Clinical trial NCT05870813: CLEAR-B: Cancer Landscape - Early Adjuvant Retrospective Registry - Breast Cancer
Official title: Cancer Landscape - Early Adjuvant Retrospective Registry - Breast Cancer (CLEAR-B)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Cancer
HER2-negative Breast Cancer
Hormone Receptor Positive Breast Carcinoma
Lead sponsor: Institut fuer Frauengesundheit
Sponsor class: OTHER
Collaborators: name: AGO Breast Study Group e.V.
name: Novartis Pharmaceuticals
First posted: 2023-05-23
Enrollment: 3000
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Premenopausal patients with early-stage breast cancer who have been diagnosed from January 2016 to June 2019 with an intermediate or high recurrence risk in a certified breast cancer center (DKG/DGS).

Brief summary: This is a non-interventional retrospective cohort study of premenopausal patients with HR+/HER2- breast cancer who are treated in the adjuvant setting with either Tamoxifen, Tamoxifen + Ovarial Function Suppression or Aromatase inhibitor + Ovarial Function Suppression.

Detailed description: The treatment landscape concerning the adjuvant endocrine therapy in premenopausal patients with early-stage hormone receptor positive (HRpos) breast cancer is quite heterogeneous and therapy recommendations can vary. Tamoxifen (TAM) is a common treatment option that does not require OFS, but research suggests that adding OFS to tamoxifen may improve outcomes. Aromatase inhibitors (AI) are another option, but they can only be used with OFS for premenopausal patients. Studies have shown that AI + OFS improves disease-free survival compared to TAM + OFS, but it may lead to additional side effects such as osteopenia and bone fractures.

The CLEAR-B study aims to provide a detailed description of the therapy landscape in this therapeutic setting, including recurrence rates and overall survival with AI compared to TAM, as well as a comparison of the chosen therapies within prognostic subgroups.

CLEAR-B is a retrospective cohort study, collecting data of premenopausal patients who were diagnosed with early-stage breast cancer between January 2016 and June 2019 in a certified breast cancer center. These patients had an intermediate or high risk of cancer recurrence, as defined by (neo)adjuvant chemotherapy, and/or pT≥2cm at the timepoint of definitive surgery and/or at least one positive lymph node at the time of definite surgery (pN+).

The primary objective is to compare the invasive disease-free survival (iDFS) of patients who were treated with AI + OFS vs. those who were treated with TAM ± OFS. Additionally, the study will compare distant disease-free survival (DDFS) and overall survival (OS) between the two groups and perform subgroup analyses according to risk stratification (stage II and III). This study will be conducted at around 75 certified breast cancer centers and will enroll up to 3000 patients.

Eligibility criteria: Inclusion Criteria:

* Female patients with a first primary diagnosis of hormone receptor-positive, HER2- negative unilateral early breast cancer for whom an endocrine treatment is indicated
* Patients must be at least 18 years of age but not older than 60
* Premenopausal defined as all statements must be true

  * No oophorectomy before the diagnosis of breast cancer
  * Women with uterus: Regular, physiological menses at the timepoint of therapy decision for anti-endocrine treatment in the absence of contraceptives and hormonal treatment
  * Women without uterus and remaining ovaries: premenopausal hormone levels must be documented at the time of therapy decision for anti-endocrine treatment
* Patients with an intermediate or high-risk early-stage breast cancer defined as: At least one of the following must be fulfilled

  * (Neo)adjuvant chemotherapy
  * pT≥2cm at the timepoint of definitive surgery
  * at least one positive lymph node at the time of definite surgery (pN+)
* Patient must be previously registered in and must have been documented as part of the certification process for a certified breast cancer center according to the Deutsche Krebsgesellschaft/Deutsche Gesellschaft für Senologie
* Breast Cancer must have been diagnosed between Jan 2016 and Jun 2019

Exclusion Criteria:

* Patients with a low recurrence risk (see inclusion criteria for definition)
* Locally advanced breast cancer or distant metastases at diagnosis
* Male biological sex
* Patients not treated in a certified breast cancer center
* Treatment with CDK4/6Previous diagnosis of invasive breast cancer or in situ breast cancer
* Concurrent invasive malignancy
* Bilateral breast cancer at the timepoint of diagnosis
* Previous diagnosis of invasive breast cancer or in situ breast cancer is not allowed

Primary outcomes:
measure: iDFS
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of iDFS
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Secondary outcomes:
measure: Comparison of DDFS
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of OS
timeFrame: First start of adjuvant endocrine therapy until date of death up to 5 years
measure: Comparison of iDFS in Cohort TAM
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of DDFS in Cohort TAM
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of OS in Cohort TAM
timeFrame: First start of adjuvant endocrine therapy until date of death up to 5 years
measure: Comparison of iDFS (TAM+OFS and AI+OFS)
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of DDFS (TAM+OFS and AI+OFS)
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of OS (TAM+OFS and AI+OFS)
timeFrame: First start of adjuvant endocrine therapy until date of death up to 5 years
measure: Comparison of iDFS (TAM-OFS and AI+OFS)
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of DDFS (TAM-OFS and AI+OFS)
timeFrame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
measure: Comparison of OS (TAM-OFS and AI+OFS)
timeFrame: First start of adjuvant endocrine therapy until date of death up to 5 years
measure: Influence of disease stage
timeFrame: Baseline until onset of disease progression or death up to 5 years
measure: Risk Factors
timeFrame: Baseline until onset of disease progression or death up to 5 years
measure: NATALEE Comparison
timeFrame: Baseline until onset of disease progression or death up to 5 years
Other outcomes:
measure: Therapy frequencies
timeFrame: Baseline
measure: Adherence
timeFrame: End of Treatment/ Treatment termination up to 5 years
Locations:
city: Erlangen
country: Germany
facility: Department of Gynecology and Obstetrics, Erlangen University Hospital
Study officials:
References: