A Study of Palbociclib in Combination With Bazedoxifene in Hormone Receptor Positive Breast Cancer

Inclusion Criteria

• Participants must have histologically confirmed invasive breast cancer that is metastatic or unresectable locally advanced. Histological documentation of metastatic/recurrent breast cancer is not required if there is unequivocal evidence for recurrence of the breast cancer.
• Estrogen and/or progesterone receptor positive breast cancer (>10% staining), as determined by pathology from either primary or metastatic site(s). Central confirmation is not required.
• HER2 negative, defined as 0-1+ by immunohistochemistry or FISH-negative (HER2 copy number <6 and HER2/CEP17 ratio < 2.0). Central confirmation is not required.
• Postmenopausal women are eligible. Postmenopausal is defined as any of the following:
• Age ≥60 years
• Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range.
• Premenopausal women who have been on a GnRH agonist for at least 3 consecutive months prior to study entry are eligible. Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment.
• Status-post bilateral oophorectomy-After adequate healing post surgery.
• Women, age ≥18 years of age. Men are excluded.
• Because no dosing or adverse event data are currently available on the use of palbociclib and bazedoxifene in participants <18 years of age, children are excluded from this study. In addition, breast cancer is exceedingly rare in individuals under 18 years of age.
• Participants must have measurable disease by RECIST 1.1. See section 11 for the definition of measurable disease.
• Bone only disease if there are lytic lesions is also allowed and treatment response will be evaluated based on the MD Anderson criteria. See section 11.
• Endocrine resistant breast cancer, defined as either:
• Relapsed while on adjuvant endocrine therapy or within 1 year of completion of adjuvant endocrine therapy

--- -or-

• Progression through at least one line of endocrine therapy for metastatic or locally advanced breast cancer. There is no limit on the number of prior endocrine therapies received.
• Patients may have received up to one prior line of chemotherapy for metastatic or unresectable locally advanced breast cancer.
• Patients may have initiated bisphosphonate therapy prior to start of protocol therapy. Bisphosphonate therapy may continue during protocol treatment. Such patients will have bone lesions considered evaluable for progression
• Patients must be at least 2 weeks from prior chemotherapy or radiotherapy, or any investigational drug product, with adequate recovery of toxicity to baseline, or grade <1, with the exception of alopecia and hot flashes. There is no washout period for prior endocrine therapy.
• ECOG Performance Status 0-1 (Appendix A)
• Life expectancy of greater than 3 months
• Willingness to undergo research biopsy under the following circumstances:
• Patients with "easily accessible disease"
• Patients with skin or chest wall disease amenable to a punch biopsy under local anesthesia are required to undergo a baseline biopsy and a biopsy at the time of disease progression as part of this protocol.
• Patients with a breast mass or axillary lymph node amenable to an image-guided core biopsy are also required to undergo a baseline biopsy and a biopsy at the time of disease progression as part of this protocol.
• Patients with malignant ascites fluid or a malignant pleural effusion of sufficient volume to be amenable to tap (either in-office or image-guided) are also required to undergo a baseline tap and a tap at the time of disease progression as part of this protocol.
• Patients who undergo a research biopsy procedure for the purpose of this protocol, and in whom inadequate tissue is obtained, are still eligible and are not required to undergo a repeat biopsy in order to enter the study.
• Patients will be approached during cycle 1 about providing