RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying the side effects of trastuzumab and to see how well it works in treating older women with early-stage breast cancer.
OBJECTIVES: Primary * To evaluate the 3-year cumulative incidence of cardiac events in women 60 years and older with HER2-positive breast cancer who receive single agent trastuzumab (Herceptin®) in the adjuvant setting. Secondary * To evaluate the 1-year cumulative incidence of asymptomatic cardiac left ventricular dysfunction in women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab in the adjuvant setting. * To evaluate long-term cardiac toxicity (5-year cumulative incidence of cardiac events) in women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab in the adjuvant setting. * To assess the relation between physiologic markers of chronic heart failure and trastuzumab-related cardiac dysfunction in women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab. * To assess the relation between pro-inflammatory cytokines and trastuzumab-related cardiac dysfunction in women 60 years and older with Her2-positive breast cancer. * To determine the effect of this drug on the health-related quality of life and functional, cognitive, and mental status of women 60 years and older with Her2-positive breast cancer. * To determine the 5-year disease-free survival and overall survival of women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab in the adjuvant setting. OUTLINE: This is a multicenter study. Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52. After completion of study therapy, patients are followed periodically for 4 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α).
Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Wake Forrest
Winston-Salem, North Carolina, United States
Lake/University Seidman Cancer Center
Cleveland, Ohio, United States
Percent of Participants Experiencing Cardiac Events at 1 Year
Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.
Time frame: At 1 year
Percent of Participants Experiencing Cardiac Events at 3 Years
Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.
Time frame: At 3 years
Percent of Participants Experiencing Cardiac Events at 5 Years
Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.
Time frame: At 5 years
Percent of Participants of Asymptomatic Left Ventricular (LV) Cardiac Dysfunction at 1 Year
One-year cumulative incidence of LV cardiac dysfunction as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation
Time frame: At 1 year
Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Three Years
Three-year cumulative incidence of LV cardiac dysfunction as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation
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Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
University Suburban Health Center
Cleveland, Ohio, United States
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, United States
Southwest General Health Center
Cleveland, Ohio, United States
UHHS Westlake Medical Center
Cleveland, Ohio, United States
UH-Monarch
Mayfield Heights, Ohio, United States
Sharon Health Center
Wadsworth, Ohio, United States
...and 1 more locations
Time frame: At 3 years
Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Five Years
Five-year cumulative incidence as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation
Time frame: At 5 years
Percent of Participants With Disease-free Survival (DFS)
Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time frame: At 1 year
Percent of Participants With DFS
Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time frame: At 2 years
Percent of Participants With Disease-free Survival (DFS)
Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time frame: At 3 years
Percent of Participants With Disease-free Survival (DFS)
Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time frame: At 5 years
Overall Survival (OS) as Measured by Percent of Participants Alive at 1 Year
OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time frame: Up to 1 years
Overall Survival (OS) as Measured by Percent of Participants Alive at 2 Years
OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time frame: Up to 2 years
Overall Survival (OS) as Measured by Percent of Participants Alive at 3 Years
OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time frame: Up to 3 years
Overall Survival (OS) as Measured by Percent of Participants Alive at 5 Years
OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time frame: Up to 5 years
Mean Change in Quality of Life From Baseline to Mid-treatment
Quality of life was assessed by using the mean change in Functional Assessment of Cancer Therapy-Breast (FACTB) scoring instrument. The Functional Assessment of Cancer Therapy-Breast (FACT-B) is a 37-item instrument designed to measure five domains of HRQOL in breast cancer patients: Physical, social, emotional, and functional well-being, as well as a breast-cancer subscale (BCS). Each question response is based on a 5-point Likert-type scale. Scores range from 0-148. High scores indicate better QOL.
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Quality of Life From Baseline to End of Treatment
Quality of life was assessed by using the mean change in Functional Assessment of Cancer Therapy-Breast (FACTB) scoring instrument. The Functional Assessment of Cancer Therapy-Breast (FACT-B) is a 37-item instrument designed to measure five domains of HRQOL in breast cancer patients: Physical, social, emotional, and functional well-being, as well as a breast-cancer subscale (BCS). Each question response is based on a 5-point Likert-type scale. Scores range from 0-148. High scores indicate better QOL.
Time frame: From baseline to end-of-treatment (52 weeks)
Mean Change in Functional Status
Mean Change in ADL/IADL scores From Baseline to Mid-treatment. The functional status will be measured by a Comprehensive Geriatric Assessment comprised of two validated instruments: Katz's Activity of Daily Living (ADL) instrument and Lawton's Instrumental of Activities of Daily Living (IADL). The IADL scale contains eight items with a summary score from 0 (low function) to 8 (high function), with higher scores indicating higher function. The ADL scale contains six items with a summary score of 0 to 6, with higher scores indicating higher independence. A score of 6 indicates complete independence; a score of 4 indicates moderate impairment; 2 or less indicates severe functional impairment. The scores of both scales will be added together for a comprehensive geriatric assessment score.
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Functional Status
Mean Change in ADL/IADL scores From Baseline to End of Treatment. The functional status will be measured by a Comprehensive Geriatric Assessment comprised of two validated instruments: Katz's Activity of Daily Living (ADL) instrument and Lawton's Instrumental of Activities of Daily Living (IADL). The IADL scale contains eight items with a summary score from 0 (low function) to 8 (high function), with higher scores indicating higher function. The ADL scale contains six items with a summary score of 0 to 6, with higher scores indicating higher independence. A score of 6 indicates complete independence; a score of 4 indicates moderate impairment; 2 or less indicates severe functional impairment. The scores of both scales will be added together for a comprehensive geriatric assessment score.
Time frame: baseline to end-of-treatment (52 weeks)
Mean Change in Cognitive Status
Mean Change in Mini Mental Status Exam (MMSE scores) From Baseline to Mid-treatment. The Mini-Mental Status Exam contains 11 items to gauge cognitive function. The minimum score is 0. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The higher the score, the better the participant's function (Scores 30-24 indicate uncertain cognitive impairment; scores 23-18 indicate mild to moderate cognitive impairment; scores 17-0 indicate severe cognitive impairment).
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Cognitive Status
Mean Change in Mini Mental Status Exam (MMSE scores) From Baseline to End of Treatment. The Mini-Mental Status Exam contains 11 items to gauge cognitive function. The minimum score is 0. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The higher the score, the better the participant's function (Scores 30-24 indicate uncertain cognitive impairment; scores 23-18 indicate mild to moderate cognitive impairment; scores 17-0 indicate severe cognitive impairment).
Time frame: From baseline to end-of-treatment (52 weeks)
Mean Change in Psychosocial Status (Depression)
Mean Change in Geriatric Depression Scores From Baseline to Mid-treatment. The Geriatric Depression Scale (GDS) is a validated tool with 15 items. The minimum score is 0, and the maximum is 15. Scores of 0-4 are considered normal, depending on age, education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression.
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Psychosocial Status (Depression)
Mean Change in Geriatric Depression Scores from Baseline to End of Treatment. The Geriatric Depression Scale (GDS) is a validated tool with 15 items. The minimum score is 0, and the maximum is 15. Scores of 0-4 are considered normal, depending on age, education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression.
Time frame: From baseline to end-of-treatment (52 weeks)
Mean Change in Psychosocial Status (Social Support)
Mean Change in MOS social support scores From Baseline to Mid-treatment. The Medical Outcomes Study (MOS) Social Support survey tool measures multiple domains. It is a 19-item tool comprised of four subscales in one overall summary index. The subscales are Emotional/Informational Support, Tangible Support, Affectionate support, and Positive Social Interaction. The overall index score is determined by calculating the mean of all 19 items. Scores range from 19 to 95, with higher scores indicating high support availability to participants.
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Psychosocial Status (Social Support)
Mean Change in MOS social support scores From Baseline to End of Treatment. The Medical Outcomes Study (MOS) Social Support survey tool measures multiple domains. It is a 19-item tool comprised of four subscales in one overall summary index. The subscales are Emotional/Informational Support, Tangible Support, Affectionate support, and Positive Social Interaction. The overall index score is determined by calculating the mean of all 19 items. Scores range from 19 to 95, with higher scores indicating high support availability to participants.
Time frame: From baseline to end-of-treatment (52 weeks)
Mean Change in Nutritional Status
Mean Change in Mini Nutrition Assessment scores From Baseline to Mid-treatment. The Mini Nutritional Screening is a scale comprised of six questions. The sum of the six questions is totaled to determine a score which is designed to assess if there is a risk of malnutrition. The highest score possible, 14, indicated no risk, and the minimum score of 0 indicates the highest risk possible. 12 points or greater is considered no risk or normal. Meanwhile, a score below 11 indicates possible malnutrition.
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Nutritional Status
Mean Change in Mini Nutrition Assessment scores From Baseline to End of Treatment. The Mini Nutritional Screening is a scale comprised of six questions. The sum of the six questions is totaled to determine a score which is designed to assess if there is a risk of malnutrition. The highest score possible, 14, indicated no risk, and the minimum score of 0 indicates the highest risk possible. 12 points or greater is considered no risk or normal. Meanwhile, a score below 11 indicates possible malnutrition.
Time frame: From baseline to end-of-treatment (52 weeks)
Mean Change in Pro-inflammatory Cytokines
Mean change in pro-inflammatory cytokines from baseline to mid-treatment
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Pro-inflammatory Cytokines
Mean change in pro-inflammatory cytokines from baseline to end of treatment
Time frame: From baseline to end-of-treatment (52 weeks)
Mean Change in Plasma Cardiac Markers
Mean change in plasma cardiac markers from baseline to mid-treatment
Time frame: From Baseline to mid-treatment (week 26)
Mean Change in Plasma Cardiac Markers
Mean change in plasma cardiac markers from baseline end of treatment
Time frame: From baseline to end-of-treatment (52 weeks)