Radiological and Biological Tumoural and Peri-tumoural Factors in Neoadjuvant Endocrine-treated Breast Cancers

Breast Cancer Clinical Trial

— BARONET  

Official title:

Radiological and Biological Tumoural and Peri-tumoural Factors in Neoadjuvant Endocrine-treated Breast Cancers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02701348
• Other study ID #: 2015ON09
• Status: Completed
• Phase: N/A
• Start date: May 2016
• Est. completion date: December 24, 2020

Study information

• Verified date: August 2021
• Source: NHS Tayside
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to monitor the change in cancer size in women with breast cancer on anti-hormone treatment using different types of assessment including ultrasound scan (US), shearwave elastography (SWE) and magnetic resonance imaging (MRI), and assess how this corresponds to the changes in the cancer biology.

Description:

Background Endocrine resistance is a significant problem in the management of breast cancer, with increasing evidence that the tumour microenvironment is influential on tumour growth and disease resistance. The neoadjuvant setting provides an excellent opportunity to observe tumour response to treatment in vivo, allowing development of methods for monitoring and predicting response to treatment.

Aims To assess potential radiological and biological tumoural and peri-tumoural biomarkers in patients before and during neoadjuvant endocrine treatment. Our hypothesis is that there will be less response in women with abnormal peri-tumoural stroma, and that tumours with high monocarboxyl transporter (MCT4) and loss of caveolin-1 in stroma are resistant to endocrine treatment.

Techniques and Methodology Patients with primary breast cancer receiving neoadjuvant letrozole will undergo radiological assessment with digital mammogram, US including SWE, and MRI. Core biopsies will be taken at diagnosis and at surgery from tumour and peri-tumoural stroma, and assessed for biomarkers lysyl oxidase (LOX), fibronectin, collagen, proliferation, MCT4 and caveolin-1. All data will be correlated to peri-tumoural abnormalities on MRI and SWE.

Impact on breast cancer research This study will provide information on the ability of SWE and MRI to predict and detect endocrine resistance, correlated with biological markers that are associated with endocrine resistance. Identifying resistant tumours can prevent unnecessary treatment and reduce risks of recurrence as alternative or additional therapies can be utilised.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 24, 2020
• Est. primary completion date: December 24, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Postmenopausal women: Defined as >12 months amenorrhoea in absence of medical therapy known to induce this; or bilateral oophorectomy; or if last menses <12 months before starting treatment, FSH >35 IU/L and LH >40 IU/L.

• ER positive (Allred score >3) invasive breast cancer

• Staging as T1-4, N0-2, M0

• Patient agreed to neoadjuvant endocrine therapy as recommended by MDT

• Fresh tissue stored at time of diagnostic core biopsy

• Suitable for, and tolerant of MRI scan

• Fit for surgical intervention at time of entry into study

Exclusion Criteria:

• Premenopausal or unable to determine menopausal status

• Not fit for surgical intervention due to co-morbidities

• Contraindication for MRI (including severe claustrophobia)

• Current use of HRT, or HRT use at time of diagnostic core biopsy

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Other:
• Shearwave elastography
Patients with primary breast cancer receiving neoadjuvant letrozole will undergo radiological assessment with digital mammogram, ultrasound (US) including shearwave elastography (SWE). These will be performed at 3 monthly intervals until surgical intervention is considered feasible.

Drug:
• Letrozole
Patients will be receiving neoadjuvant letrozole as standard therapy for breast cancer

Procedure:
• Breast core biopsy
Core biopsies will be taken at diagnosis, and at the time of surgery to allow biological assessment of changes in tumour

Other:
• Magnetic Resonance Imaging
Breast MRI scans will be performed at time of diagnosis and prior to surgery to allow comparison of MRI change and response to treatment

Locations

Country	Name	City	State
United Kingdom	Stefani Clinical Trials Unit, Ninewells Hospital and Medical School	Dundee	Angus

Sponsors (1)

Lead Sponsor	Collaborator
NHS Tayside

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Proliferative response	Pathological response to treatment by proliferation (Ki67) (%)	At surgery, min 3 months max 24 months
Primary	Change in Pathological response	Residual cancer burden score	At surgery, min 3 months max 24 months
Primary	Change in Shearwave stiffness	shearwave stiffness (kPa)	0,3,6, up to 24 months
Secondary	Change in peritumoural imaging on MRI	MRI - digital contrast enhanced (DCE) and diffusion weighted imaging (DWI)	0 months and surgery (min 3 months, max 24 months)
Secondary	caveolin-1	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
Secondary	Monocarboxyl transport 4	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
Secondary	lysyl oxidase	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
Secondary	fibronectin	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
Secondary	collagen	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)