Utilizing Multiomic Advanced Diagnostics to Identify CDK 4/6 Inhibitor Response Predictors and a Post-treatment Multiomic Signature for Patients With ER+/HER2- Metastatic Breast Cancer

Inclusion Criteria:

- Patients must have histologically or cytologically proven diagnosis of adenocarcinoma
of the breast with evidence of locoregionally recurrent or metastatic disease.

- Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP
2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by
immunohistochemistry based on local laboratory results.

- Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by
IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and
must not be positive (HER2/CEP17 ratio must be < 2, and HER2 copy number < 6
signals/cell), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by
institutional standards.

- Must be candidates to receive endocrine therapy and palbociclib or ribociclib as
first-line treatment for their advanced disease. Patients will be considered eligible
for study enrollment if they have started on treatment with a standard dose and
schedule of palbociclib or ribociclib and endocrine therapy (aromatase inhibitor or
fulvestrant) as long as they have not started palbociclib or ribociclib treatment for
longer than 4 weeks from time of study enrollment, have sufficient tissue to perform
the proposed tissue analysis and must meet all other eligibility criteria. Endocrine
therapy can be initiated up to 4 weeks prior to starting palbociclib or ribociclib.

- Patients must have measurable disease by RECIST v.1.1 or bone disease as their only
site of disease (with bone lesions confirmed by CT, MRI or bone X-ray).

- No prior treatment with chemotherapy for a diagnosis of locoregionally recurrent or
metastatic breast cancer is allowed.

- Be ≥ 18 years of age

- Have an ECOG score of 0-1

- Postmenopausal women defined as women with:

- Prior bilateral surgical oophorectomy, or

- Medically confirmed post-menopausal status defined as spontaneous cessation of
regular menses for at least 12 consecutive months or follicle-stimulating hormone
(FSH), luteinizing hormone (LH) and estradiol blood levels in their respective
postmenopausal ranges.

- Premenopausal women will be considered eligible for study participation if they are
receiving medical ovarian suppression with luteinizing hormone-releasing hormone
(LHRH) agonists with documented estradiol blood levels in their respective
postmenopausal ranges.

- Archive tumor tissue (obtained from a biopsy or surgical resection of a metastatic
lesion done within 4 months from study enrollment) availability is required for
patient participation. If the available tissue is insufficient for the required
baseline analysis, the patients are given the option to repeat the biopsy for the
purpose of study participation as long as they have not already started palbociclib or
ribociclib.

- Understand and provide written informed consent prior to initiation of any
study-specific procedures.

Exclusion Criteria:

- Lack of archive tumor tissue from a biopsy or surgical resection of a metastatic
lesion done within 4 months of study enrollment. Patients will be given an option to
have a repeated biopsy of a metastatic lesion if they had a diagnostic tumor biopsy
intended for use in the current study that was performed more than 4 months prior to
analysis, or there is insufficient tissue from the initial biopsy to complete the
analysis, as long as they have not started treatment with a CDK 4/6 inhibitor.
Otherwise, the patient will be excluded from the study participation.

- Have symptomatic CNS metastasis. Patients with a history of CNS metastases who have
been treated with whole brain irradiation must be stable without symptoms for 4 weeks
after completion of treatment, with image documentation required, and must be either
off steroids or on a stable does of steroids for ≥ 4 weeks prior to enrollment.

- Have uncontrolled concurrent illness including, but not limited to, ongoing or active
serious infection, symptomatic congestive heart failure, unstable angina pectoris,
unstable cardiac arrhythmias, psychiatric illness, or situations that would limit
compliance with the study requirements or ability to willingly give written informed
consent.