Estradiol Plus Olaparib for Breast Cancer (PHOEBE)

Patients with endocrine-resistant ER+/HER2- breast cancer are eligible. Patients will be treated with the combination of 17b-estradiol and olaparib for 2 cycles, and then treated with single-agent 17b-estradiol until disease progression. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined.

Inclusion criteria

• Post-menopausal women with ER+/HER2- breast cancer.
• Metastatic or locoregional recurrence not amenable to treatment with curative intent.
• Received ≥1 prior line of endocrine-based therapy in the advanced/metastatic setting.

Exclusion criteria

• During study treatment, no concurrent anti-cancer therapies are allowed with the following exceptions:

o Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) permitted.

• Any investigational cancer therapy or systemic chemotherapy in the last 3 weeks.
• Any radiation therapy in the last 2 weeks.
• Known CNS disease, unless clinically stable for ≥ 3 months.
• Concomitant use of known strong or moderate CYP3A inhibitors.
• Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy.
• History of any of the following:

• Deep venous thrombosis
• Pulmonary embolism
• Stroke
• Acute myocardial infarction
• Congestive heart failure
• Previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%
• Severe renal impairment (creatinine clearance ≤ 30 mL/min).