Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant
plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced
AR+/ER+/Her2- BC who will have local surgery after ~4 months on treatment. After consent, all
patients will get a tissue biopsy, and than half the patients will get fulvestrant alone
(standard dosing) and the other half of the patients will get fulvestrant plus enzalutamide.
At ~4 weeks, a biopsy will be done and therapy will be continued. Hormone therapy will
continue for ~4 months at which point the patients will undergo surgical resection.

Inclusion Criteria:

- ER+ Her2- breast cancer

- Stage at least T2 or greater

- Planned to get local surgery

- Postmenopausal, or if pre- or peri- menopausal, then will need to have concurrent
ovarian suppression.

- At least 18 years of age

- Not on anticoagulants

- PS 0-2

- Able to swallow study drug and comply with study requirements

- ANC >1000/uL, platelets >75,000/uL at screening visit

- Total bilirubin < 1.5 times upper limit of normal (ULN) at the screening visit unless
an alternate nonmalignant etiology exists (eg, Gilbert's disease)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN or <
5 times ULN if patient has documented liver metastases

- Creatinine < 1.5 times ULN

- INR < 1.5 times ULN, or if on warfarin, can safely transition off for biopsy

- Willing to donate blood for research at 4 time points

- Willing to undergo core biopsies for research at study entry and at ~4 weeks.

- Willing to donate tissue to research from the surgical specimen

- Written informed consent obtained prior to biopsies and blood samples

Exclusion Criteria:

- Current or previously treated brain or leptomeningeal metastases

- History of seizures

- Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide,
enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464).

- Systemic estrogens or androgens within 14 days before initiating therapy. Vaginal
estrogens are allowed if necessary for patient comfort.