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

Overview

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.

Primary outcome measures

• 5-year distant recurrence-free interval (dRFI, according to STEEP criteria version 2.0) [Time frame: 5 years]

Secondary outcome measures (12)

• 10-year dRFI [Time frame: 10 years]
• 5-year dRFI [Time frame: 5 years]
• 10-year dRFI [Time frame: 10 years]
• 5-year dDFS [Time frame: 5 years]
• 10-year dDFS [Time frame: 10 years]
• 5-year OS [Time frame: 5 years]
• 10-year OS [Time frame: 10 years]
• 5-year breast cancer-free interval (BCFI, according to STEEP 2.0) [Time frame: 5 years]
• 10-year breast cancer-free interval (BCFI, according to STEEP 2.0) [Time frame: 10 years]
• EORTC quality of life questionnaire BR23 [Time frame: every 3 months within 1st year]
• EORTC quality of life questionnaire C30 [Time frame: every 3 months within 1st year]
• EORTC quality of life questionnaire BR23 [Time frame: every 6 months within 2nd year]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Germany · 71 centers

• Klinikum-Mittelbaden GmbH, Studienzentrale/Brustzentrum — Baden-Baden
• Helios Klinikum Pforzheim, Brustzentrum — Pforzheim
• Diakonieklinikum Stuttgart, Brustzetrum — Stuttgart
• Universitätsfrauenklinik Ulm - Frauenheilkunde und Geburtshilfe — Ulm
• GRN Klinik Weinheim/ Gynäkologie/Brustzentrum — Weinheim
• ViDia Christliche Kliniken Karlsruhe — Karlsruhe
• Studienzentrum Onkologie Ravensburg — Ravensburg
• Klinikum St. Marien Amberg — Amberg
• … and 63 more centers

Identifiers

NCT: NCT05792150 · WSG-NIS04 / PROOFS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗