Intervention: Letrozole
Trial phase: Phase 4
ATC code: L02BG04
SMILES: N#Cc1ccc(C(c2ccc(C#N)cc2)n2cncn2)cc1
Sex: Female
Age groups: Adult
Healthy volunteers: No
Participants at risk: 18
Group description: Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.

Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:

Serum Estradiol level <150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level >350 pg/ml - 7.5 mg;
Eligibility criteria:
Inclusion Criteria:

Female breast cancer patient with breast cancer diagnosis after surgery and before undergoing chemotherapy desiring fertility preservation with oocyte or embryo cryopreservation
Healthy subject according to documented medical history and physical examination who has been diagnosed with breast cancer (estrogen and progesterone receptor positive and/or negative)
Age less that 45 years at time of informed consent
Verbal or written clearance from medical or surgical oncologist to undergo controlled ovarian hyperstimulation-IVF
Delay to chemotherapy treatment will not jeopardize cancer treatment outcome
Ovarian stimulation will not affect cancer treatment plan
Transvaginal ultrasound scan (US) within one month of starting stimulation with no clinically significant pelvic mass
Serum FSH level (Day 2-4) less than 25
Negative pregnancy test prior to beginning Letrozole or gonadotropin therapy
Willing and able to comply with the protocol
Voluntary provision of written informed consent, prior to any study related procedure that was not part of normal medical care, with the understanding that the subject can withdraw consent at any time without prejudice to her future medical care
Willingness to provide follow-up information on herself and babies born as part of this study

Exclusion Criteria:

Patients not medically cleared by their oncologist
Patients with stage IV breast cancer based on the poor prognosis, general health of the patient, and higher uncertainty with delaying chemotherapy
Any clinically relevant abnormal laboratory value (FSH >25 miu/ml, renal function, (greater than two times normal value), hepatic function (greater than two times normal value), blood biochemistry, hematology (elevated white blood count greater than 1.5 times the normal value, hemoglobin <10mg/dL, thrombocytopenia), abnormal cholesterol profile (total cholesterol ≥ 300mg/dL, abnormal LDL greater than 2 times normal value,) based on a fasting sample during the screening phase
Contraindications for the use of gonadotropins (i.e. Tumors other than breast cancer, pregnancy, lactation, undiagnosed vaginal bleeding)
Recent or current medical conditions where the patient is not medically stable to undergo stimulation or egg retrieval, HIV infection, diabetes, cardiovascular disease, gastrointestinal, hepatic disease, undiagnosed pelvic mass, renal or pulmonary disease
History or presence of alcohol or drug abuse within 12 months of signing consent
History of severe allergic or anaphylactic reactions or hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol
Administration of investigational drugs within three months prior to signing the informed consent
Use of insulin sensitizing agents at least one month prior to signing informed consent
Any patient who is not a candidate for IVF