Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer (HERA)

• ClinicalTrials.gov Identifier: NCT00045032
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Results First Posted: April 27, 2017
• Last Update Posted: April 27, 2017
• Sponsor: Hoffmann-La Roche
• Collaborators: Breast International Group; European Organisation for Research and Treatment of Cancer - EORTC; NCIC Clinical Trials Group; ETOP IBCSG Partners Foundation
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

The purpose of this trial is to evaluate Herceptin treatment for 1 year and 2 years (versus observation/no Herceptin) in women with HER2-overexpressing primary breast cancer who have completed (neo-)adjuvant systemic chemotherapy, definitive surgery, and radiotherapy, if applicable. Efficacy and safety will be assessed for 10 years from randomization for each participant. All participants will continue to be followed for survival until 10 years after enrollment of the last participant.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Herceptin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5099 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Three-Arm, Multicenter Comparison of 1 Year and 2 Years of Herceptin Versus No Herceptin in Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy
• Study Start Date: November 2001
• Actual Primary Completion Date: March 2005
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Observation Arm; Participants who have completed definitive surgery and systemic adjuvant chemotherapy will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin will be provided.
Experimental: Herceptin 1-Year Arm; Participants who have completed definitive surgery and systemic adjuvant chemotherapy will receive Herceptin for 1 year or until disease recurrence, whichever occurs first. Participants will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Drug: Herceptin; Herceptin will be given as a loading dose of 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks.; Other Name: Trastuzumab
Experimental: Herceptin 2-Year Arm; Participants who have completed definitive surgery and systemic adjuvant chemotherapy will receive Herceptin for 2 years or until disease recurrence, whichever occurs first. Participants will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Drug: Herceptin; Herceptin will be given as a loading dose of 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks.; Other Name: Trastuzumab

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an Independent Data Monitoring Committee (IDMC) in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
2. Percentage of Participants With DFS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
3. DFS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: Year 2 ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95 percent (%) confidence interval (CI) were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
4. DFS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: Year 2 ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
5. Percentage of Participants With DFS Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.
6. DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 3 ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
7. DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 5 ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
8. DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 7 ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
9. DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 8 ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
10. Percentage of Participants With DFS Events Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum of 10 years) ]
    DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.
11. DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 3 ]
    DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
12. DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 5 ]
    DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
13. DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 7 ]
    DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
14. DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 8 ]
    DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
15. DFS Rate at Year 9 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 9 ]
    DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
16. DFS Rate at Year 10 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 10 ]
    DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Secondary Outcome Measures :

1. Percentage of Participants With DFS Events in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum of 10 years) ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.
2. DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up [ Time Frame: Years 3, 5, 7, 8, 9, 10 ]
   DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
3. Percentage of Participants With Overall Survival (OS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
   OS events referred to death from any cause. The percentage of participants who died was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
4. Percentage of Participants With OS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
   OS events referred to death from any cause. The percentage of participants who died was reported. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
5. OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: Year 2 ]
   OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
6. OS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: Year 2 ]
   OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
7. Percentage of Participants With OS Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
   OS events referred to death from any cause. The percentage of participants who died was reported.
8. OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
   OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
9. Percentage of Participants With OS Events Compared to Observation: 11-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 11 years) ]
   OS events referred to death from any cause. The percentage of participants who died was reported.
10. OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 9, 10, 11, 12 ]
    OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.
11. Percentage of Participants With OS Events in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 11 years) ]
    OS events referred to death from any cause. The percentage of participants who died was reported.
12. OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 9, 10, 11, 12 ]
    OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.
13. Percentage of Participants With Recurrence-Free Survival (RFS) Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.
14. RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
15. Percentage of Participants With RFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.
16. RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
17. Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.
18. DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
19. Percentage of Participants With DDFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.
20. DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
21. Percentage of Participants With Tumor Recurrence (TR) Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
22. TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without TR of the present breast cancer (i.e., the TR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
23. Percentage of Participants With TR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
24. TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without TR of the present breast cancer (i.e., the TR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
25. Percentage of Participants With Distant Tumor Recurrence (DTR) Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
26. DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without DTR (i.e., the DTR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
27. Percentage of Participants With DTR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
28. DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without DTR (i.e., the DTR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
29. Percentage of Participants With Restricted Disease-Free Survival (RDFS) Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants with at least one RDFS event was reported.
30. RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants free of RDFS events (i.e., the RDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
31. Percentage of Participants With Primary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum up to 10 years) ]
    Primary cardiac endpoint events included the occurrence of any of the following between randomization and new therapy for recurrent disease: symptomatic New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) confirmed by a cardiologist with a drop in left ventricular ejection fraction (LVEF) at least 10 percentage points from Baseline and to a value less than (<) 50%, and documentation of definite or probable cardiac death. Definite cardiac death included CHF, myocardial infarction, or primary arrhythmia. Probable cardiac death included unexpected sudden death within 24 hours of a cardiac event (syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology. The percentage of participants with at least one primary cardiac endpoint event was reported. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.
32. Percentage of Participants With Secondary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum up to 10 years) ]
    Secondary cardiac endpoint events included NYHA Class I or II CHF with a drop in LVEF measured by multiple-gated acquisition or electrocardiogram, unless the subsequent assessment of LVEF indicated a return to levels that did not meet the definition of a significant LVEF drop. A significant LVEF drop was defined as an absolute reduction of at least 10 percentage points from Baseline and to a value <50%. The percentage of participants with at least one secondary cardiac endpoint event was reported, excluding those with both a primary and secondary cardiac endpoint event. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Non-metastatic primary invasive breast cancer overexpressing HER2 (determined by immunohistochemistry 3+ or positive fluorescence in situ hybridization test) that has been histologically confirmed, adequately excised, axillary node positive or negative, and tumor size at least T1c according to Tumor/Node/Metastasis (TNM) staging
• Completion of at least 4 cycles of (neo-)adjuvant systemic chemotherapy, definitive surgery, and radiotherapy, if applicable
• Known hormone receptor status
• Baseline left ventricular ejection fraction (LVEF) greater than or equal to (≥) 55 percent (%)

Exclusion Criteria:

• Prior invasive breast carcinoma
• Other malignancies except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
• Clinical T4 tumors
• Cumulative doxorubicin exposure greater than (>) 360 milligrams per meter-squared (mg/m^2) or epirubicin >720 mg/m^2 or any prior anthracyclines unrelated to the present breast cancer
• Peripheral stem cell or bone marrow stem cell support
• Prior mediastinal irradiation except for internal mammary node irradiation for the present breast cancer
• Non-irradiated internal mammary nodes or supraclavicular lymph node involvement
• Prior anti-HER2 therapy for any other reason or other prior biologic or immunotherapy for breast cancer
• Concurrent anti-cancer treatment in another investigational trial
• Serious cardiac or pulmonary conditions/illness, or any other conditions that could interfere with planned treatment
• Poor hematologic, hepatic, or renal function
• Pregnancy or lactation
• Women of childbearing potential or less than 1 year post-menopause unwilling to use adequate contraceptive measures

Contacts and Locations

Locations

Argentina

Hospital Aleman de Buenos Aires

Buenos Aires, Argentina, 1118

Australia, Australian Capital Territory

Saint John of God Hospital

Geelong, Australian Capital Territory, Australia, 3220

Australia, Queensland

Toowoomba Hospital

Toowoomba, Queensland, Australia, 4350

Australia, Victoria

Andrew Love Cancer Centre

Geelong, Victoria, Australia, 3220

Australia, Western Australia

Mount Hospital

Perth, Western Australia, Australia, 6000

Austria

Landeskrankenhaus Feldkirch

Feldkirch-Tisis, Austria, 6807

Innsbruck Universitaetsklinik

Innsbruck, Austria, A-6020

Landeskrankenhaus Klagenfurt

Klagenfurt, Austria, 9026

St. Vincent's Hospital

Linz Donau, Austria, A-4010

Landeskrankenanstalten - Salzburg

Salzburg, Austria, A-5020

Landeskrankenhaus St. Poelten

St. Poelten, Austria, 3100

Universitaetsklinik fuer Innere Medizin I

Vienna, Austria, 1090

Wilhelminenspital der Stadt Wien

Vienna, Austria, A-1160

LKH Villach

Villach, Austria, 9500

LKH Voecklabruck

Voecklabruck, Austria, 4840

A. oe. Krankenhaus Wiener Neustadt

Wiener Neustadt, Austria, A-2700

Belgium

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, Belgium, 2020

Reseau Hospitalier De Medecine Sociale

Baudour, Belgium, 7331

Hopital Universitaire Erasme

Brussels, Belgium, 1070

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, Belgium, 1090

Institut Jules Bordet

Brussels, Belgium, B-1000

Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, Belgium, 6000

Cazk Groeninghe - Campus St-Niklaas

Kortrijk, Belgium, B-8500

Centre Hospitalier Universitaire de Tivoli

La Louviere, Belgium, 7100

U.Z. Gasthuisberg

Leuven, Belgium, B-3000

Clinique Saint-Joseph

Liege, Belgium, B 4000

CHU Liege - Domaine Universitaire du Sart Tilman

Liege, Belgium, B-4000

Clinique Sainte Elisabeth

Namur, Belgium, 5000

Hospital Serruys Ziekenhuis

Oostende, Belgium, 8400

Centre Hospitalier Peltzer-La Tourelle

Verviers, Belgium, B-4800

Brazil

Porto Alegre Hospital

Porto Alegre, Rio Grande do Sul, Brazil, 90035-003

Hospital Sao Lucas da PUCRS

Porto Alegre, Brazil, 90610-000

Hospital Santa Rita

Porto Alegre, Brazil, 91330-490

Instituto Nacional de Cancer

Rio de Janeiro, Brazil, 20560-120

Faculdade De Medicina Do ABC

Santo Andre, Brazil, 09060-650

Canada, Alberta

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, Canada, T2N 4N2

Canada, British Columbia

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, Canada, V1Y 5L3

Fraser Valley Cancer Centre at British Columbia Cancer Agency

Surrey, British Columbia, Canada, V3V 1Z2

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, Canada, V5Z 4E6

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada, V8R 6V5

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R2H 2A6

Canada, Ontario

Royal Victoria Hospital of Barrie

Barrie, Ontario, Canada, L4M 6M2

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

Trillium Health Centre - Mississauga Site

Mississauga, Ontario, Canada, L5B 1B8

Algoma Regional Cancer Program at Sault Area Hospital

Sault Sainte Marie, Ontario, Canada, P6A 2C4

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, Canada, L2R 5K3

Toronto East General Hospital

Toronto, Ontario, Canada, M4C 3E7

Mount Sinai Hospital - Toronto

Toronto, Ontario, Canada, M5G 1X5

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Windsor Regional Cancer Centre at Windsor Regional Hospital

Windsor, Ontario, Canada, N8W 2X3

Canada, Prince Edward Island

Prince Edward Island Cancer Centre at Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada, C1A 8T5

Canada, Quebec

Hopital du Saint-Sacrement, Quebec

Quebec City, Quebec, Canada, G1S 4L8

Canada, Saskatchewan

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, Canada, S4T 7T1

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada, S7N 4H4

Chile

Fundacion Arturo Lopez Perez

Santiago, Chile, 29

Hospital Clinico San Borja Arriaran

Santiago, Chile

Hospital Dr. Sotero Del Rio

Santiago, Chile

Hospital Militar

Santiago, Chile

Instituto Nacional Del Cancer

Santiago, Chile

China

Queen Mary Hospital

Hong Kong, China

Tuen Mun Hospital

Hong Kong, China

Tongji Medical University

Wuhan, China, 430030

Colombia

Instituto Nacional De Cancerologia

Bogota, Colombia

Croatia

Clinical Hospital Center Split

Split, Croatia, 21000

Denmark

Centralsygehus I Esbjerg

Esbjerg, Denmark, 6700

Herning Central Hospital

Herning, Denmark, 7400

Hillerod Hospital

Hillerod, Denmark, 3400

Centralsygehuset I Naestved

Naestved, Denmark, 4700

Sonderborg Sygehus

Sonderborg, Denmark, 6400

France

Centre Regional Francois Baclesse

Caen, France, 14076

Centre Hospital Regional Universitaire de Limoges

Limoges, France, 87042

Hopital Clinique Claude Bernard

Metz, France, 57072

Germany

Charite - Campus Charite Mitte

Berlin, Germany, D-10117

Evangelisches Bethesda Krankenhaus GmbH

Essen, Germany, D-45355

Universitaetsklinikum Freiburg

Freiburg, Germany, D-79106

Martin Luther Universitaet

Halle, Germany, D-06097

Henriettenstiftung Krankenhaus

Hanover, Germany, D-30559

Universitaets-Hautklinik Heidelberg

Heidelberg, Germany, D-69115

St. Vincentius-Kliniken

Karlsruhe, Germany, D-76137

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, Germany, D-24105

Kreiskrankenhaus Leonberg - Frauenklinik

Leonberg, Germany, D-71229

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, Germany, D-39120

Frauenklinik Vom Roten Kreuz

Munich, Germany, 80637

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, Germany, D-81675

Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt

Rostock, Germany, D-18059

Universitaet Ulm

Ulm, Germany, D-89075

Dr. Horst-Schmidt-Kliniken

Wiesbaden, Germany, D-65199

Greece

University of Crete School of Medicine

Heraklion, Crete, Greece, 71110

Evaggelismos Hospital

Athens, Greece, 10676

Guatemala

Centro Medico

Guatemala City, Guatemala, 01010

Hospital Roosevelt

Guatemala City, Guatemala, 01010

Hong Kong

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Hungary

Semmelweis University

Budapest, Hungary, 1082

National Institute of Oncology

Budapest, Hungary, 1122

Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia

Budapest, Hungary, H-1032

Ireland

Cork University Hospital

Cork, Ireland

Israel

Sieff Hospital

Safed, Israel, 13110

Italy

Ospedale San Lazzaro

Alba, Italy, 12051

Ospedale Presenti Fenaroli

Alzano-Lombardo, Italy, 24022

Centro di Riferimento Oncologico - Aviano

Aviano, Italy, 33081

Ospedali Riuniti di Bergamo

Bergamo, Italy, 24100

Ospedale degli Infermi - ASL 12

Biella, Italy, 13900

Ospedale Bellaria

Bologna, Italy, I-40139

Spedali Civili di Brescia

Brescia, Italy, 25124

Ospedale Oncologico A. Businco

Cagliari, Italy, 09100

Ospedale B. Ramazzini

Carpi, Italy, 41012

Ospedale Valduce

Como, Italy, 22100

Ospedale Santa Croce

Cuneo, Italy, 12100

Universita Degli Studi Di Florence

Firenze (Florence), Italy, 50121

Azienda Ospedaliero Careggi

Florence, Italy, 50139

Morgagni-Pierantoni Ospedale

Forli, Italy, 47100

Istituto Nazionale per la Ricerca sul Cancro

Genoa, Italy, 16132

Ospedale A. Manzoni

Lecco, Italy, 23900

Presidio Ospedaliero

Livorno, Italy, 57100

Carlo Poma Hospital

Mantova, Italy, 46100

European Institute of Oncology

Milan, Italy, 20141

Ospedale Niguarda Ca'Granda

Milan, Italy, 20162

University of Modena Hospital and Reggio Emilia School of Medicine

Modena, Italy, 41100

Azienda Ospedaliera Di Parma

Parma, Italy, 43100

I.R.C.C.S. Policlinico San Matteo

Pavia, Italy, 27100

Policlinico Monteluce

Perugia, Italy, 06122

Azienda Ospedaliera

Reggio Emilia, Italy, 42100

Ospedale San Filippo Neri

Rome, Italy, 00135

Ospedale Sant' Eugenio

Rome, Italy, 00144

Istituto Clinico Humanitas

Rozzano, Italy, 20089

Ospedale Civile ASL 1

Sassari, Italy, 07100

Primario U.O. di Oncologia Medica

Trento, Italy, 38100

Ospedale Ostetrico Ginecologica Sant Anna

Turin, Italy, 10126

Universita di Torino

Turin, Italy, 10126

Japan

Tokai University School Of Medicine

Kanagawa, Japan, 259-1193

Tokyo Metropolitan - Komagome Hospital

Tokyo, Japan, 113-8677

Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of, 110-744

Yonsei Cancer Center at Yonsei University Medical Center

Seoul, Korea, Republic of, 120-752

Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands, 6202 AZ

Maasland Hospital

Sittard, Netherlands, 6131 BK

Diakonessenhuis Utrecht

Utrecht, Netherlands, 3508 TG

Poland

Medical University of Gdansk

Gdansk, Poland, 80-211

Oncologic Center

Gliwice, Poland, 44-101

Medical University

Poznan, Poland, 61-878

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, Poland, 02-781

Portugal

Instituto Portugues de Oncologia, Centro Regional de Coimbra

Coimbra, Portugal, 3000-075

Hospitais da Universidade de Coimbra (HUC)

Coimbra, Portugal, 3000

Maternidade Byssaia Barreto

Coimbra, Portugal, 3000

Hospital Distrital De Faro

Faro, Portugal, 8000

University Hospital of Santa Maria

Lisboa, Portugal, 1649-035

Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.

Lisbon, Portugal, 1099-023 Codex

Russian Federation

Moscow Oncology Hospital

Moscow, Russian Federation, 107005

P.A. Hertzen Research Oncology Institute

Moscow, Russian Federation, 125284

Singapore

Johns Hopkins Singapore International Medical Centre

Singapore, Singapore, 308433

South Africa

Groote Schuur Hospital

Cape Town, South Africa, 7925

Parklands Hospital

Durban, South Africa, 4001

Sandton Oncology Centre

Johannesburg, South Africa, 2121

Medical Oncology Centre of Rosebank

Johannesburg, South Africa, 2193

Pretoria - East Hospital

Lynnwood, South Africa, 0081

Spain

Hospital De La Ribera

Alzira, Spain, 46600

Hospital Del Mar

Barcelona, Spain, 08003

Hospital Universitario San Cecilio de Granada

Granada, Spain, 18003

Hospital General Universitario De Guadalajara

Guadalajara, Spain, 19002

Hospital Juan Ramon Jimenez

Huelva, Spain, 21005

Hospital Cuidad de Jaen

Jaen, Spain, 23007

Centro Oncologico De Galicia Jose Antonio Quirogay Pineyro

La Coruna, Spain, 15009

Hospital Universitario Canarias

La Laguna, Spain, 38320

Hospital de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, Spain, 35020

Hospital Insular de Gran Canaria

Las Palmas, Spain, G.C.

Hospital de la Princesa

Madrid, Spain, 28006

Complejo Hospitalario Santa Maria

Orense, Spain, 32005

Complejo Hospitalario de Pontevedra

Pontevedra, Spain, 36001

Consorci Hospitalari del Parc Tauli

Sabadell, Spain, 08208

Hospital Universitario Nuestra Senora de la Candelaria

Santa Cruz de Tenerife, Spain, 38010

Hospital Universidad Virgen Del Rocio

Sevilla, Spain, E- 41013

Hospital Virgen Del La Salud

Toledo, Spain, 45004

Hospital General Universitario Valencia

Valencia, Spain, 41014

Complexo Hospitalario Xeral de Vigo

Vigo Pontevedra, Spain, 36204

Hospital Universitario Miguel Servet

Zaragoza, Spain, 59009

Sweden

University Hospital of Linkoping

Linkoping, Sweden, S-581 85

University Hospital of Malmoe

Malmo, Sweden, 20502

Sahlgrenska University Hospital - Molndal at Gothenburg University

Molndal, Sweden, S-43180

Karolinska University Hospital - Huddinge

Stockholm, Sweden, S-171 76

Umea Universitet

Umea, Sweden, SE-901 87

Uppsala University Hospital

Uppsala, Sweden, SE-75185

Switzerland

Kantonspital Aarau

Aarau, Switzerland, 5001

Universitaetsspital-Basel

Basel, Switzerland, CH-4031

Inselspital Bern

Bern, Switzerland, CH-3010

Spitaeler Chur AG

Chur, Switzerland, CH-7000

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland, CH-1011

Ospedale Beata Vergine

Mendrisio, Switzerland, CH-6850

Kantonsspital - St. Gallen

St. Gallen, Switzerland, CH-9007

UniversitaetsSpital Zuerich

Zurich, Switzerland, CH-8091

Thailand

Chulalongkorn University Hospital

Bangkok, Thailand, 10330

Ramathibodi Hospital

Bangkok, Thailand, 10400

United Kingdom

Bradford Hospitals NHS Trust

Bradford, England, United Kingdom, BD9 6RJ

Broomfield Hospital

Chelmsford, Essex, England, United Kingdom, CM1 7ET

Saint Margaret's Hospital

Epping Essex, England, United Kingdom, CM16 6TN

Diana Princess of Wales Hospital

Grimsby, England, United Kingdom, DN33 2BA

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, United Kingdom, HD3 3EA

Princess Royal Hospital

Hull, England, United Kingdom, HU8 9HE

Cookridge Hospital at Leeds Teaching Hospital NHS Trust

Leeds, England, United Kingdom, LS16 6QB

Imperial College of Medicine

London, England, United Kingdom, W12 0NN

James Cook University Hospital

Middlesbrough, England, United Kingdom, TS4 3BW

Northern Centre for Cancer Treatment at Newcastle General Hospital

Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE

Cancer Research Centre at Weston Park Hospital

Sheffield, England, United Kingdom, S1O 2SJ

Airedale General Hospital

West Yorkshire, England, United Kingdom, BD20 6TD

Southend NHS Trust Hospital

Westcliff-On-Sea, England, United Kingdom, SS0 0RY

Sponsors and Collaborators

Hoffmann-La Roche

Breast International Group

European Organisation for Research and Treatment of Cancer - EORTC

NCIC Clinical Trials Group

ETOP IBCSG Partners Foundation

Investigators

• Study Chair: Martine J. Piccart-Gebhart, MD, PhD; Jules Bordet Institute
• Study Chair: Robert E. Coleman, MD, FRCP; Cancer Research Centre at Weston Park Hospital
• Study Chair: Karen A. Gelmon, MD; British Columbia Cancer Agency
• Study Chair: Kathleen I. Pritchard, MD; Toronto Sunnybrook Regional Cancer Centre
• Study Chair: Olivia Pagani, MD; Ospedale Beata Vergine

More Information

Publications of Results:

Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R; Herceptin Adjuvant (HERA) Trial Study Team. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011 Mar;12(3):236-44. doi: 10.1016/S1470-2045(11)70033-X. Epub 2011 Feb 25.

Procter M, Suter TM, de Azambuja E, Dafni U, van Dooren V, Muehlbauer S, Climent MA, Rechberger E, Liu WT, Toi M, Coombes RC, Dodwell D, Pagani O, Madrid J, Hall M, Chen SC, Focan C, Muschol M, van Veldhuisen DJ, Piccart-Gebhart MJ. Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin Adjuvant (HERA) trial. J Clin Oncol. 2010 Jul 20;28(21):3422-8. doi: 10.1200/JCO.2009.26.0463. Epub 2010 Jun 7.

Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U, Rueschoff J, Jordan B, Dolci S, Abramovitz M, Stoss O, Viale G, Gelber RD, Piccart-Gebhart M, Leyland-Jones B. Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol. 2009 Jun 20;27(18):2962-9. doi: 10.1200/JCO.2008.19.7939. Epub 2009 Apr 13.

Untch M, Gelber RD, Jackisch C, Procter M, Baselga J, Bell R, Cameron D, Bari M, Smith I, Leyland-Jones B, de Azambuja E, Wermuth P, Khasanov R, Feng-Yi F, Constantin C, Mayordomo JI, Su CH, Yu SY, Lluch A, Senkus-Konefka E, Price C, Haslbauer F, Suarez Sahui T, Srimuninnimit V, Colleoni M, Coates AS, Piccart-Gebhart MJ, Goldhirsch A; HERA Study Team. Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol. 2008 Jun;19(6):1090-6. doi: 10.1093/annonc/mdn005. Epub 2008 Feb 21.

McCaskill-Stevens W, Procter M, Goodbrand J, et al.: Disease-free survival according to local immunohistochemistry for HER2 and central fluorescence in situ hydridization for patients treated with adjuvant chemotherapy with and without trastuzumab in the HERA (BIG 01-01) trial. [Abstract] Breast Cancer Res Treat 106 (1): A-71, S18, 2007.

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sanchez Rovira P, Piccart-Gebhart MJ; HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36. doi: 10.1016/S0140-6736(07)60028-2.

Suter TM, Procter M, van Veldhuisen DJ, Muscholl M, Bergh J, Carlomagno C, Perren T, Passalacqua R, Bighin C, Klijn JG, Ageev FT, Hitre E, Groetz J, Iwata H, Knap M, Gnant M, Muehlbauer S, Spence A, Gelber RD, Piccart-Gebhart MJ. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol. 2007 Sep 1;25(25):3859-65. doi: 10.1200/JCO.2006.09.1611. Epub 2007 Jul 23.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. doi: 10.1056/NEJMoa052306.

Other Publications:

Jahanzeb M. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008 Aug;8(4):324-33. doi: 10.3816/CBC.2008.n.037.

Shiroiwa T, Fukuda T, Shimozuma K, Ohashi Y, Tsutani K. The model-based cost-effectiveness analysis of 1-year adjuvant trastuzumab treatment: based on 2-year follow-up HERA trial data. Breast Cancer Res Treat. 2008 Jun;109(3):559-66. doi: 10.1007/s10549-007-9679-4. Epub 2007 Jul 28.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yerushalmi R, Dong B, Chapman JW, Goss PE, Pollak MN, Burnell MJ, Levine MN, Bramwell VHC, Pritchard KI, Whelan TJ, Ingle JN, Shepherd LE, Parulekar WR, Han L, Ding K, Gelmon KA. Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials. Ann Oncol. 2017 Jul 1;28(7):1560-1568. doi: 10.1093/annonc/mdx152.

Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C; Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205. doi: 10.1016/S0140-6736(16)32616-2. Epub 2017 Feb 17. Erratum In: Lancet. 2019 Mar 16;393(10176):1100.

Loi S, Dafni U, Karlis D, Polydoropoulou V, Young BM, Willis S, Long B, de Azambuja E, Sotiriou C, Viale G, Ruschoff J, Piccart MJ, Dowsett M, Michiels S, Leyland-Jones B. Effects of Estrogen Receptor and Human Epidermal Growth Factor Receptor-2 Levels on the Efficacy of Trastuzumab: A Secondary Analysis of the HERA Trial. JAMA Oncol. 2016 Aug 1;2(8):1040-7. doi: 10.1001/jamaoncol.2016.0339.

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.

de Azambuja E, Procter MJ, van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J, Untch M, Smith IE, Gianni L, Baselga J, Jackisch C, Cameron DA, Bell R, Leyland-Jones B, Dowsett M, Gelber RD, Piccart-Gebhart MJ, Suter TM. Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01). J Clin Oncol. 2014 Jul 10;32(20):2159-65. doi: 10.1200/JCO.2013.53.9288. Epub 2014 Jun 9.

Zabaglo L, Stoss O, Ruschoff J, Zielinski D, Salter J, Arfi M, Bradbury I, Dafni U, Piccart-Gebhart M, Procter M, Dowsett M; HERA Trial Study Team. HER2 staining intensity in HER2-positive disease: relationship with FISH amplification and clinical outcome in the HERA trial of adjuvant trastuzumab. Ann Oncol. 2013 Nov;24(11):2761-6. doi: 10.1093/annonc/mdt275. Epub 2013 Jul 25.

Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Kohne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. doi: 10.1016/S0140-6736(13)61094-6. Epub 2013 Jul 18.

Metzger-Filho O, Procter M, de Azambuja E, Leyland-Jones B, Gelber RD, Dowsett M, Loi S, Saini KS, Cameron D, Untch M, Smith I, Gianni L, Baselga J, Jackisch C, Bell R, Sotiriou C, Viale G, Piccart-Gebhart M. Magnitude of trastuzumab benefit in patients with HER2-positive, invasive lobular breast carcinoma: results from the HERA trial. J Clin Oncol. 2013 Jun 1;31(16):1954-60. doi: 10.1200/JCO.2012.46.2440. Epub 2013 Apr 15.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00045032
• Other Study ID Numbers: BO16348; BIG-01-01; EU-20216; ROCHE-B016348E; ROCHE-B016348C; EORTC-10011; CAN-NCIC-MA24; IBCSG-28-02
• First Posted: January 27, 2003
• Results First Posted: April 27, 2017
• Last Update Posted: April 27, 2017
• Last Verified: March 2017

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents