Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

Conditions

Breast Cancer

Keywords

pre-operative, endocrine treatment, drug resistance

Brief summary

To investigate prospectively whether short term endocrine treatment can induce molecular changes, predictive for therapy response.

Detailed description

We will perform a randomized, open-label, single-institution study. It will compare the efficacy of three different endocrine treatment regimens (Anastrozole +/- Fulvestrant or Tamoxifen) in changing proliferation-index and inducing apoptosis during a 2-6 week pre-operative treatment period in breast cancer patients. These results will be correlated to gene expression profiles, phosphorylation status of the ER, SNPs in CYP450 sequences, tamoxifen metabolite concentrations, changes in estrogen serum levels and protein expression patterns.

Reinema FV, Sweep FCGJ, Adema GJ, Peeters WJM, Martens JWM, Bussink J, Span PN.

2023-02-0816 citations

10.1186/s40170-023-00304-4

IHC-based Ki67 as response biomarker to tamoxifen in breast cancer window trials enrolling premenopausal women

Stacey E. P. Joosten, Marius Wellenstein, Rutger H.T. Koornstra, Annelot van Rossum, Joyce Sanders et al. (17 authors)

npj Breast Cancer2021-10-203 citations

10.1038/s41523-021-00344-3

Abstract P6-08-06: Neoadjuvant tamoxifen therapy synchronizes ERα binding and gene expression profiles

SC Linn, TM Severson, Ekaterina Nevedomskaya, J. P. Peeters, Annelot van Rossum et al. (15 authors)

Cancer Research2016-02-15

10.1158/1538-7445.sabcs15-p6-08-06

Abstract A38: Effects on epigenomic, transcriptomic, and genomic landscape of neoadjuvant tamoxifen in estrogen receptor alpha breast cancer

Tesa Severson, Ekaterina Nevedomskaya, Justine Peeters, Annelot van Rossum, Thomas Kuilman et al. (13 authors)

Molecular Cancer Research2016-02-01

10.1158/1557-3125.advbc15-a38

Interventions

DRUGAnastrozole

1 mg,QD,PO

DRUGAnastrozole+Fulvestrant

Anastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter

DRUGTamoxifen

loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

No

Inclusion criteria

* Patients with proven invasive adenocarcinoma of the breast * Any tumor with a size ≥ 1cm (NOT inflammatory breast cancer) * WHO-performance score 0 or 1 * Written informed consent

Exclusion criteria

* Clues of metastatic disease by clinical examination according to most recent NABON guidelines * Multicentric breast cancer * Inflammatory breast cancer * Hormone replacement during the last 12 months * Other systemic treatment during the waiting time till surgery * Already planned date for surgery within the next 2 weeks * Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol * Patient's refusal to undergo a core biopsy procedure of the primary tumor before the start of treatment NB: a concomitant malignancy within the last five years is not an exclusion criterium, because survival is not the primary endpoint. Just as prior invasive breast cancer or DCIS within the last 15 years is not an exclusion criterium. NB: Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during the study.

Design outcomes

Primary

Measure	Time frame
Decrease in tumor cell proliferation and induced apoptosis.	At baseline and after 2-6 weeks of endocrine treatment

Secondary

Measure	Time frame
Comparison of changes in gene expression after different endocrine treatment exposures	At baseline and after endocrine treatment

Countries

Netherlands

Outcome results

None listed