Plasma Circulating Tumor DNA Analyses in ER+ Metastatic Breast Cancer

The primary objective of this 110 patient correlative biomarker study is to evaluate whether
changes in mutant ESR1 allele fraction in plasma circulating tumor DNA (ctDNA) are predictive
of progression-free survival in metastatic ER+ breast cancer patients who are receiving 2nd,
3rd, or 4th line systemic endocrine therapy. A secondary goal of this study is to explore the
prevalence and kinetics of hotspot and non-hotspot ctDNA ESR1 mutations in this patient
population, prior to initiating a new line of endocrine therapy as well as upon clinical
progression, to identify potential mechanisms of resistance. Although initially to be opened
at UNC Chapel Hill, our goal is to expand enrollment to include Rex Cancer Center in Raleigh,
North Carolina, and collaborating institutions through the Translational Breast Cancer
Research Consortium.

Inclusion Criteria:

- Age ≥ 18 years of age

- Female gender

- Biopsy proven diagnosis of breast cancer

- Stage IV disease diagnosed either by radiographic studies or biopsy

- ER+ by immunohistochemistry on primary and/or metastatic tissue biopsy (>10%)

- HER2 non-amplified (1+ or below by immunohistochemistry, and/or Her2 FISH <2
HER2-to-CEP17 ratio)

- Progressed on at least one prior line of endocrine therapy for metastatic disease

- Three or fewer prior endocrine-containing therapies for recurrent/metastatic disease

- Two or fewer prior lines of cytotoxic chemotherapy for recurrent/metastatic disease

- Plans to initiate 2nd, 3rd, or 4th line endocrine therapy for metastatic disease

- Recent re-staging scans within 4 weeks of study enrollment, with radiographically
identifiable disease

- No concurrent or prior diagnosis of malignancy other than breast cancer for the past 5
years. Patients with a history of in situ cancer or basal or localized squamous cell
skin cancer remain eligible

- Intends to pursue treatment as well as clinical and radiographic follow-up at UNC
Health Care

- Signed an institutional review board (IRB)-approved informed consent document for this
protocol and HIPAA consent form

Exclusion Criteria:

- < 18 years of age

- Tissue biopsies that support the presence of both ER+ and ER- metastatic breast cancer
in the same patient

- Dementia, altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent

- Pregnant or lactating women