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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Shearwave elastography; Drug: Letrozole; Procedure: Breast core biopsy; Other: Magnetic Resonance Imaging

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • Stefani Clinical Trials Unit, Ninewells Hospital and Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Proliferative response	Pathological response to treatment by proliferation (Ki67) (%)	At surgery, min 3 months max 24 months
Change in Pathological response	Residual cancer burden score	At surgery, min 3 months max 24 months
Change in Shearwave stiffness	shearwave stiffness (kPa)	0,3,6, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
caveolin-1	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
Monocarboxyl transport 4	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
lysyl oxidase	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
fibronectin	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)
collagen	peri-tumoural immunohistochemical analysis	0 months and at time of surgery (min 3 months, max 24 months)

Collaborators and Investigators

• Sponsor: NHS Tayside
• Investigators: Principal Investigator: E. Jane Macaskill, MBChB, MD, FRCSEd, NHS Tayside

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): December 24, 2020
• Study Completion (Actual): December 24, 2020

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: March 7, 2016
• First Posted (Estimate): March 8, 2016

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: August 5, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: neoadjuvant endocrine
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Aromatase Inhibitors
• Other Study ID Numbers: 2015ON09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual data sharing