A Phase II Trial of Letrozole Plus OSI-774 (Tarceva) in Post-menopausal Women With ER and/or PR-Positive Metastatic Breast Cancer

Inclusion Criteria

- Patients must have estrogen (ER) and/or progesterone receptor (PgR)-positive,
histologically confirmed adenocarcinoma of the breast with measurable (but not
operable) locally recurrent disease, or measurable and/or evaluable metastatic
disease (see protocol section 10.3), including isolated bone metastases.

- Patients with available paraffin tissue blocks from either the primary or the
metastatic site must submit tissue blocks for retrospective EGFR and HER2 analysis.
If tissue blocks cannot be submitted, 20 unstained slides from each paraffin block
must be submitted.

- All patients must be post-menopausal females as defined by one of the following:

- Prior bilateral oophorectomy

- Prior bilateral ovarian irradiation

- No menstrual period for 12 months or longer

- If age 55 years or less and < 12 months from last menstrual period, patient must
have a serum estradiol < or equal to 30 and an FSH level > 40.

- Patients must not have had more than 1 prior chemotherapy regimen for metastatic
disease and have fully recovered from any grade 2-4 toxicities related to
chemotherapy. No concurrent chemotherapy is allowed while on protocol therapy.

- Patients may have had 1 prior hormonal therapy for metastatic disease. This includes:
tamoxifen, fulvestrant, anastrozole, exemestane, aminoglutethimide, megace, and
letrozole. Patients may have received tamoxifen or aromatase inhibitors in the
adjuvant setting.

- Patients must not have had prior therapy with EGF receptor inhibitors.

- Previous but not concomitant therapy with trastuzumab (Herceptin) is allowed.
Patients must not have received Herceptin within 4 weeks of initiation of protocol
therapy.

- Patients must have an ECOG performance status of 0, 1, or 2.

- Patients must have adequate hematologic, hepatic, and renal function as defined by
the following within 2 weeks of initiation of therapy:

- Absolute neutrophils > or equal to 1,500/mm3 and platelets > or equal to
100,000/mm3.

- Bilirubin < than or equal to 1.5 upper limit of normal.

- SGOT and SGPT < or equal to 2.5 upper limit of normal.

- Creatinine < or equal to 1.5 upper limit of normal.

- INR, PTT and PT in the normal range.

- Must be 18 years of age or older.

- Patients must not have a history of central nervous system metastases or unevaluated
CNS symptoms suggestive of possible brain metastases.

- Patients may receive concurrent radiation therapy to painful bone metastases or areas
of impending bone fracture as long as radiation therapy is initiated prior to study
entry and sites of evaluable disease outside the radiation port(s) are available for
follow-up. Patients who have received prior radiotherapy must have recovered from
toxicity induced by this treatment.

- Patients < 55 years of age must not have received Luteinizing hormone releasing
hormone (LHRH) antagonists within 3 months prior to protocol therapy.

- Patients must not suffer from medical or psychiatric conditions that would interfere
with ability to provide informed consent, communicate side effects, or comply with
protocol requirements including maintenance of a compliance/pill diary.

- Patients must be disease-free of prior invasive cancers for > 5 years with the
exception of basal or squamous cancer of the skin or cervical carcinoma in situ.