SOFT: Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

• Sponsor: ETOP IBCSG Partners Foundation (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00066690
• Collaborator: Breast International Group (Other), Cancer and Leukemia Group B (Other), National Cancer Institute (NCI) (NIH), NSABP Foundation Inc (Other), NCIC Clinical Trials Group (Other), North Central Cancer Treatment Group (Other), Southwest Oncology Group (Other)
• Enrollment: 3,066
• Locations: 500
• Arms: 3
• Anticipated Duration (Months): 263.5
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Ovarian function suppression combined with hormone therapy using tamoxifen or exemestane may fight breast cancer by reducing the production of estrogen. It is not yet known whether suppression of ovarian function plus either tamoxifen or exemestane is more effective than tamoxifen alone in preventing the recurrence of hormone-responsive breast cancer.

PURPOSE: This randomized phase III trial studies ovarian suppression with either tamoxifen or exemestane to see how well they work compared to tamoxifen alone in treating premenopausal women who have undergone surgery for hormone-responsive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer	Drug: Exemestane; Other: Laboratory Biomarker Analysis; Procedure: Oophorectomy; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Drug: Tamoxifen; Drug: Triptorelin	Phase 3

Detailed Description

OBJECTIVES:

• Compare the disease-free survival, breast cancer-free interval, distant recurrence-free interval and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with tamoxifen + ovarian function suppression (by triptorelin, oophorectomy, or ovarian irradiation) or exemestane + ovarian function suppression vs. tamoxifen alone. The primary comparison is ovarian function suppression with either tamoxifen or exemestane vs. tamoxifen alone.

• Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, prior adjuvant/neoadjuvant chemotherapy (yes vs no), and number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more) and intended initial method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation). Treatment duration is 5 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3066 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Trial Evaluating the Role of Ovarian Function Suppression and the Role of Exemestane as Adjuvant Therapies for Premenopausal Women With Endocrine Responsive Breast Cancer
• Actual Study Start Date: Dec 17, 2003
• Actual Primary Completion Date: May 1, 2014
• Anticipated Study Completion Date: Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tamoxifen Tamoxifen 20mg orally daily for 5 years	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Drug: Tamoxifen; Tamoxifen 20mg orally daily for 5 years; Other Names: Apo-Tamox Clonoxifen Dignotamoxi Ebefen Emblon Estroxyn Fentamox Gen-Tamoxifen Genox ICI 46,474 ICI-46474 Jenoxifen Kessar Ledertam Lesporene Nolgen Noltam Nolvadex Nolvadex-D Nourytam Novo-Tamoxifen Novofen Noxitem Oestrifen Oncotam PMS-Tamoxifen Soltamox TAM Tamax Tamaxin Tamifen Tamizam Tamofen Tamoxasta TAMOXIFEN CITRATE Tamoxifeni Citras Zemide
Experimental: T+OFS Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Oophorectomy; Undergo bilateral surgical oophorectomy; Other Names: Female Castration Ovariectomy ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Radiation: Radiation Therapy; Undergo ovarian irradiation; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RADIATION Radiotherapeutics Radiotherapy RT Therapy, Radiation ; Drug: Tamoxifen; Tamoxifen 20mg orally daily for 5 years; Other Names: Apo-Tamox Clonoxifen Dignotamoxi Ebefen Emblon Estroxyn Fentamox Gen-Tamoxifen Genox ICI 46,474 ICI-46474 Jenoxifen Kessar Ledertam Lesporene Nolgen Noltam Nolvadex Nolvadex-D Nourytam Novo-Tamoxifen Novofen Noxitem Oestrifen Oncotam PMS-Tamoxifen Soltamox TAM Tamax Tamaxin Tamifen Tamizam Tamofen Tamoxasta TAMOXIFEN CITRATE Tamoxifeni Citras Zemide ; Drug: Triptorelin; 3.75 mg by im injection q28 days for 5 years; Other Names: 6-D-Tryptophan-LH-RH 6-D-Tryptophanluteinizing Hormone-releasing Factor AY-25650 CL-118,532 Decapeptyl Detryptoreline GnRH analogue Trelstar Depot Decapeptyl Depot
Experimental: E+OFS Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Drug: Exemestane; Exemestane 25mg orally daily for 5 years plus ovarian function suppression; Other Names: Aromasin FCE-24304 ; Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Oophorectomy; Undergo bilateral surgical oophorectomy; Other Names: Female Castration Ovariectomy ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Radiation: Radiation Therapy; Undergo ovarian irradiation; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RADIATION Radiotherapeutics Radiotherapy RT Therapy, Radiation ; Drug: Triptorelin; 3.75 mg by im injection q28 days for 5 years; Other Names: 6-D-Tryptophan-LH-RH 6-D-Tryptophanluteinizing Hormone-releasing Factor AY-25650 CL-118,532 Decapeptyl Detryptoreline GnRH analogue Trelstar Depot Decapeptyl Depot

Outcome Measures

Primary Outcome Measures

1. Disease-free Survival [5-year estimates, reported at a median follow-up of 67 months.]

   Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow-up.

Secondary Outcome Measures

1. Breast Cancer-free Interval [5-year estimates, reported at a median follow-up of 67 months.]

   Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.

2. Distant Recurrence-free Interval [5-year estimates, reported at a median follow-up of 67 months.]

   Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free Interval is defined as the time from randomization to invasive breast cancer recurrence at distant site, or invasive contralateral breast cancer; or censored at date of last follow up.

3. Overall Survival [8-year estimates, reported at a median follow-up of 8 years]

   Estimated percentage of patients alive at 8 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Premenopausal women (estradiol [E2] in the premenopausal range [according to institution parameters]) who meet the following criteria:

• Patients who did not receive chemotherapy should be randomized within 12 weeks after definitive surgery; such patients should have estradiol (E2) in the premenopausal range following surgery; the only patients who do not require testing of estradiol (E2) to confirm premenopausal status are those who have been menstruating regularly during the 6 months prior to randomization and have not used any form of hormonal contraception or any other hormonal treatments during the 6 months prior to randomization

• Patients who received prior adjuvant and/or neoadjuvant chemotherapy should be randomized after completing chemotherapy and within 8 months of the final dose of chemotherapy as soon as premenopausal status is confirmed; all such patients should have premenopausal status confirmed by an estradiol (E2) in the premenopausal range between 2 weeks and 8 months after completing chemotherapy

• Adjuvant trastuzumab (Herceptin ®) is allowable, and is not considered to be chemotherapy for eligibility timing determination

• Patients with temporary chemotherapy-induced amenorrhea who regain premenopausal status within eight months of the final dose of chemotherapy are eligible; (please note that some patients taking tamoxifen or aromatase inhibitors, even without evidence of menses, may have ovarian function recovery following chemotherapy and resume estradiol secretion); in patients wishing to participate in the study, with postmenopausal hormone levels shortly after chemotherapy, it is recommended to recheck their estradiol level at a later timepoint within 8 months of completing chemotherapy, even in the absence of return of menses

• Histologically proven, resected breast cancer; pathology material should be available for submission for central review as part of the quality control measures for this protocol

• Patients must have hormone receptor positive tumors; if there is more than one breast tumor, each tumor must be hormone receptor positive; hormone receptors must be determined using immunohistochemistry; estrogen receptor (ER) and/or progesterone receptor (PgR) must be greater than or equal to 10% of the tumor cells positive by immunohistochemical evaluation; biochemical determination alone is not acceptable

• The tumor must be confined to the breast and axillary nodes without detected metastases elsewhere, with the exception of tumor detected in internal mammary chain nodes by sentinel node procedure; patients who received neoadjuvant therapy must have had operable disease prior to neoadjuvant treatment to be eligible; patients who had a pathological evaluation with tru cut or core biopsy of invasive breast cancer prior to neoadjuvant therapy and were found to have no invasive tumor in the pathological specimen from definitive surgery are eligible; for these patients, pre-neoadjuvant tumor characteristics will be used for defining eligibility; in case of persistent disease, pathology findings from the definitive surgery should be used

• Patients must have had proper surgery for primary breast cancer with no known clinical residual loco-regional disease:

• A total mastectomy; radiotherapy is optional after mastectomy OR

• A breast-conserving procedure (lumpectomy, quadrantectomy or partial mastectomy with margins clear of invasive cancer and ductal breast carcinoma in situ [DCIS]); the local pathologist must document negative margins of resection in the pathology report; if all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed; likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed; radiation therapy to the conserved breast is required; patients may be randomized before, during or after completion of radiation therapy to the breast

• Either axillary lymph node dissection (pathological examination of at least 6 nodes recommended) or a negative axillary sentinel node biopsy (pN0[sn]) is required; patients with negative or microscopically axillary positive sentinel nodes (pN1mi: micrometastasis none > 2.0 mm) do not require further axillary therapy; those with positive sentinel nodes must have either an axillary dissection or radiation of axillary nodes

• For International Breast Cancer Study Groups (IBCSG) centers, patients must have completed baseline Quality of Life (QL) Forms prior to randomization; the only exceptions are cognitive or physical impairment that interferes with QL assessment or inability to read any of the languages available on IBCSG QL forms; for non-IBCSG centers, extent of participation in the QL study is to be determined at the activation of the trial for each cooperative group

• Written informed consent must be signed and dated by the patient and the investigator prior to randomization

• Patients must be accessible for follow-up

• Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines

Exclusion Criteria:

• Patients who are postmenopausal (i.e., do not have an estradiol [E2] level in the premenopausal range) after surgery or after chemotherapy, whichever is later

• Patients with distant metastatic disease

• Patients with locally advanced inoperable breast cancer including inflammatory breast cancer or supraclavicular node involvement or with enlarged internal mammary nodes (unless pathologically negative) are not eligible; patients with involved internal mammary nodes detected by sentinel node biopsy that are not enlarged are eligible

• Patients with positive final margins (referring to only DCIS and invasive cancer, not lobular breast carcinoma in situ [LCIS]), except as noted; DCIS at a margin is permitted if a complete mastectomy has been performed

• Patients with clinically detectable residual axillary disease

• Patients with a history of prior ipsilateral or contralateral invasive breast cancer; patients with synchronous bilateral invasive breast cancer (diagnosed histologically within 2 months) are eligible if the bilateral disease meets all other eligibility criteria

• Patients with previous or concomitant invasive malignancy are not eligible; the exceptions are patients with the following (and only the following) malignancies (previous or concomitant) who are eligible if adequately treated:

• Basal or squamous cell carcinoma of the skin

• In situ non-breast carcinoma without invasion

• Contra- or ipsilateral in situ breast carcinoma

• Non-breast invasive malignancy diagnosed at least 5 years ago and without recurrence:

• Stage I papillary thyroid cancer

• Stage Ia carcinoma of the cervix

• Stage Ia or b endometrioid endometrial cancer

• Borderline or stage I ovarian cancer

• Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung, etc.) that would prevent prolonged follow-up; patients with previous thrombosis (e.g., deep vein thrombosis [DVT]) and/or embolism can be included only if medically suitable

• Patients who have had a bilateral oophorectomy or ovarian irradiation; patients who will be recommended to undergo oophorectomy within 5 years (e.g., breast cancer susceptibility gene [BRCA]1/2 gene carriers) and therefore for whom randomization to a treatment arm without OFS is inappropriate

• Patients with a history of noncompliance to medical regimens and patients who are considered potentially unreliable

• Patients who are pregnant or lactating at the time of randomization or who desire a pregnancy within 5 years; patients planning to use additional hormonal therapy apart from the randomized treatment during the next five years including all types of hormonal contraception; a pregnancy test is recommended for women of child-bearing potential who are sexually active and not using reliable contraceptive methods

• Patients who received endocrine therapy (including neoadjuvant and adjuvant) for more than 8 months after their breast cancer diagnosis; patients who are receiving endocrine therapy at randomization (and have received it for less than 8 months) may continue such therapy until protocol-specified tamoxifen/exemestane is initiated

• Patients who were taking tamoxifen or other selective estrogen receptor modulator (SERM) (e.g. Raloxifene) or hormone replacement therapy (HRT) within one year prior to their breast cancer diagnosis; prior oral contraceptives are allowed

• Patients who have received GnRH analogues as part of their breast cancer treatment prior to randomization

• Patients with psychiatric, addictive, or any disorder that would prevent compliance with protocol requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
3	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
4	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
5	Mills - Peninsula Hospitals	Burlingame	California	United States	94010
6	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
7	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
8	John Muir Medical Center-Concord Campus	Concord	California	United States	94520
9	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
10	Kaiser Permanente-Fremont	Fremont	California	United States	94538
11	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
12	Glendale Memorial Hospital and Health Center	Glendale	California	United States	91204
13	Marin General Hospital	Greenbrae	California	United States	94904
14	Scripps Cancer Center	La Jolla	California	United States	92037
15	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
16	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
17	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
18	Memorial Medical Center	Modesto	California	United States	95355
19	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
20	Sutter Cancer Research Consortium	Novato	California	United States	94945
21	Bay Area Tumor Institute	Oakland	California	United States	94609
22	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
23	Tom K Lee Inc	Oakland	California	United States	94609
24	Kaiser Permanente-Oakland	Oakland	California	United States	94611
25	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
26	Stanford Cancer Institute	Palo Alto	California	United States	94304
27	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
28	Eisenhower Medical Center	Rancho Mirage	California	United States	92270
29	Mercy Regional Cancer Center	Redding	California	United States	96001
30	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
31	Kaiser Permanente-Richmond	Richmond	California	United States	94801
32	Kaiser Permanente-Roseville	Roseville	California	United States	95661
33	Mercy General Hospital	Sacramento	California	United States	95819
34	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
35	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
36	Salinas Valley Memorial	Salinas	California	United States	93901
37	University of California San Diego	San Diego	California	United States	92103
38	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
39	Veterans Administration-San Diego Medical Center	San Diego	California	United States	92161
40	San Francisco General Hospital	San Francisco	California	United States	94110
41	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
42	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
43	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
44	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
45	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
46	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
47	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
48	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
49	Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95405
50	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
51	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
52	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
53	John Muir Medical Center-Walnut Creek	Walnut Creek	California	United States	94598
54	The Medical Center of Aurora	Aurora	Colorado	United States	80012
55	Boulder Community Hospital	Boulder	Colorado	United States	80301
56	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
57	Memorial Hospital Colorado Springs	Colorado Springs	Colorado	United States	80909
58	Denver Health Medical Center	Denver	Colorado	United States	80204
59	Porter Adventist Hospital	Denver	Colorado	United States	80210
60	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
61	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
62	Denver Veterans Administration Medical Center	Denver	Colorado	United States	80220
63	Rose Medical Center	Denver	Colorado	United States	80220
64	Colorado Cancer Research Program NCORP	Denver	Colorado	United States	80222
65	The Shaw Regional Cancer Center	Edwards	Colorado	United States	81632
66	Swedish Medical Center	Englewood	Colorado	United States	80113
67	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
68	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
69	North Colorado Medical Center	Greeley	Colorado	United States	80631
70	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
71	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
72	Longmont United Hospital	Longmont	Colorado	United States	80501
73	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
74	North Suburban Medical Center	Thornton	Colorado	United States	80229
75	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
76	Hartford Hospital	Hartford	Connecticut	United States	06102
77	Norwalk Hospital	Norwalk	Connecticut	United States	06856
78	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
79	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut	United States	06904
80	Charlotte Hungerford Hospital Center for Cancer Care	Torrington	Connecticut	United States	06790
81	Bayhealth Medical Center at Kent General	Dover	Delaware	United States	19901
82	Beebe Medical Center	Lewes	Delaware	United States	19958
83	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
84	Nanticoke Memorial Hospital	Seaford	Delaware	United States	19973
85	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
86	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
87	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
88	Cancer Research Network Inc	Boca Raton	Florida	United States	33428
89	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
90	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
91	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
92	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
93	Jupiter Medical Center	Jupiter	Florida	United States	33458
94	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
95	Florida Cancer Specialists - Sarasota Downtown	Sarasota	Florida	United States	34236
96	Piedmont Hospital	Atlanta	Georgia	United States	30309
97	Emory University/Winship Cancer Institute	Atlanta	Georgia	United States	30322
98	Atlanta Regional CCOP	Atlanta	Georgia	United States	30342
99	Northside Hospital	Atlanta	Georgia	United States	30342
100	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342
101	Augusta Oncology Associates PC-Saint Sebastian	Augusta	Georgia	United States	30901
102	Well Star Cobb Hospital	Austell	Georgia	United States	30106
103	John B Amos Cancer Center	Columbus	Georgia	United States	31904
104	Dekalb Medical Center	Decatur	Georgia	United States	30033
105	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
106	Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
107	Southern Regional Medical Center	Riverdale	Georgia	United States	30274
108	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia	United States	30165
109	Memorial University Medical Center	Savannah	Georgia	United States	31404
110	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
111	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
112	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
113	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
114	Graham Hospital Association	Canton	Illinois	United States	61520
115	Memorial Hospital	Carthage	Illinois	United States	62321
116	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612
117	Rush University Medical Center	Chicago	Illinois	United States	60612
118	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
119	Weiss Memorial Hospital	Chicago	Illinois	United States	60640
120	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
121	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
122	Eureka Hospital	Eureka	Illinois	United States	61530
123	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
124	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
125	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
126	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
127	Mason District Hospital	Havana	Illinois	United States	62644
128	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
129	Kewanee Hospital	Kewanee	Illinois	United States	61443
130	Mcdonough District Hospital	Macomb	Illinois	United States	61455
131	Loyola University Medical Center	Maywood	Illinois	United States	60153
132	Edward Hospital/Cancer Center	Naperville	Illinois	United States	60540
133	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
134	Community Cancer Center Foundation	Normal	Illinois	United States	61761
135	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
136	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
137	Pekin Hospital	Pekin	Illinois	United States	61554
138	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
139	Proctor Hospital	Peoria	Illinois	United States	61614
140	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
141	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
142	Illinois Valley Hospital	Peru	Illinois	United States	61354
143	Valley Radiation Oncology	Peru	Illinois	United States	61354
144	Perry Memorial Hospital	Princeton	Illinois	United States	61356
145	OSF Saint Anthony Medical Center	Rockford	Illinois	United States	61108
146	Sarah Culbertson Memorial Hospital	Rushville	Illinois	United States	62681
147	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
148	Memorial Medical Center	Springfield	Illinois	United States	62781
149	Carle Cancer Center	Urbana	Illinois	United States	61801
150	Elkhart General Hospital	Elkhart	Indiana	United States	46515
151	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
152	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana	United States	46202
153	Community Hospital East	Indianapolis	Indiana	United States	46219
154	Community Regional Cancer Care-North	Indianapolis	Indiana	United States	46256
155	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
156	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
157	IU Health Arnett Cancer Care	Lafayette	Indiana	United States	47904
158	Horizon Oncology Center	Lafayette	Indiana	United States	47905
159	Saint Joseph Regional Medical Center - Mishawaka	Mishawaka	Indiana	United States	46545
160	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
161	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
162	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
163	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa	United States	52402
164	Saint Luke's Hospital	Cedar Rapids	Iowa	United States	52402
165	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
166	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
167	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
168	Genesis Medical Center - East Campus	Davenport	Iowa	United States	52803
169	Mercy Capitol	Des Moines	Iowa	United States	50307
170	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
171	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
172	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
173	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
174	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
175	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
176	Finley Hospital	Dubuque	Iowa	United States	52001
177	Medical Associates Clinic PC	Dubuque	Iowa	United States	52001
178	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
179	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
180	Memorial Hospital of Arkansas City	Arkansas City	Kansas	United States	67005
181	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
182	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
183	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
184	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
185	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
186	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
187	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
188	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
189	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
190	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
191	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas	United States	66606
192	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
193	Associates In Womens Health	Wichita	Kansas	United States	67208
194	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
195	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
196	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
197	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
198	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
199	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana	United States	71103
200	Eastern Maine Medical Center	Bangor	Maine	United States	04401
201	Mercy Hospital	Portland	Maine	United States	04101
202	Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
203	Harbor Hospital Center	Baltimore	Maryland	United States	21225
204	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
205	Suburban Hospital	Bethesda	Maryland	United States	20814
206	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
207	Kaiser Permanente - Largo Medical Center	Largo	Maryland	United States	20774
208	Kaiser Permanente - Towson Medical Center	Lutherville	Maryland	United States	21093
209	Kaiser Permanente - Shady Grove Medical Center	Rockville	Maryland	United States	20850
210	Tufts Medical Center	Boston	Massachusetts	United States	02111
211	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
212	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
213	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
214	Brigham and Women's Faulkner Hospital	Boston	Massachusetts	United States	02130
215	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
216	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
217	Emerson Hospital/MGH Cancer Center	Concord	Massachusetts	United States	01742
218	Mass General/North Shore Cancer Center	Danvers	Massachusetts	United States	01923
219	MetroWest Medical Center-Framingham Union Hospital	Framingham	Massachusetts	United States	01702
220	Lowell General Hospital	Lowell	Massachusetts	United States	01854
221	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462
222	South Shore Hospital	South Weymouth	Massachusetts	United States	02190
223	Bixby Medical Center	Adrian	Michigan	United States	49221
224	Hickman Cancer Center	Adrian	Michigan	United States	49221
225	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
226	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
227	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
228	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
229	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
230	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
231	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
232	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
233	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
234	Allegiance Health	Jackson	Michigan	United States	49201
235	Marquette General Hospital	Marquette	Michigan	United States	49855
236	Mid-Michigan Medical Center - Midland	Midland	Michigan	United States	48670
237	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
238	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
239	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
240	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
241	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
242	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
243	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
244	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
245	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
246	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
247	Unity Hospital	Fridley	Minnesota	United States	55432
248	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
249	Meeker County Memorial Hospital	Litchfield	Minnesota	United States	55355
250	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
251	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
252	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
253	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
254	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
255	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
256	Mayo Clinic	Rochester	Minnesota	United States	55905
257	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
258	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
259	Regions Hospital	Saint Paul	Minnesota	United States	55101
260	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota	United States	55102
261	United Hospital	Saint Paul	Minnesota	United States	55102
262	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
263	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
264	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
265	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
266	Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
267	Keesler Medical Center	Keesler Air Force Base	Mississippi	United States	39534
268	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
269	Saint Anthony's Medical Center	Saint Louis	Missouri	United States	63128
270	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
271	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
272	Montana Cancer Consortium NCORP	Billings	Montana	United States	59101
273	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
274	Benefis Healthcare-West Campus	Great Falls	Montana	United States	59405
275	Great Falls Clinic	Great Falls	Montana	United States	59405
276	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
277	Renown Regional Medical Center	Reno	Nevada	United States	89502
278	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire	United States	03301
279	Exeter Hospital	Exeter	New Hampshire	United States	03833
280	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire	United States	03106
281	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire	United States	03431
282	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
283	Elliot Hospital	Manchester	New Hampshire	United States	03103
284	Frisbie Hospital	Rochester	New Hampshire	United States	03867
285	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
286	The Cancer Institute of New Jersey Hamilton	Hamilton	New Jersey	United States	08690
287	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
288	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
289	Morristown Medical Center	Morristown	New Jersey	United States	07960
290	Virtua Memorial	Mount Holly	New Jersey	United States	08060
291	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
292	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
293	Virtua Voorhees	Voorhees	New Jersey	United States	08043
294	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
295	Hematology Oncology Associates	Albuquerque	New Mexico	United States	87106
296	Presbyterian Kaseman Hospital	Albuquerque	New Mexico	United States	87110
297	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
298	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
299	Kings County Hospital	Brooklyn	New York	United States	11203
300	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
301	University Hospital of Brooklyn	Brooklyn	New York	United States	11203
302	Brookdale Hospital Medical Center	Brooklyn	New York	United States	11212
303	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
304	Adirondack Cancer Center	Glens Falls	New York	United States	12801
305	Northwell Health NCORP	Lake Success	New York	United States	11042
306	North Shore University Hospital	Manhasset	New York	United States	11030
307	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
308	Saint Vincent's Hospital and Medical Center of New York	New York	New York	United States	10011
309	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
310	Weill Medical College of Cornell University	New York	New York	United States	10065
311	Staten Island University Hospital	Staten Island	New York	United States	10305
312	Mission Hospital-Memorial Campus	Asheville	North Carolina	United States	28801
313	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina	United States	28816
314	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27216
315	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
316	Carolinas HealthCare System NorthEast	Concord	North Carolina	United States	28025
317	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
318	FirstHealth of the Carolinas-Moore Regional Hosiptal	Pinehurst	North Carolina	United States	28374
319	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
320	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
321	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina	United States	27104
322	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
323	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
324	Altru Cancer Center	Grand Forks	North Dakota	United States	58201
325	Altru Hospital	Grand Forks	North Dakota	United States	58201
326	Trinity Cancer Care Center	Minot	North Dakota	United States	58701
327	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
328	Aultman Health Foundation	Canton	Ohio	United States	44710
329	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
330	University of Cincinnati	Cincinnati	Ohio	United States	45267
331	Case Western Reserve University	Cleveland	Ohio	United States	44106
332	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
333	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
334	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
335	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
336	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
337	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
338	Grant Medical Center	Columbus	Ohio	United States	43215
339	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
340	Doctors Hospital	Columbus	Ohio	United States	43228
341	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
342	Miami Valley Hospital	Dayton	Ohio	United States	45409
343	Samaritan North Health Center	Dayton	Ohio	United States	45415
344	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45420
345	Grady Memorial Hospital	Delaware	Ohio	United States	43015
346	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
347	Kettering Medical Center	Kettering	Ohio	United States	45429
348	Fairfield Medical Center	Lancaster	Ohio	United States	43130
349	Lima Memorial Hospital	Lima	Ohio	United States	45804
350	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
351	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
352	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
353	Licking Memorial Hospital	Newark	Ohio	United States	43055
354	Saint Charles Hospital	Oregon	Ohio	United States	43616
355	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
356	North Coast Cancer Care	Sandusky	Ohio	United States	44870
357	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
358	Flower Hospital	Sylvania	Ohio	United States	43560
359	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
360	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
361	University of Toledo	Toledo	Ohio	United States	43614
362	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
363	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
364	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
365	Upper Valley Medical Center	Troy	Ohio	United States	45373
366	Fulton County Health Center	Wauseon	Ohio	United States	43567
367	Saint Ann's Hospital	Westerville	Ohio	United States	43081
368	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
369	Greene Memorial Hospital	Xenia	Ohio	United States	45385
370	Tod Children's Hospital - Forum Health	Youngstown	Ohio	United States	44501
371	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
372	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
373	Bend Memorial Clinic	Bend	Oregon	United States	97701
374	Saint Charles Medical Center-Bend	Bend	Oregon	United States	97701
375	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
376	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
377	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
378	Providence Portland Medical Center	Portland	Oregon	United States	97213
379	Western Oncology Research Consortium	Portland	Oregon	United States	97213
380	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
381	Kaiser Permanente	Portland	Oregon	United States	97227
382	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
383	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
384	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
385	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
386	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
387	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
388	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
389	Penn State Hershey Cancer Institute-Clinical Trials Office	Hershey	Pennsylvania	United States	17033-0850
390	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
391	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania	United States	19047
392	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
393	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
394	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
395	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
396	Aria Health-Torresdale Campus	Philadelphia	Pennsylvania	United States	19114
397	Chestnut Hill Health System	Philadelphia	Pennsylvania	United States	19118
398	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
399	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
400	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
401	Scranton Hematology Oncology	Scranton	Pennsylvania	United States	18510
402	Grand View Hospital	Sellersville	Pennsylvania	United States	18960
403	Geisinger Medical Group	State College	Pennsylvania	United States	16801
404	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
405	Chester County Hospital	West Chester	Pennsylvania	United States	19380
406	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
407	WellSpan Health-York Hospital	York	Pennsylvania	United States	17403
408	Rhode Island Hospital	Providence	Rhode Island	United States	02903
409	Women and Infants Hospital	Providence	Rhode Island	United States	02905
410	Miriam Hospital	Providence	Rhode Island	United States	02906
411	AnMed Health Hospital	Anderson	South Carolina	United States	29621
412	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
413	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
414	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
415	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota	United States	57105
416	Medical X-Ray Center	Sioux Falls	South Dakota	United States	57105
417	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
418	Erlanger Medical Center	Chattanooga	Tennessee	United States	37403
419	Memorial Hospital	Chattanooga	Tennessee	United States	37404
420	Jones Clinic	Germantown	Tennessee	United States	38138
421	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
422	Nashville Oncology Associates PC	Nashville	Tennessee	United States	37203
423	Meharry Medical College	Nashville	Tennessee	United States	37208
424	Medical City Dallas Hospital	Dallas	Texas	United States	75230
425	Zale Lipshy University Hospital	Dallas	Texas	United States	75235
426	Clements University Hospital	Dallas	Texas	United States	75390
427	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
428	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
429	M D Anderson Cancer Center	Houston	Texas	United States	77030
430	Doctor's Hospital of Laredo	Laredo	Texas	United States	78041
431	Covenant Medical Center-Lakeside	Lubbock	Texas	United States	79410
432	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas	United States	78229
433	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
434	Scott and White Memorial Hospital	Temple	Texas	United States	76508
435	Southwestern Vermont Medical Center	Bennington	Vermont	United States	05201
436	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
437	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
438	Kaiser Permanente - Fair Oaks Medical Center	Fairfax	Virginia	United States	22033
439	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
440	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
441	MultiCare Auburn Medical Center	Auburn	Washington	United States	98001
442	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
443	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
444	Saint Francis Hospital	Federal Way	Washington	United States	98003
445	Saint Clare Hospital	Lakewood	Washington	United States	98499
446	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
447	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
448	Group Health Cooperative of Puget Sound Oncology Consortium	Seattle	Washington	United States	98112
449	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
450	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
451	University of Washington Medical Center	Seattle	Washington	United States	98195
452	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
453	MultiCare Allenmore Hospital	Tacoma	Washington	United States	98405
454	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
455	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
456	Multicare Health System	Tacoma	Washington	United States	98415
457	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
458	Edwards Comprehensive Cancer Center	Huntington	West Virginia	United States	25701
459	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
460	Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
461	Midelfort Clinic-Clairemont Campus	Eau Claire	Wisconsin	United States	54702
462	Aurora Cancer Care-Southern Lakes	Elkhorn	Wisconsin	United States	53121
463	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
464	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
465	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
466	Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
467	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311-6519
468	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
469	UW Health Oncology-One South Park	Madison	Wisconsin	United States	53715
470	Dean Hematology and Oncology Clinic	Madison	Wisconsin	United States	53717
471	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
472	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
473	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
474	Vince Lombardi Cancer Clinic-Marinette	Marinette	Wisconsin	United States	54143
475	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
476	Medical Consultants Limited	Milwaukee	Wisconsin	United States	53215
477	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
478	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
479	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
480	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
481	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
482	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
483	BCCA-Cancer Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
484	Penticton Regional Hospital	Penticton	British Columbia	Canada	V2A 3G6
485	BCCA-Fraser Valley Cancer Centre	Surrey	British Columbia	Canada	V3V 1Z2
486	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
487	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
488	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
489	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
490	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
491	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
492	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario	Canada	K1H 8L6
493	Health Sciences North	Sudbury	Ontario	Canada	P3E 5J1
494	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario	Canada	P7B 6V4
495	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
496	CSSS Champlain-Charles Le Moyne	Greenfield Park	Quebec	Canada	J4V 2H1
497	CHUM-Hotel Dieu du Montreal	Montreal	Quebec	Canada	H2W 1T8
498	Hopital Du Sacre-Coeur de Montreal	Montreal	Quebec	Canada	H4J 1C5
499	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
500	International Breast Cancer Study Group	Bern		Switzerland	3008

Sponsors and Collaborators

• ETOP IBCSG Partners Foundation
• Breast International Group
• Cancer and Leukemia Group B
• National Cancer Institute (NCI)
• NSABP Foundation Inc
• NCIC Clinical Trials Group
• North Central Cancer Treatment Group
• Southwest Oncology Group

Investigators

• Principal Investigator: Gini Fleming, ETOP IBCSG Partners Foundation

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 1, 2017
• Study Protocol - Jul 14, 2011

More Information

Publications

• Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. doi: 10.1056/NEJMoa1412379. Epub 2014 Dec 11.

• Responsible Party: ETOP IBCSG Partners Foundation
• ClinicalTrials.gov Identifier: NCT00066690
• Other Study ID Numbers: IBCSG 24-02 / BIG 2-02; NCI-2009-01086; CDR0000316456; BIG 2-02; 2004-000166-13; IBCSG-24-02; U24CA075362; NCT00917969; NCT02140190
• First Posted: Aug 7, 2003
• Last Update Posted: Mar 11, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by ETOP IBCSG Partners Foundation: tamoxifen; ovarian function suppression + tamoxifen; ovarian function suppression + exemestane
• Additional relevant MeSH terms: Breast Neoplasms; Tamoxifen; Triptorelin Pamoate; Exemestane; Tryptophan

Study Results

Participant Flow

Recruitment Details	3066 patients were randomized between 17Dec03 and 27Jan11 at 426 centers in 25 countries.

Arm/Group Title	Tamoxifen	T+OFS	E+OFS
Arm/Group Description	Tamoxifen 20mg orally daily for 5 years	Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Period Title: Overall Study
STARTED	1021	1024	1021
COMPLETED	423	502	457
NOT COMPLETED	598	522	564

Baseline Characteristics

Arm/Group Title	Tamoxifen	T+OFS	E+OFS	Total
Arm/Group Description	Tamoxifen 20mg orally daily for 5 years	Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Total of all reporting groups
Overall Participants	1018	1015	1014	3047
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	43	43	43	43
Sex/Gender, Customized (percent of participants) [Number]
Female	100 9.8%	100 9.9%	100 9.9%	300 9.8%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaskan native	1 0.1%	5 0.5%	3 0.3%	9 0.3%
Asian	36 3.5%	34 3.3%	33 3.3%	103 3.4%
Black/African American	32 3.1%	27 2.7%	34 3.4%	93 3.1%
Hawaiian/Pacific Islander	5 0.5%	4 0.4%	3 0.3%	12 0.4%
White/Caucasian	877 86.1%	873 86%	866 85.4%	2616 85.9%
Other	4 0.4%	2 0.2%	3 0.3%	9 0.3%
Unknown	19 1.9%	22 2.2%	22 2.2%	63 2.1%
Hispanic/Latino/South American native	44 4.3%	48 4.7%	50 4.9%	142 4.7%
Lymph-node status (percent of participants) [Number]
Negative	65.03 6.4%	65.22 6.4%	66.17 6.5%	196.42 6.4%
Positive	34.97 3.4%	34.78 3.4%	33.83 3.3%	103.58 3.4%
Tumor size (percent of participants) [Number]
Unknown	2.65 0.3%	2.46 0.2%	2.07 0.2%	7.18 0.2%
<=2 cm	66.40 6.5%	64.63 6.4%	66.86 6.6%	197.89 6.5%
>2cm	30.94 3%	32.91 3.2%	31.07 3.1%	94.92 3.1%
Tumor grade (percent of participants) [Number]
Unknown	2.36 0.2%	2.36 0.2%	2.17 0.2%	6.89 0.2%
1	27.01 2.7%	26.11 2.6%	24.36 2.4%	77.48 2.5%
2	48.33 4.7%	50.64 5%	53.65 5.3%	152.62 5%
3	22.30 2.2%	20.89 2.1%	19.82 2%	63.01 2.1%
HER2-status (percent of participants) [Number]
Unknown	4.32 0.4%	2.86 0.3%	2.66 0.3%	9.84 0.3%
Negative	84.18 8.3%	85.42 8.4%	84.52 8.3%	254.12 8.3%
Positive	11.49 1.1%	11.72 1.2%	12.82 1.3%	36.03 1.2%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival
Description	Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow-up.
Time Frame	5-year estimates, reported at a median follow-up of 67 months.

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Tamoxifen	T+OFS	E+OFS
Arm/Group Description	Tamoxifen 20mg orally daily for 5 years	Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Measure Participants	1018	1015	1014
Number (95% Confidence Interval) [percentage of participants]	84.7 8.3%	86.6 8.5%	89 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, T+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Tamoxifen was the reference group in the estimation of the hazard ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, E+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.53 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Tamoxifen was the reference group in the estimation of the hazard ratio.

2. Secondary Outcome

Title	Breast Cancer-free Interval
Description	Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.
Time Frame	5-year estimates, reported at a median follow-up of 67 months.

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Tamoxifen	T+OFS	E+OFS
Arm/Group Description	Tamoxifen 20mg orally daily for 5 years	Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Measure Participants	1018	1015	1014
Number (95% Confidence Interval) [percentage of participants]	86.4 8.5%	88.4 8.7%	90.9 9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, T+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.3 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Tamoxifen was the reference group in the estimation of the hazard ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, E+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.49 to 0.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Tamoxifen was the reference group in the estimation of the hazard ratio.

3. Secondary Outcome

Title	Distant Recurrence-free Interval
Description	Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free Interval is defined as the time from randomization to invasive breast cancer recurrence at distant site, or invasive contralateral breast cancer; or censored at date of last follow up.
Time Frame	5-year estimates, reported at a median follow-up of 67 months.

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Tamoxifen	T+OFS	E+OFS
Arm/Group Description	Tamoxifen 20mg orally daily for 5 years	Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)	Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Measure Participants	1018	1015	1014
Number (95% Confidence Interval) [percentage of participants]	90.7 8.9%	91.3 9%	93.0 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, T+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	T was the reference group in the estimation of the hazard ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, E+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.52 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	T was the reference group in the estimation of hazard ratio.

4. Secondary Outcome

Title	Overall Survival
Description	Estimated percentage of patients alive at 8 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.
Time Frame	8-year estimates, reported at a median follow-up of 8 years

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Tamoxifen	T+OFS	E+OFS
Arm/Group Description	Tamoxifen 20mg orally daily for 5 years Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Tamoxifen: Tamoxifen 20mg orally daily for 5 years	Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation) Laboratory Biomarker Analysis: Correlative studies Oophorectomy: Undergo bilateral surgical oophorectomy Quality-of-Life Assessment: Ancillary studies Radiation Therapy: Undergo ovarian irradiation Tamoxifen: Tamoxifen 20mg orally daily for 5 years Triptorelin: 3.75 mg by im injection q28 days for 5 years	Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation) Exemestane: Exemestane 25mg orally daily for 5 years plus ovarian function suppression Laboratory Biomarker Analysis: Correlative studies Oophorectomy: Undergo bilateral surgical oophorectomy Quality-of-Life Assessment: Ancillary studies Radiation Therapy: Undergo ovarian irradiation Triptorelin: 3.75 mg by im injection q28 days for 5 years
Measure Participants	1018	1015	1014
Number (95% Confidence Interval) [percentage of participants]	91.5 9%	93.3 9.2%	92.1 9.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, T+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments	[not specified]
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.48 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	T was the reference group in the estimation of the hazard ratio

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen, E+OFS
	Comments
	Type of Statistical Test	Superiority
	Comments	[not specified]
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	T was the reference group in the estimation of hazard ratio

Adverse Events

Time Frame	Assessed every 3 months for the first year, then every 6 month until year 6. Reported at a median follow-up of 67 months.
Adverse Event Reporting Description	Targeted AEs and other grade 3 or higher AEs were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Arm/Group Title	Tamoxifen		T+OFS		E+OFS
Arm/Group Description	Tamoxifen 20mg orally daily for 5 years		Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)		Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
All Cause Mortality
	Tamoxifen		T+OFS		E+OFS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	87/1007 (8.6%)		68/1007 (6.8%)		80/1001 (8%)
Serious Adverse Events
	Tamoxifen		T+OFS		E+OFS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	315/1007 (31.3%)		375/1007 (37.2%)		375/1001 (37.5%)
Blood and lymphatic system disorders
Hemoglobin	2/1007 (0.2%)		2/1007 (0.2%)		2/1001 (0.2%)
Cardiac disorders
Cardiac Arrhythmia-Other (Specify)	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Cardiac-ischemia/infarction	4/1007 (0.4%)		1/1007 (0.1%)		3/1001 (0.3%)
Conduction abnormality/Atrioventricular heart block - AV block-third degree (complete AV block)	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Conduction abnormality/Atrioventricular heart block - Sick sinus syndrome	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Left ventricular diastolic dysfunction	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Left ventricular systolic dysfunction	0/1007 (0%)		2/1007 (0.2%)		3/1001 (0.3%)
Pain - Cardiac/heart	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Restrictive cardiomyopathy	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Right ventricular dysfunction (cor pulmonale)	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Supraventricular and nodal arrhythmia - Atrial fibrillation	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Supraventricular and nodal arrhythmia - Sinus arrhythmia	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Supraventricular and nodal arrhythmia - Supraventricular tachycardia	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Valvular heart disease	2/1007 (0.2%)		0/1007 (0%)		0/1001 (0%)
Ear and labyrinth disorders
Auditory/Ear-Other (Specify)	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Hearing: patients without baseline audiogram and not enrolled in a monitoring program	1/1007 (0.1%)		0/1007 (0%)		1/1001 (0.1%)
Endocrine disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis)	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
Thyroid function, low (hypothyroidism)	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Adrenal insufficiency	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Endocrine-Other (Specify)	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Eye disorders
Cataract	1/1007 (0.1%)		0/1007 (0%)		1/1001 (0.1%)
Ocular/Visual-Other (Specify)	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Optic disc edema	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Retinal detachment	3/1007 (0.3%)		1/1007 (0.1%)		1/1001 (0.1%)
Vision-flashing lights/floaters	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Gastrointestinal disorders
Distention/bloating, abdominal	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Necrosis, GI - Ileum	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Obstruction, GI - Small bowel NOS	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Stricture/stenosis (including anastomotic), GI - Small bowel NOS	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Ulcer, GI - Anus	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Colitis	2/1007 (0.2%)		1/1007 (0.1%)		1/1001 (0.1%)
Constipation	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Diarrhea	1/1007 (0.1%)		2/1007 (0.2%)		1/1001 (0.1%)
Dysphagia (difficulty swallowing)	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Gastrointestinal-Other (Specify)	2/1007 (0.2%)		1/1007 (0.1%)		2/1001 (0.2%)
Heartburn/dyspepsia	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
Hemorrhoids	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
Mucositis/stomatitis (functional/symptomatic) - Oral cavity	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Nausea	0/1007 (0%)		4/1007 (0.4%)		2/1001 (0.2%)
Pain - Abdomen NOS	3/1007 (0.3%)		3/1007 (0.3%)		4/1001 (0.4%)
Pain - Rectum	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Pancreatitis	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
Vomiting	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
General disorders
Fatigue (asthenia, lethargy, malaise)	32/1007 (3.2%)		36/1007 (3.6%)		33/1001 (3.3%)
Death not associated with CTCAE term - Death NOS	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Death not associated with CTCAE term - Sudden death	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Edema: limb	2/1007 (0.2%)		0/1007 (0%)		0/1001 (0%)
Flu-like syndrome	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Injection site reaction/extravasation changes	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Pain - Chest/thorax NOS	2/1007 (0.2%)		1/1007 (0.1%)		2/1001 (0.2%)
Pain-Other (Specify)	1/1007 (0.1%)		0/1007 (0%)		1/1001 (0.1%)
Hepatobiliary disorders
Cholecystitis	2/1007 (0.2%)		2/1007 (0.2%)		2/1001 (0.2%)
Hepatobiliary/Pancreas-Other (Specify)	3/1007 (0.3%)		2/1007 (0.2%)		4/1001 (0.4%)
Liver dysfunction/failure (clinical)	1/1007 (0.1%)		5/1007 (0.5%)		1/1001 (0.1%)
Pain - Gallbladder	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/1007 (0.1%)		2/1007 (0.2%)		6/1001 (0.6%)
Allergy/Immunology-Other (Specify)	0/1007 (0%)		2/1007 (0.2%)		0/1001 (0%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Foreign body (e.g., graft, implant)	1/1007 (0.1%)		2/1007 (0.2%)		1/1001 (0.1%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Skin (cellulitis)	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Urinary tract NOS	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Infection (documented clinically/microbiologically) w/Grade 3/4 neutrophils -Gallbladder	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Abdomen NOS	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Appendix	1/1007 (0.1%)		2/1007 (0.2%)		1/1001 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary)	1/1007 (0.1%)		1/1007 (0.1%)		1/1001 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Kidney	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	2/1007 (0.2%)		3/1007 (0.3%)		0/1001 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Pelvis NOS	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	4/1007 (0.4%)		10/1007 (1%)		12/1001 (1.2%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Soft tissue NOS	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	0/1007 (0%)		1/1007 (0.1%)		2/1001 (0.2%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Vagina	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Wound	3/1007 (0.3%)		3/1007 (0.3%)		1/1001 (0.1%)
Infection with unknown ANC - Heart (endocarditis)	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Infection with unknown ANC - Rectum	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Infection with unknown ANC - Skin (cellulitis)	3/1007 (0.3%)		2/1007 (0.2%)		1/1001 (0.1%)
Infection with unknown ANC - Wound	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Infection-Other (Specify)	0/1007 (0%)		1/1007 (0.1%)		2/1001 (0.2%)
Injury, poisoning and procedural complications
Hemorrhage/bleeding associated with surgery, intra-operative or post-operative	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Wound complication, non-infectious	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
Fracture	8/1007 (0.8%)		8/1007 (0.8%)		12/1001 (1.2%)
Intra-operative injury - Vein NOS	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Rash: dermatitis associated with radiation - Radiation	2/1007 (0.2%)		0/1007 (0%)		1/1001 (0.1%)
Thrombosis/embolism (vascular access-related)	17/1007 (1.7%)		17/1007 (1.7%)		7/1001 (0.7%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	1/1007 (0.1%)		3/1007 (0.3%)		2/1001 (0.2%)
AST, SGOT (serum glutamic oxaloacetic transaminase)	1/1007 (0.1%)		1/1007 (0.1%)		0/1001 (0%)
Creatinine	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
GGT (gamma-glutamyl transpeptidase)	2/1007 (0.2%)		3/1007 (0.3%)		5/1001 (0.5%)
Leukocytes (total WBC)	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Weight loss	0/1007 (0%)		2/1007 (0.2%)		2/1001 (0.2%)
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)	1/1007 (0.1%)		9/1007 (0.9%)		5/1001 (0.5%)
Potassium, serum-low (hypokalemia)	2/1007 (0.2%)		2/1007 (0.2%)		0/1001 (0%)
Iron overload	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Pancreatic endocrine: glucose intolerance	3/1007 (0.3%)		14/1007 (1.4%)		3/1001 (0.3%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Lumbar spine-range of motion	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Musculoskeletal/Soft Tissue-Other (Specify)	2/1007 (0.2%)		1/1007 (0.1%)		3/1001 (0.3%)
Myositis (inflammation/damage of muscle)	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Osteoporosis	1/1007 (0.1%)		3/1007 (0.3%)		2/1001 (0.2%)
Pain - Back	1/1007 (0.1%)		1/1007 (0.1%)		1/1001 (0.1%)
Pain - Chest wall	1/1007 (0.1%)		0/1007 (0%)		1/1001 (0.1%)
Pain - Extremity-limb	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Pain - Joint	64/1007 (6.4%)		55/1007 (5.5%)		119/1001 (11.9%)
Pain - Muscle	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Nervous system disorders
Hemorrhage, CNS	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
CNS cerebrovascular ischemia	4/1007 (0.4%)		1/1007 (0.1%)		3/1001 (0.3%)
Cognitive disturbance	1/1007 (0.1%)		1/1007 (0.1%)		1/1001 (0.1%)
Dizziness	3/1007 (0.3%)		0/1007 (0%)		5/1001 (0.5%)
Memory impairment	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Myelitis	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Neurology-Other (Specify)	2/1007 (0.2%)		1/1007 (0.1%)		2/1001 (0.2%)
Neuropathy: cranial - CN V Motor-jaw muscles; Sensory-facial	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Neuropathy: cranial - CN VIII Hearing and balance	0/1007 (0%)		1/1007 (0.1%)		1/1001 (0.1%)
Neuropathy: sensory	1/1007 (0.1%)		5/1007 (0.5%)		4/1001 (0.4%)
Pain - Head/headache	6/1007 (0.6%)		10/1007 (1%)		10/1001 (1%)
Pain - Neuralgia/peripheral nerve	0/1007 (0%)		2/1007 (0.2%)		6/1001 (0.6%)
Syncope (fainting)	1/1007 (0.1%)		2/1007 (0.2%)		4/1001 (0.4%)
Vasovagal episode	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Psychiatric disorders
Insomnia	29/1007 (2.9%)		46/1007 (4.6%)		45/1001 (4.5%)
Mood alteration - anxiety	2/1007 (0.2%)		2/1007 (0.2%)		1/1001 (0.1%)
Mood alteration - depression	38/1007 (3.8%)		44/1007 (4.4%)		37/1001 (3.7%)
Psychosis (hallucinations/delusions)	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Renal and urinary disorders
Incontinence, urinary	6/1007 (0.6%)		5/1007 (0.5%)		4/1001 (0.4%)
Obstruction, GU - Ureter	0/1007 (0%)		1/1007 (0.1%)		4/1001 (0.4%)
Stricture/stenosis (including anastomotic), GU - Ureter	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Renal failure	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Renal/Genitourinary-Other (Specify)	49/1007 (4.9%)		19/1007 (1.9%)		11/1001 (1.1%)
Reproductive system and breast disorders
Hemorrhage, GU - Ovary	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Hemorrhage, GU - Uterus	5/1007 (0.5%)		1/1007 (0.1%)		3/1001 (0.3%)
Hemorrhage, GU - Vagina	5/1007 (0.5%)		1/1007 (0.1%)		1/1001 (0.1%)
Stricture/stenosis (including anastomotic), GU - Uterus	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Irregular menses (change from baseline)	4/1007 (0.4%)		2/1007 (0.2%)		0/1001 (0%)
Pain - Breast	2/1007 (0.2%)		0/1007 (0%)		1/1001 (0.1%)
Pain - Ovulatory	1/1007 (0.1%)		1/1007 (0.1%)		0/1001 (0%)
Pain - Pelvis	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Pain - Vagina	14/1007 (1.4%)		22/1007 (2.2%)		19/1001 (1.9%)
Sexual/Reproductive Function-Other (Specify)	0/1007 (0%)		2/1007 (0.2%)		2/1001 (0.2%)
Respiratory, thoracic and mediastinal disorders
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Apnea	1/1007 (0.1%)		0/1007 (0%)		2/1001 (0.2%)
Dyspnea (shortness of breath)	2/1007 (0.2%)		2/1007 (0.2%)		2/1001 (0.2%)
Hypoxia	1/1007 (0.1%)		1/1007 (0.1%)		0/1001 (0%)
Obstruction/stenosis of airway - Bronchus	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Pain - Pleura	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Pleural effusion (non-malignant)	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Pneumonitis/pulmonary infiltrates	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Skin and subcutaneous tissue disorders
Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	0/1007 (0%)		0/1007 (0%)		1/1001 (0.1%)
Dermatology/Skin-Other (Specify)	2/1007 (0.2%)		1/1007 (0.1%)		0/1001 (0%)
Pain - Skin	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Pruritus/itching	0/1007 (0%)		3/1007 (0.3%)		0/1001 (0%)
Soft tissue necrosis - Thorax	0/1007 (0%)		1/1007 (0.1%)		0/1001 (0%)
Vascular disorders
Hematoma	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Hot flashes/flushes	76/1007 (7.5%)		133/1007 (13.2%)		107/1001 (10.7%)
Hypertension	54/1007 (5.4%)		75/1007 (7.4%)		68/1001 (6.8%)
Thrombosis/thrombus/embolism	0/1007 (0%)		2/1007 (0.2%)		0/1001 (0%)
Vascular-Other (Specify)	1/1007 (0.1%)		0/1007 (0%)		0/1001 (0%)
Other (Not Including Serious) Adverse Events
	Tamoxifen		T+OFS		E+OFS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	951/1007 (94.4%)		982/1007 (97.5%)		980/1001 (97.9%)
Cardiac disorders
Cardiac-ischemia/infarction	1/1007 (0.1%)		2/1007 (0.2%)		5/1001 (0.5%)
Gastrointestinal disorders
Nausea	239/1007 (23.7%)		215/1007 (21.4%)		228/1001 (22.8%)
General disorders
Fatigue (asthenia, lethargy, malaise)	571/1007 (56.7%)		595/1007 (59.1%)		591/1001 (59%)
Injection site reaction/extravasation changes	4/1007 (0.4%)		88/1007 (8.7%)		84/1001 (8.4%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	31/1007 (3.1%)		42/1007 (4.2%)		46/1001 (4.6%)
Injury, poisoning and procedural complications
Fracture	41/1007 (4.1%)		46/1007 (4.6%)		51/1001 (5.1%)
Thrombosis/embolism (vascular access-related)	5/1007 (0.5%)		3/1007 (0.3%)		2/1001 (0.2%)
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)	15/1007 (1.5%)		37/1007 (3.7%)		17/1001 (1.7%)
Pancreatic endocrine: glucose intolerance	15/1007 (1.5%)		21/1007 (2.1%)		28/1001 (2.8%)
Musculoskeletal and connective tissue disorders
Osteoporosis	123/1007 (12.2%)		198/1007 (19.7%)		316/1001 (31.6%)
Pain - Joint	631/1007 (62.7%)		700/1007 (69.5%)		778/1001 (77.7%)
Nervous system disorders
Hemorrhage, CNS	14/1007 (1.4%)		9/1007 (0.9%)		8/1001 (0.8%)
CNS cerebrovascular ischemia	2/1007 (0.2%)		1/1007 (0.1%)		0/1001 (0%)
Psychiatric disorders
Insomnia	437/1007 (43.4%)		529/1007 (52.5%)		549/1001 (54.8%)
Libido	427/1007 (42.4%)		477/1007 (47.4%)		492/1001 (49.2%)
Mood alteration - depression	431/1007 (42.8%)		478/1007 (47.5%)		476/1001 (47.6%)
Renal and urinary disorders
Incontinence, urinary	156/1007 (15.5%)		180/1007 (17.9%)		120/1001 (12%)
Reproductive system and breast disorders
Pain - Vagina	224/1007 (22.2%)		240/1007 (23.8%)		290/1001 (29%)
Vaginal dryness	421/1007 (41.8%)		500/1007 (49.7%)		541/1001 (54%)
Skin and subcutaneous tissue disorders
Sweating (diaphoresis)	486/1007 (48.3%)		621/1007 (61.7%)		566/1001 (56.5%)
Vascular disorders
Hot flashes/flushes	727/1007 (72.2%)		806/1007 (80%)		820/1001 (81.9%)
Hypertension	119/1007 (11.8%)		158/1007 (15.7%)		165/1001 (16.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.