Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial) (TAILORx)

• ClinicalTrials.gov Identifier: NCT00310180
• Recruitment Status: Active, not recruiting
• First Posted: April 3, 2006
• Results First Posted: March 12, 2019
• Last Update Posted: May 23, 2023
• Sponsor: National Cancer Institute (NCI)
• Collaborators: American College of Surgeons; Cancer and Leukemia Group B; NSABP Foundation Inc; NCIC Clinical Trials Group; North Central Cancer Treatment Group; SWOG Cancer Research Network
• 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 Adenocarcinoma; Hormone Receptor Positive; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIB Breast Cancer AJCC v7
• Interventions: Drug: Anastrozole; Drug: Exemestane; Other: Laboratory Biomarker Analysis; Drug: Letrozole; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Drug: Tamoxifen Citrate
• Enrollment: 10273

Participant Flow

Recruitment Details	This study was activated on April 7, 2006 and closed to registrations on October 6, 2010. A total of 11,232 patients were preregistered for Recurrence Score evaluation and 10,273 proceeded to register on the study.
Pre-assignment Details	Patients needed to be preregistered to the trial for ONCOTYPE recurrence score test, patients then were assigned or randomized to one of the four arms based on the recurrence score.

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
Period Title: Overall Study
Started	1629	3458	3449	1737
No On-study Data	0	2	10	172
Ineligible	3	4	6	7
No Follow-up Data	7	55	131	245
Completed [1]	1619	3399	3312	1389
Not Completed	10	59	137	348
[1] Patients analyzed in the main analysis

Baseline Characteristics

Arm/Group Title		Arm A	Arm B	Arm C	Arm D	Total
Arm/Group Description		Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Total of all reporting groups
Overall Number of Baseline Participants		1619	3399	3312	1389	9719
Baseline Analysis Population Description		All eligible patients who had on-study data and follow-up data were included in the analysis
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1619 participants	3399 participants	3312 participants	1389 participants	9719 participants
	<=40 years	58 3.6%	154 4.5%	157 4.7%	79 5.7%	448 4.6%
	41-50 years	371 22.9%	985 29.0%	920 27.8%	330 23.8%	2606 26.8%
	51-60 years	563 34.8%	1235 36.3%	1206 36.4%	512 36.9%	3516 36.2%
	61-70 years	518 32.0%	868 25.5%	895 27.0%	395 28.4%	2676 27.5%
	71-75 years	109 6.7%	157 4.6%	134 4.0%	73 5.3%	473 4.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1619 participants	3399 participants	3312 participants	1389 participants	9719 participants
	Female	1619 100.0%	3399 100.0%	3312 100.0%	1389 100.0%	9719 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1619 participants	3399 participants	3312 participants	1389 participants	9719 participants
	American Indian or Alaska Native	8 0.5%	11 0.3%	16 0.5%	4 0.3%	39 0.4%
	Asian	82 5.1%	140 4.1%	132 4.0%	51 3.7%	405 4.2%
	Native Hawaiian or Other Pacific Islander	8 0.5%	7 0.2%	14 0.4%	1 0.1%	30 0.3%
	Black or African American	107 6.6%	236 6.9%	235 7.1%	115 8.3%	693 7.1%
	White	1361 84.1%	2883 84.8%	2783 84.0%	1162 83.7%	8189 84.3%
	More than one race	2 0.1%	5 0.1%	2 0.1%	1 0.1%	10 0.1%
	Unknown or Not Reported	51 3.2%	117 3.4%	130 3.9%	55 4.0%	353 3.6%
Recurrence score [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1619 participants	3399 participants	3312 participants	1389 participants	9719 participants
	0-5	432 26.7%	0 0.0%	0 0.0%	0 0.0%	432 4.4%
	6-10	1187 73.3%	0 0.0%	0 0.0%	0 0.0%	1187 12.2%
	11-15	0 0.0%	1214 35.7%	1159 35.0%	0 0.0%	2373 24.4%
	16-20	0 0.0%	1368 40.2%	1344 40.6%	0 0.0%	2712 27.9%
	21-25	0 0.0%	817 24.0%	809 24.4%	0 0.0%	1626 16.7%
	26-30	0 0.0%	0 0.0%	0 0.0%	598 43.1%	598 6.2%
	31-35	0 0.0%	0 0.0%	0 0.0%	315 22.7%	315 3.2%
	36-40	0 0.0%	0 0.0%	0 0.0%	158 11.4%	158 1.6%
	41-50	0 0.0%	0 0.0%	0 0.0%	202 14.5%	202 2.1%
	>50	0 0.0%	0 0.0%	0 0.0%	116 8.4%	116 1.2%
		[1] Measure Description: The Oncotype DX assay is a 21-gene assay that predicts the likelihood of chemotherapy benefit and 10-year risk of distant recurrence to inform adjuvant treatment decisions in certain women with early-stage invasive breast cancer. Oncotype DX test results assign a Recurrence Score, and the Oncotype DX Recurrence Score is a continuous score, ranged between 0 and 100, that provides an individual estimate of the 10 year risk of distant recurrence and predicts the likelihood of benefit from chemotherapy. Higher score indicate higher risk of recurrence.

Outcome Measures

1. Primary Outcome

Title	5-year Disease-free Survival
Description	Disease-free survival (DFS) is defined to be time from randomization to first event, where the first event is any of ipsilateral breast tumor recurrence, local recurrence, regional recurrence, distant recurrence, contralateral second primary invasive cancer, second primary non-breast invasive cancer (excluding non-melanoma skin cancers), or death without evidence of recurrence. The distribution of DFS (eg, 5-year DFS rate) is estimated using Kaplan-Meier method, and compared between the two randomized arms (arm B vs. arm C) using stratified log rank test and stratified Cox proportional hazard model.
Time Frame	Assessed every 6 months within 5 years from registration and then annually up to 20 years, DFS rate estimated at 5 years

Outcome Measure Data

Analysis Population Description

All eligible patients who had on-study data and follow-up data were included in the analysis

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description:	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
Overall Number of Participants Analyzed	1619	3399	3312	1389
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	94.0; (92.6 to 95.1)	92.8; (91.8 to 93.6)	93.1; (92.1 to 93.9)	87.6; (85.5 to 89.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm C
	Comments	This study uses a noninferiority design, but the noninferiority question is formulated using the conventional superiority null hypothesis of equal DFS on the two arms (that is, the null hypothesis is that Arm B is not inferior to Arm C). The alternative hypothesis is that Arm B has substantially worse DFS than Arm C, specified by a hazard ratio for B vs. C of 1.322.
	Type of Statistical Test	Superiority
	Comments	Since the noninferiority comparison is formulated using a conventional superiority null hypothesis described as above, a type II error corresponds to concluding that Arm B is not inferior when in fact it is. The design therefore uses a one-sided type I error of 10% and is planned to have 95% power (5% type II error). If the null hypothesis is rejected (at the one-sided 10% level), then it will be concluded that endocrine therapy alone is inferior to chemoendocrine therapy.
Statistical Test of Hypothesis	P-Value	0.13
	Comments	One-sided p value for stratified Cox proportional hazard analysis, stratified on recurrence score, tumor size and menopausal status.
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.24
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	5-year Distant Recurrence-free Interval
Description	Distant recurrence-free interval (DRFI) is defined as time from date of randomization or registration to the date of distant recurrence of breast cancer, or of death with distant recurrence, if death is the first manifestation of distant recurrence. The distribution of DRFI (eg, 5-year DRFI rate) is estimated using Kaplan-Meier method.
Time Frame	Assessed every 6 months within 5 years from registration and then annually up to 20 years, DRFI rate estimated at 5 years

Outcome Measure Data

Analysis Population Description

All eligible patients who had on-study data and follow-up data

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description:	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
Overall Number of Participants Analyzed	1619	3399	3312	1389
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	99.3; (98.8 to 99.6)	98.0; (97.4 to 98.4)	98.2; (97.6 to 98.6)	93.0; (91.4 to 94.4)

3. Secondary Outcome

Title	5-year Recurrence-free Interval
Description	Recurrence-free interval (RFS) is defined as time from date of randomization or registration to the date of first recurrence of breast cancer (ipsilateral breast tumor recurrence, local/regional recurrence, distant recurrence) or to the date of death with recurrence, if death is the first manifestation of recurrence. The distribution of RFS (eg, 5-year RFS rate) is estimated using Kaplan-Meier method.
Time Frame	Assessed every 6 months within 5 years from registration and then annually up to 20 years, RFS rate estimated at 5 years

Outcome Measure Data

Analysis Population Description

All eligible patients who had on-study data and follow-up data were included in the analysis

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description:	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
Overall Number of Participants Analyzed	1619	3399	3312	1389
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	98.8; (98.1 to 99.2)	96.9; (96.2 to 97.4)	97.0; (96.3 to 97.6)	91.0; (89.1 to 92.5)

4. Secondary Outcome

Title	5-year Overall Survival
Description	Overall survival (OS) is defined as time from date of randomization or registration to date of death from any cause. The distribution of OS (eg, 5-year OS rate) is estimated using Kaplan-Meier method.
Time Frame	Assessed every 6 months within 5 years from registration and then annually up to 20 years, OS rate estimated at 5 years

Outcome Measure Data

Analysis Population Description

All eligible patients who had on-study data and follow-up data were included in the analysis

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description:	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
Overall Number of Participants Analyzed	1619	3399	3312	1389
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	98.0; (97.2 to 98.6)	98.0; (97.5 to 98.5)	98.1; (97.6 to 98.5)	95.9; (94.6 to 96.9)

5. Secondary Outcome

Title	5-year Disease-free Survival by Age and Recurrence Score Groups
Description	Disease-free survival (DFS) is defined to be time from randomization to first event, where the first event is any of ipsilateral breast tumor recurrence, local recurrence, regional recurrence, distant recurrence, contralateral second primary invasive cancer, second primary non-breast invasive cancer (excluding non-melanoma skin cancers), or death without evidence of recurrence. DFS is evaluated by recurrence score (0-10 vs. 11-15 vs. 16-20 vs. 21-25 vs. >25) and age groups (<=50 vs. 51-65 vs. 65-75). The distribution of DFS (eg, 5-year DFS rate) is estimated using Kaplan-Meier method.
Time Frame	Assessed every 6 months within 5 years from registration and then annually up to 20 years, DFS rate estimated at 5 years

Outcome Measure Data

Analysis Population Description

All eligible patients who had on-study data and follow-up data were included in the analysis

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description:	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
Overall Number of Participants Analyzed	1619	3399	3312	1389
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
RS 0-10 & Age<=50	95.1; (92.4 to 96.8)	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
RS 0-10 & Age 51-65	94.7; (93.0 to 96.1)	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
RS 0-10 & Age 66-75	90.5; (86.5 to 93.3)	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
RS 11-15 & Age <=50	NA [2]; (NA to NA)	95.1; (92.5 to 96.8)	94.3; (91.1 to 96.3)	NA [2]; (NA to NA)
RS 11-15 & Age 51-65	NA [2]; (NA to NA)	95.5; (93.4 to 96.9)	93.9; (91.7 to 95.6)	NA [2]; (NA to NA)
RS 11-15 & Age 66-75	NA [2]; (NA to NA)	87.1; (80.9 to 91.4)	91.4; (85.3 to 95.0)	NA [2]; (NA to NA)
RS 16-20 & Age <=50	NA [3]; (NA to NA)	92.0; (89.0 to 94.2)	94.7; (92.1 to 96.4)	NA [3]; (NA to NA)
RS 16-20 & Age 51-65	NA [3]; (NA to NA)	94.3; (92.3 to 95.8)	92.2; (89.9 to 94.0)	NA [3]; (NA to NA)
RS 16-20 & Age 66-75	NA [3]; (NA to NA)	90.1; (84.6 to 93.8)	90.2; (84.8 to 93.8)	NA [3]; (NA to NA)
RS 21-25 & Age <=50	NA [4]; (NA to NA)	86.3; (81.1 to 90.2)	92.1; (87.7 to 95.0)	NA [4]; (NA to NA)
RS 21-25 & Age 51-65	NA [4]; (NA to NA)	91.6; (88.4 to 93.9)	93.4; (90.5 to 95.4)	NA [4]; (NA to NA)
RS 21-25 & Age 66-75	NA [4]; (NA to NA)	93.8; (87.9 to 96.8)	90.9; (84.2 to 94.9)	NA [4]; (NA to NA)
RS >25 & Age <=50	NA [5]; (NA to NA)	NA [5]; (NA to NA)	NA [5]; (NA to NA)	86.4; (82.1 to 89.7)
RS >25 & Age 51-65	NA [5]; (NA to NA)	NA [5]; (NA to NA)	NA [5]; (NA to NA)	87.5; (84.7 to 89.9)
RS >25 & Age 66-75	NA [5]; (NA to NA)	NA [5]; (NA to NA)	NA [5]; (NA to NA)	89.8; (84.4 to 93.4)

[1]

Patients with RS of 0-10 were assigned to arm A

[2]

Patients with RS of 11-15 were randomized to arm B or arm C

[3]

Patients with RS of 16-20 were randomized to arm B or arm C

[4]

Patients with RS of 21-25 were randomized to arm B or arm C

[5]

Patients with RS of >25 were assigned to arm D

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm C
	Comments	Treatment interaction test was performed for the 9 age by RS subsets (3 groups for each, age groups <=50 vs. 51-65 vs. 66-75; RS groups 0-10 vs. 11-25 vs. >25) in patients randomized to arms B and C
	Type of Statistical Test	Other
	Comments	Treatment-by-Age and RS subset was performed via Cox proportional hazard analysis
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

6. Secondary Outcome

Title	To Compare the Outcomes Projected at 10 Years by Adjuvant! With Those Made by the Genomic Health Oncotype DX Test
Description	Adjuvant! is not currently available; additional work combining classical information with genomic tests will be reported separately.
Time Frame	Assessed at 10 years after study entry

Outcome Measure Data

Analysis Population Description

Outcome will never be analyzed.

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description:	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

7. Secondary Outcome

Title	5-year Disease-free Survival by Individual RS Gene Groups
Description	Disease-free survival (DFS) is defined to be time from randomization to first event, where the first event is any of ipsilateral breast tumor recurrence, local recurrence, regional recurrence, distant recurrence, contralateral second primary invasive cancer, second primary non-breast invasive cancer (excluding non-melanoma skin cancers), or death without evidence of recurrence. The distribution of DFS (eg, 5-year DFS rate) is estimated using Kaplan-Meier method. 5-year DFS by individual RS gene groups (Proliferation Gene Group, HER2 Gene Group, ER Gene Group, Invasion Gene Group, and Other Genes) will be estimated in each arm.
Time Frame	Assessed every 6 months within 5 years from registration and then annually up to 20 years

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Both the chemotherapy and endocrine therapy given on this study were standard therapies for this population. To simplify the effort required for participating sites, adverse event data were not collected.
Adverse Event Reporting Description	Both the chemotherapy and endocrine therapy given on this study were standard therapies for this population. To simplify the effort required for participating sites, adverse event data were not collected.
Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Group 1 (Oncotype DX recurrence score =< 10): Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO	Group 2 (Oncotype DX recurrence score 11-25): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials	Group 3 (Oncotype DX recurrence score >= 26): Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in Group 2 who are assigned to receive both types of treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Tamoxifen: Given PO Combination chemotherapy: including oral CMF, IV CMF, standard AC, dose dense AC, standard AC-T, dose dense AC-T, FEC, TAC, TC, other protocol-specified regimens if participating in other CTSU trials including chemotherapy, and other regimens not protocol-specified if not participating in CTSU trials
All-Cause Mortality
	Arm A	Arm B	Arm C	Arm D
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0	0/0	0/0
Serious Adverse Events
	Arm A	Arm B	Arm C	Arm D
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0	0/0	0/0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A	Arm B	Arm C	Arm D
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0	0/0	0/0

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: ECOG-ACRIN statistician
• Organization: ECOG-ACRIN Cancer Research Group
• Phone: 617-632-3000
• EMail: eatrials@jimmy.harvard.edu

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

Sadigh G, Gray RJ, Sparano JA, Yanez B, Garcia SF, Timsina LR, Obeng-Gyasi S, Gareen I, Sledge GW, Whelan TJ, Cella D, Wagner LI, Carlos RC. Assessment of Racial Disparity in Survival Outcomes for Early Hormone Receptor-Positive Breast Cancer After Adjusting for Insurance Status and Neighborhood Deprivation: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Oncol. 2022 Apr 1;8(4):579-586. doi: 10.1001/jamaoncol.2021.7656.

Yanez B, Gray RJ, Sparano JA, Carlos RC, Sadigh G, Garcia SF, Gareen IF, Whelan TJ, Sledge GW, Cella D, Wagner LI. Association of Modifiable Risk Factors With Early Discontinuation of Adjuvant Endocrine Therapy: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Oncol. 2021 Jun 17;7(8):1-7. doi: 10.1001/jamaoncol.2021.1693. Online ahead of print.

Lynch SM, Russell NM, Barron S, Wang CA, Loughman T, Dynoodt P, Fender B, Lopez-Ruiz C, O'Grady A, Sheehan KM, Fay J, Amberger-Murphy V, Saha A, Klinger R, Gonzalez CA, Al-Attar N, Rahman A, O'Leary D, Lanigan FT, Bracken AP, Crown J, Kelly CM, O'Connor DP, Gallagher WM. Prognostic value of the 6-gene OncoMasTR test in hormone receptor-positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors. Eur J Cancer. 2021 Jul;152:78-89. doi: 10.1016/j.ejca.2021.04.016. Epub 2021 Jun 2.

Freidlin B, Hu C, Korn EL. Are restricted mean survival time methods especially useful for noninferiority trials? Clin Trials. 2021 Apr;18(2):188-196. doi: 10.1177/1740774520976576. Epub 2021 Feb 24.

Wagner LI, Gray RJ, Sparano JA, Whelan TJ, Garcia SF, Yanez B, Tevaarwerk AJ, Carlos RC, Albain KS, Olson JA Jr, Goetz MP, Pritchard KI, Hayes DF, Geyer CE, Dees EC, McCaskill-Stevens WJ, Minasian LM, Sledge GW Jr, Cella D. Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results From TAILORx. J Clin Oncol. 2020 Jun 10;38(17):1875-1886. doi: 10.1200/JCO.19.01866. Epub 2020 Apr 9.

Sparano JA, Gray RJ, Makower DF, Albain KS, Saphner TJ, Badve SS, Wagner LI, Kaklamani VG, Keane MM, Gomez HL, Reddy PS, Goggins TF, Mayer IA, Toppmeyer DL, Brufsky AM, Goetz MP, Berenberg JL, Mahalcioiu C, Desbiens C, Hayes DF, Dees EC, Geyer CE Jr, Olson JA Jr, Wood WC, Lively T, Paik S, Ellis MJ, Abrams J, Sledge GW Jr. Clinical Outcomes in Early Breast Cancer With a High 21-Gene Recurrence Score of 26 to 100 Assigned to Adjuvant Chemotherapy Plus Endocrine Therapy: A Secondary Analysis of the TAILORx Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):367-374. doi: 10.1001/jamaoncol.2019.4794.

Korn EL, Gray RJ, Freidlin B. Noninferiority trials with nonadherence to the assigned randomized treatment. Clin Trials. 2019 Dec;16(6):673-681. doi: 10.1177/1740774519868479. Epub 2019 Aug 14.

Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med. 2019 Jun 20;380(25):2395-2405. doi: 10.1056/NEJMoa1904819. Epub 2019 Jun 3.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2018 Jul 12;379(2):111-121. doi: 10.1056/NEJMoa1804710. Epub 2018 Jun 3.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Perez EA, Olson JA Jr, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2015 Nov 19;373(21):2005-14. doi: 10.1056/NEJMoa1510764. Epub 2015 Sep 27.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00310180
• Obsolete Identifiers: NCT00554931
• Other Study ID Numbers: NCI-2009-00707; NCI-2009-00707 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); ECOG-PACCT-1; 06-482; CDR0000472066; PACCT-1; PACCT-1 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); PACCT-1 ( Other Identifier: CTEP ); U10CA180820 ( U.S. NIH Grant/Contract ); U10CA021115 ( U.S. NIH Grant/Contract )
• First Submitted: March 29, 2006
• First Posted: April 3, 2006
• Results First Submitted: December 17, 2018
• Results First Posted: March 12, 2019
• Last Update Posted: May 23, 2023