Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease

Berchuck, Andrew; Rodriguez, G.; Kinney, R. B.; Soper, John T.; Dodge, Richard K.; Clarke‐Pearson, Daniel L.; Bast, Robert C.

doi:10.1016/0002-9378(91)90615-x

Cited by 239 publications

(52 citation statements)

References 12 publications

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“…HER-2/neu , resulting from amplification of the HER-2/neu gene, is associated with poor clinical outcome in 25 ± 30% of carcinomas of the breast (Slamon et al, 1987), as well as in other human malignancies (Semba et al, 1985;Slamon et al, 1989;Berchuck et al, 1991;Yonemura et al, 1991;Hetzel et al, 1992;Lukes et al, 1994;Press et al, 1994;Saari et al, 1995). The murine monoclonal antibody 4D5 has speci®city for a juxtamembrane epitope in the extracellular domain (ECD) of the p185 HER-2/neu protein (Fendly et al, 1990) and is capable of eliciting an antiproliferative eect against murine cells transformed by HER-2/neu as well as human malignant cell lines and xenografts overexpressing this oncogene (Chazin et al, 1992).…”

Section: Overexpression Of P185mentioning

confidence: 99%

Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers

Pegram

Hsu

Lewis³

et al. 1999

Oncogene

612

282

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Previous studies have demonstrated a synergistic interaction between rhuMAb HER2 and the cytotoxic drug cisplatin in human breast and ovarian cancer cells. To de®ne the nature of the interaction between rhuMAb HER2 and other classes of cytotoxic drugs, we applied multiple drug eect/combination index (CI) isobologram analysis to a variety of chemotherapeutic drug/rhuMAb HER2 combinations in vitro. Synergistic interactions at clinically relevant drug concentrations were observed for rhuMAb HER2 in combination with cisplatin (CI=0.48, P=0.003), thiotepa (CI=0.67, P=0.0008), and etoposide (CI=0.54, P=0.0003). Additive cytotoxic eects were observed with rhuMAb HER2 plus doxorubicin (CI=1.16, P=0.13), paclitaxel (CI=0.91, P=0.21), methotrexate (CI=1.15, P=0.28), and vinblastine (CI=1.09, P=0.26). One drug, 5-¯uorouracil, was found to be antagonistic with rhuMAb HER2 in vitro (CI=2.87, P=0.0001). In vivo drug/rhuMAb HER2 studies were conducted with HER-2/neu-transfected, MCF7 human breast cancer xenografts in athymic mice. Combinations of rhuMAb HER2 plus cyclophosphamide, doxorubicin, paclitaxel, methotrexate, etoposide, and vinblastine in vivo resulted in a signi®cant reduction in xenograft volume compared to chemotherapy alone (P50.05). Xenografts treated with rhuMAb HER2 plus 5-¯uorouracil were not signi®cantly dierent from 5-uorouracil alone controls consistent with the subadditive eects observed with this combination in vitro. The synergistic interaction of rhuMAb HER2 with alkylating agents, platinum analogs and topoisomerase II inhibitors, as well as the additive interaction with taxanes, anthracyclines and some antimetabolites in HER-2/neuoverexpressing breast cancer cells demonstrates that these are rational combinations to test in human clinical trials.

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Section: Overexpression Of P185mentioning

confidence: 99%

Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers

Pegram

Hsu

Lewis³

et al. 1999

Oncogene

612

282

View full text Add to dashboard Cite

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“…The c-erbB2 oncogene has been established to have close relation with endometrial adenocarcinoma outcome, being regulated by estrogens and glucocorticoids (Markogiannakis et al 1997). Overexpression of this gene product has been related to cancers leading to increased fatality (Berchuck et al 1991) and is associated with the presence of intraperitoneal metastatic disease (Bezwoda 2000;Cherchi et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic value and survival of endometrial cancer patients

Lambropoulou

Παπαδόπουλος

Tripsianis

et al. 2009

J Cancer Res Clin Oncol

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“…A role for the HER-2/ neu alteration in metastasis has also been suggested given the increased occurrence of visceral metastasis (Kallioniema et al, 1991) and higher incidence of micrometastatic bone marrow disease (Pantel et al, 1993) in patients with HER-2/neu overexpression. In addition, expression of HER-2/neu has prognostic signi®cance in patients with gastric (Yonemura et al, 1991), endometrial (Berchuck et al, 1991;Hetzel et al, 1992;Lukes et al, 1994;Saari et al, 1995), and salivary gland cancers (Semba et al, 1985;Press et al, 1994). The exact role alteration of HER-2/neu receptor expression plays in the pathogenesis of these cancers remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells

et al. 1997

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Recent studies indicate that oncogenes may be involved in determining the sensitivity of human cancers to chemotherapeutic agents. To de®ne the eect of HER-2/neu oncogene overexpression on sensitivity to chemotherapeutic drugs, a full-length, human HER-2/neu cDNA was introduced into human breast and ovarian cancer cells. In vitro dose-response curves following exposure to 7 dierent classes of chemotherapeutic agents were compared for HER-2-and control-transfected cells. Chemosensitivity was also tested in vivo for HER-2-and control-transfected human breast and ovarian cancer xenografts in athymic mice. These studies indicate that HER-2/neu overexpression was not sucient to induce intrinsic, pleomorphic drug resistance. Furthermore, changes in chemosensitivity pro®les resulting from HER-2/neu transfection observed in vitro were cell line speci®c. In vivo, HER-2/neu-overexpressing breast and ovarian cancer xenografts were responsive to dierent classes of chemotherapeutic drugs compared to control-treated xenografts with no statistically signi®cant dierences between HER-2/neu-overexpressing and nonoverexpressing xenografts. We found no instance in which HER-2/neu-overexpressing xenografts were rendered more sensitive to chemotherapeutic drugs in vivo. HER-2/neu-overexpressing xenografts consistently exhibited more rapid regrowth than control xenografts following initial response to chemotherapy suggesting that a high rate of tumor cell proliferation rather than intrinsic drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in human cancers.

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Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease

Cited by 239 publications

References 12 publications

Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers

Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers

Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic value and survival of endometrial cancer patients

The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells

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