Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery

Inclusion Criteria for all patients (Groups A and B):

- Signed informed consent obtained prior to any study specific assessments and
procedures

- Age ≥18 years

- Premenopausal and postmenopausal women, or men

- Current pathologic diagnosis of DCIS of the breast of any receptor status; History of
previous DCIS allowed provided that the patient is currently off systemic
risk-reduction endocrine therapy; History of previous invasive breast cancer
adequately treated and that is currently in remission and unrelated to current DCIS
(based on primary tumor location) is allowed as long as patient is currently off
systemic therapy for that invasive cancer for at least 4 weeks prior to pre-treatment
biopsy (diagnostic biopsy); Patients with multifocal or multicentric lesions are
allowed, as long as at least one lesion is histologically confirmed DCIS and overall
clinical AJCC Stage 0 or I.

- A formalin-fixed paraffin-embedded (FFPE) tumor tissue block from diagnostic biopsy
must be transmitted to MedStar Georgetown University Hospital Pathology Department
repository and confirmation of receipt must be available prior to enrollment.

- Positive Rb by immunohistochemistry in the DCIS component of the lesion - must be
performed at CLIA-approved setting (for instance, MGUH); Rb staining will be
considered positive when 1+ or above (in a scale of 0, 1+, 2+ or 3+)

- In the absence of histologic diagnosis of DCIS, patient may undergo fresh biopsy for
eligibility, provided: this invasive procedure is not a Fine Needle Aspiration (FNA);
AND this procedure is a core biopsy, stereotactic biopsy or incisional biopsy of the
suspicious breast lesion; AND the primary lesion is not completely resected during the
procedure.

- The patient is candidate for and is willing to receive definitive surgical therapy for
DCIS

- ECOG performance status 0-1

- Willingness to provide a sample of tissue collected at definitive surgery for research

Inclusion criteria specific to treatment Group A:

- Patients must be able and willing to swallow and retain oral medication

- Absolute neutrophil count (ANC) ≥ 1,500/mm3

- Platelets ≥ 120,000/mm3

- Hemoglobin ≥ 10g/dL

- Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
within normal range in patients with documented Gilbert's Syndrome.

- Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT)
≤ 1.5 × institutional ULN

- Serum creatinine within normal institutional limits or creatinine clearance ≥ 50
mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.

- Pregnancy must be ruled out: serum or urine pregnancy test must be negative within 14
days of treatment start in women of childbearing potential. Pregnancy testing does not
need to be pursued in patients who are judged as postmenopausal before enrollment, or
who have undergone tubal ligation, bilateral oophorectomy, total hysterectomy.

- Willingness to undergo adequate contraception if childbearing potential; women of
childbearing potential and male patients randomized into treatment Group A must use
adequate contraception for the duration of protocol treatment and for 3 months after
the last treatment with palbociclib if they are in Group A; adequate contraception is
defined as one highly effective form (i.e. abstinence, (fe)male sterilization) OR two
effective forms (e.g. non-hormonal IUD and condom / occlusive cap with spermicidal
foam / gel / film / cream / suppository).

Exclusion Criteria for all patients (Groups A and B):

- Concurrent therapy with other Investigational Products

- Invasive carcinoma present in the diagnostic biopsy, microinvasion is allowed

- Uncontrolled intercurrent illness including (active infection, symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, pulmonary
embolism in the past 6 months, or psychiatric illness/social situations that would
limit compliance with study requirements).

- Unable to comply with study requirements

- Hormone therapies containing estrogen, progesterone, GnRH agonists and antagonists
within 4 weeks from diagnostic biopsy.

- Therapy with any CDK inhibitor in the past 3 months

Exclusion criteria specific to treatment Group A:

- History of allergic reactions attributed to compounds of chemical or biologic
composition similar to palbociclib

- Presence of a condition that would interfere with enteric absorption of palbociclib

- Pregnant women, or women of childbearing potential without a negative pregnancy test
(serum or urine) within 7 days prior to enrollment; breastfeeding must be discontinued
prior to study entry (Group A only).

- Patients on combination antiretroviral therapy, i.e. those who are HIV+ (potential for
pharmacokinetic interactions or increased immunosuppression with palbociclib).

- Patients receiving any medications or substances that are potent inhibitors or
inducers of CYP3A isoenzymes within 7 days of enrollment or during participation on
study

- Patients with clinically significant history of liver disease, including viral or
other known hepatitis, current alcohol abuse, or cirrhosis, etc.