Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

• ClinicalTrials.gov Identifier: NCT01272037
• Recruitment Status: Active, not recruiting
• First Posted: January 7, 2011
• Results First Posted: June 27, 2023
• Last Update Posted: May 16, 2024
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Breast Ductal Carcinoma In Situ; Invasive Breast Carcinoma; Multicentric Breast Carcinoma; Multifocal Breast Carcinoma; Synchronous Bilateral Breast Carcinoma
• Interventions: Drug: Anastrozole; Drug: Exemestane; Other: Laboratory Biomarker Analysis; Drug: Letrozole; Other: Quality-of-Life Assessment; Drug: Systemic Chemotherapy; Drug: Tamoxifen Citrate
• Enrollment: 5018

Participant Flow

Recruitment Details

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.

Arm/Group Title	Chemo and Endocrine Therapy	Endocrine Therapy Alone
Arm/Group Description	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.	Participants receive a protocol-approved endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started	2511	2507
Completed	1504	1547
Not Completed	1007	960
Reason Not Completed
Death	25	28
Adverse Event	12	7
Withdrawal by Subject	175	93
Disease progression	70	111
Other reason	42	41
Delinquent data	24	19
Reason under review	33	29
On treatment	626	632

Baseline Characteristics

Arm/Group Title		Chemo and Endocrine Therapy	Endocrine Therapy Alone	Total
Arm/Group Description		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.	Participants receive a protocol-approved endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Number of Baseline Participants		2511	2507	5018
Baseline Analysis Population Description		Randomized participants who were eligible for the study.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	2511 participants	2507 participants	5018 participants
		57.9; (28.0 to 87.6)	57.2; (18.3 to 86.0)	57.5; (18.3 to 87.6)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	< 40 years	67 2.7%	80 3.2%	147 2.9%
	40-49 years	530 21.1%	547 21.8%	1077 21.5%
	50-59 years	837 33.3%	838 33.4%	1675 33.4%
	60-69 years	777 30.9%	761 30.4%	1538 30.6%
	>= 70 years	300 11.9%	281 11.2%	581 11.6%
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	Female	2511 100.0%	2507 100.0%	5018 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Description: This trial only included female participants.
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	Hispanic or Latino	297 11.8%	325 13.0%	622 12.4%
	Not Hispanic or Latino	1731 68.9%	1695 67.6%	3426 68.3%
	Unknown or Not Reported	483 19.2%	487 19.4%	970 19.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	White	1667 66.4%	1628 64.9%	3295 65.7%
	Black	130 5.2%	121 4.8%	251 5.0%
	Asian	154 6.1%	170 6.8%	324 6.5%
	Other/Unknown	560 22.3%	588 23.5%	1148 22.9%
Menopausal Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	Premenopausal	834 33.2%	831 33.1%	1665 33.2%
	Postmenopausal	1677 66.8%	1676 66.9%	3353 66.8%
		[1] Measure Description: Premenopausal was defined as: < 6 months since last menstrual period and no prior bilateral oophorectomy and not on estrogen replacement. Postmenopausal was defined as: prior bilateral oophorectomy, or > 12 months since last menstrual period with no prior hysterectomy. If these categories did not apply, premenopausal was defined as age < 50 and postmenopausal was defined as age >= 50.
Recurrence Score [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	0-13	1076 42.9%	1071 42.7%	2147 42.8%
	14-25	1435 57.1%	1436 57.3%	2871 57.2%
		[1] Measure Description: The Oncotype DX® Recurrence Score is based on a 21-gene breast cancer assay. The score ranges from 0-100, with higher scores indicating a worse prognosis. This study included participants with a score of 0-25.
Axillary Surgery; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	Axillary lymph-node dissection, with or without sentinel-node mapping	1569 62.5%	1571 62.7%	3140 62.6%
	Sentinel-node biopsy without axillary lymph-node dissection	942 37.5%	936 37.3%	1878 37.4%
Positive Nodes; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2511 participants	2507 participants	5018 participants
	1 node	1628 64.8%	1647 65.7%	3275 65.3%
	2 nodes	643 25.6%	623 24.9%	1266 25.2%
	3 nodes	231 9.2%	229 9.1%	460 9.2%
	Not reported	9 0.4%	8 0.3%	17 0.3%

Outcome Measures

1. Primary Outcome

Title	Invasive Disease-Free Survival (IDFS)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title		Chemo and Endocrine Therapy	Endocrine Therapy Alone
Arm/Group Description:		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.	Participants receive a protocol-approved endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed		2487	2497
Measure Type: Number; Unit of Measure: percentage of participants
Premenopausal	Number Analyzed	829 participants	826 participants
		93.9	89.0
Postmenopausal	Number Analyzed	1658 participants	1671 participants
		91.3	91.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemo and Endocrine Therapy, Endocrine Therapy Alone
	Comments	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.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.35
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	A Cox model was used that included treatment arm, recurrence score, menopausal status, and the chemotherapy*recurrence score interaction term.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.05
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Chemo and Endocrine Therapy, Endocrine Therapy Alone
	Comments	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.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	A Cox model was used that included treatment arm, recurrence score, menopausal status, and the chemotherapy*menopausal status interaction term.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; 1.15 to 2.54
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Chemo and Endocrine Therapy, Endocrine Therapy Alone
	Comments	This analysis includes only premenopausal participants.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.83
	Estimation Comments	To compare the Chemo and Endocrine Therapy arm to the Endocrine Therapy Alone arm, a Cox model was used with adjustment for the continuous recurrence score.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Chemo and Endocrine Therapy, Endocrine Therapy Alone
	Comments	This analysis includes only postmenopausal participants.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.89
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.26
	Estimation Comments	To compare the Chemo and Endocrine Therapy arm to the Endocrine Therapy Alone arm, a Cox model was used with adjustment for the continuous recurrence score.

2. Secondary Outcome

Title	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	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

Outcome Measure Data

Analysis Population Description

Eligible participants who received at least one dose of protocol treatment and assessed for Adverse Event.

Arm/Group Title	Chemo and Endocrine Therapy	Endocrine Therapy Alone
Arm/Group Description:	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.	Participants receive a protocol-approved endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	2062	2342
Measure Type: Number; Unit of Measure: Participants
Abdominal infection	1	0
Abdominal pain	7	0
Acute kidney injury	1	0
Alanine aminotransferase increased	4	2
Alkaline phosphatase increased	1	0
Allergic reaction	6	1
Anemia	20	0
Anorexia	2	0
Anxiety	2	1
Arthralgia	48	35
Aspartate aminotransferase increased	0	1
Atrial fibrillation	3	1
Back pain	1	1
Blood and lymphatic system disorders - Other	4	0
Bone marrow hypocellular	1	0
Bone pain	15	5
Breast infection	2	0
Bronchial infection	1	0
CD4 lymphocytes decreased	2	1
Cardiac arrest	1	0
Cataract	0	1
Catheter related infection	3	0
Chest pain - cardiac	1	0
Chest wall pain	0	1
Colitis	5	0
Constipation	4	0
Death NOS	0	1
Dehydration	11	0
Depression	3	6
Dermatitis radiation	4	4
Device related infection	4	0
Diarrhea	31	3
Dizziness	3	1
Dry mouth	1	0
Dry skin	1	0
Dyspareunia	1	1
Dyspepsia	1	0
Dyspnea	2	0
Ear pain	2	0
Edema limbs	1	0
Ejection fraction decreased	1	0
Erythema multiforme	1	0
Erythroderma	1	1
Esophagitis	3	0
Fatigue	48	9
Febrile neutropenia	83	1
Fever	3	0
Flank pain	1	0
Flu like symptoms	1	0
GGT increased	2	0
Gastric hemorrhage	1	0
Gastric ulcer	1	0
Gastrointestinal disorders - Other, specify	1	0
Gastrointestinal pain	1	0
General disorders and admin site conditions - Other	2	0
Generalized muscle weakness	4	0
Headache	7	1
Heart failure	1	0
Hematuria	1	0
Hemorrhoids	1	0
Hot flashes	12	14
Hyperglycemia	16	1
Hyperhidrosis	1	0
Hypertension	8	6
Hypokalemia	5	0
Hyponatremia	2	0
Hypotension	3	1
INR increased	0	1
Infections and infestations - Other, specify	3	0
Injection site reaction	1	0
Insomnia	9	4
Irregular menstruation	3	1
Joint range of motion decreased	1	0
Kidney infection	1	0
Left ventricular systolic dysfunction	1	0
Leukemia secondary to oncology chemotherapy	2	0
Leukocytosis	4	0
Lipase increased	1	0
Localized edema	1	1
Lung infection	6	0
Lymphedema	1	1
Lymphocyte count decreased	20	0
Menorrhagia	0	1
Mucositis oral	23	0
Muscle weakness lower limb	1	0
Musculoskeletal and connective tiss disorder - Other	1	0
Myalgia	24	8
Myelitis	1	0
Myocardial infarction	2	0
Nausea	21	0
Neck pain	2	0
Neoplasms benign, malignant and unspecified - Other	3	0
Nervous system disorders - Other, specify	1	0
Neutrophil count decreased	150	1
Osteoporosis	1	0
Pain	2	0
Pain in extremity	2	1
Palmar-plantar erythrodysesthesia syndrome	7	0
Paresthesia	2	0
Peripheral ischemia	0	1
Peripheral motor neuropathy	4	0
Peripheral sensory neuropathy	21	2
Platelet count decreased	3	0
Pleuritic pain	1	0
Pneumonitis	8	0
Premature menopause	1	0
Pruritus	5	1
Radiation recall reaction (dermatologic)	2	0
Rash acneiform	1	0
Rash maculo-papular	8	2
Renal and urinary disorders - Other, specify	1	0
Reproductive system and breast disorders - Other	1	0
Sepsis	5	0
Sinus tachycardia	1	0
Skin and subcutaneous tissue disorders - Other	6	5
Skin infection	9	0
Skin ulceration	1	0
Stroke	2	3
Suicidal ideation	1	0
Supraventricular tachycardia	1	1
Surgical and medical procedures - Other, specify	2	4
Syncope	3	0
Thromboembolic event	9	4
Tinnitus	1	0
Typhlitis	1	0
Upper gastrointestinal hemorrhage	1	0
Upper respiratory infection	1	0
Urinary tract infection	4	0
Urticaria	4	0
Uterine hemorrhage	0	1
Vaginal dryness	0	4
Vaginal hemorrhage	1	1
Vascular access complication	1	0
Vomiting	19	0
Watering eyes	4	0
Weight gain	4	1
Weight loss	2	0
White blood cell decreased	65	0
Wound dehiscence	1	0

3. Secondary Outcome

Title	Overall Survival (OS)
Description	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

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Distant Disease-Free Survival (DDFS)
Description	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

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Local Disease-Free Interval (LDFI)
Description	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

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Participant-Reported Anxiety
Description	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

Outcome Measure Data Not Reported

7. Secondary Outcome

Title	Participant-Reported Health Status
Description	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

Outcome Measure Data Not Reported

8. Post-Hoc Outcome

Title	Distant Relapse-Free Survival (DRFS)
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants

Arm/Group Title		Chemo and Endocrine Therapy	Endocrine Therapy Alone
Arm/Group Description:		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.	Participants receive a protocol-approved endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed		2487	2497
Measure Type: Number; Unit of Measure: percentage of participants
Premenopausal participants	Number Analyzed	829 participants	826 participants
		96.1	92.8
Postmenopausal participants	Number Analyzed	1658 participants	1671 participants
		94.4	94.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemo and Endocrine Therapy, Endocrine Therapy Alone
	Comments	This analysis includes only premenopausal participants.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.87
	Estimation Comments	[Not Specified]
Other Statistical Analysis		To compare DRFS between the Chemo and Endocrine Therapy arm and the Endocrine Therapy Alone arm, a Cox model was used with adjustment for the continuous recurrence score.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Chemo and Endocrine Therapy, Endocrine Therapy Alone
	Comments	This analysis includes only postmenopausal participants.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.70
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.37
	Estimation Comments	To compare DRFS between the Chemo and Endocrine Therapy arm and the Endocrine Therapy Alone arm, a Cox model was used with adjustment for the continuous recurrence score.

Adverse Events

Time Frame	Adverse Events were assessed for the duration of treatment and follow-up until death or 3 years after randomization. All-Cause Mortality was assessed up to 5 years from randomization. CTCAE Version 4.0 was used for routine toxicity reporting. Version 5.0 was used for Serious Adverse Event (SAE) reporting.
Adverse Event Reporting Description	Only participants who received protocol treatment and assessed for adverse event were included in the adverse event result: 2062 in the Chemo and Endocrine Therapy arm and 2342 in the Endocrine Therapy Alone arm. All-Cause mortality is reported for all eligible and evaluable participants (2487 in the Chemo and Endocrine arm and 2497 in the endocrine therapy arm). Due to eligibility changes found after the primary analysis, the number at risk differs from the Outcomes Section.
Arm/Group Title	Chemo and Endocrine Therapy	Endocrine Therapy Alone
Arm/Group Description	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.	Participants receive a protocol-approved endocrine therapy for 5-10 years in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Chemo and Endocrine Therapy	Endocrine Therapy Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	161/2487 (6.47%)	175/2497 (7.01%)
Serious Adverse Events
	Chemo and Endocrine Therapy	Endocrine Therapy Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	14/2062 (0.68%)	9/2342 (0.38%)
Blood and lymphatic system disorders
Anemia †	1/2062 (0.05%)	0/2342 (0.00%)
Cardiac disorders
Cardiac arrest †	2/2062 (0.10%)	2/2342 (0.09%)
Gastrointestinal disorders
Gastrointestinal disorders-Other †	1/2062 (0.05%)	0/2342 (0.00%)
Typhlitis †	1/2062 (0.05%)	0/2342 (0.00%)
Upper gastrointestinal hemorrhage †	1/2062 (0.05%)	0/2342 (0.00%)
General disorders
Death NOS †	1/2062 (0.05%)	1/2342 (0.04%)
Multi-organ failure †	0/2062 (0.00%)	1/2342 (0.04%)
Infections and infestations
Device related infection †	1/2062 (0.05%)	0/2342 (0.00%)
Sepsis †	3/2062 (0.15%)	0/2342 (0.00%)
Injury, poisoning and procedural complications
Injury, poison and procedural complications - Other †	1/2062 (0.05%)	0/2342 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukemia secondary to oncology chemotherapy †	1/2062 (0.05%)	0/2342 (0.00%)
Neoplasms benign, malignant and unspecified - Other †	0/2062 (0.00%)	1/2342 (0.04%)
Nervous system disorders
Stroke †	0/2062 (0.00%)	3/2342 (0.13%)
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions-Other †	0/2062 (0.00%)	1/2342 (0.04%)
Vascular disorders
Thromboembolic event †	2/2062 (0.10%)	0/2342 (0.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Chemo and Endocrine Therapy	Endocrine Therapy Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	151/2062 (7.32%)	2/2342 (0.09%)
Investigations
Neutrophil count decreased †	151/2062 (7.32%)	2/2342 (0.09%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Breast Committee Statistician
• Organization: SWOG Statistics and Data Management Center
• Phone: 206-667-4623
• EMail: dlew@fredhutch.org

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

Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, Lin NU, Perez EA, Goldstein LJ, Chia SKL, Dhesy-Thind S, Rastogi P, Alba E, Delaloge S, Martin M, Kelly CM, Ruiz-Borrego M, Gil-Gil M, Arce-Salinas CH, Brain EGC, Lee ES, Pierga JY, Bermejo B, Ramos-Vazquez M, Jung KH, Ferrero JM, Schott AF, Shak S, Sharma P, Lew DL, Miao J, Tripathy D, Pusztai L, Hortobagyi GN. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. 2021 Dec 16;385(25):2336-2347. doi: 10.1056/NEJMoa2108873. Epub 2021 Dec 1.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01272037
• Other Study ID Numbers: NCI-2011-02623; NCI-2011-02623 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S12-03603; CDR0000692475; PS1007_A11PAMDREVW01; SWOG-S1007; S1007 ( Other Identifier: SWOG ); S1007 ( Other Identifier: CTEP ); U10CA032102 ( U.S. NIH Grant/Contract ); U10CA180830 ( U.S. NIH Grant/Contract ); U10CA180888 ( U.S. NIH Grant/Contract )
• First Submitted: January 6, 2011
• First Posted: January 7, 2011
• Results First Submitted: April 25, 2023
• Results First Posted: June 27, 2023
• Last Update Posted: May 16, 2024