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NCT00005970 · CITED IN SOURCE DOCUMENTS

Doxorubicin Hydrochloride, Cyclophosphamide, and Pacltaxel With or Without Trastuzumab in Treating Women With HER2-Positive Node-Positive or High-Risk Node-Negative Breast Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2020-08-14

This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and trastuzumab to see how well they work compared to combination chemotherapy alone in treating women with breast cancer that is human epidermal growth factor receptor 2 (HER2)-positive and has spread to the lymph nodes or high-risk and has not spread to the lymph nodes. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * Required tumor parameters for node positive disease: NOTE: This study will continue to use the American Joint Committee on Cancer (AJCC) 5th edition for TNM classification and staging * Operable, histologically confirmed adenocarcinoma of the female breast and positive lymph nodes * Node positivity may be determined by either an axillary node dissection or a positive sentinel node finding by hematoxylin and eosin (H\&E) * NOTE: Positive nodes refers to H\&E visible nodal metastases; immunohistochemistry (IHC) positive only cells in lymph nodes will not be considered positive nodes * One or more positive lymph nodes whose tumors are T1-3, pN1-2, M0 are eligible * cN2 disease is not eligible * pN2 disease is eligible * One positive lymph node by sentinel node biopsy or at least 6 axillary nodes must be examined on axillary node dissection with at least one positive lymph node * Metaplastic carcinoma is eligible * ER/PgR determination * HER-2 positive (pre-entry requirement for registration) * FISH must show gene amplification OR * IHC assay must show a strong positive (3+) staining score * NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the determination of degree of IHC staining or FISH amplification * Required tumor parameters for high-risk node-negative disease; NOTE: This study will continue to use the AJCC 5th edition for TNM classification and staging * Operable, histologically confirmed adenocarcinoma of the female breast and negative lymph nodes * Node status may be determined by either axillary node dissection or sentinel node biopsy with H\&E staining; to be considered node negative, either of the following must be true: 1) negative sentinel node biopsy or 2) no positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection * NOTE: IHC positive only cells in lymph nodes will not be considered positive nodes * Tumors \> 2.0 cm (irrespective of hormonal receptor status) or \> 1.0 cm if ER-negative and PR-negative disease * ER/PgR determination * HER-2 positive (pre-entry requirement for registration) * FISH must show gene amplification OR * IHC assay must show a strong positive (3+) staining score * NOTE: DCIS components should not be counted in the determination of degree of IHC staining or FISH amplification * =\< 84 days from mastectomy or =\< 84 days from axillary dissection or sentinel node detection if the patient's most extensive breast surgery was a breast sparing procedure; (This timing is per a decision by the Breast Intergroup) * Surgical resection margins. All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy with axillary node dissection * Mastectomy: There will be no evidence of gross or microscopic tumor (invasive or DCIS) at the surgical resection margins noted in the final surgery or pathology reports; patients with close margins are eligible * Segmental mastectomy (lumpectomy): Margins must be clear of invasive cancer and DCIS * Axillary dissection or sentinel node dissection: There will be no gross residual adenopathy * TAM therapy * May have received up to four weeks of TAM therapy, or any other hormonal agent, for this malignancy * May have received TAM or raloxifene for purposes of chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (including previous breast cancer if lobular carcinoma in situ \[LCIS\]) but must be discontinued before registration on this study * May never have received TAM, raloxifene, or any other hormonal agent * Absolute neutrophil count (ANC) \>= 1500/mm\^3 * Platelets (PLT) \>= 100,000/mm\^3 * Total bilirubin =\< 1.5 x upper normal limit (UNL) * Aspartate aminotransferase (AST) =\< 2.0 x UNL * Left ventricular ejection fraction (LVEF) within institutional normal range; if LVEF is \> 75%, the investigator should consider performing a second review of the multigated acquisition (MUGA)/echocardiogram or performing a repeat MUGA/echocardiogram prior to registration; such re-reviews or repeat MUGA/echocardiogram are not permitted after registration * Willingness to discontinue sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to registration and while on study * Willingness to discontinue any hormonal agent such as raloxifene (Evista) prior to registration and while on study * Non-breast malignancies that have not recurred within the last 5 years and are deemed to be at low risk for recurrence EXCEPTIONS: These non-breast malignancies are eligible even if diagnosed =\< 5 years prior to registration: * Squamous or basal cell carcinoma of the skin that has been effectively treated * Carcinoma in situ of the cervix that has been treated by surgery only * Lobular carcinoma in situ (LCIS) of the ipsilateral or contralateral breast treated by surgery and/or tamoxifen only * Patients undergoing breast conservation therapy (i.e., lumpectomy and axillary dissection) must have plans to receive radiation therapy to the breast +/- regional lymphatics following completion of the chemotherapy; for patients treated with mastectomy, the use of radiation therapy is required for 4 or more positive lymph nodes and must be started after completion of chemotherapy; the use of radiation therapy is at the discretion of the investigator for 0-3 positive lymph nodes but, if used, must be started after the completion of chemotherapy * Prior to registration, the physician must designate if it is planned for the patient to receive radiation therapy (for adjuvant radiation therapy post-mastectomy or, less commonly, post-conservative therapy but not primary breast radiation as part of breast conserving treatment) * Willing and able to sign an informed consent * Gene amplified by FISH or strong positivity (3+) by HercepTest on central review; Note: The patient registers based on community HER-2 testing using FISH or IHC, AC chemotherapy is initiated; the tumor block or slides must be received =\< 2 weeks from time of registration to the North Central Cancer Treatment Group (NCCTG) Operations Office for central HER-2 testing Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, intrauterine device \[IUD\], surgical sterilization, or abstinence, etc.); hormonal birth control methods are not permitted * Locally advanced tumors (classification T4) at diagnosis including tumors fixed to chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge) * Prior history of breast cancer, except LCIS * Bilateral invasive carcinoma, either metachronous or synchronous (EXCEPTION: Patients diagnosed with unilateral invasive carcinoma and metachronous or synchronous DCIS of the contralateral breast treated with mastectomy are eligible) * Prior chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer * Active, unresolved infection * Active cardiac disease * Any prior myocardial infarction * History of documented congestive heart failure (CHF) * Current use of digitalis or beta-blockers for CHF * Any prior history of arrhythmia or cardiac valvular disease requiring medications or clinically significant * Current use of medications for treatment of arrhythmias or angina pectoris * Current uncontrolled hypertension (diastolic \> 100 mmHg or systolic \> 200 mmHg) * Clinically significant pericardial effusion * Prior anthracycline or taxane therapy for any malignancy * Sensitivity to benzyl alcohol * Neurology/Neuropathy-Sensory \>= grade 2 per the National Cancer Institute's (NCI's) Common Toxicity Criteria Version 2.0; EXCEPTION: Any chronic neurologic disorder will be looked at on a case-by-case basis by the study chair
healthy Volunteers
false
minimum Age
18 Years
sex
FEMALE
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV over 20-30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour beginning on day 1 of week 13 and continuing weekly for 12 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.
    intervention Names
    1. Drug: Aromatase Inhibition Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Doxorubicin Hydrochloride
    4. Other: Laboratory Biomarker Analysis
    5. Drug: Paclitaxel
    6. Drug: Tamoxifen Citrate
    label
    Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)
    type
    EXPERIMENTAL
  2. description
    Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab (Herceptin®) IV over 30-90 minutes beginning on day 1 of week 25 and continuing weekly for 52 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.
    intervention Names
    1. Drug: Aromatase Inhibition Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Doxorubicin Hydrochloride
    4. Other: Laboratory Biomarker Analysis
    5. Drug: Paclitaxel
    6. Drug: Tamoxifen Citrate
    7. Biological: Trastuzumab
    label
    Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    type
    EXPERIMENTAL
  3. description
    Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I. Patients then receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes beginning on day 1 of week 13 and continuing weekly for 12 courses. Patients then receive trastuzumab IV over 30 minutes beginning on day 1 of week 25 and continuing weekly for 40 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.
    intervention Names
    1. Drug: Aromatase Inhibition Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Doxorubicin Hydrochloride
    4. Other: Laboratory Biomarker Analysis
    5. Drug: Paclitaxel
    6. Drug: Tamoxifen Citrate
    7. Biological: Trastuzumab
    label
    Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)
    2. Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    3. Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    description
    Given orally
    name
    Aromatase Inhibition Therapy
    other Names
    1. Aromatase Inhibition
    type
    DRUG
  2. arm Group Labels
    1. Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)
    2. Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    3. Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Carloxan
    4. Ciclofosfamida
    5. Ciclofosfamide
    6. Cicloxal
    7. Clafen
    8. Claphene
    9. CP monohydrate
    10. CTX
    11. CYCLO-cell
    12. Cycloblastin
    type
    DRUG
  3. arm Group Labels
    1. Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)
    2. Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    3. Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    description
    Given IV
    name
    Doxorubicin Hydrochloride
    other Names
    1. 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    2. ADM
    3. Adriacin
    4. Adriamycin
    5. Adriamycin Hydrochloride
    6. Adriamycin PFS
    7. Adriamycin RDF
    8. ADRIAMYCIN, HYDROCHLORIDE
    9. Adriamycine
    10. Adriblastina
    11. Adriblastine
    12. Adrimedac
    type
    DRUG
  4. arm Group Labels
    1. Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)
    2. Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    3. Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  5. arm Group Labels
    1. Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)
    2. Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    3. Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    description
    Given IV
    name
    Paclitaxel
    other Names
    1. Anzatax
    2. Asotax
    3. Bristaxol
    4. Praxel
    5. Taxol
    6. Taxol Konzentrat
    type
    DRUG
  6. arm Group Labels
    1. Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)
    2. Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    3. Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    description
    Given orally
    name
    Tamoxifen Citrate
    other Names
    1. Apo-Tamox
    2. Clonoxifen
    3. Dignotamoxi
    4. Ebefen
    5. Emblon
    6. Estroxyn
    7. Fentamox
    8. Gen-Tamoxifen
    9. Genox
    10. ICI 46,474
    11. ICI-46474
    12. Jenoxifen
    type
    DRUG
  7. arm Group Labels
    1. Arm II (AC, paclitaxel, trastuzumab, tamoxifen)
    2. Arm III (AC, paclitaxel, trastuzumab, tamoxifen)
    description
    Given IV
    name
    Trastuzumab
    other Names
    1. ABP 980
    2. ALT02
    3. Anti-c-ERB-2
    4. Anti-c-erbB2 Monoclonal Antibody
    5. Anti-ERB-2
    6. Anti-erbB-2
    7. Anti-erbB2 Monoclonal Antibody
    8. Anti-HER2/c-erbB2 Monoclonal Antibody
    9. Anti-p185-HER2
    10. c-erb-2 Monoclonal Antibody
    11. HER2 Monoclonal Antibody
    12. Herceptin
    type
    BIOLOGICAL
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
3436
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Will be estimated using the Kaplan-Meier method. A stratified log-rank test will be used to assess whether DFS differs with respect to the addition of trastuzumab to a chemotherapy regimen including AC and paclitaxel. Ninety-five percent confidence intervals will be reported for relative risks, for DFS at the 5-year point, and for absolute benefit as defined by differences in DFS and OS.
    measure
    Duration of DFS
    time Frame
    Time from registration to first adverse event, assessed up to 15 years
secondary Outcomes
  1. description
    Will be estimated using the Kaplan-Meier method. A stratified log-rank test will be used to assess whether OS differs with respect to the addition of trastuzumab to a chemotherapy regimen including AC and paclitaxel. Ninety-five percent confidence intervals will be reported for relative risks, for OS at the 5-year point, and for absolute benefit as defined by differences in DFS and OS.
    measure
    Overall survival
    time Frame
    Time from registration to death due to any cause, assessed up to 15 years
Full study description
brief Summary
This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and trastuzumab to see how well they work compared to combination chemotherapy alone in treating women with breast cancer that is human epidermal growth factor receptor 2 (HER2)-positive and has spread to the lymph nodes or high-risk and has not spread to the lymph nodes. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer.
detailed Description
PRIMARY OBJECTIVES: I. To compare the combination of doxorubicin hydrochloride and cyclophosphamide (AC) followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of disease free survival (DFS). (Stage I) II. To compare the combination of AC followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of the rate of cardiac events. (Stage I) III. To compare the combination AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of DFS. (Stage II) IV. To compare the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of DFS. (Stage II) V. To compare the combination AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of the rate of cardiac events. (Stage II) SECONDARY OBJECTIVES: I. To compare the combination of AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of overall survival (OS). II. To compare the combination AC followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of OS. III. To compare the sequential schedule of the combination AC, weekly paclitaxel, and trastuzumab with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of OS. TERTIARY OBJECTIVES: I. To determine whether higher levels of shed ECD (extracellular domain) or autoantibodies to human epidermal growth factor receptor (HER)-2 and HER-1 measured in the serum prior to treatment are prognostic for DFS and survival. II. To determine the concordance of central review of HER-2 overexpression as measured by the HercepTest (DAKO) and Vysis fluorescence in situ hybridization (FISH). III. For each treatment arm, levels of brain natriuretic peptide (BNP), troponin-T (TnT), troponin-I (cTnI), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 (IL-6), CD40 ligand, and troponin levels will be compared and contrasted. IV. To determine whether genetic markers are prognostic for cardiac adverse events associated with treatment. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM I\*: Patients receive doxorubicin hydrochloride intravenously (IV) and cyclophosphamide IV over 20-30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour beginning on day 1 of week 13 and continuing weekly for 12 courses in the absence of disease progression or unacceptable toxicity. NOTE: \*Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment. ARM II\*: Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab IV over 30-90 minutes beginning on day 1 of week 25 and continuing weekly for 52 courses in the absence of disease progression or unacceptable toxicity. NOTE: \*Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment. ARM III: Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I. Patients then receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes beginning on day 1 of week 13 and continuing weekly for 12 courses. Patients then receive trastuzumab IV over 30 minutes beginning on day 1 of week 25 and continuing weekly for 40 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal estrogen receptor (ER)- or progesterone receptor (PR)-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 15 years or until disease progression.
Source references
references
  1. citation
    Chumsri S, Pai T, Ma Y, Li Z, Gil A, Moreno-Aspitia A, Colon-Otero G, Pogue-Geile KL, Rasgoti P, Paik S, Perez EA, Thompson EA. Clinical Treatment Score Post-5 Years (CTS5) and Late Recurrence Risk in Hormone Receptor-Positive, HER2-Positive Breast Cancer. J Natl Compr Canc Netw. 2024 Aug 26;22(7):463-468. doi: 10.6004/jnccn.2024.7015.
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    pmid
    35610260
    type
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  3. citation
    Caparica R, Ma Y, De Angelis C, Richard F, Desmedt C, Awada A, Piccart M, Perez EA, Moreno-Aspitia A, Badve S, Thompson EA, de Azambuja E. Beta-2 Adrenergic Receptor Gene Expression in HER2-Positive Early-Stage Breast Cancer Patients: A Post-hoc Analysis of the NCCTG-N9831 (Alliance) Trial. Clin Breast Cancer. 2022 Jun;22(4):308-318. doi: 10.1016/j.clbc.2021.11.012. Epub 2021 Dec 2.
    pmid
    34980541
    type
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  4. citation
    Chumsri S, Li Z, Serie DJ, Mashadi-Hossein A, Colon-Otero G, Song N, Pogue-Geile KL, Gavin PG, Paik S, Moreno-Aspitia A, Perez EA, Thompson EA. Incidence of Late Relapses in Patients With HER2-Positive Breast Cancer Receiving Adjuvant Trastuzumab: Combined Analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31. J Clin Oncol. 2019 Dec 10;37(35):3425-3435. doi: 10.1200/JCO.19.00443. Epub 2019 Oct 17.
    pmid
    31622131
    type
    DERIVED
  5. citation
    Chumsri S, Serie DJ, Li Z, Pogue-Geile KL, Soyano-Muller AE, Mashadi-Hossein A, Warren S, Lou Y, Colon-Otero G, Knutson KL, Perez EA, Moreno-Aspitia A, Thompson EA. Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials. Clin Cancer Res. 2019 Jul 15;25(14):4422-4430. doi: 10.1158/1078-0432.CCR-18-2206. Epub 2019 Feb 26.
    pmid
    30808774
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  6. citation
    Norton N, Fox N, McCarl CA, Tenner KS, Ballman K, Erskine CL, Necela BM, Northfelt D, Tan WW, Calfa C, Pegram M, Colon-Otero G, Perez EA, Clynes R, Knutson KL. Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer. Breast Cancer Res. 2018 Jun 14;20(1):52. doi: 10.1186/s13058-018-0989-8.
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  7. citation
    Perez EA, Ballman KV, Tenner KS, Thompson EA, Badve SS, Bailey H, Baehner FL. Association of Stromal Tumor-Infiltrating Lymphocytes With Recurrence-Free Survival in the N9831 Adjuvant Trial in Patients With Early-Stage HER2-Positive Breast Cancer. JAMA Oncol. 2016 Jan;2(1):56-64. doi: 10.1001/jamaoncol.2015.3239.
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    26469139
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    Perez EA, Baehner FL, Butler SM, Thompson EA, Dueck AC, Jamshidian F, Cherbavaz D, Yoshizawa C, Shak S, Kaufman PA, Davidson NE, Gralow J, Asmann YW, Ballman KV. The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831. Breast Cancer Res. 2015 Oct 1;17(1):133. doi: 10.1186/s13058-015-0643-7.
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    26429296
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    O'Sullivan CC, Bradbury I, Campbell C, Spielmann M, Perez EA, Joensuu H, Costantino JP, Delaloge S, Rastogi P, Zardavas D, Ballman KV, Holmes E, de Azambuja E, Piccart-Gebhart M, Zujewski JA, Gelber RD. Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer and Tumors </= 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials. J Clin Oncol. 2015 Aug 20;33(24):2600-8. doi: 10.1200/JCO.2015.60.8620. Epub 2015 Jun 22.
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    Perez EA, Thompson EA, Ballman KV, Anderson SK, Asmann YW, Kalari KR, Eckel-Passow JE, Dueck AC, Tenner KS, Jen J, Fan JB, Geiger XJ, McCullough AE, Chen B, Jenkins RB, Sledge GW, Winer EP, Gralow JR, Reinholz MM. Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant Trastuzumab Trial. J Clin Oncol. 2015 Mar 1;33(7):701-8. doi: 10.1200/JCO.2014.57.6298. Epub 2015 Jan 20.
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    Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. doi: 10.1200/JCO.2014.55.5730. Epub 2014 Oct 20.
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    25332249
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  12. citation
    Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. doi: 10.1200/JCO.2011.36.7045. Epub 2011 Oct 31.
    pmid
    22042958
    type
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Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-31d335a25ad0fc61b8dd
      requested nct id
      NCT00005970
      primary nct id
      NCT00005970
      source kind
      fda_spl_label
      source url
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        rapy phase) discontinued intravenous trastuzumab due to cardiac toxicity. Among 64 patients receiving adjuvant chemotherapy (studies NSABP B31 and NCCTG N9831; NCT00005970) who developed congestive heart failure (CHF), one patient died of cardiomyopathy, one patient died suddenly without documented etiology, and 33 patients were
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        n group.</p></li><li>In the combined analysis of the <a href="/clinicaltrials/NCT00004067">NSABP-B-31</a> (NCT00004067) and intergroup <a href="/clinicaltrials/NCT00005970">NCCTG-N9831</a> (NCT00005970) trials, trastuzumab was given weekly, concurrently, or immediately after the paclitaxel component of the AC with paclitaxel regi
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        mbined analysis of the <a href="/clinicaltrials/NCT00004067">NSABP-B-31</a> (NCT00004067) and intergroup <a href="/clinicaltrials/NCT00005970">NCCTG-N9831</a> (NCT00005970) trials, trastuzumab was given weekly, concurrently, or immediately after the paclitaxel component of the AC with paclitaxel regimen.[<a href="#cit/section_6.1
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        for trastuzumab-treated patients was 4.1%, compared with 0.8% of patients in the control arm (95% CI, 1.7%&#8211;4.9%).</li><li>In the <a href="/clinicaltrials/NCT00005970">NCCTG-N9831</a> trial, 39 cardiac events were reported in the three arms over a 3-year period. The 3-year cumulative incidence of cardiac events was 0.35% in
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        Updated: April 25, 2025
        datetime
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        display
        April 25, 2025

    Preserved source evidence · Not medical advice