlates to increased copies at the protein level, broadly consistent with the data presented here [22]. This finding is consistent with prior studies that reported longer OS in trastuzumab-treated patients with advanced gastric cancer with higher levels of ERBB2 amplification measured by ISH [23].…”
Section: Discussionsupporting
confidence: 85%
“…In addition, a post hoc exploratory analysis in the ToGA study found that patients with high HER2 expression (e.g., IHC 3+ or IHC2+ and FISH positive) had significantly longer OS when treated with trastuzumab plus chemotherapy compared with patients treated with chemotherapy alone [12]. A possible explanation for this finding is that a higher ERBB2 CN may confer increased sensitivity to trastuzumab, as the cancer cell is inherently more 'addicted' to overexpressed HER2 protein, with the assumption that gene CN correlates to increased copies at the protein level, broadly consistent with the data presented here [22]. This finding is consistent with prior studies that reported longer OS in trastuzumab-treated patients with advanced gastric cancer with higher levels of ERBB2 amplification measured by ISH [23].…”
Section: Discussionsupporting
confidence: 85%
“…8 Ellega ˚rd and his colleagues reported that copy numbers of ERBB2 and PTPN2 was one of significant prognostic factors in breast cancer after trastuzumab treatment. 9 However, for early-onset breast cancer, the recent biomarkers were still limited, and the novel biomarkers identification was also urgently needed.…”
Section: Introductionmentioning
confidence: 99%
“…HER2-associated PI3K/Akt signalling pathway may play a critical role in trastuzumab resistance. In a recent study, Ellegard et al discovered that high-grade ERBB2 gene amplification level of more than 6 copies could improve OS and PFS, and more than 3 copies of PTPN2 gene were related to shorter OS and PFS in HER2 positive patients who received trastuzumab for treatment ( 32 ).…”
Section: Resultsmentioning
confidence: 99%
“…There were 3 studies including patients diagnosed with PMBC (22)(23)(24), in which there was 1 study focusing on hormone receptor (HR) positive patients. There were 10 studies focusing on the effect of specific factors, such as drugs and biomarkers, on prognosis (25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”
Section: Selection and Characteristics Of Studiesmentioning
confidence: 99%