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Quantitative measurements of HER2 and phospho-HER2 expression : correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab . BACKGROUND Preoperative therapy with chemotherapy and the HER2-targeted monoclonal antibody trastuzumab is valuable for patients with large or locally advanced HER2-positive ( HER2+ ) breast cancers but traditional methods of measuring HER2 expression do not accurately stratify patients for likelihood of response . Quantitative immunofluorescent approaches have the potential to provide a mathematically continuous measure of HER2 . Here we seek to determine whether quantitative measurement of HER2 or phospho-HER2 correlates with likelihood of response to trastuzumab- containing neoadjuvant therapy . METHODS We evaluated core biopsy samples from 27 HER2+ breast cancer patients enrolled in a preoperative clinical trial using trastuzumab , nab-paclitaxel and carboplatin combination therapy ( BrUOG BR-211B ( NCT00617942 ) ) . Tumor core biopsies were taken before initiation of treatment and 9-13 days after patients received " run-in " doses of either single agent trastuzumab or nab-paclitaxel . The AQUA method of quantitative immunofluorescence was used for analysis of in situ protein expression . Patients then received 18 weeks of treatment , followed by surgery to assess pathologic response to the neoadjuvant regimen . RESULTS A HER2 score of 2111 by AQUA analysis has been shown to be equivalent to HER2 3+ by immunohistochemical staining in previous studies . Of 20 evaluable patients , 10 cases who achieved a pathologic complete response ( pathCR ) with neoadjuvant treatment had a mean HER2 level of 10251 compared with 4766 in the patients without pathCR ( p = 0.0021 ) . Measurement of phospho-HER2 showed no difference in pathCR vs non-pathCR groups . In 9 patients who had HER2 levels repeated after a single treatment with trastuzumab there was no evidence of a reduction in the HER2 or phospho-HER2 levels following that exposure . CONCLUSIONS High levels of HER2 are associated with achievement of a pathCR in the preoperative setting , while levels of Phospho-HER2 were not predictive of response . This data suggests that accurate measurement of HER2 may help determine the likelihood of response in the pre-surgical setting . Further validation in larger cohorts is required , but this pilot data shows the feasibility of this approach .
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Intervention_Pharmacological
neoadjuvant chemotherapy and trastuzumab
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Intervention_Pharmacological
Preoperative therapy with chemotherapy
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Intervention_Pharmacological
HER2-targeted monoclonal antibody trastuzumab
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Intervention_Pharmacological
trastuzumab , nab-paclitaxel and carboplatin combination therapy
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Intervention_Pharmacological
trastuzumab
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Intervention_Pharmacological
nab-paclitaxel
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Outcome_Physical
pathologic response
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Outcome_Physical
pathologic complete response ( pathCR )
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Outcome_Physical
Measurement of phospho-HER2
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Outcome_Physical
in the HER2 or phospho-HER2 levels
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Outcome_Physical
High levels of
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Outcome_Physical
levels of Phospho-HER2
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Participant_Condition
patients with large or locally advanced HER2-positive ( HER2+ ) breast cancers
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Participant_Condition
core biopsy samples from 27 HER2+ breast cancer patients enrolled in a preoperative clinical trial using trastuzumab , nab-paclitaxel and carboplatin combination therapy ( BrUOG BR-211B ( NCT00617942 ) )