• Proportion of patients experiencing clinical benefit (complete response, partial response, and stable disease) for ≥ 24 weeks [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To determine the rate of clinical benefit (complete response [CR], partial response [PR], and stable disease [SD]) in patients with hormone-dependent locally recurrent or metastatic breast cancer treated with letrozole in combination with erlotinib hydrochloride.

Secondary

• To determine the time to progression (TTP) in patients treated with this regimen.
• To evaluate the antitumor activity, as determined by CR and PR rates, of this regimen in these patients.
• To evaluate the safety of this regimen in these patients.
• To determine if tumors that are positive for EGFR or Ser118 ER, or that overexpress HER2 exhibit a longer TTP from the combination compared to tumors that do not express or overexpress these molecules.

OUTLINE: This is a multicenter study. Patients are stratified according to prior hormone therapy (hormone-therapy naive/first-line therapy vs prior hormonal therapy with either tamoxifen or an aromatase inhibitor in the adjuvant or metastatic setting/second-line therapy)

Patients receive oral letrozole and oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.

Previously collected tumor tissue samples are analyzed for EGFR and Ser118 ER (cell signaling) via immunohistochemistry and HER2 gene amplification or excess copies of the HER2 gene via fluorescent in situ hybridization (FISH).

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast
• Measurable (but not operable) locally recurrent disease or measurable and/or evaluable metastatic disease, including isolated bone metastases
• No history of CNS metastases or unevaluated CNS symptoms suggestive of possible brain metastases

• Hormone receptor status:

  • Estrogen- and/or progesterone receptor-positive

PATIENT CHARACTERISTICS:

• Female

• Postmenopausal, as defined by 1 of the following:

  • Prior bilateral oophorectomy
  • Prior bilateral ovarian irradiation
  • No menstrual period for 12 months or longer
  • Serum estradiol level of ≤ 30 and an FSH level of > 40 for patients ≤ 55 year of age and < 12 months since last menstrual period
• ECOG performance status of 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN
• INR and PTT normal
• No medical or psychiatric conditions that would interfere with the ability to provide informed consent, communicate side effects, or comply with protocol requirements including maintenance of a compliance/pill diary
• Disease-free of prior invasive cancers for > 5 years except for basal or squamous cancer of the skin or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• Prior tamoxifen or aromatase inhibitors in the adjuvant setting allowed
• More than 3 months since prior luteinizing hormone-releasing hormone antagonists for patients ≤ 55 years of age
• More than 4 weeks since prior and no concurrent trastuzumab (Herceptin®)
• No prior EGF receptor inhibitors
• No more than 1 prior chemotherapy regimen for metastatic disease and recovered
• No concurrent chemotherapy

• No more than 1 prior hormonal therapy for metastatic disease, including any of the following:

  • Tamoxifen
  • Fulvestrant
  • Anastrozole
  • Exemestane
  • Aminoglutethimide
  • Megace
  • Letrozole
• Concurrent radiotherapy to painful bone metastases or areas of impending bone fracture allowed provided radiotherapy is initiated prior to study entry and sites of evaluable disease outside the radiation ports are available for follow up
• Recovered form prior radiotherapy