Breast Cancer Liquid Biopsy Trial

The purpose of this study is to continue to develop a liquid biopsy (minimally invasive blood test) that can be used to confirm if breast cancer has spread throughout the body and if this liquid biopsy test can provide comparable information to a highly invasive tissue biopsy. The knowledge gained in this study could be used in future studies to confirm cancer recurrence using a safe and minimally invasive procedure. The research will consist of looking for tumor cell(s) circulating in the blood stream and if they are present to characterize them so that more information about the disease can be collected. This information may help us to better understand how to fight cancer.

An estimated 287,850 women will be diagnosed with invasive breast cancer in the US in 2022 (cancer.org). Most women with breast cancer present with disease confined to the breast and local lymph nodes, where surgical removal of lesions is standard of care and well-managed. Those diagnosed and treated for primary breast cancer often recur with metastatic disease more than 5 years after initial diagnosis. (Pan, NEJM 2017).

Sadly, when lesions emerge in other areas, after months or decades with no evidence of disease, mortality rates rise. The most common sites of distant recurrence of breast cancer are the bone, lung, liver, and brain, (Lin, NCCN 2012), all of which are difficult to biopsy, and obtain pathological evidence of malignancy because metastatic lesions: 1) are not always accessible/deeply located, 2) are prone to under sampling, and 3) may present dense fibrotic tissue. In addition, tissue biopsy methods in metastatic lesions have been shown to:

1. have low patient compliance,
2. have high discordance rate with malignant lesions at imaging,
3. be incompatible with longitudinal monitoring.

As a result, at a critical point in patient care, there is still a current unmet need for diagnostic information to guide decision-making.

As established widely in published literature over the past decade, receptor status often changes between primary and metastatic disease, and during lines of metastatic treatments, changing the trajectory of the disease and further highlighting the need for longitudinal evaluation of receptor status. Occult micro-metastases or minimal residual disease (MRD) cannot be detected with current medical modalities and can originate metastatic relapse at distant sites. For this reason, cellular and molecular liquid biopsy approaches that enable detection of disease relapse allow therapy escalation many months earlier than overt relapse detected by imaging which as result may increase patients' survival. Based on discussions, interviews, and surveys of both thought-leading academics and community-based medical oncologists, there is an evident opportunity to improve patient care. Moreover, the market shows receptivity to a blood-based test for these inaccessible cases as well as improve identification of patients at high risk of relapse or eligible for earlier treatment escalation compared to current tissue biopsy testing in practice today.

In this clinical trial the purpose is to examine the potential of blood draws as a rapid and less invasive alternative to biopsies. Additionally, to compare the results of Epic Sciences' liquid biopsy test, DefineMBC, with results of standard-of-care (SoC) pathology results from metastatic contemporaneous tissue biopsies. With the implementation of our newest Registry Arm of patients, our goal is also to provide participating physician investigators the results Epic Sciences' liquid biopsy test, Define MBC, for breast cancer subjects with no central pathology data and utilize physician feedback for test experience improvements.

Eligibility Criteria:
Arm 1 Inclusion criteria:

* All subjects must be capable of providing informed consent
* Subjects (≥ 18 years of age) must have had a prior primary breast cancer diagnosis of any subtype at least six (6) months before presentation with suspected metastases or be presenting with de novo metastasis. o Patients on adjuvant treatment for primary disease are eligible provided clinical progression (suspected recurrence) is evident based on radiological assessment
* Subjects must have suspected recurrent metastatic BC or MBC with clinical signs of progression that will be confirmed/evaluated by tissue biopsy that is expected to yield tissue adequate for histologic examination. Note that patients presenting with de novo metastasis are eligible provided a tissue biopsy meets the above criteria.
* Tissue biopsy of a suspected metastatic lesion must be taken prior to treatment for metastatic disease and can be either: (i) after liquid biopsy blood draw for this study, or (ii) at least one week prior to liquid biopsy blood draw for this study.
* The suspected metastases biopsied may be from any lesion outside the ipsilateral breast and axilla, infra/supraclavicular areas.
* In those with suspected metastases in contralateral axilla, infra/supraclavicular areas, only a new contralateral breast primary must be excluded by imaging.
* No history of any other cancers (except for non-melanoma skin cancer)
* Ability to access 3-month outcome data (de-identified, consented patients included for second draw at 3-month timepoint or within 14 days for the first post-treatment imaging, whichever comes first).
* Data from contemporaneous diagnosis (metastatic recurrence or de novo) and in applicable past diagnosis (primary) must be accessible, including a pathology report that details standard markers and morphology describing how malignancy/cancer of origin was determined.

Arm 1 Exclusion Criteria:

* Unable to provide informed consent
* New treatment commences prior to liquid biopsy blood collection
* Previous history of an invasive non-breast cancer (except for non-melanoma skin cancer)
* Subjects not undergoing a tissue biopsy at time of blood draw (for suspected breast cancer recurrence or prior to beginning new line of metastatic treatment)
* Subjects with only a new contralateral breast primary tumor

Arm 2 Inclusion criteria:

* Capable of providing informed consent
* Subjects (≥ 18 years of age) must have had a prior primary breast cancer diagnosis of any subtype at least six (6) months before presentation with suspected metastases or be presenting with de novo metastasis.
* Patients on adjuvant treatment for primary disease are eligible provided clinical progression (suspected recurrence) is evident based on radiological assessment
* The suspected metastasis biopsied may be from any lesion outside the ipsilateral breast and axilla, infra/supraclavicular areas.
* In those with suspected metastases in contralateral axilla, infra/supraclavicular areas only, a new contralateral breast primary must be excluded by imaging.
* Confirmation of progression of MBC must be confirmed by imaging
* (Optional) Tissue biopsy of suspected metastatic lesion must be taken prior to treatment for metastatic disease and can be either: (i) after liquid biopsy blood draw for this study, or (ii) at least one week prior to liquid biopsy blood draw for this study.
* No history of any other cancers (except for non-melanoma skin cancer)
* Data from primary BCa diagnosis must be accessible, including detailed description with standard markers and morphology describing how malignancy/cancer of origin was determined.
* Subject must exhibit clinical signs of breast cancer recurrence or progression of previously confirmed metastatic breast cancer

Arm 2 Exclusion Criteria:

* Subjects unable to provide informed consent
* New treatment regimen commences prior to liquid biopsy blood collection
* Subjects on treatment for MBC with no imaging evidence of clinical progression
* Previous history of an invasive non-BC apart from cancers treated with curative intent at least five (5) years previously with no recurrence since diagnosis, with the exception of a non-melanoma skin cancer