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

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

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.

Study Overview

• Status: Recruiting
• Conditions: 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 Type: Observational
• Enrollment (Estimated): 1470

Contacts and Locations

• Study Contact: Name: Anja Braschoss, MD; Phone Number: 04917682119153; Email: anja.braschoss@wsg-online.com
• Study Contact Backup: Name: Julian Moellers; Phone Number: 00492161566 23-0; Email: julian.moellers@wsg-online.com

Study Locations

• Germany
  • Berlin, Germany, 10367
    • Recruiting
    • Medionko - Praxisklinik Krebsheilkunde Frauen
    • Contact: Gülten Oskay-Özcelik, PD Dr. med.
    • Contact: Alena Keil
  • Berlin, Germany, 12559
    • Recruiting
    • DRK Kliniken Berlin Köpenick
    • Contact: Anke Kleine-Tebbe, Dr. med.
    • Contact: Manuela Rösler
  • Bottrop, Germany
    • Recruiting
    • Marienhospital, Klinik für Gynäkologie und Geburtshilfe
    • Contact: Hans-Christian Kolberg, PD Dr.
    • Contact: Katharina Freienstein
  • Bremen, Germany, 28239
    • Recruiting
    • DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH
    • Contact: Karen Wimmer-Freys, Dr.
    • Contact: Stina Eckardt
  • Hamburg, Germany, 20259
    • Recruiting
    • AGAPLESION Diakonie Hamburg
    • Contact: Mustafa Celalettin Ugur, Dr.
    • Contact: Mirjam Ahrens
  • Hamburg, Germany, 21073
    • Recruiting
    • Gynäkologische Praxisklinik Hamburg-Harburg
    • Contact: Christoph Großmann, Dr. med.
    • Contact: Belma Salihadgic
  • Hamburg, Germany, 22307
    • Recruiting
    • Asklepios Klinik Barmbek
    • Contact: Katharina Maria Seiffert, Dr.med.
    • Contact: Sabine Drießelmann
  • Krefeld, Germany
    • Recruiting
    • Helios Klinikum Krefeld, Zentrum für Ambulante Gynäkologische Onkologie - Studienabteilung
    • Contact: Gunther Rogmans, Dr.
    • Contact: Gerswin Garcia
  • Schwerte, Germany
    • Recruiting
    • MKS St. Paulus Schwerte (ehemals Marienkrankenhaus)
    • Contact: Sarah Wetzig
    • Contact: Kristin Backhaus
  • Traunstein, Germany
    • Recruiting
    • Klinikum Traunstein, Frauenklinik Südostbayern
    • Contact: Christian Schindlbeck, Prof. Dr.
    • Contact: Ursula Ghasemi
  • Baden-Wüttemberg
    • Karlsruhe, Baden-Wüttemberg, Germany, 76135
      • Recruiting
      • ViDia Christliche Kliniken Karlsruhe
      • Contact: Oliver Tomé, Dr.
    • Ravensburg, Baden-Wüttemberg, Germany, 88212
      • Recruiting
      • Studienzentrum Onkologie Ravensburg
      • Contact: Thomas Decker, Prof. Dr.med
      • Contact: Irina Gossen
  • Bayern
    • Amberg, Bayern, Germany, 9224
      • Recruiting
      • Klinikum St. Marien Amberg
      • Contact: Tanja Hauzenberger, Dr. med
      • Contact: Jacqueline Roy
    • München, Bayern, Germany, 80336
      • Recruiting
      • Klinikum der Universität München
      • Contact: Nadia Harbeck, Prof. Dr.
      • Contact: Beate Rank
    • München, Bayern, Germany, 80639
      • Recruiting
      • Med. Zentrum f. Hämatologie und Onkologie München
      • Contact: Oliver Stötzer, PD Dr.
      • Contact: Heike Fengler
  • Hessen
    • Hanau, Hessen, Germany, 63450
      • Recruiting
      • Klinikum Hanau GmbH
      • Contact: Thomas Müller, Prof. Dr.
      • Contact: Violeta Fricker
    • Wiesbaden, Hessen, Germany, 65189
      • Recruiting
      • St. Josefs-Hospital Wiesbaden GmbH
      • Contact: Antje Lehnert, Dr. med.
      • Contact: Andrea Lunkenheimer
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18059
      • Recruiting
      • Klinikum Südstadt
      • Contact: Juliane Terpe-Weiland, Dr. med.
      • Contact: Michaela Stecher
  • NRW
    • Aachen, NRW, Germany, 52066
      • Recruiting
      • Marienhospital Aachen
      • Contact: Mahmoud Danaei, Dr.
      • Contact: Birgit Dreyer
    • Bonn, NRW, Germany, 53111
      • Recruiting
      • Gynäkologisches Zentrum
      • Contact: Christian Kurbacher, PD Dr. med
      • Contact: Andrea Kremer- Heß
    • Bonn, NRW, Germany, 53127
      • Recruiting
      • Universitätsklinikum Bonn Frauenheilkunde
      • Contact: Anne Bachmann
      • Contact: Sigrid Clade
    • Datteln, NRW, Germany, 45711
      • Recruiting
      • St. Vincenz-Krankenhaus Datteln
      • Contact: Ayoub Abdu, Dr. med.
      • Contact: Silvia Schneider
    • Düsseldorf, NRW, Germany, 40235
      • Recruiting
      • Luisenkrankenhaus GmbH Co KG
      • Contact: Athina Kostara, Dr. med.
      • Contact: Anne Huelsewiesche
    • Düsseldorf, NRW, Germany, 40479
      • Recruiting
      • Marien Hospital Dusseldorf
      • Contact: Jens-Peter Kruse
      • Contact: David Tschirch
    • Köln, NRW, Germany, 51067
      • Recruiting
      • Kliniken der Stadt Koln
      • Contact: Lotta Fischer, Dr.
      • Contact: Claudia Weise
    • Moenchengladbach, NRW, Germany, 41061
      • Recruiting
      • Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus
      • Principal Investigator: Oleg Gluz, PD Dr.
      • Contact: Oleg Gluz, PD. Dr. med.; Email: oleg.gluz@wsg-online.com
      • Contact: Iris Scheffen, Dr. med.; Email: iris.scheffen@wsg-online.com
    • Rheine, NRW, Germany, 48431
      • Recruiting
      • Mathias-Spital-Rheine
      • Contact: Sebastian Bröckling, Dr. med.
      • Contact: Denise Ernst
    • Troisdorf, NRW, Germany, 53840
      • Recruiting
      • Praxisnetzwerk Hämatologie/int. Onkologie
      • Contact: Helmut Forstbauer, Dr. med.
      • Contact: Sarah Wackerow
    • Unna, NRW, Germany, 59423
      • Recruiting
      • Christliches Klinikum Unna gGmbH
      • Contact: Cristin Kühn, Dr. med.
      • Contact: Vanessa Schuster
    • Wesel, NRW, Germany, 46485
      • Recruiting
      • Evangelisches Krankenhaus Wesel GmbH
      • Contact: Daniela Rezek, Dr. med.
      • Contact: Aniela Klonowski
    • Wuppertal, NRW, Germany, 42283
      • Recruiting
      • Helios Klinikum Wuppertal
      • Contact: Vesna Bjelic-Radisic, Prof. Dr.
      • Contact: Manuela Smiljanic
  • Rheinland-Pfalz
    • Worms, Rheinland-Pfalz, Germany, 67550
      • Recruiting
      • Klinikum Worms
      • Contact: Antje Nixdorf, Dr. med.
      • Contact: Tanja Knoll

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

For this registry, it is planned to screen N=3000 pre- and perimenopausal patients with early breast cancer who meet the inclusion criteria, i.e., intermediate to high clinical risk for recurrence, and who will receive or have received a routine genomic testing by MammaPrint® with a low/ultralow genomic risk.

It is anticipated that 75% of these patients will be nodal negative and 25% nodal positive.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
10-year dRFI	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)	10 years
5-year dRFI	dRFI, according to STEEP criteria 2.0,in all patients treated by SOC chemotherapy treatment followed by ET+/-OFS	5 years
10-year dRFI	dRFI, according to STEEP criteria 2.0,in all patients treated by SOC chemotherapy treatment followed by ET+/-OFS	10 years
5-year dDFS	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 years
10-year dDFS	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	10 years
5-year OS	overall survival (OS) in all patients and all treatment groups	5 years
10-year OS	overall survival (OS) in all patients and all treatment groups	10 years
5-year breast cancer-free interval (BCFI, according to STEEP 2.0)	BCFI in all patients and all treatment groups	5 years
10-year breast cancer-free interval (BCFI, according to STEEP 2.0)	BCFI in all patients and all treatment groups	10 years
EORTC quality of life questionnaire BR23	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.	every 3 months within 1st year
EORTC quality of life questionnaire C30	compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.	every 3 months within 1st year
EORTC quality of life questionnaire BR23	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.	every 6 months within 2nd year
EORTC quality of life questionnaire C30	compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.	every 6 months within 2nd year
EORTC quality of life questionnaire BR23	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.	yearly until 5 years
EORTC quality of life questionnaire C30	compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.	yearly until 5 years
adherence to OFS and endocrine treatment	Duration of intake of OFS and endocrine treatment in all patients	10 years
concordance between BluePrint®/MammaPrint® molecular subtyping results vs. pathological immune-histochemistry results	concordance between BluePrint®/MammaPrint® molecular subtyping results and pathological immune-histochemistry results with respect to tumour type	10 years
endocrine response measured by post-endocrine Ki-67	post-endocrine Ki-67 (≤10% and/or relative change vs. baseline) in patients treated by preoperative ET	10 years
5-year iDFS in node-negative patients with ultralow MammaPrint	node-negative patients with ultralow MammaPrint® treated by shorter duration of ET (2-3 years at investigator decision)	5 years
10-year iDFS in node-negative patients with ultralow MammaPrint	node-negative patients with ultralow MammaPrint® treated by shorter duration of ET (2-3 years at investigator decision)	10 years

Collaborators and Investigators

• Sponsor: West German Study Group
• Collaborators: Agendia
• Investigators: Principal Investigator: Oleg Gluz, PD 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; Principal Investigator: Rachel Wuerstlein, Prof. Dr., Westdeutsche Studiengruppe GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2022
• Primary Completion (Estimated): March 1, 2035
• Study Completion (Estimated): June 1, 2035

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: chemotherapy; HR+; female; HER2-; early breast cancer; EBC; ET; OFS
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: WSG-NIS04 / PROOFS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No