A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer

Breast Neoplasms Clinical Trial

— MONARCH 2  

Official title:

MONARCH 2: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Fulvestrant With or Without Abemaciclib, a CDK4/6 Inhibitor, for Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02107703
• Other study ID #: 15362
• Secondary ID: I3Y-MC-JPBL2013-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 22, 2014
• Est. completion date: December 30, 2024

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either abemaciclib + fulvestrant or fulvestrant alone. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio. The study will last about 9 months for each participant.

For the endocrine naïve cohort, all participants will received abemaciclib + fulvestrant.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 669
• Est. completion date: December 30, 2024
• Est. primary completion date: February 14, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Have a diagnosis of HR+, HER2- breast cancer

• Have locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria:

• relapsed with radiologic evidence of progression while receiving neoadjuvant or adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression

• relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression

• relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease

• presented de novo with metastatic disease and then relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease

• for the endocrine naïve cohort: Must not have received prior endocrine therapy in current or prior disease setting

• Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin

• Have a negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if postmenopausal status is due to ovarian suppression with a GnRH agonist

• Have either measurable disease or nonmeasurable bone only disease

• Have a performance status =1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy

Exclusion Criteria

• Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease

• Have clinical evidence or history of central nervous system metastasis

• Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, everolimus, or any CDK4/6 inhibitor. For the endocrine naïve cohort: In addition, have received treatment with any prior endocrine therapy

• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days prior to randomization of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively

• Have received recent (within 28 days prior to randomization) yellow fever vaccination

• Have had major surgery within 14 days prior to randomization of study drug to allow for post-operative healing of the surgical wound and site(s)

• Have a personal history within the last 12 months of any of the following conditions:

syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest

• Have inflammatory breast cancer or a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years

• Have received an autologous or allogeneic stem-cell transplant

• Have active bacterial or fungal infection, or detectable viral infection

• Have initiated bisphosphonates or approved Receptor activator of nuclear factor kappa-B (RANK) ligand targeted agents <7 days prior to randomization

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Abemaciclib
Administered Orally
• Fulvestrant
Administered IM
• Placebo
Administered Orally

Locations

Country	Name	City	State
Australia	Monash Cancer Centre	East Bentleigh	Victoria
Australia	Ashford Cancer Centre Research	Kurralta Park	South Australia
Australia	Icon Cancer Centre South Brisbane	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	St. John of God Subiaco Hospital	Subiaco	Western Australia
Belgium	UZ Brussel	Brussel	Bruxelles-Capitale, Région De
Belgium	Antwerp University Hospital	Edegem	Antwerpen
Belgium	UZ Leuven	Leuven	Vlaams-Brabant
Belgium	Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman	Liège
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	Humber River Hospital	Toronto	Ontario
Canada	Unity Health Toronto, St. Michael's Hospital	Toronto	Ontario
Denmark	Aalborg Universitets hospital	Aalborg
Denmark	Herlev and Gentofte Hospital	Copenhagen	Hovedstaden
Denmark	Roskilde Sygehus	Roskilde
Finland	Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)	Helsinki	Uusimaa
Finland	Tampereen yliopistollinen sairaala	Tampere	Pirkanmaa
Finland	Turun Yliopistollinen Keskussairaala	Turku
France	CHU Besançon	Besancon	Doubs
France	Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne	Clermont-Ferrand	Puy-de-Dôme
France	Polyclinique De Blois	La Chaussee Saint Victor
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans
Germany	Gemeinschaftspraxis hop-augsburg	Augsburg	Bayern
Germany	Facharztzentrum Eppendorf	Hamburg
Germany	Klinikum Ludwigsburg	Ludwigsburg	Baden-Württemberg
Germany	Klinikum der Ludwig-Maximilians-Universitaet Muenchen	München	Bayern
Germany	Universitaetsklinikum Tuebingen	Tübingen	Baden-Württemberg
Greece	Agios Savvas Regional Cancer Hospital	Athens	Attikí
Greece	Chania General Hospital 'Agios Georgios'	Chania
Greece	University General Hospital of Heraklion	Heraklion	Krítí
Greece	University Hospital of Patras	Patras	Acha?a
Italy	Ospedale Bellaria - Azienda USL di Bologna	Bologna
Italy	Azienda Ospedaliero Universitaria S.Anna	Cona	Emilia-Romagna
Italy	Istituto Oncologico Veneto IRCCS	Padova
Italy	Istituto Nazionale Tumori Regina Elena	Rome	Roma
Japan	Tokyo Met Cancer & Infectious Diseases Center Komagome Hp	Bunkyo-ku	Tokyo
Japan	Chiba cancer center	Chiba-shi	Chiba
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Saitama Prefectural Cancer Center	Ina-machi	Saitama
Japan	Sagara Hospital	Kagoshima
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	St. Marianna University School of Medicine Hospital	Kawasaki	Kanagawa
Japan	Japanese Foundation for Cancer Research	Koto	Tokyo
Japan	Kurume General Hospital	Kurume	Fukuoka
Japan	Kyoto University Hospital	Kyoto
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata
Japan	Hyogo College of Medicine	Nishinomiya	Hyogo
Japan	National Hospital Organization Osaka Medical Center	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Jichi Medical University Hospital	Shimotsuke	Tochigi
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do [Chungbuk]
Korea, Republic of	Inha University Hospital	Incheon	Incheon-gwangyeoksi [Incheon]
Korea, Republic of	Gachon University Gil Medical Center	Namdong-gu	Incheon-gwangyeoksi [Incheon]
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	The Catholic Univ. of Korea Seoul St. Mary's Hospital	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Ulsan University Hospital	Ulsan	Ulsan-Kwangyokshi
Mexico	Centro Oncológico Internacional (COI)	Guadalajara	Jalisco
Mexico	Preparaciones Oncológicas S.C.	Leon	Guanajuato
Mexico	Grupo Medico Camino Sc	Mexico City	Distrito Federal
Mexico	Instituto Nacional de Cancerologia	Mexico City	Distrito Federal
Mexico	OCA Hospital	Monterrey	Nuevo León
Mexico	Tecnologico de Monterrey	Monterrey	Nuevo León
Mexico	Hospital Angeles	Tijuana	Baja California
Poland	Bialostockie Centrum Onkologii, Oddzial Onkologii Klinicznej	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo-Akcyjna	Lodz	Lódzkie
Puerto Rico	Puerto Rico Hematology/Oncology Group	Bayamon
Romania	Ianuli Med Consult SRL	Bucharest
Romania	S.C. MedisProf SRL	Cluj-Napoca	Cluj
Romania	Centrul de Oncologie "Sfântul Nectarie"	Craiova	Dolj
Russian Federation	Arkhangelsk Clinical Oncological Dispensary	Arkhangelsk	Arkhangel'skaya Oblast'
Russian Federation	Regional Budgetary Healthcare Institution 'Ivanovo Regional Oncology Dispensary'	Ivanovo	Ivanovskaya Oblast'
Russian Federation	Kursk Regional Oncology Dispensary	Kursk
Russian Federation	Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF	Moscow	Moskva
Russian Federation	N.N.Petrov Research Institute of Oncology	Saint Petersburg	Sankt-Peterburg
Russian Federation	Saint-Petersburg City Clinical Oncology Dispensary	Saint Petersburg	Sankt-Peterburg
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Universitario Arnau de Vilanova de Lleida	Lleida	Lleida [Lérida]
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad De
Spain	Hospital General Universitario Morales Meseguer	Murcia	Murcia, Región De
Spain	Hospital Quirónsalud Valencia	Valencia	València
Switzerland	Universitätsspital Basel	Basel	Basel Stadt
Switzerland	HUG-Hôpitaux Universitaires de Genève	Genève
Switzerland	Spital Thun	Thun	Berne
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	Chang Gung Memorial Hospital at Kaohsiung	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch	Taoyuan
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	Palm Beach Cancer Institue	Atlantis	Florida
United States	Pharmasite Research, Inc.	Baltimore	Maryland
United States	Billings Clinic	Billings	Montana
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Washington University Medical School	Creve Coeur	Missouri
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Oncology Consultants P.A.	Houston	Texas
United States	St. Bernards Medical Center	Jonesboro	Arkansas
United States	Freeman Cancer Institute	Joplin	Missouri
United States	St Lukes Hospital	Kansas City	Missouri
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	University of California - San Diego	La Jolla	California
United States	Breslin Cancer Center	Lansing	Michigan
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	The Boston Baskin Cancer Group	Memphis	Tennessee
United States	Minnesota Oncology/Hematology PA	Minneapolis	Minnesota
United States	SMO Sarah Cannon Research Inst.	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Palm Beach Cancer Institue	Palm Beach Gardens	Florida
United States	Quincy Medical Group	Quincy	Illinois
United States	Kaiser Permanente	Riverside	California
United States	Rochester General Hospital	Rochester	New York
United States	Rochester General Hospital	Rochester	New York
United States	Harbin Clinic	Rome	Georgia
United States	Washington University Medical School	Saint Louis	Missouri
United States	Washington University Medical School	Saint Louis	Missouri
United States	Washington University Medical School	Saint Peters	Missouri
United States	Florida Cancer Specialists - North	Saint Petersburg	Florida
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Univ of California San Francisco	San Francisco	California
United States	Sanford Research/USD	Sioux Falls	South Dakota
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Stanford University Clinic	Stanford	California
United States	Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center	Tampa	Florida
United States	Oklahoma Cancer Specialists & Research Institute, LLC	Tulsa	Oklahoma
United States	St Mary Regional Cancer Center	Walla Walla	Washington
United States	Palm Beach Cancer Institue	Wellington	Florida
United States	Palm Beach Cancer Institue	West Palm Beach	Florida
United States	Novant Health, Oncology Research Institute	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  Finland,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Switzerland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.	From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Secondary	Overall Survival (OS)	OS defined as the time from the date of randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The final analysis of the OS outcome was conducted after 440 OS events had been observed.	From Date of Randomization until Death Due to Any Cause (Up To 72 Months)
Secondary	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Secondary	Duration of Response (DOR)	DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Secondary	Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])	Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Secondary	Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR])	Clinical benefit rate defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months.CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions.PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants=(participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100.PD was at least a 20% increase in sum of the diameters of target lesions,with reference being the smallest sum on study and an absolute increase of at least 5 mm or unequivocal progression of non-target lesions,or 1 or more new lesions.	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Secondary	Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf)	A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, End of Study (Up To 31 Months)
Secondary	Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20	Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC[0-8]) was evaluated for Abemaciclib and Metabolites M2 and M20.	Cycle 1 Day 1 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose
Secondary	Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L)	European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, End of Study (Up To 31 Months)
Secondary	Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, Short Term Follow Up (Up To 31 Months)
Secondary	Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire	EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.	Baseline, Short Term Follow Up (Up To 31 Months)