The purpose of this study is to perform an in depth analysis of changes in the tumor immune
microenvironment in patients undergoing treatment with standard of care endocrine therapy and
abemaciclib in the advanced setting via singe cell RNA sequencing. The investigators will
also correlate changes in serum estrogen levels to changes in tumor and peripheral immune
cell repertoire and function (including regulatory T cell populations, B cells,
myeloid-derived suppressor cell populations, T cell activation and T cell exhaustion).This
study has two cohorts with 15 patients in each cohort.
1. Women age ≥ 18
2. Locally advanced/unresectable or metastatic breast cancer
3. Histologically documented estrogen receptor positive adenocarcinoma of the breast that
is (any progesterone status allowed):
- ER positive defined as ≥ 10 % tumor cells positive for ER by immunohistochemistry
(IHC), irrespective of staining intensity.
- HER2 negative status is determined by:
- IHC 1+, as defined by incomplete membrane staining that is faint/barely
perceptible and within > 10% of invasive tumor cells, or
- IHC 0, as defined by no staining observed or membrane staining that is incomplete
and is faint/barely perceptible and within ≤ 10% of the invasive tumor cells, or
- FISH negative based on:
- Single-probe average HER2 copy number < 4.0 signals / cell, or
- Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals
4. Patients should have plans to initiate standard of care endocrine therapy with
non-steroidal aromatase inhibitor (letrozole, anastrazole) OR fulvestrant plus
abemaciclib in the advanced/metastatic first-line or second-line setting per treating
5. Patients should be willing and able to undergo fresh biopsy pretreatment and at 4
weeks into treatment.
6. Patients should have an accessible lesion representative of recurrent or metastatic
breast cancer for biopsy. Patients will undergo a tissue biopsy or tissue collection
for research purposes only. Sites for tissue acquisition include the breast,
skin/chest wall, soft tissue, liver, bone. Research directed lung biopsies and brain
biopsies are not permitted. Procedures for tissue acquisition are restricted to those
performed under local anesthesia or IV conscious sedation; biopsies that require
general anesthesia are not permitted in this situation.
7. Patients who received chemotherapy must have recovered (Common Terminology Criteria
for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for
residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout
period of at least 21 days is required between last chemotherapy dose and
randomization (provided the patient did not receive radiotherapy).
8. Patients who received radiotherapy must have completed and fully recovered from the
acute effects of radiotherapy.
9. The patient is able to swallow oral medications.
10. The patient has adequate organ function for all of the following criteria, as defined
- ANC ≥1.5 × 10^9/L
- Platelets ≥100 × 10^9/L
- Hemoglobin ≥ 8 g/dL. * Patients may receive erythrocyte transfusions to achieve
this hemoglobin level at the discretion of the investigator. Initial treatment
must not begin earlier than the day after the erythrocyte transfusion.
- Total bilirubin ≤1.5 × ULN *Patients with Gilbert's syndrome with a total
bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are
- ALT and AST ≤ 3 × ULN
- Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil
count; AST = aspartate aminotransferase; ULN = upper limit of normal.
11. Able and willing to complete the informed consent process
12. Agree to have bio-specimens stored for future research
1. History of concurrent active malignancy within last 5 years (excluding basal cell skin
cancer, resected squamous cell carcinoma of the skin)
2. Current use of hormonal birth control (copper IUD allowed) or estrogen replacement
3. Active autoimmune disease that has required systemic treatment in past 6 months (ie,
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, or similar treatment) is not considered a
form of systemic treatment.
4. History of a serious or life-threatening allergic reaction to local anesthetics (e.g.,
lidocaine, xylocaine) used during a biopsy procedure
5. Immunodeficient subjects, E.G., receiving systemic steroid therapy greater than
physiologic doses or any other form of immunosuppressive therapy within 30 days prior
to the first dose of endocrine therapy treatment
6. Concurrent use of other oncologic therapies in the adjuvant setting other than
7. Patients with disease not amenable to biopsy
8. The patient has serious and/or uncontrolled preexisting medical condition(s) that, in
the judgment of the investigator, would preclude participation in this study (for
example, interstitial lung disease, severe dyspnea at rest or requiring oxygen
therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min],
history of major surgical resection involving the stomach or small bowel, or
preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition
resulting in baseline Grade 2 or higher diarrhea).
9. Females who are pregnant or lactating.
10. The patient has active systemic bacterial infection (requiring intravenous [IV]
antibiotics at time of initiating study treatment), fungal infection, or detectable
viral infection (such as known human immunodeficiency virus positivity or with known
active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening
is not required for enrollment.
11. The patient has a personal history of any of the following conditions: syncope of
cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but
not limited to, ventricular tachycardia and ventricular fibrillation), or sudden
12. History of bleeding disorder that would make serial biopsies unsafe.
13. Patients of active anticoagulation for history of venous thromboembolism,