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

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.

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