Clinical Study for the Treatment of Breast Cancer: the Patient Will Receive Afatinib Plus Letrozole or Letrozole Alone

Inclusion Criteria:

* Signed and dated informed consent.
* Postmenopausal females, 18 years of age or older.
* Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of locally recurrent disease not amenable to resection or radiation therapy with curative intent, or metastatic disease.
* HER2 negative breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is HER2 negative by FISH or Immunohistochemistry (IHC).
* ER positive breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is ER+ with low expression (H-score \[1-159\]).
* Paraffin-embedded tumor block(s) or 15 to 20 unstained slides available for centralized assessment of ER, PR, and HER2.
* Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 or bone-only non measurable disease.
* Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
* Adequate hematological, hepatic and renal functions.
* Baseline left ventricular ejection fraction (LVEF) 50%.
* Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

* Brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
* Prior treatment with any type of systemic therapy for advanced disease.
* Prior treatment with letrozole in (neo)adjuvant setting with disease-free interval ≤ 12 months from completion of treatment until randomization.
* Prior treatment with any anti HER-family targeted therapy in (neo)adjuvant setting.
* Any concurrent or previous malignancy within 5 years prior to randomization, except for adequately and radically treated basal or squamous skin cancer, or carcinoma in situ of the cervix, or other non-invasive/in-situ neoplasm.
* Non-measurable disease according to RECIST 1.1, with the exception of bone-only non-measurable disease.
* Known pre-existing interstitial lung disease.
* Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom.
* History or presence of clinically relevant cardiovascular abnormalities as per investigator assessment.
* Any other concomitant serious illness or organ system dysfunction as per investigator assessment
* Any contraindication to oral agents.
* Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
* Known or suspected active drug or alcohol abuse.
* Known hypersensitivity to afatinib or letrozole or the excipients of any of the trial drugs.
* Concomitant treatment with strong inhibitor of P-gp.
* Any ongoing acute clinically significant toxic effect of prior anticancer therapy or any persisting complication of prior surgery.
* Subjects with known history of keratitis, ulcerative keratitis or severe dry eye.
* Participation in the active phase of other clinical trials of investigational agents in which last study treatment was administered within 2 weeks prior to randomization