Biomarkers as potential predictors of pathologic complete response (pCR) in the NOAH trial of neoadjuvant trastuzumab in patients (pts) with HER2-positive locally advanced breast cancer (LABC)

Giannì, L.; Eiermann, W.; Pusztai, L.; Семиглазов, Владимир; Hoegel, B.; Koehler, Andreas; Manikhas, George; Bates, Mark; Valagussa, Pinuccia; Baselga, J.

doi:10.1200/jco.2008.26.15_suppl.504

Cited by 12 publications

(16 citation statements)

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“…Therefore, it was determined that PR status was predictive of a pCR. 47 In a multivariate analysis of patients with HER2-positive disease who received trastuzumab, c-myc amplification and lower HER3 total immunoreactivity were associated significantly with the likelihood of achieving a pCR (P < .05).…”

Section: Neoadjuvant Trastuzumab In Locally Advanced Breast Cancermentioning

confidence: 94%

“…47 Grade 3 or 4 AEs reported by more than 1 patient in the trastuzumab arm were febrile neutropenia (1.7%; n ¼ 2) and neutropenia (2.6%; n ¼ 3). 46 Incidence rates for these AEs were similar in patients with HER2-positive disease who did not receive trastuzumab (1.8% and 4.4%, respectively).…”

Section: Neoadjuvant Trastuzumab In Locally Advanced Breast Cancermentioning

confidence: 98%

“…46 Exploratory biomarker studies from the NOAH trial also have been reported. 47 The objective of these studies was to correlate standard clinical variables, including clinical tumor (T) classification, lymph node (N) status, and hormone receptor status, and potential biomarkers with pCR (defined as no residual invasive cancer in breast or lymph nodes regardless of the presence of ductal carcinoma in situ [DCIS]). In total, 247 pretreatment core biopsies (75.5%) were assayed for c-myc (by fluorescent in situ hybridization [FISH]), phosphatase and tensin homolog (by immunohistochemistry [IHC]), and insulin-like growth factor 1 receptor (by IHC), in addition to ER and PR.…”

Section: Neoadjuvant Trastuzumab In Locally Advanced Breast Cancermentioning

confidence: 99%

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Trastuzumab‐based neoadjuvant therapy in patients with HER2‐positive breast cancer

Chang

2010

Cancer

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Overexpression, or gene amplification, of the human epidermal growth factor receptor 2 (HER2) is evident in 20% to 25% of breast cancers. The biologic agent trastuzumab is an HER2-targeted monoclonal antibody that inhibits the proliferation of tumor cells and induces tumor cell death through multiple mechanisms of action. Currently, trastuzumab is approved for use in the adjuvant and metastatic settings. Trials combining trastuzumab with neoadjuvant chemotherapy suggest that patients with HER2-positive breast cancer also may benefit from preoperative trastuzumab. For this article, the author reviewed efficacy and safety data from key studies of patients who received neoadjuvant trastuzumab-based therapy. Studies were identified from literature searches of publication and congress databases. The results of 3 large phase 3 trials (the M. D. Anderson Cancer Center neoadjuvant trastuzumab trial, the Neoadjuvant Herceptin [NOAH] trial, and the German Breast Group/Gynecologic Oncology Study Group ''GeparQuattro'' trial) demonstrated that, compared with chemotherapy alone, neoadjuvant trastuzumab plus chemotherapy significantly increased pathologic complete response rates to as high as 65%. Improvements in disease-free, overall, and event-free survival also were reported in the NOAH trial. In addition to demonstrated efficacy, a low incidence of cardiac dysfunction suggests that neoadjuvant trastuzumab is both effective and well tolerated. Similar results have been reported in a range of phase 2 studies using different trastuzumab-based regimens. These encouraging data led the National Comprehensive Cancer Network to recommend treating patients who have operable, locally advanced, HER2-positive breast cancer with neoadjuvant paclitaxel plus trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide plus trastuzumab. Cancer 2010;116:2856-67. V C 2010 American Cancer Society.KEYWORDS: neoadjuvant, trastuzumab, HER-2, chemotherapy, biologic, breast cancer, breast conservation surgery, lymph node management.Breast cancer (BC) is the most frequently diagnosed form of cancer among women in the United States. 1 Of the various subtypes of BC, tumors that have gene amplification or protein overexpression of human epidermal growth factor receptor 2 (HER2) are among the most aggressive and are associated with poor clinical outcomes compared with tumors that do not have HER2 overexpression. 2-4 Of the total number of patients diagnosed with BC in the United States, 20% to 25% will have tumors that exhibit HER2 gene amplification or protein overexpression. 2,5,6 Trastuzumab (Herceptin), a humanized, monoclonal antibody that blocks the activity of HER2, is the only anti-HER2 agent that is approved for adjuvant therapy in patients who have HER2-positive disease with either positive or negative lymph node status, estrogen receptor (ER)/progesterone receptor (PR)-negative disease, or a high-risk feature, either in combination with chemotherapy or as a single agent after chemotherapy. Adjuvant trastuzumab significantly imp...

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Section: Neoadjuvant Trastuzumab In Locally Advanced Breast Cancermentioning

confidence: 94%

Section: Neoadjuvant Trastuzumab In Locally Advanced Breast Cancermentioning

confidence: 98%

Section: Neoadjuvant Trastuzumab In Locally Advanced Breast Cancermentioning

confidence: 99%

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Trastuzumab‐based neoadjuvant therapy in patients with HER2‐positive breast cancer

Chang

2010

Cancer

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“…Of these, only a few have shown predictive value. Increased levels of HER-2 mRNA have been associated with benefit from neoadjuvant trastuzumab for patients with estrogen receptor-positive disease [87][88][89], and c-myc amplification or negative progesterone receptor status predicts benefit from neoadjuvant trastuzumab [90]. Recent biomarker analyses There is currently limited guidance available from published guidelines and product monographs specifically addressing the cardiac monitoring of patients with HER-2-positive ABC who are receiving HER-2-directed therapy.…”

Section: Correlative Datamentioning

confidence: 99%

HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

et al. 2013

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Untreated human epidermal growth factor receptor‐2 (HER‐2)‐positive advanced breast cancer (ABC) is an aggressive disease, associated with a poor prognosis and short overall survival. HER‐2‐directed therapy prolongs both time to disease progression and overall survival when combined with chemotherapy and has become the standard of care for those with HER‐2‐positive breast cancer in the early and advanced settings. Despite the remarkable therapeutic impact HER‐2‐directed therapy has had on disease outcomes, some patients with HER‐2‐positive disease will have primary resistant disease and others will respond initially but will eventually have progression, underscoring the need for other novel therapeutic options. This article reviews recent phase III trial data and discusses a practical approach to sequencing of HER‐2‐directed therapy in patients with HER‐2‐positive ABC. The significant cumulative survival gains seen in these trials are slowly reshaping the landscape of HER‐2‐positive ABC outcomes.

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“…Based on data from the NSABP B-31 trastuzumab adjuvant trial, tumors that feature coamplification of the c-MYC oncogene and HER-2 benefited by the addition of trastuzumab to chemotherapy in terms of both recurrence-free survival and OS, compared with patients whose tumors lacked the c-MYC amplification [316]. In a neoadjuvant study, PgR-negative status and c-MYC amplification were both associated with higher pCR rates after the addition of trastuzumab to chemotherapy [317]. Thus c-MYC gene copy status may be a biomarker of trastuzumab response in the adjuvant or neoadjuvant settings, although this requires large-scale studies for confirmation.…”

Section: Shedding Of Her-2 Proteinmentioning

confidence: 99%

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

et al. 2009

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1. Contrast the current strengths and limitations of the three main slide-based techniques (IHC, FISH, and CISH) currently in clinical use for testing breast cancer tissues for HER-2 status.2. Compare the efficacy of trastuzumab-and lapatinib-based regimens in the adjuvant and metastatic settings as reported in published clinical trials and regulatory approval databases.3. Contrast the list of biomarkers that have been associated with clinical resistance to trastuzumab and lapatinib and describe their current level of validation.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTThe human epidermal growth factor receptor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER-2 gene amplification and protein overexpression in the absence of anti-HER-2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER-2-positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER-2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER-2-positive disease. The major marketed slide-based HER-2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ

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Biomarkers as potential predictors of pathologic complete response (pCR) in the NOAH trial of neoadjuvant trastuzumab in patients (pts) with HER2-positive locally advanced breast cancer (LABC)

Cited by 12 publications

References 0 publications

Trastuzumab‐based neoadjuvant therapy in patients with HER2‐positive breast cancer

Trastuzumab‐based neoadjuvant therapy in patients with HER2‐positive breast cancer

HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

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