Monitoring Symptoms to Help Young Women Take Hormone Therapy for Stage I-III Breast Cancer, ASPEN Study

Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial

Official title:

A Randomized Phase III Trial Comparing Active Symptom Monitoring Plus Patient Education Versus Patient Education Alone to Improve Persistence With Endocrine Therapy in Young Women With Stage I-III Breast Cancer (ASPEN)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05568472
• Other study ID #: S2010
• Secondary ID: NCI-2022-06902S2
• Status: Recruiting
• Phase: N/A
• Start date: March 29, 2023
• Est. completion date: May 1, 2028

Study information

• Verified date: November 2023
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares the effect of active symptom monitoring and patient education to patient education alone in helping young women with stage I-III breast cancer stay on their hormone therapy medicines. The patient education tool contains interactive weblinks which provide patients with education material about breast cancer and side effects of therapy. Symptom monitoring is a weblink via email or text message with questions asking about symptoms. Hormone therapy for breast cancer can cause side effects, and may cause some women to stop treatment early. Asking about symptoms more often may help women keep taking hormone therapy medicines.

Description:

PRIMARY OBJECTIVE:

I. To compare persistence with the initially prescribed oral endocrine therapy (ET) through 72 weeks for young women being treated for hormone-receptor positive stage I-III breast cancer randomized to Active Symptom Monitoring (ASM) + patient education or patient education alone.

SECONDARY OBJECTIVES:

I. To compare patient-reported adherence with the initially prescribed oral ET over time as assessed with the Voils measure between the two arms.

II. To compare worst pain as assessed with the Brief Pain Inventory, in aromatase inhibitors-treated (AI-treated) participants over time between the two arms.

III. To compare hot flashes as assessed with the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) Endocrine Symptoms Scale in tamoxifen-treated participants over time between the two arms.

EXPLORATORY OBJECTIVES:

I. To describe key treatment-emergent symptoms as assessed with the Brief Pain Inventory, the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile, the PROMIS Cognitive Function, and the FACT-ES Endocrine Symptoms Scale over time between the two arms.

II. To develop a composite risk prediction model (including demographics, socioeconomic variables, and clinical variables) to identify participants who are most likely to benefit from ASM.

III. To examine associations between baseline symptom bother as assessed with the GP5 item from the FACT-ES and persistence with oral ET.

IV. To examine the pattern by arm of treatment toxicity from the oral ET agents that are prescribed in this study over time during the first 24 weeks.

V. To compare biochemically determined adherence with the initially prescribed oral ET as assessed with centrally evaluated drug concentrations and metabolites between ASM + patient education and patient education alone over time.

VI. To examine associations overall and by arm between baseline estradiol concentrations evaluated centrally and development of treatment-emergent symptoms as assessed with the Brief Pain Inventory, the PROMIS-29 Profile, the PROMIS Cognitive Function, and the FACT-ES endocrine symptoms scale.

VII. To determine patterns of change overall and by arm in centrally evaluated estradiol concentrations during study participation in participants with chemotherapy-induced ovarian failure, those receiving gonadotrophin releasing hormone (GnRH) agonist therapy, and those who had undergone bilateral salpingo-oophorectomy.

VIII: To identify inherited genetic variants using genome-wide genotyping that contribute to development of endocrine therapy-emergent toxicity.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients are asked 6 brief questions about symptoms weekly by email, text, or phone call for the first 6 months, then every 4 weeks for 12 months. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at baseline, 3, 12, and 18 months.

ARM II: Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at 3, 12, and 18 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 540
• Est. completion date: May 1, 2028
• Est. primary completion date: May 1, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must be female and have Stage I, II, or III hormone receptor positive breast cancer based on clinical or pathologic evaluation

• Participants must have been pre- or peri-menopausal at the time of breast cancer diagnosis by satisfying one of the following:

• had a menstrual period (by self-report) within the 12 months before breast cancer diagnosis, or

• had a serum or plasma estradiol and/or follicle stimulating hormone (FSH) concentration consistent with premenopausal status (based on institutional standards) within the 12 months before breast cancer diagnosis or when checked after breast cancer diagnosis

• Participants must have started initial treatment with standard of care oral endocrine therapy (ET) (i.e., tamoxifen, anastrozole, exemestane, or letrozole; within 14 days prior to randomization or be planning to start initial treatment with standard of care oral ET within 14 days after randomization

• Participants who currently have ovarian function (estradiol above the postmenopausal range) must be planning to undergo ovarian suppression or ablation concomitantly with oral ET medication, starting before or at the same time as oral ET initiation. Participants with chemotherapy-induced amenorrhea or ovarian failure at time of registration must be planning to start ovarian suppression or ablation if they have recurrence of ovarian function during study participation (circulating estradiol concentration in the premenopausal range or recurrence of menses)

• Participants must have completed surgery for treatment of breast cancer at least 14 days prior to randomization NOTE: Concomitant radiotherapy at the time of randomization and/or during study participation is allowed

• Participants who received chemotherapy must have finished it at least 14 days prior to randomization NOTE: Concomitant maintenance targeted or biologic therapy (e.g., human epidermal growth factor receptor 2 [anti-HER2] therapy, poly-ADP ribose polymerase [PARP] inhibitor therapy, CDK4/6 inhibitor therapy, osteoclast inhibitor therapy) at the time of randomization and/or during study participation is allowed

• Participants must be >= 18 years of age

• Participants must have a complete medical history within 60 days prior to randomization

• Participants must be able to complete Patient-Reported Outcome (PRO) instruments in English or Spanish

Participants must:

• agree to complete PROs at all scheduled assessments and

• complete the pre-registration (baseline) PRO forms within 14 days prior to randomization

• Participants must be able to complete symptom questions on a web browser (on a smartphone, tablet, or computer) or respond via voice on a telephone in English or Spanish. Participants must agree to complete symptom questions at all scheduled assessments NOTE: Participants who do not have access to the internet and who cannot receive telephone calls for interactive voice response system (IVRS) assessments are not eligible

• Participants must be offered the opportunity to participate in specimen banking for translational medicine. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) specimen tracking system

• Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

Exclusion Criteria:

• Participants must not have distant metastatic breast cancer

• Participants who have started or plan to start treatment with tamoxifen during study participation must not have received prior tamoxifen for treatment or prevention of breast cancer

• Participants who have started or plan to start treatment with an aromatase inhibitor during study participation must not have received prior aromatase inhibitor therapy for treatment or prevention of breast cancer

• Participants must not be taking or planning to take oral estrogen-or progesterone-containing treatments during study participation

NOTES:

• Participants who start or plan to start treatment with an aromatase inhibitor may have previously received tamoxifen for prevention of breast cancer or treatment of a prior cancer

• Participants may have received prior treatment with an aromatase inhibitor for infertility treatment

• Participants must not be planning to become pregnant during the 80 weeks of study participation

• Participants must not receive additional anti-cancer treatments (i.e., experimental therapy, immunotherapy, biologics, etc.) as part of another clinical trial

• Participants must not have a non-breast malignancy for which they are currently receiving treatment

Related Conditions & MeSH terms

• Anatomic Stage I Breast Cancer AJCC v8
• Anatomic Stage II Breast Cancer AJCC v8
• Anatomic Stage III Breast Cancer AJCC v8
• Breast Neoplasms

Intervention

Other:
• Best Practice
Standard of care hormone therapy and standard visit with clinician

Procedure:
• Biospecimen Collection
Undergo correlative studies
• Endocrine Drug Therapy
Undergo endocrine therapy

Behavioral:
• Health Education
Receive list of websites

Other:
• Questionnaire Administration
Ancillary studies
• Symptom Specific Assessment Tool
Receive a weblink via email or text message and asked 6 brief questions about symptoms

Locations

Country	Name	City	State
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	The Queen's Medical Center - West Oahu	'Ewa Beach	Hawaii
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Mayo Clinic Health System in Albert Lea	Albert Lea	Minnesota
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	Northside Hospital	Atlanta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	AIS Cancer Center at San Joaquin Community Hospital	Bakersfield	California
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Kaiser Permanente-Woodlawn Medical Center	Baltimore	Maryland
United States	Mercy Medical Center	Baltimore	Maryland
United States	Summa Health System - Barberton Campus	Barberton	Ohio
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Advocate Good Shepherd Hospital	Barrington	Illinois
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Beverly Hospital	Beverly	Massachusetts
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Kaiser Permanente-Burke Medical Center	Burke	Virginia
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Marshall Cancer Center	Cameron Park	California
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	AtlantiCare Health Park-Cape May Court House	Cape May Court House	New Jersey
United States	Mercy Cancer Center ?? Carmichael	Carmichael	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Caro Cancer Center	Caro	Michigan
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Morton Plant Hospital	Clearwater	Florida
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Main Line Health Center-Collegeville	Collegeville	Pennsylvania
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	AMG Crystal Lake - Oncology	Crystal Lake	Illinois
United States	Aurora Saint Luke's South Shore	Cudahy	Wisconsin
United States	Carle at The Riverfront	Danville	Illinois
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Broward Health North	Deerfield Beach	Florida
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Bayhealth Hospital Kent Campus	Dover	Delaware
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Epic Care-Dublin	Dublin	California
United States	Kaiser Permanente Dublin	Dublin	California
United States	Northside Hospital - Duluth	Duluth	Georgia
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	STCC at DHR Health Institute for Research and Development	Edinburg	Texas
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	AtlantiCare Surgery Center	Egg Harbor Township	New Jersey
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Advocate Sherman Hospital	Elgin	Illinois
United States	Mercy Cancer Center - Elk Grove	Elk Grove	California
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Main Line Health Center-Exton	Exton	Pennsylvania
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Kaiser Permanente-Gaithersburg Medical Center	Gaithersburg	Maryland
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Grand Valley Oncology	Grand Junction	Colorado
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Advocate South Suburban Hospital	Hazel Crest	Illinois
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Hawaii Diagnostic Radiology Services LLC	Honolulu	Hawaii
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Jupiter Medical Center	Jupiter	Florida
United States	Straub Medical Center - Kahului Clinic	Kahului	Hawaii
United States	Castle Medical Center	Kailua	Hawaii
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kaiser Permanente - Kensington Medical Center	Kensington	Maryland
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	The Watson Clinic	Lakeland	Florida
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Sparrow Hospital	Lansing	Michigan
United States	Kaiser Permanente - Largo Medical Center	Largo	Maryland
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Northside Hospital - Gwinnett	Lawrenceville	Georgia
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Condell Memorial Hospital	Libertyville	Illinois
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Kaiser Permanente Lutherville - Timonium Medical Center	Lutherville	Maryland
United States	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Kaiser Permanente Tysons Corner Medical Center	McLean	Virginia
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Summa Health Medina Medical Center	Medina	Ohio
United States	Garnet Health Medical Center	Middletown	New York
United States	Bayhealth Hospital Sussex Campus	Milford	Delaware
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Saint Joseph Mount Sterling	Mount Sterling	Kentucky
United States	Marshfield Medical Center - Neillsville	Neillsville	Wisconsin
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Bryn Mawr Health Center	Newtown Square	Pennsylvania
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Bay Area Tumor Institute	Oakland	California
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Northwestern Medicine Orland Park	Orland Park	Illinois
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Lahey Medical Center-Peabody	Peabody	Massachusetts
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Capital Health Medical Center-Hopewell	Pennington	New Jersey
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Phoenixville Hospital	Phoenixville	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	South Florida Baptist Hospital	Plant City	Florida
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Kaiser Permanente- Marshall Medical Offices	Redwood City	California
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	West Suburban Medical Center	River Forest	Illinois
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mercy Cancer Center - Rocklin	Rocklin	California
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Kaiser Permanente-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Saint John's Cancer Institute	Santa Monica	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Saint Vincent Hospital Cancer Center at Sheboygan	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Tampa General Hospital	Tampa	Florida
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Holy Name Hospital	Teaneck	New Jersey
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	UM Saint Joseph Medical Center	Towson	Maryland
United States	Munson Medical Center	Traverse City	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	South Georgia Medical Center/Pearlman Cancer Center	Valdosta	Georgia
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Kaiser Permanente-Capitol Hill Medical Center	Washington	District of Columbia
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Shenandoah Oncology PC	Winchester	Virginia
United States	Winchester Hospital	Winchester	Massachusetts
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Woodland Memorial Hospital	Woodland	California
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
SWOG Cancer Research Network	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Symptom bother	Assessed using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) "I am bothered by side effects of treatment" (GP5) question. This is rated on a scale of 0 ("not at all") to 4 ("very much") with higher values indicating worse physical well-being over the past 7 days.	Up to 18 months
Other	Symptom burden: average pain	Will be measured using the Brief Pain Inventory - Short Form (BPI-SF) average pain question "Please rate your pain by marking the box beside the number that best describes your pain on the average", range 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine."	Up to 18 months
Other	Symptom burden: pain interference	Will be measured using the Brief Pain Inventory - Short Form (BPI-SF) pain interference scale, range 0 to 10, with lower values representing "no interference" and 10 signifying "complete interference."	Up to 18 months
Other	Symptom burden: overall health profile	Will be measured using the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) profile subscales: fatigue (33-76), sleep disturbance (32-74), physical function (22-57), depression (41-80), anxiety (40-82), and ability to participate in social roles and activities (27-65). Raw scores (range 4-20 for all subscales) are converted to T scores (approximate ranges shown next to subscale), with mean 50 and standard deviation 10. The T score conversion is handled programmatically by Health Measures and depends upon the number of questions answered, minimums and maximums may differ from those shown here. Higher T scores represent more of the characteristic being measured (e.g., higher T score on fatigue score represents more fatigue, but higher T score on physical function represents better physical function).	Up to 18 months
Other	Symptom burden: cognitive function	Will be measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 4a. Raw scores (range 4 to 20) are converted to a T score with mean 50, and standard deviation 10. The approximate minimum and maximum T scores for this scale are 24 and 62 respectively, with higher T scores representing better cognitive function. T score conversion is handled programmatically by Health Measures and depends upon the number of questions answered; actual minimums and maximums may differ depending upon the number of questions answered.	Up to 18 months
Other	Symptom burden: endocrine symptoms	Will be measured using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) Endocrine Symptoms Scale. This is a 19-item subscale with range 0 to 76, with higher values representing better quality of life.	Up to 18 months
Other	Estradiol concentration	Plasma concentrations of estradiol will be quantitated centrally using a tandem mass spectroscopy-based ultrasensitive estradiol assay	Up to 18 months
Other	Adherence to medications based on plasma concentrations	Objectively assessed biochemically by quantitating tamoxifen and AI drug and metabolite plasma concentrations as previously described.	Up to 18 months
Other	Genotyping	Germline deoxyribonucleic acid (DNA) will be genotyped by the University of Michigan Advanced Genomics Core using technology available at the time the analysis is performed	Up to 18 months
Primary	Persistence with initially prescribed oral estrogen (ET) medication	Will be assessed by the treating provider at each study visit every 12 weeks and prospectively documented on the S2010 treatment log, including any switch from the initially prescribed oral ET. Persistence with initially prescribed oral ET by intervention arm out to 72 weeks will be described using Kaplan-Meier plots. Potential differences by arm will be tested using multivariable Cox regression. Persistence with any oral ET (aromatase inhibitor [AI] and/or tamoxifen) at 72 weeks by arm will be examined in a consistent manner. The study stratification variables (age [< 45 vs >= 45], chemotherapy [yes/no], and ET [AI vs tamoxifen]), as well as race, ethnicity, and disease stage, will be included as covariates in the regression models. In the timeframe of evaluation, censored events (newly diagnosed cancer, cancer recurrence, or death) are anticipated to be low.	From randomization to discontinuation of the initially prescribed ET for more than 60 days or switching to a new oral ET medication, assessed up to 72 weeks
Secondary	Occurrence of any non-adherence	Will be assessed using the Voils validated adherence tool that both determines the extent of nonadherence as well as reasons for non-adherence. Kaplan Meier plots will be used to describe patterns of non-adherence between arms. Multivariable Cox regression will be used to assess this secondary endpoint.	Up to 18 months
Secondary	Worst pain	Will be measured using the Brief Pain Inventory - Short Form (BPI-SF) "worst pain" question ("Please rate your pain by circling the one number that best describes your pain at its worst in the last 24 hours") in the subset of patients planning to receive AI treatment. Worst pain is measured on an 11-point scale of 0 ("no pain") to 10 ("pain as bad as you can imagine"). Linear regression will be used, adjusting for the stratification factors and the baseline score.	Up to 12 weeks
Secondary	Incidence of hot flashes	Will be assessed using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) "I have hot flashes/hot flushes" (ES1) question in the subset of patients planning to receive tamoxifen therapy. Hot flashes/hot flushes are measured on a scale of 0 ("not at all") to 4 ("very much"), with higher values indicating increased concern over the past 7 days. Linear regression will be used to compare scores between arms, adjusting for the stratification factors and the baseline score.	Up to 12 weeks