Statement: Prior exposure to exemestane is not allowed for patients in the secondary trial, however, the primary trial may accept patients despite this.
Primary_evidence: Inclusion Criteria   Pathologically confirmed diagnosis of invasive breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy;   Tumor size >2cm, measured on imaging or estimated by physical exam;   No contraindications for primary chemotherapy;   Planned definitive breast surgery (mastectomy or lumpectomy/breast conservation) following completion of neoadjuvant therapy;   Age 18 years or older;   ECOG Performance Status  2 (Karnofsky  60%; see Appendix II);   Normal organ and marrow function as follows:   leukocytes  3,000/μl;   absolute neutrophil count  1,500/μl;   platelets  100,000/μl;   total bilirubin within normal institutional limits;   AST(SGOT)/ALT(SGPT)  2.5 times the institutional upper limit of normal;   creatinine within normal institutional limits; OR   creatinine clearance  30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal;   If female, postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by a pregnancy test as per institutional Standard of Care (SOC), and willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation;   Able to understand and willing to sign a written informed consent document and a HIPAA authorization in accordance with institutional guidelines;   Exclusion Criteria   Previous treatment (chemotherapy, radiation, or surgery) to involved breast; including hormone therapy;   Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;   Medically unstable;   Under age 18;   Pregnant or nursing;   Previous malignancy, other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, from which the patient has been disease free for less than 5 years.
Secondary_evidence: Inclusion Criteria:   Post-menopausal women (either through bilateral oophorectomy or amenorrhoeic for 24 months)   Histological confirmation of Breast Cancer with documented ER+ receptor status   Safety run-in: Relapsing during/within 12 months of completion of a single regimen of adjuvant endocrine therapy with non-steroidal AI and/ tamoxifen or progression following 1st line endocrine therapy with non-steroidal AL   Rand phase IIa: Received at least 1 prior endocrine therapy in the metastatic setting or have relapsed during/ within 6 months of completion of adjuvant endocrine therapy (either non-steroidal AI or tamoxifen or a combination of both). Chemotherapy administered in the adjuvant setting is permitted.   Rand phase IIa: Mandatory provision of tumour sample to confirm FGFR1 polysomy or gene amplification. At least one measurable lesion that can be accurately assessed by CT/MRI/x-ray at baseline and follow up visits Exclusion Criteria:   Prior exposure to exemestane (safety run-in) / fulvestrant (randomized phase IIa), or any agent known to inhibit FGFRs.   More than 1 prior regimen of chemotherapy for breast cancer   ECG recordings that demonstrate significant abnormalities in cardiac rate, rhythm or conduction   History of hypersensitivity to active or inactive excipients of AZD4547 or exemestane (safety run-in ) or fulvestrant (Randomized phase), including castor oil, or drugs with a similar chemical structure or class to AZD4547 or exemestane or fulvestrant.   Randomized phase IIa: bleeding/blood clotting conditions that would prevent the administration of the fulvestrant injection into the buttocks