Clinical trial NCT05792150: PROOFS-Registry - Premenopausal Women With Breast Cancer Optimally Treated With OFS
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Female Breast Cancer
Keywords: HR+
HER2-
EBC
early breast cancer
female
OFS
ET
chemotherapy
Lead sponsor: West German Study Group
Sponsor class: OTHER
Collaborators: name: Agendia
First posted: 2023-03-31
Enrollment: 1470
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 5-year distant recurrence-free interval (dRFI, according to STEEP criteria version 2.0)
timeFrame: 5 years
Secondary outcomes:
measure: 10-year dRFI
timeFrame: 10 years
measure: 5-year dRFI
timeFrame: 5 years
measure: 10-year dRFI
timeFrame: 10 years
measure: 5-year dDFS
timeFrame: 5 years
measure: 10-year dDFS
timeFrame: 10 years
measure: 5-year OS
timeFrame: 5 years
measure: 10-year OS
timeFrame: 10 years
measure: 5-year breast cancer-free interval (BCFI, according to STEEP 2.0)
timeFrame: 5 years
measure: 10-year breast cancer-free interval (BCFI, according to STEEP 2.0)
timeFrame: 10 years
measure: EORTC quality of life questionnaire BR23
timeFrame: every 3 months within 1st year
measure: EORTC quality of life questionnaire C30
timeFrame: every 3 months within 1st year
measure: EORTC quality of life questionnaire BR23
timeFrame: every 6 months within 2nd year
measure: EORTC quality of life questionnaire C30
timeFrame: every 6 months within 2nd year
measure: EORTC quality of life questionnaire BR23
timeFrame: yearly until 5 years
measure: EORTC quality of life questionnaire C30
timeFrame: yearly until 5 years
measure: adherence to OFS and endocrine treatment
timeFrame: 10 years
measure: concordance between BluePrint®/MammaPrint® molecular subtyping results vs. pathological immune-histochemistry results
timeFrame: 10 years
measure: endocrine response measured by post-endocrine Ki-67
timeFrame: 10 years
measure: 5-year iDFS in node-negative patients with ultralow MammaPrint
timeFrame: 5 years
measure: 10-year iDFS in node-negative patients with ultralow MammaPrint
timeFrame: 10 years
Other outcomes:
Locations:
city: Karlsruhe
country: Germany
facility: ViDia Christliche Kliniken Karlsruhe
state: Baden-Wüttemberg
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie Ravensburg
state: Baden-Wüttemberg
city: Amberg
country: Germany
facility: Klinikum St. Marien Amberg
state: Bayern
city: München
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: München
country: Germany
facility: Med. Zentrum f. Hämatologie und Onkologie München
state: Bayern
city: Hanau
country: Germany
facility: Klinikum Hanau GmbH
state: Hessen
city: Wiesbaden
country: Germany
facility: St. Josefs-Hospital Wiesbaden GmbH
state: Hessen
city: Rostock
country: Germany
facility: Klinikum Südstadt
state: Mecklenburg-Vorpommern
city: Aachen
country: Germany
facility: Marienhospital Aachen
state: NRW
city: Bonn
country: Germany
facility: Gynäkologisches Zentrum
state: NRW
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn Frauenheilkunde
state: NRW
city: Datteln
country: Germany
facility: St. Vincenz-Krankenhaus Datteln
state: NRW
city: Düsseldorf
country: Germany
facility: Luisenkrankenhaus GmbH Co KG
state: NRW
city: Düsseldorf
country: Germany
facility: Marien Hospital Düsseldorf
state: NRW
city: Köln
country: Germany
facility: Kliniken der Stadt Köln
state: NRW
city: Moenchengladbach
country: Germany
facility: Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus
state: NRW
city: Rheine
country: Germany
facility: Mathias-Spital-Rheine
state: NRW
city: Troisdorf
country: Germany
facility: Praxisnetzwerk Hämatologie/int. Onkologie
state: NRW
city: Unna
country: Germany
facility: Christliches Klinikum Unna gGmbH
state: NRW
city: Wesel
country: Germany
facility: Evangelisches Krankenhaus Wesel GmbH
state: NRW
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal
state: NRW
city: Worms
country: Germany
facility: Klinikum Worms
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Medionko - Praxisklinik Krebsheilkunde Frauen
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Köpenick
city: Bottrop
country: Germany
facility: Marienhospital, Klinik für Gynäkologie und Geburtshilfe
city: Bremen
country: Germany
facility: DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH
city: Hamburg
country: Germany
facility: AGAPLESION Diakonie Hamburg
city: Hamburg
country: Germany
facility: Gynäkologische Praxisklinik Hamburg-Harburg
city: Hamburg
country: Germany
facility: Asklepios Klinik Barmbek
city: Krefeld
country: Germany
facility: Helios Klinikum Krefeld, Zentrum für Ambulante Gynäkologische Onkologie - Studienabteilung
city: Schwerte
country: Germany
facility: MKS St. Paulus Schwerte (ehemals Marienkrankenhaus)
city: Traunstein
country: Germany
facility: Klinikum Traunstein, Frauenklinik Südostbayern
Study officials:
affiliation: Westdeutsche Studiengruppe GmbH
name: Oleg Gluz, PD Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Westdeutsche Studiengruppe GmbH
name: Rachel Wuerstlein, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Westdeutsche Studiengruppe GmbH
name: Monika Graeser, PD Dr.
role: STUDY_DIRECTOR
affiliation: LMU Clinics, Breast Centre and CCC
name: Nadia Harbeck, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: KEM, Clinics Essen-Mitte
name: Sherko Kuemmel, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Westdeutsche Studiengruppe GmbH
name: Ulrike Nitz, Prof. Dr.
role: STUDY_DIRECTOR
affiliation: Univewrsity Hospital Tuebingen
name: Andreas Hartkopf, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: