PROOFS-Registry - Premenopausal Women With Breast Cancer Optimally Treated With OFS

Sponsor

West German Study Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT05792150

Collaborator

Agendia (Industry)

1,470

Enrollment

Locations

149.8

Anticipated Duration (Months)

294

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is only limited data for premenopausal patients in general, as well as for differences in the use of OFS in the subgroups of pre- and perimenopausal patients, respectively. The WSG ADAPT trial data on the impact of postmenopausal status and/or use of OFS within 3-4 weeks endocrine induction therapy show relevant impact of OFS/postmenopausal status on Ki-67 response; also, secondary amenorrhea after (neo-)adjuvant chemotherapy was a positive predictor of outcome due to OFS [8, 9].

This registry will give insights in the real-world use of OFS and the effect of secondary amenorrhea in female pre- and perimenopausal patients with or without previous use of chemotherapy and with different endocrine treatments (ET +/- GnRH).

As adherence over time (5-10 years) plays a major role in the endocrine treatment, the registry will follow patients' treatments for up to 10 years and include QoL information.

Results of MammaPrint® (MammaPrint® Index) as indicating factor for chemotherapy use and risk classification, thus, choice of adjuvant treatment (chemotherapy, OFS combined with endocrine therapy, or endocrine therapy alone) will be correlated to outcome under real-world conditions.

Baseline, treatment, and relapse data shall be collected to gain further insight in the treatment paths, treatment adherence, and outcome of such patients.

Condition or Disease	Intervention/Treatment	Phase
Female Breast Cancer

Detailed Description

This registry aims

to confirm an excellent outcome in pre-/perimenopausal patients treated by endocrine therapy (+ ovarian suppression) in patients with low genomic risk by MammaPrint® without chemotherapy use in a real-world setting.
to evaluate management of ovarian function in patients treated by adjuvant chemotherapy according to investigator decision.
to evaluate adherence to endocrine therapy (+/- ovarian function suppression).
to evaluate the prognostic impact of clinicopathological markers (e.g., estrogen receptor (ER), progesterone receptor (PR), HER2 receptor, Ki-67 at baseline and after preoperative endocrine therapy (if any performed) by local pathology assessment compared to genomic signature result.
to assess the course of quality of life (QLQ BR23 and QLQ-C30) until 5 years of treatment with OFS (Baseline, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, 5 years)

In general, WSG aim to assess the quality of surveillance care in younger breast cancer patients. WSG want to gain knowledge about endocrine induction treatment for indication of chemotherapy followed by endocrine treatment or endocrine treatment alone. Also, WSG aim at changes in duration of endocrine treatment (especially in high-risk patients up to 10 years) and introduction of intensified endocrine therapy (OFS) in combination with GnRH-analogues since publication of the SOFT and TEXT trials.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1470 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Real World Data and Long-term FU of Pre-/Perimenopausal Women With Luminal EBC With Intermediate to High Clinical and Low Genomic Recurrence-risk Measured by MammaPrint®, Treated by SOC ET+OFS or SOC Chemotherapy Treatment Followed by ET

Actual Study Start Date :

Dec 7, 2022

Anticipated Primary Completion Date :

Mar 1, 2035

Anticipated Study Completion Date :

Jun 1, 2035

Outcome Measures

Primary Outcome Measures

5-year distant recurrence-free interval (dRFI, according to STEEP criteria version 2.0) [5 years]
dRFIin all patients treated by (intensified) endocrine therapy alone (and with ovarian suppression in cases with enhanced clinical risk according to current AGO-recommendations)

Secondary Outcome Measures

10-year dRFI [10 years]
dRFI, according to STEEP criteria 2.0, in all patients treated by (intensified) endocrine therapy alone (with ovarian suppression in cases with higher clinical risk)
5-year dRFI [5 years]
dRFI, according to STEEP criteria 2.0,in all patients treated by SOC chemotherapy treatment followed by ET+/-OFS
10-year dRFI [10 years]
dRFI, according to STEEP criteria 2.0,in all patients treated by SOC chemotherapy treatment followed by ET+/-OFS
5-year dDFS [5 years]
distant disease-free survival (dDFS, according to STEEP 2.0) in all patients and all treatment groups (i.e., patients treated by ET alone, ET + GnRH, chemotherapy followed by ET, chemotherapy followed by ET + GnRH, OFS-treated patients)
10-year dDFS [10 years]
distant disease-free survival (dDFS, according to STEEP 2.0) in all patients and all treatment groups (i.e., patients treated by ET alone, ET + GnRH, chemotherapy followed by ET, chemotherapy followed by ET + GnRH, OFS-treated patients)treatment followed by ET+/-OFS
5-year OS [5 years]
overall survival (OS) in all patients and all treatment groups
10-year OS [10 years]
overall survival (OS) in all patients and all treatment groups
5-year breast cancer-free interval (BCFI, according to STEEP 2.0) [5 years]
BCFI in all patients and all treatment groups
10-year breast cancer-free interval (BCFI, according to STEEP 2.0) [10 years]
BCFI in all patients and all treatment groups
EORTC quality of life questionnaire BR23 [every 3 months within 1st year]
compare the course of Qol between baseline and further defined timepoints; 23 items, symptom scales/items and functional scales/items, all of the scales and single-item measures range in score from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning, whilst a high score for the symptom scales represents a high level of symptomatology or problems.
EORTC quality of life questionnaire C30 [every 3 months within 1st year]
compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.
EORTC quality of life questionnaire BR23 [every 6 months within 2nd year]
compare the course of Qol between baseline and further defined timepoints; 23 items, symptom scales/items and functional scales/items, all of the scales and single-item measures range in score from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning, whilst a high score for the symptom scales represents a high level of symptomatology or problems.
EORTC quality of life questionnaire C30 [every 6 months within 2nd year]
compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.
EORTC quality of life questionnaire BR23 [yearly until 5 years]
compare the course of Qol between baseline and further defined timepoints; 23 items, symptom scales/items and functional scales/items, all of the scales and single-item measures range in score from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning, whilst a high score for the symptom scales represents a high level of symptomatology or problems.
EORTC quality of life questionnaire C30 [yearly until 5 years]
compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.
adherence to OFS and endocrine treatment [10 years]
Duration of intake of OFS and endocrine treatment in all patients
concordance between BluePrint®/MammaPrint® molecular subtyping results vs. pathological immune-histochemistry results [10 years]
concordance between BluePrint®/MammaPrint® molecular subtyping results and pathological immune-histochemistry results with respect to tumour type
endocrine response measured by post-endocrine Ki-67 [10 years]
post-endocrine Ki-67 (≤10% and/or relative change vs. baseline) in patients treated by preoperative ET
5-year iDFS in node-negative patients with ultralow MammaPrint [5 years]
node-negative patients with ultralow MammaPrint® treated by shorter duration of ET (2-3 years at investigator decision)
10-year iDFS in node-negative patients with ultralow MammaPrint [10 years]
node-negative patients with ultralow MammaPrint® treated by shorter duration of ET (2-3 years at investigator decision)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients are eligible for participation in the registry only if they meet all the following criteria:

Female breast cancer patients
Pre- or perimenopausal at registry entry (age <60 years and state after hysterectomy or amenorrhea for <12 months; confirmation by blood hormone levels (FSH and estradiol in premenopausal range as per local normal range) recommended)
Primary tumor diagnosis not older than three months prior to inclusion (primary diagnosis defined as date of initial tumor biopsy)
Estrogen- and/or progesterone-receptor-positive/HER2 negative early breast cancer without any clinical signs of metastases
Adequate risk for recurrence:
intermediate clinical risk for recurrence, defined as (clinical in case of neoadjuvant treatment):
c/pT1 and
c/pN0 and
Ki-67 15-24% or
G2 or
patients, who do not meet these criteria but are at intermediate clinical risk for recurrence at investigator decision (e.g., very young age, low expression of hormone receptors, existing co-morbidities, familial cancer burden, etc.) can be included on individual decision basis or
high clinical risk for recurrence, defined as either (clinical in case of neoadjuvant treatment):
c/pT2-4 or
c/pN1 or
Ki-67 ≥25% or
G3
Low genomic risk of recurrence by MammaPrint® (tested on treatment naïve tumor specimen)
Luminal-type by BluePrint®
Treatment according to standard-of-care (e.g., AGO Guidelines) planned or started (until completion of local therapy the latest (including started or completed endocrine induction therapy), started, or planned adjuvant or neoadjuvant treatment)
Availability of untreated tumor material (core biopsy if preoperative endocrine therapy performed or neoadjuvant treatment intended or surgery specimen)
Capability to give written informed consent
Nodal positive patients will be accepted to the registry up to 25% of the genomic low/ultralow-risk population (n=441).

Exclusion Criteria:

Patients will not be eligible for the registry for any of the following reasons:

Any other genomic testing, besides MammaPrint®, has been performed on the tumor material
Medical or psychological conditions that would not permit the patient to sign informed consent
Legal incapacity or limited legal capacity
Current participation in any interventional clinical trial which tests anticancer drugs, immunotherapeutics, or antibody treatment for any type of neoplasm
Non-compliance of the patient

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus	Moenchengladbach	NRW	Germany	41061
2	Marienhospital, Klinik für Gynäkologie und Geburtshilfe	Bottrop		Germany
3	Helios Klinikum Krefeld, Zentrum für Ambulante Gynäkologische Onkologie - Studienabteilung	Krefeld		Germany
4	MKS St. Paulus Schwerte (ehemals Marienkrankenhaus)	Schwerte		Germany
5	Klinikum Traunstein, Frauenklinik Südostbayern	Traunstein		Germany

Sponsors and Collaborators

West German Study Group
Agendia

Investigators

Principal Investigator: Oleg Gluz, PD Dr., Westdeutsche Studiengruppe GmbH
Principal Investigator: Rachelq Wuerstlein, Prof. Dr., Westdeutsche Studiengruppe GmbH
Study Director: Monika Graeser, PD Dr., Westdeutsche Studiengruppe GmbH
Principal Investigator: Nadia Harbeck, Prof. Dr., LMU Clinics, Breast Centre and CCC
Principal Investigator: Sherko Kuemmel, Prof. Dr., KEM, Clinics Essen-Mitte
Study Director: Ulrike Nitz, Prof. Dr., Westdeutsche Studiengruppe GmbH
Principal Investigator: Andreas Hartkopf, Prof. Dr., Univewrsity Hospital Tuebingen