Epidemiology and Treatment of HR+/HER2- Breast Cancer in England (ROTOR)
March 27, 2026 updated by: Novartis Pharmaceuticals
The aim of this study was to describe the epidemiology, treatment pathway, treatment access, wastage of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), and health care resource use among adults with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (BC) in England, including their treatment pathway leading to progression to metastatic BC for those who were initially diagnosed with early BC.
This was a retrospective cohort study using linked registry and administrative data.
Study Overview
Status
Completed
Conditions
Study Type
Observational
Enrollment (Actual)
218677
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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London, United Kingdom, W12 7FQ
- Novartis
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Sampling Method
Non-Probability Sample
Study Population
Adults captured in the cancer registry with a diagnosis of HR+/HER2- early BC or metastatic BC between 01 April 2012 and 31 December 2022.
Description
Inclusion criteria:
- Patient with a registered diagnosis of International Classification of Diseases,10th Revision (ICD-10) code C50: malignant neoplasm of the breast, between 01 April 2012 and 31 December 2022.
- Patient ≥18 years of age at diagnosis.
- Patient with estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), i.e., hormone receptor positive (HR+) breast cancer
- Patient with human epidermal growth factor receptor 2 negative (HER2-) breast cancer.
Additional inclusion criteria for patients with metastatic BC were defined as:
- Tumor stage IV at diagnosis or on subsequent treatment or
- Tumor Node Metastases (TNM) staging indicative of M1 at diagnosis or on subsequent treatment or
- Record with ICD-10 codes indicating secondary malignant neoplasm C77* (excluding C771 and C773), C78*, or C79* or
- Initiation of treatment specified for metastatic BC, defined as ribociclib or palbociclib from 01 January 2017 to the end of the study period or abemaciclib from 01 January 2017 to 31 May 2022 or
- Record of treatment for distant/metastatic recurrence.
An additional inclusion criterion for patients with early BC was:
• No evidence of metastatic disease (defined above) before or up to 100 days after the first BC diagnosis date.
Additional inclusion criteria for patients in the NATALEE Trial-aligned sub-cohort:
- Patient with stage IIa BC at diagnosis (i.e., T0-1 N1 or T2 N0 with Grade 3 tumor), or
- Stage IIb BC at diagnosis (i.e., T2 N1, T3 N0), or
- Stage III BC at diagnosis.
Exclusion criteria:
- Patient's sex unknown.
- Patient with ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS).
- Patient with a diagnosis of Second Edition of the International Classification of Diseases for Oncology (ICD-0-O2) code 0, 1, or 2 denoting non-malignant disease.
Patient with any indication of co-positive disease before or within 6 months after diagnosis (i.e., HR+ and HER2+) including:
- treated with trastuzumab
- treated with tyrosine kinase inhibitors (TKIs)
- Any registered BC tumor or evidence of metastatic cancer prior to index date.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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HR+/HER2- Early BC Cohort
Adults with a diagnosis of HR+/HER2- early BC between 01 April 2012 and 31 December 2022.
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HR+/HER2- Metastatic BC Cohort
Adults with a diagnosis of HR+/HER2- de novo or progressed metastatic BC between 01 April 2012 and 31 December 2022.
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NATALEE Trial-aligned Sub-cohort
Patients from the HR+/HER2- Early BC Cohort consisting of patients with stage II BC and stage III BC.
This sub-group closely resembled the NATALEE trial population.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Time Between Start of Endocrine Therapy (ET) and Disease Progression
Time Frame: Up to approximately 12 years and 7 months
|
Disease progression events include:
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Up to approximately 12 years and 7 months
|
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Time between Non-metastatic Recurrence and Disease Progression
Time Frame: Up to approximately 12 years and 7 months
|
Disease progression events include:
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Up to approximately 12 years and 7 months
|
|
Time Between Metastatic Recurrence and Death
Time Frame: Up to approximately 12 years and 7 months
|
Up to approximately 12 years and 7 months
|
|
|
Number of Patients With Disease Progression by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Health states:
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Up to approximately 12 years and 7 months
|
|
Invasive Disease-Free Survival (iDFS)
Time Frame: Up to approximately 12 years and 7 months
|
iDFS was defined as time between start of ET to the first of any of non-metastatic recurrence, metastatic recurrence, non-breast invasive cancer, or death from any cause.
|
Up to approximately 12 years and 7 months
|
|
Hazard Ratio for Disease Progression Between Health States
Time Frame: Up to approximately 12 years and 7 months
|
Health states:
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Up to approximately 12 years and 7 months
|
|
Number of Patients by Number of Lines of Systemic Anti-cancer Therapy (SACT) Received
Time Frame: Up to approximately 12 years and 7 months
|
Up to approximately 12 years and 7 months
|
|
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Number of Patients who Received Radiotherapy
Time Frame: Up to approximately 12 years and 7 months
|
Up to approximately 12 years and 7 months
|
|
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Time From BC diagnosis to Treatment Initiation by Line of Therapy (LOT)
Time Frame: Up to approximately 12 years and 7 months
|
Up to approximately 12 years and 7 months
|
|
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Number of Patients by Treatment Received Within Each LOT Ranked by Frequency of Use
Time Frame: Up to approximately 12 years and 7 months
|
Treatments were ranked by most common (rank 1) to least common (rank 3).
|
Up to approximately 12 years and 7 months
|
|
Duration of Treatment Received for Each LOT by Rank Order
Time Frame: Up to approximately 12 years and 7 months
|
Treatments were ranked by most common (rank 1) to least common (rank 3).
|
Up to approximately 12 years and 7 months
|
|
Number of Patients by Treatment Classes per LOT
Time Frame: Up to approximately 12 years and 7 months
|
Up to approximately 12 years and 7 months
|
|
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Percentage of Patients by First SACT Used During Year of Diagnosis by Geographical Region
Time Frame: Up to approximately 1 year
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Up to approximately 1 year
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Number of Patients Diagnosed With Early BC and Metastatic BC by Year of Diagnosis
Time Frame: 3 years
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3 years
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Number of Patients Diagnosed with Early BC and Metastatic BC by Geographical Region
Time Frame: 3 years
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3 years
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Number of Metastatic BC Patients by First-line Chemotherapy and Age Group
Time Frame: Up to approximately 7 years and 10 months
|
Treatments were categorized as anthracycline with taxane, anthracycline without taxane, taxane without anthracycline, CDK4/6i, and other.
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Up to approximately 7 years and 10 months
|
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Number of Metastatic BC Patients by First-line Chemotherapy and Ethnicity
Time Frame: Up to approximately 7 years and 10 months
|
Treatments were categorized as anthracycline with taxane, anthracycline without taxane, taxane without anthracycline, CDK4/6i, and other.
|
Up to approximately 7 years and 10 months
|
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Number of Metastatic BC Patients by First-line Chemotherapy and Deprivation Quintile
Time Frame: Up to approximately 7 years and 10 months
|
Deprivation quintiles ranged from 1 (least deprived) to 5 (most deprived).
Treatments were categorized as anthracycline with taxane, anthracycline without taxane, taxane without anthracycline, CDK4/6i, and other.
|
Up to approximately 7 years and 10 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of Patients by Demographic Category
Time Frame: Baseline
|
Demographics included:
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Baseline
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Number of Patients by Clinical Characteristic Category
Time Frame: Baseline
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Clinical characteristics include:
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Baseline
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Time From First Early BC Diagnosis to Metastatic BC Diagnosis
Time Frame: Up to approximately 10 years and 7 months
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Up to approximately 10 years and 7 months
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Number of Early BC Patients who Discontinued Treatment Within 6 Months of Treatment Initiation
Time Frame: 6 months
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6 months
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Number of Early BC Patients by Reason for Discontinuing Treatment Within 6 Months of Treatment Initiation
Time Frame: 6 months
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6 months
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Number of Patients Adherent to Treatment Among Early BC Patients who Progressed to Metastatic BC
Time Frame: Up to approximately 12 years and 7 months
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Patients were considered adherent when the number of completed treatment cycles was greater than or equal to the number of planned treatment cycles per patient.
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Up to approximately 12 years and 7 months
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Number of Patients With Metastatic BC Treated With a CDK4/6i
Time Frame: Up to approximately 7 years and 10 months
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CDK4/6is included ribociclib, palbociclib and abemaciclib.
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Up to approximately 7 years and 10 months
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Time From Metastatic BC Diagnosis to Initiation of CDK4/6i Treatment
Time Frame: Up to approximately 7 years and 10 months
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CDK4/6is included ribociclib, palbociclib and abemaciclib.
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Up to approximately 7 years and 10 months
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Duration of CDK4/6i Treatment Among Patients With Metastatic BC
Time Frame: Up to approximately 7 years and 10 months
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CDK4/6is included ribociclib, palbociclib and abemaciclib.
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Up to approximately 7 years and 10 months
|
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Number of Patients With Metastatic BC Treated With a CDK4/6i who Received Electrocardiograms (ECGs) Outside of Standard of Care Recommendations
Time Frame: Up to approximately 7 years and 10 months
|
CDK4/6is included ribociclib, palbociclib and abemaciclib.
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Up to approximately 7 years and 10 months
|
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Hazard Ratio for Factors Associated With Progression Free Survival (PFS) Among Patients With HR+/HER2- BC
Time Frame: Up to approximately 12 years and 7 months
|
Factors included age group, ethnicity, deprivation quintile, geographical region, and first LOT. PFS for early BC patients was defined as the time from date of first breast surgery (or diagnosis if no surgery) until the earliest of: new surgical procedures (breast surgery); change in category A SACT treatment or new radiotherapy at least 3 months after initial surgery (or diagnosis if no surgery); non-metastatic recurrence, metastatic recurrence, death. PFS for metastatic BC patients was defined as the time from date of diagnosis with metastatic BC until the earliest of: change in category A SACT treatment or new radiotherapy at least 3 months after diagnosis with metastatic BC; a new metastasis record after diagnosis with metastatic BC; death. Category A treatment classes were categorized as anthracycline without taxane, taxane without anthracycline, anthracycline with taxane, CDK4/6i, and other. |
Up to approximately 12 years and 7 months
|
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Odds Ratio for Factors Associated With Timeliness of Initiating Treatment Following Metastatic BC Diagnosis
Time Frame: Up to approximately 12 years and 7 months
|
Factors included age group, ethnicity, deprivation quintile, and geographical region.
Timeliness of treatment was defined as having received treatment within 31 days of decision to treat for metastatic BC diagnosis.
|
Up to approximately 12 years and 7 months
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Odds Ratio for Factors Associated With Metastatic Status at First Presentation
Time Frame: Up to approximately 12 years and 7 months
|
Factors included age group, ethnicity, deprivation quintile, and geographical region.
Metastatic status at first presentation was defined as de novo or progressed metastatic disease.
|
Up to approximately 12 years and 7 months
|
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Number of Metastatic BC Patients Treated With a CDK4/6i by Number of Dose Reductions Experienced
Time Frame: Up to approximately 7 years and 10 months
|
CDK4/6is included ribociclib, palbociclib, or abemaciclib.
|
Up to approximately 7 years and 10 months
|
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Length of CDK4/6i Treatment for Patients With Metastatic BC by Number of Dose Reductions
Time Frame: Up to approximately 7 years and 10 months
|
CDK4/6is included ribociclib, palbociclib, or abemaciclib.
|
Up to approximately 7 years and 10 months
|
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Number of CDK4/6i Treatment Cycles Received Before a Dose Reduction
Time Frame: Up to approximately 7 years and 10 months
|
CDK4/6is included ribociclib, palbociclib, or abemaciclib.
A treatment cycle is 28 days.
|
Up to approximately 7 years and 10 months
|
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Cost Associated With CDK4/6i Wastage due to Dose Reduction
Time Frame: Up to approximately 7 years and 10 months
|
CDK4/6is included ribociclib, palbociclib, or abemaciclib.
|
Up to approximately 7 years and 10 months
|
|
Number of Metastatic BC Patients who Switched CDK4/6i Categorized by the Treatment Patients Switched From and To
Time Frame: Up to approximately 7 years and 10 months
|
CDK4/6is included ribociclib, palbociclib, or abemaciclib.
|
Up to approximately 7 years and 10 months
|
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Number of Patients by All-cause Healthcare Admission and Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Healthcare admissions included inpatient admissions, outpatient appointments, and emergency care visits. Health states:
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Up to approximately 12 years and 7 months
|
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Number of All-cause Healthcare Admissions per Patient per Month (PPPM) by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Healthcare admissions included inpatient admissions, outpatient appointments, and emergency care visits. Health states:
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Up to approximately 12 years and 7 months
|
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Number of BC-related Healthcare Admissions PPPM by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
BC-related healthcare admissions included inpatient admissions and outpatient appointments. Health states:
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Up to approximately 12 years and 7 months
|
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Number of Inpatient Bed Days PPPM by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Health states:
|
Up to approximately 12 years and 7 months
|
|
Number of Patients by Toxicity-related Inpatient Admission and Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Toxicity-related admissions were defined as those with a record of a chemotherapy side effect, including but not limited to neutropenic sepsis, cardiotoxicity and arrhythmia, diarrhea and vomiting causing dehydration requiring admission to hospital, and fragility fractures. Health states:
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Up to approximately 12 years and 7 months
|
|
Number of Patients by Toxicity-related Outpatient Appointment and Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Toxicity-related care was defined as an outpatient appointment with a specialty that corresponds to the specified toxicity, including but not limited to cardiology, gastroenterology, and rheumatology or orthopedic surgery. Health states:
|
Up to approximately 12 years and 7 months
|
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Number of Toxicity-related Inpatient Admissions PPPM by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Toxicity-related admissions were defined as those with a record of a chemotherapy side effect, including but not limited to neutropenic sepsis, cardiotoxicity and arrhythmia, diarrhea and vomiting causing dehydration requiring admission to hospital, and fragility fractures. Health states:
|
Up to approximately 12 years and 7 months
|
|
Number of Toxicity-related Outpatient Appointments PPPM by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Toxicity-related care was defined as an outpatient appointment with a specialty that corresponds to the specified toxicity, including but not limited to cardiology, gastroenterology, and rheumatology or orthopedic surgery. Health states:
|
Up to approximately 12 years and 7 months
|
|
Median Cost PPPM of All-cause Healthcare Admissions by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Healthcare admissions included inpatient admissions, outpatient appointments, and emergency care visits. Health states:
|
Up to approximately 12 years and 7 months
|
|
Median Cost PPPM of BC-related Healthcare Admissions by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
BC-related healthcare admissions included inpatient admissions and outpatient appointments. Health states:
|
Up to approximately 12 years and 7 months
|
|
Median Cost PPPM of Toxicity-related Inpatient Admissions by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Toxicity-related admissions were defined as those with a record of a chemotherapy side effect, including but not limited to neutropenic sepsis, cardiotoxicity and arrhythmia, diarrhea and vomiting causing dehydration requiring admission to hospital, and fragility fractures. Health states:
|
Up to approximately 12 years and 7 months
|
|
Median Cost PPPM of Toxicity-related Outpatient Appointments by Health State Transition
Time Frame: Up to approximately 12 years and 7 months
|
Toxicity-related care was defined as an outpatient appointment with a specialty that corresponds to the specified toxicity, including but not limited to cardiology, gastroenterology, and rheumatology or orthopedic surgery. Health states:
|
Up to approximately 12 years and 7 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 8, 2023
Primary Completion (Actual)
July 18, 2025
Study Completion (Actual)
July 18, 2025
Study Registration Dates
First Submitted
March 23, 2026
First Submitted That Met QC Criteria
March 23, 2026
First Posted (Actual)
March 27, 2026
Study Record Updates
Last Update Posted (Actual)
April 1, 2026
Last Update Submitted That Met QC Criteria
March 27, 2026
Last Verified
March 1, 2026
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLEE011AGB02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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