Inclusion Criteria:  Histologically confirmed locally advanced stage ER+ and/or PR+ and HER2- breast cancer [by ASCO/CAP guidelines: primary tumor size 2 cm or greater OR if primary tumor size is <2 cm with lymph node involvement (Stage II)] who are candidates for palbociclib in combination with concurrent ovarian suppression and letrozole per treating physician. At least 19 years of age. ECOG performance status ≤ 2 (see Appendix A)  Normal bone marrow and organ function as defined below:  Absolute neutrophil count ≥ 1,500/mcl Platelets ≥ 100,000/mcl Total bilirubin ≤ IULN or total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in subjects with documented Gilbert's syndrome AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN (up to 5 x IULN in subjects with liver disease) Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above institutional normal Pre-menopausal subjects defined by: Age <60 with no prior bilateral oophorectomy and having menses in the preceding 12 months in the absence of taking chemotherapy, tamoxifen or torimefene or ovarian suppression. If any of these agents were used, measurements of FSH and estradiol have to be made to determine menopausal status. Post menopausal subjects defined by: Age >60 Or absence of menstruation in the preceding 12 months without taking chemotherapy, tamoxifen, torimefene or ovarian suppression. If any of these agents were used, measurements of FSH and estradiol have to be made to determine menopausal status. If none of these are applicable fully, subject may be judged premenopausal according to local policies. Participating subjects must agree to use adequate contraception for the duration of protocol treatment and for 6 months after the last treatment with palbociclib. 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). Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Able to swallow and retain oral medication. Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).  Exclusion Criteria:  Prior therapy with any CDK inhibitor. Currently receiving any other investigational agents. Currently receiving exogenous hormone therapy (topical vaginal estrogen therapy is allowed). Known metastatic disease A history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or other agents used in the study. Receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days prior to registration. Clinically significant history of liver disease as defined by active hepatitis and/or cirrhosis with compromised liver function. A condition that would interfere with enteric absorption. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry. Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with palbociclib. In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy. Male Sex