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

Recruiting

• Conditions: Female Breast Cancer

• Registration Number: NCT05792150
• Lead Sponsor: West German Study Group

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.

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 Timeline

• Study Start: 2022-12-07
• Study First Submitted: 2023-02-13
• Study First Submitted QC: 2023-03-30
• Study First Posted: 2023-03-31
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-11
• Last Update Posted: 2024-11-12
• Primary Completion: 2035-03
• Study Completion: 2035-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 1470

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
10-year breast cancer-free interval (BCFI, according to STEEP 2.0)	10 years	BCFI in all patients and all treatment groups
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
adherence to OFS and endocrine treatment	10 years	Duration of intake of OFS and endocrine treatment in all patients
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
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)
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 dRFI	5 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)
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
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.
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
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.
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)

Trial Locations

Locations (32)

ViDia Christliche Kliniken Karlsruhe; 🇩🇪 Karlsruhe, Baden-Wüttemberg, Germany

Studienzentrum Onkologie Ravensburg; 🇩🇪 Ravensburg, Baden-Wüttemberg, Germany

Med. Zentrum f. Hämatologie und Onkologie München; 🇩🇪 München, Bayern, Germany

Klinikum St. Marien Amberg; 🇩🇪 Amberg, Bayern, Germany

Klinikum der Universität München; 🇩🇪 München, Bayern, Germany

Klinikum Hanau GmbH; 🇩🇪 Hanau, Hessen, Germany

Klinikum Südstadt; 🇩🇪 Rostock, Mecklenburg-Vorpommern, Germany

St. Josefs-Hospital Wiesbaden GmbH; 🇩🇪 Wiesbaden, Hessen, Germany

Marienhospital Aachen; 🇩🇪 Aachen, NRW, Germany

Universitätsklinikum Bonn Frauenheilkunde; 🇩🇪 Bonn, NRW, Germany

Gynäkologisches Zentrum; 🇩🇪 Bonn, NRW, Germany

St. Vincenz-Krankenhaus Datteln; 🇩🇪 Datteln, NRW, Germany

Kliniken der Stadt Köln; 🇩🇪 Köln, NRW, Germany

Marien Hospital Düsseldorf; 🇩🇪 Düsseldorf, NRW, Germany

Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus; 🇩🇪 Moenchengladbach, NRW, Germany

Luisenkrankenhaus GmbH Co KG; 🇩🇪 Düsseldorf, NRW, Germany

Mathias-Spital-Rheine; 🇩🇪 Rheine, NRW, Germany

Praxisnetzwerk Hämatologie/int. Onkologie; 🇩🇪 Troisdorf, NRW, Germany

Christliches Klinikum Unna gGmbH; 🇩🇪 Unna, NRW, Germany

Evangelisches Krankenhaus Wesel GmbH; 🇩🇪 Wesel, NRW, Germany

Helios Klinikum Wuppertal; 🇩🇪 Wuppertal, NRW, Germany

DRK Kliniken Berlin Köpenick; 🇩🇪 Berlin, Germany

DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH; 🇩🇪 Bremen, Germany

Klinikum Worms; 🇩🇪 Worms, Rheinland-Pfalz, Germany

Medionko - Praxisklinik Krebsheilkunde Frauen; 🇩🇪 Berlin, Germany

Marienhospital, Klinik für Gynäkologie und Geburtshilfe; 🇩🇪 Bottrop, Germany

AGAPLESION Diakonie Hamburg; 🇩🇪 Hamburg, Germany

Gynäkologische Praxisklinik Hamburg-Harburg; 🇩🇪 Hamburg, Germany

Asklepios Klinik Barmbek; 🇩🇪 Hamburg, Germany

Helios Klinikum Krefeld, Zentrum für Ambulante Gynäkologische Onkologie - Studienabteilung; 🇩🇪 Krefeld, Germany

MKS St. Paulus Schwerte (ehemals Marienkrankenhaus); 🇩🇪 Schwerte, Germany

Klinikum Traunstein, Frauenklinik Südostbayern; 🇩🇪 Traunstein, Germany