Breast Ductal Carcinoma In Situ, Invasive Breast Carcinoma, Multicentric Breast Carcinoma, Multifocal Breast Carcinoma, Synchronous Bilateral Breast Carcinoma
Conditions
Brief summary
This randomized phase III clinical trial studies how well tamoxifen citrate, anastrozole, letrozole, or exemestane with or without chemotherapy work in treating patients with breast cancer that has spread from where it began in the breast to surrounding normal tissue (invasive). Estrogen can cause the growth of breast cancer cells. Hormone therapy, using tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumor cells. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, may fight breast cancer by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving tamoxifen citrate, anastrozole, letrozole, or exemestane is more effective with combination chemotherapy in treating patients with breast cancer.
Detailed description
PRIMARY OBJECTIVE: I. To determine the effect of chemotherapy in patients with node positive breast cancer who do not have high recurrence scores (RS) by Oncotype DX®. SECONDARY OBJECTIVES: I. To compare overall survival (OS), distant disease-free survival (DDFS) and local disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS. II. To compare the toxicity across the treatment arms. III. To perform other molecular assays or test other signatures that measure prognosis and potential benefit of chemotherapy and compare them to Oncotype DX®. IV. To determine the impact of management with Oncotype DX® on patient-reported anxiety (co-primary Health-Related Quality of Life \[HRQL\] outcome) prior to screening, after disclosure of test results, and during the randomized trial. V. To determine the impact of Oncotype DX® on the initial management cost of node-positive, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. VI. To compare patient-reported utilities (e.g., quality of life \[QOL\]) for those randomized to chemotherapy versus no chemotherapy. VII. Using modeling and DFS information from the trial, to estimate the cost-effectiveness of management with Oncotype DX® vs usual care. VIII. To determine the role of other assays as predictors of DFS, DDFS, and LDFI for patients randomized to chemotherapy versus no chemotherapy. IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on patient-reported fatigue and cognitive concerns (secondary HRQL outcomes). X. To determine the impact of management with Oncotype DX® on patient-reported decision conflict, perceptions regarding Oncotype DX® testing, and survivor concerns prior to screening, after disclosure of test results, and during the randomized trial (secondary HRQL outcomes). XI. The presence of circulating tumor cells (CTC+) using two CTC platforms will be assessed at up to two time points to assess late recurrence in those still at risk for the primary outcome. XII. To compare clinically reported menopausal status with status categorized by serum hormone levels determined from baseline serum in women under age 55 years and to assess subsequent association with outcomes. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then yearly for 15 years.
Interventions
DRUGAnastrozole
Given PO
DRUGExemestane
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGLetrozole
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies (closed as of 12/1/12)
DRUGSystemic Chemotherapy
Given IV
DRUGTamoxifen Citrate
Given PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes) invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2 status; estrogen and progesterone receptor positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as either estrogen receptor (ER) or progesterone receptor (PR) \>= 1% positive nuclear staining; HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number \< 4.0 signals per cell by single probe or HER-2/CEP ration \< 2.0 with an average copy number \< 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2 equivocal is not eligible * Patients with multifocal, multicentric and synchronous bilateral breast cancers are allowed * Multifocal disease is defined as more than one invasive cancer \< 2 cm from the largest lesion within the same breast quadrant; (NOTE: the Oncotype DX® testing must be completed on the largest lesion) * Multicentric disease is defined as more than one invasive cancer \>= 2 cm from the largest lesion within the same breast quadrant or more than one lesion in different quadrants (NOTE: Oncotype DX® testing should be completed on all tumors and the determination for eligibility should be made on the highest recurrence score) * Synchronous bilateral disease is defined as invasive breast cancer with positive lymph nodes (axillary or intramammary) in at least one breast, diagnosed within 30 days of each other; (NOTE: the Oncotype DX® testing should be completed on both tumors and the tumor with the highest recurrence score should be used) * Patients will have undergone axillary staging by sentinel node biopsy or axillary lymph nodes dissection (ALND); patients must have at least one, but no more than three known positive lymph nodes (pN1a, pN1b or pN1c); patients with micrometastases as the only nodal involvement (pN1mi) are not eligible; patients with positive sentinel node are not required to undergo full axillary lymph node dissection; this is at the discretion of the treating physician; axillary node evaluation is to be performed per the standard of care at each institution * Patients with a prior diagnosis of contralateral ductal carcinoma in situ (DCIS) are eligible if they underwent a mastectomy or lumpectomy with whole breast radiation; prior partial breast irradiation, including brachytherapy, is not allowed; patients with a prior diagnosis of ipsilateral DCIS or invasive breast cancer who received radiation to that breast are not eligible * Patients must have had either breast-conserving surgery with planned radiation therapy or total mastectomy (with or without planned postmastectomy radiation); patients must have clear margins from both invasive breast cancer and DCIS (as per local institutional guidelines); lobular carcinoma in situ (LCIS) at the margins is allowed * Registration of patients who have not yet undergone Oncotype DX® screening must occur no later than 56 days after definitive surgery; (for all patients, Step 2 Registration must occur within 84 days after definitive surgery); if the Oncotype DX® Breast Cancer Assay has not been performed, patients must be willing to submit tissue samples for testing to determine the Recurrence Score value; a representative block or unstained sections from the representative block are sent directly to Genomic Health for Oncotype DX® Breast Cancer Assay which will be performed according to the standard commercial process * If the Oncotype DX® Recurrence Score is already known and is 25 or less, the patient must be registered to Step 2 immediately following Step 1 registration; if the Oncotype DX® Recurrence Score is already known and is greater than 25, the patient is ineligible * Patients must be females \>= 18 years of age. As the Oncotype DX® recurrence score has not been validated in men with breast cancer, men are not eligible for this study * Patients must have a complete history and physical examination within 28 days prior to registration * Patients must have a performance status of 0-2 by Zubrod criteria * Patients must be able to receive taxane and/or anthracycline based chemotherapy * Patients must not have received an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to registration * No other prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years * The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12; patients who consented to QOL prior to 12/1/12 should continue to complete QOL forms per their expectation report; patients who are able to complete a questionnaire in English must be offered the opportunity to participate in the Quality of Life and Economic Substudy; (The Quality of Life and Economic Substudy is available to U.S. INSTITUTIONS ONLY); patients who are not able to complete a questionnaire in English are registered to S1007 without participating in the Quality of Life and Economic Substudy * Patients who consent to participate in the Quality of Life and Economic Substudy and who do not yet know the results of their Oncotype DX® screening must agree to complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment between 14 days prior to and 7 days after Step 1 Registration * Patients who consent to participate in the Quality of Life and Economic Substudy and who do already know their Oncotype DX® Recurrence Score (and it is 25 or less) will proceed to Step 2 Registration without completing the S1007 Health-Related Quality of Life Questionnaire Enrollment Form (but will complete the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form) * Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; for Step 1 registration of patients who have not yet submitted specimens for the Oncotype DX Breast Cancer Assay, the appropriate consent form is the Step 1 Consent Form; for both Step 1 and Step 2 registration of patients whose Recurrence Score is already known and is 25 or less, the appropriate consent form is the Step 2 Consent Form * As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * STEP 2 REGISTRATION * Recurrence score (RS) by Oncotype DX® must be =\< 25 * Step 2 Registration must take place within 84 days after definitive surgery; patients must not have begun chemotherapy or endocrine therapy for their breast cancer prior to randomization * Patients randomized to either arm may also co-enroll in phase III trials that compare local therapies, or compare systemic therapies (such as chemotherapy, if randomized to Arm I of S1007) * The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12; patients at U.S. INSTITUTIONS who consent to participate in the Quality of Life and Economic Substudy must agree to complete the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form after Recurrence Score results and randomized treatment status are known but before treatment has been initiated * Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; for all patients the appropriate consent form for this registration is the Step 2 Consent * STEP 3 REGISTRATION CBALR TM Substudy * Patients must be disease-free, with no prior invasive recurrence at time of registration to Step 3 * Patients must be registered to Step 3 no more than 8 years after randomization (Step 2 Registration) and must agree to have samples drawn within 28 days after registration to Step 3 * Patients must agree to have blood samples collected at up to 3 timepoints: 1) within 28 days after registration to Step 3, 2) 2-3 years after time of registration to Step 3, and 3) At time of invasive recurrence (if applicable). Patients must also agree to have tissue submitted at time of invasive recurrence (if applicable) from the invasive recurrence biopsy (where tissue is available)
Exclusion criteria
* Patients must not have inflammatory breast cancer and must not have metastatic disease * Patients must not have begun chemotherapy or endocrine therapy for their breast cancer prior to registration * Patients must not require chronic treatment with systemic steroids (inhaled steroids are allowed) or other immunosuppressive agents * Patients must not be pregnant or nursing; women of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease-Free Survival (IDFS) | 5 years after randomization | From date of randomization (2nd Registration) to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. This is the STEEP definition of invasive disease-free survival. Kaplan-Meier estimates were calculated for the 5-year IDFS rate. Due to the results of the third prespecified interim analysis, prespecified separate analyses were conducted for all outcomes by menopausal status (see Statistical Analysis 2). The NCI and data and safety monitoring committee recommended early reporting of the data. After the primary analysis, changes in eligibility status were identified for three participants, making the population of eligible and evaluable participants different between the reporting of this outcome and both the Participant Flow section and the Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duration of treatment and follow-up until death or 3 years after randomization | Only adverse events that are possibly, probably, or definitely related to study drug are reported. Assessed at 6, 12, 24, and 36 months after randomization. |
| Overall Survival (OS) | 5.5 years after randomization | Time from date of randomization (2nd Registration) to date of death due to any cause. Participants last known to be alive are censored at their last contact date. |
| Distant Disease-Free Survival (DDFS) | 5.5 years after randomization | Time from date of randomization (2nd Registration) to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Participants last known to be alive who have not experienced distant recurrence, or second primary cancer are censored at their last contact date. This secondary outcome requires continuing to follow the patient after local recurrence in order to ascertain subsequent distant recurrence. Invasive recurrence is defined as: appearance of any new invasive lesion(s) during or after protocol treatment. Whenever possible, recurrences should be documented histologically. Invasive recurrence includes local, regional, or distant recurrence with an invasive component. A new diagnosis of ipsilateral or contralateral DCIS without an invasive component is not considered to be a recurrence. |
| Local Disease-Free Interval (LDFI) | From date of randomization to a maximum of 5.5 years or death | Time from date of randomization (2nd Registration) to date of invasive local or regional recurrence. Participants last known to be alive without recurrence are censored at their last contact date. Participants with distant recurrence, second primary cancer or death are censored at the time of that event. Invasive recurrence is defined as: appearance of any new invasive lesion(s) during or after protocol treatment. Whenever possible, recurrences should be documented histologically. Invasive recurrence includes local, regional, or distant recurrence with an invasive component. A new diagnosis of ipsilateral or contralateral DCIS without an invasive component is not considered to be a recurrence. |
| Participant-Reported Anxiety | 6 months after randomization | Anxiety is evaluated with the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Anxiety Short Form. Raw PROMIS scores can be re-scaled into T-scores based on a reference population with a mean score of 50 and a standard deviation of 10. Higher scores reflect greater anxiety. PROMIS Anxiety scores at the 6 month timepoint will be compared between the two randomized study arms separately by menopausal status. |
| Participant-Reported Health Status | 6 months after randomization | Assessed using the EuroQol-5D (EQ-5D), in which participants rate their health status in five different health-related domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The raw scores can be converted to index scores on a scale of 0 to 1, where a higher index score represents better health. EQ-5D index scores at the 6-month timepoint will be compared between the two randomized study arms separately by menopausal status. |
Countries
Canada, Colombia, France, Ireland, Mexico, Puerto Rico, Saudi Arabia, South Korea, Spain, United States
Contacts
PRINCIPAL_INVESTIGATORKevin M Kalinsky
SWOG Cancer Research Network
Participant flow
Pre-assignment details
9383 participants were screened and 5083 were randomized to the trial: 2547 to the Chemo and Endocrine Therapy arm and 2536 to the Endocrine Therapy Alone arm. In the Chemo and Endocrine Therapy Arm, 36 were ineligible. In the Endocrine Therapy Alone arm, 29 were ineligible. Ultimately, 5018 participants were eligible in the participant flow: 2511 in the Chemo and Endocrine Therapy arm and 2507 in the Endocrine Therapy Alone arm.
Participants by arm
| Arm | Count |
|---|---|
| Chemo and Endocrine Therapy Participants receive a protocol-approved chemotherapy regimen based on the participant and/or physician preference. Participants then receive a protocol-approved adjuvant endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity. | 2,511 |
| Endocrine Therapy Alone Participants receive a protocol-approved endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity. | 2,507 |
| Total | 5,018 |
Baseline characteristics
| Characteristic | Total | Chemo and Endocrine Therapy | Endocrine Therapy Alone |
|---|---|---|---|
| Age, Continuous | 57.5 years | 57.9 years | 57.2 years |
| Age, Customized 40-49 years | 1077 Participants | 530 Participants | 547 Participants |
| Age, Customized < 40 years | 147 Participants | 67 Participants | 80 Participants |
| Age, Customized 50-59 years | 1675 Participants | 837 Participants | 838 Participants |
| Age, Customized 60-69 years | 1538 Participants | 777 Participants | 761 Participants |
| Age, Customized >= 70 years | 581 Participants | 300 Participants | 281 Participants |
| Axillary Surgery Axillary lymph-node dissection, with or without sentinel-node mapping | 3140 Participants | 1569 Participants | 1571 Participants |
| Axillary Surgery Sentinel-node biopsy without axillary lymph-node dissection | 1878 Participants | 942 Participants | 936 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 622 Participants | 297 Participants | 325 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3426 Participants | 1731 Participants | 1695 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 970 Participants | 483 Participants | 487 Participants |
| Menopausal Status Postmenopausal | 3353 Participants | 1677 Participants | 1676 Participants |
| Menopausal Status Premenopausal | 1665 Participants | 834 Participants | 831 Participants |
| Positive Nodes 1 node | 3275 Participants | 1628 Participants | 1647 Participants |
| Positive Nodes 2 nodes | 1266 Participants | 643 Participants | 623 Participants |
| Positive Nodes 3 nodes | 460 Participants | 231 Participants | 229 Participants |
| Positive Nodes Not reported | 17 Participants | 9 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian | 324 Participants | 154 Participants | 170 Participants |
| Race/Ethnicity, Customized Black | 251 Participants | 130 Participants | 121 Participants |
| Race/Ethnicity, Customized Other/Unknown | 1148 Participants | 560 Participants | 588 Participants |
| Race/Ethnicity, Customized White | 3295 Participants | 1667 Participants | 1628 Participants |
| Recurrence Score 0-13 | 2147 Participants | 1076 Participants | 1071 Participants |
| Recurrence Score 14-25 | 2871 Participants | 1435 Participants | 1436 Participants |
| Sex: Female, Male Female | 5018 Participants | 2511 Participants | 2507 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 161 / 2,487 | 175 / 2,497 |
| other Total, other adverse events | 151 / 2,062 | 2 / 2,342 |
| serious Total, serious adverse events | 14 / 2,062 | 9 / 2,342 |
Outcome results
Primary
Invasive Disease-Free Survival (IDFS)
From date of randomization (2nd Registration) to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. This is the STEEP definition of invasive disease-free survival. Kaplan-Meier estimates were calculated for the 5-year IDFS rate. Due to the results of the third prespecified interim analysis, prespecified separate analyses were conducted for all outcomes by menopausal status (see Statistical Analysis 2). The NCI and data and safety monitoring committee recommended early reporting of the data. After the primary analysis, changes in eligibility status were identified for three participants, making the population of eligible and evaluable participants different between the reporting of this outcome and both the Participant Flow section and the Adverse Events section.
Time frame: 5 years after randomization
Population: For the participants flow and baseline characteristics summary, 5018 eligible participants were included. However, among them, there were 34 participants (10 in the chemo and endocrine arm, and 24 in the endocrine alone arm) that withdrew consent immediately after randomization; thus these participants were excluded from the survival analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemo and Endocrine Therapy | Invasive Disease-Free Survival (IDFS) | Premenopausal | 93.9 percentage of participants |
| Chemo and Endocrine Therapy | Invasive Disease-Free Survival (IDFS) | Postmenopausal | 91.3 percentage of participants |
| Endocrine Therapy Alone | Invasive Disease-Free Survival (IDFS) | Premenopausal | 89.0 percentage of participants |
| Endocrine Therapy Alone | Invasive Disease-Free Survival (IDFS) | Postmenopausal | 91.9 percentage of participants |
Comparison: This test describes the interaction of the treatment arm with the recurrence score in the analysis of invasive disease-free survival in the overall study population, to determine whether chemotherapy benefit depends on the recurrence score. If the interaction was statistically significant, the interaction term was planned to be included in the Cox model to evaluate the invasive disease-free survival outcome.p-value: 0.3595% CI: [0.98, 1.05]Regression, Cox
Comparison: This test describes the interaction of the treatment arm with menopausal status (one of the study stratification factors) in the analysis of invasive disease-free survival in the overall study population, to determine whether chemotherapy benefit depends on menopausal status. If the interaction was statistically significant, separate analyses of IDFS were planned to be conducted by menopausal status.p-value: 0.00895% CI: [1.15, 2.54]Regression, Cox
Comparison: This analysis includes only premenopausal participants.p-value: 0.00295% CI: [0.43, 0.83]Regression, Cox
Comparison: This analysis includes only postmenopausal participants.p-value: 0.8995% CI: [0.82, 1.26]Regression, Cox
Secondary
Distant Disease-Free Survival (DDFS)
Time from date of randomization (2nd Registration) to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Participants last known to be alive who have not experienced distant recurrence, or second primary cancer are censored at their last contact date. This secondary outcome requires continuing to follow the patient after local recurrence in order to ascertain subsequent distant recurrence. Invasive recurrence is defined as: appearance of any new invasive lesion(s) during or after protocol treatment. Whenever possible, recurrences should be documented histologically. Invasive recurrence includes local, regional, or distant recurrence with an invasive component. A new diagnosis of ipsilateral or contralateral DCIS without an invasive component is not considered to be a recurrence.
Time frame: 5.5 years after randomization
Secondary
Local Disease-Free Interval (LDFI)
Time from date of randomization (2nd Registration) to date of invasive local or regional recurrence. Participants last known to be alive without recurrence are censored at their last contact date. Participants with distant recurrence, second primary cancer or death are censored at the time of that event. Invasive recurrence is defined as: appearance of any new invasive lesion(s) during or after protocol treatment. Whenever possible, recurrences should be documented histologically. Invasive recurrence includes local, regional, or distant recurrence with an invasive component. A new diagnosis of ipsilateral or contralateral DCIS without an invasive component is not considered to be a recurrence.
Time frame: From date of randomization to a maximum of 5.5 years or death
Secondary
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Only adverse events that are possibly, probably, or definitely related to study drug are reported. Assessed at 6, 12, 24, and 36 months after randomization.
Time frame: Duration of treatment and follow-up until death or 3 years after randomization
Population: Eligible participants who received at least one dose of protocol treatment and assessed for Adverse Event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 6 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperhidrosis | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 9 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphedema | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin ulceration | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | GGT increased | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stroke | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 20 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Suicidal ideation | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 8 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Menorrhagia | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Surgical and medical procedures - Other, specify | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 23 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 9 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 5 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tinnitus | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness lower limb | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Typhlitis | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flank pain | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Upper gastrointestinal hemorrhage | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Upper respiratory infection | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 24 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urticaria | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Uterine hemorrhage | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myelitis | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vaginal dryness | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vaginal hemorrhage | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocardial infarction | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vascular access complication | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric hemorrhage | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 19 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 21 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | INR increased | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neck pain | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 65 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 7 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wound dehiscence | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal infection | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neoplasms benign, malignant and unspecified - Other | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 7 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nervous system disorders - Other, specify | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fever | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 150 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Allergic reaction | 6 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Injection site reaction | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 20 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Osteoporosis | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anxiety | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 48 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 9 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain in extremity | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric ulcer | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 7 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood and lymphatic system disorders - Other | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Irregular menstruation | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone marrow hypocellular | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Paresthesia | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone pain | 15 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hematuria | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Breast infection | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral ischemia | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bronchial infection | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint range of motion decreased | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CD4 lymphocytes decreased | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac arrest | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flu like symptoms | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cataract | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 21 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Catheter related infection | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Kidney infection | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest pain - cardiac | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest wall pain | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hemorrhoids | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 5 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pleuritic pain | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Left ventricular systolic dysfunction | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 0 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 8 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 11 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Premature menopause | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dermatitis radiation | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukemia secondary to oncology chemotherapy | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Device related infection | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 5 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 31 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hot flashes | 12 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Radiation recall reaction (dermatologic) | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dry mouth | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dry skin | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspareunia | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Watering eyes | 4 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspepsia | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 8 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ear pain | 2 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Renal and urinary disorders - Other, specify | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema limbs | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 16 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ejection fraction decreased | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Reproductive system and breast disorders - Other | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erythema multiforme | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Localized edema | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erythroderma | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 5 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 3 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal pain | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 48 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus tachycardia | 1 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 83 Participants |
| Chemo and Endocrine Therapy | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 6 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wound dehiscence | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fever | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flank pain | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Flu like symptoms | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | GGT increased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric hemorrhage | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastric ulcer | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal pain | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hematuria | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hemorrhoids | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hot flashes | 14 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperhidrosis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 6 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | INR increased | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Injection site reaction | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 4 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Irregular menstruation | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint range of motion decreased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Kidney infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Left ventricular systolic dysfunction | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukemia secondary to oncology chemotherapy | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Localized edema | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphedema | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Menorrhagia | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness lower limb | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 8 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myelitis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocardial infarction | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neck pain | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neoplasms benign, malignant and unspecified - Other | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nervous system disorders - Other, specify | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Osteoporosis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain in extremity | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Paresthesia | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral ischemia | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral motor neuropathy | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 2 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pleuritic pain | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Premature menopause | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Radiation recall reaction (dermatologic) | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 2 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Renal and urinary disorders - Other, specify | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Reproductive system and breast disorders - Other | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus tachycardia | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 5 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin ulceration | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stroke | 3 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Suicidal ideation | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Surgical and medical procedures - Other, specify | 4 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 4 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tinnitus | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Typhlitis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Upper gastrointestinal hemorrhage | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Upper respiratory infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urticaria | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Uterine hemorrhage | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vaginal dryness | 4 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vaginal hemorrhage | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vascular access complication | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Watering eyes | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 2 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Allergic reaction | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anxiety | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 35 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood and lymphatic system disorders - Other | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone marrow hypocellular | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bone pain | 5 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Breast infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bronchial infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CD4 lymphocytes decreased | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac arrest | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cataract | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Catheter related infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest pain - cardiac | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest wall pain | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 6 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dermatitis radiation | 4 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Device related infection | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 3 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dry mouth | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dry skin | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspareunia | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspepsia | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ear pain | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema limbs | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ejection fraction decreased | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erythema multiforme | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erythroderma | 1 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Esophagitis | 0 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 9 Participants |
| Endocrine Therapy Alone | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 0 Participants |
Secondary
Overall Survival (OS)
Time from date of randomization (2nd Registration) to date of death due to any cause. Participants last known to be alive are censored at their last contact date.
Time frame: 5.5 years after randomization
Secondary
Participant-Reported Anxiety
Anxiety is evaluated with the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Anxiety Short Form. Raw PROMIS scores can be re-scaled into T-scores based on a reference population with a mean score of 50 and a standard deviation of 10. Higher scores reflect greater anxiety. PROMIS Anxiety scores at the 6 month timepoint will be compared between the two randomized study arms separately by menopausal status.
Time frame: 6 months after randomization
Secondary
Participant-Reported Health Status
Assessed using the EuroQol-5D (EQ-5D), in which participants rate their health status in five different health-related domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The raw scores can be converted to index scores on a scale of 0 to 1, where a higher index score represents better health. EQ-5D index scores at the 6-month timepoint will be compared between the two randomized study arms separately by menopausal status.
Time frame: 6 months after randomization
Post Hoc
Distant Relapse-Free Survival (DRFS)
Time from date of randomization (2nd Registration) to date of invasive distant disease recurrence or death due to any cause. Participants last known to be alive who have not experienced distant recurrence are censored at their last contact date. This outcome requires continuing to follow the patient after local recurrence in order to ascertain subsequent distant recurrence. Kaplan-Meier estimates were calculated for the 5-year DRFS rate. Due to the results of the third prespecified interim analysis, prespecified separate analyses were conducted for all outcomes by menopausal status. The NCI and the data and safety monitoring committee recommended early reporting of the data. Due to subsequent data collection and data cleaning, the population of eligible and evaluable participants differs slightly between the reporting of this outcome and the Participant Flow section.
Time frame: 5 years after randomization
Population: Eligible and evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemo and Endocrine Therapy | Distant Relapse-Free Survival (DRFS) | Premenopausal participants | 96.1 percentage of participants |
| Chemo and Endocrine Therapy | Distant Relapse-Free Survival (DRFS) | Postmenopausal participants | 94.4 percentage of participants |
| Endocrine Therapy Alone | Distant Relapse-Free Survival (DRFS) | Premenopausal participants | 92.8 percentage of participants |
| Endocrine Therapy Alone | Distant Relapse-Free Survival (DRFS) | Postmenopausal participants | 94.4 percentage of participants |
Comparison: This analysis includes only premenopausal participants.p-value: 0.00995% CI: [0.39, 0.87]Regression, Cox
Comparison: This analysis includes only postmenopausal participants.p-value: 0.795% CI: [0.81, 1.37]Regression, Cox