Tracking Triple-negative Breast Cancer Evolution Through Therapy

Study Overview
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Brief Summary
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A prospective multicentre study which aims to examine the relationship between intratumour heterogeneity (ITH) and pathological response to neoadjuvant chemotherapy in patients with histological confirmation of triple-negative breast cancer (TNBC) who are eligible for neoadjuvant chemotherapy.

Official Title
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Tracking Triple-negative Breast Cancer Evolution Through Therapy

Conditions
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Triple-Negative Breast Neoplasm

Intervention / Treatment
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* Procedure: Biopsy
* Procedure: Biopsy (optional)
* Procedure: Biopsy (metastatic)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-years or older Patients with histological confirmation of invasive breast cancer with known receptor status suitable for neoadjuvant chemotherapy as assessed by the local investigator Estrogen receptor (ER)- and progesterone receptor (PR)-negative as defined by ≤1% of positive staining on immunohistochemistry Human epidermal growth factor receptor 2 (HER2)-negative as defined by American Society of Clinical Oncology / College of American Pathologists guidelines T1c-4 tumours (including inflammatory cancers), with any nodal status non candidate for conservative surgery upfront. Bilateral or multifocal cancer is permitted provided that all sites are HER2-negative and at least one site is ER- and PR-negative. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses Patient with social insurance coverage Exclusion Criteria: Confirmed metastatic disease at initial presentation Any contraindication to the biopsy procedure Previous or current malignancies of other origin within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol Individuals deprived of liberty or placed under the authority of a tutor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All included patients<br>Patients will undergo a biopsy and provide a blood sample prior to initiating standard neoadjuvant chemotherapy. Additional tissue samples will be collected at the following time points: (optional) biopsy of primary tumour after 4 cycles of neoadjuvant chemotherapy At the time of surgery (samples of the primary tumour and lymph nodes which are surplus to diagnostic requirements). Biopsy of a metastatic site in the event of disease recurrence. Blood samples will be obtained during neoadjuvant chemotherapy, prior to surgery and at 6-month intervals for up to 5 years post-surgery. In the event of recurrent disease, blood samples will be collected i) at the time of recurrence, ii) at the first CT scan on treatment and iii) at each subsequent relapse for up to 5 years post-surgery. | Procedure: Biopsy<br>* Biopsy of primary tumour to be performed prior to initiation of neoadjuvant chemotherapy<br>Procedure: Biopsy (optional)<br>* [Optional] biopsy of primary tumour to be performed after 4 weeks of neoadjuvant chemotherapy<br>Procedure: Biopsy (metastatic)<br>* Biopsy of metastatic site to be performed at the time of relapse<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pathological complete response (pCR) | pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis ypN0 in the current American Joint Committee on Cancer [AJCC] staging system) | pCR will be defined at the time of surgery on the tumor specimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive disease-free survival | the time from neoadjuvant treatment initiation until the date of the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence (same breast), local /regional invasive recurrence, invasive contra lateral breast cancer, appearance of metastasis, second primary invasive cancer (non-breast cancer), ipsilateral ductal carcinoma in situ, contralateral ductal carcinoma in situ, death attributable to any cause. | from surgery until 5 years post-surgery | 
| Overall survival | the time from neoadjuvant treatment until death due to any cause | from surgery until 5 years post-surgery |