Correlative Studies of ERBB-2/HER-2/NEU and p53 in CALGB Protocol 9344/INT Protocol 0148: Doxorubicin Dose Escalation, With or Without Taxol®, as Part of the CA Adjuvant Chemotherapy Regimen For Node Positive Breast Cancer: A Phase III Intergroup Study

PRIMARY OBJECTIVES:

1. To determine if amplification and/or overexpression of erbB-2 is associated with either additional or less benefit from increasing doses of doxorubicin or four cycles of paclitaxel.
2. To determine if abnormalities in p53 (mutations, deletions, protein stabilization) are associated with either additional or less benefit from increasing doses of doxorubicin or four cycles of paclitaxel.
3. To compare methods of analysis of erbB-2 and p53, using the most common means of assaying for these biomarkers, in order to determine whether one method is more predictive of clinical outcome than another, or whether methods are complementary.
4. To identify biomarkers that can be used to individually tailor the use of adjuvant dose-dense therapy.
5. To identify groups of patients who have a poor prognosis, despite adjuvant chemotherapy, who should be prospectively targeted for new approaches to adjuvant treatment.
6. To identify biomarkers that can be used to individually tailor the use of adjuvant paclitaxel therapy.
7. To identify groups of patients who have a poor prognosis despite adjuvant chemotherapy who should be prospectively targeted for new approaches to adjuvant treatment.
8. To determine if the intrinsic subtype, as determined by PAM50 assay, is associated with benefit from paclitaxel (C9344) and from dose dense chemotherapy (C9741) regardless of clinical estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status.
9. To determine if intrinsic subtype is associated with benefit from paclitaxel and from dose dense chemotherapy in the HER2 negative subset, as defined by the tissue microarray (TMA) analysis of HER2 completed in sections B2 and B3 of this protocol.
10. To determine if relapse score, as determined by PAM50 assay, is associated with benefit from paclitaxel and from dose dense chemotherapy regardless of clinical ER and HER2 status.
11. To determine if relapse score is associated with benefit from paclitaxel and from dose dense chemotherapy in the HER2 negative subset.
12. To evaluate the association of a PAM50-defined proliferation score and benefit from paclitaxel and from dose dense chemotherapy.
13. To evaluate whether patients identified as having basal breast cancer by the PAM50 assay benefit from paclitaxel.

SECONDARY OBJECTIVES:

1. To compare the performance of the PAM50-defined intrinsic subtypes with the subtype diagnoses determined by the antibody panel, developed in sections B2 and B3 of this protocol, in predicting benefit from paclitaxel and from dose dense chemotherapy in the HER2 negative subset.
2. To evaluate the prognostic value of the PAM50-defined relapse score in patients receiving no paclitaxel therapy (C9344).
3. To investigate the performance of a multivariate model including proliferation score and risk of relapse in predicting benefit from paclitaxel and from dose dense chemotherapy.

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