Patient description: The patient is a 45-year-old postmenopausal woman with cytologically confirmed breast cancer. A core biopsy revealed a 3 cm invasive ductal breast carcinoma in the left upper outer quadrant. The tumor is HER2-positive and ER/PR negative. Axillary sampling revealed 5 positive lymph nodes. CXR was remarkable for metastatic lesions. The patient is using multivitamins and iron supplements. She does not smoke or consume alcohol. She is not sexually active and has no children. She is a candidate for tumor resection and agrees to do so prior to chemotherapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-99.0,  Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer Patients eligible for in this Treatment Plan have to meet all of the following Written patient informed consent must be obtained prior to start of treatment. 1. Patient is an adult female (≥ 18 years of age) with advanced (locoregionally recurrent not amenable to curative therapy or metastatic) hormone receptor-positive, HER2-negative breast cancer 2. Patient has documented evidence of a mutation in the PIK3CA gene as determined in tumor tissue or plasma by a local laboratory. 3. If female, then the patient is postmenopausal. Postmenopausal status is defined either by Prior bilateral oophorectomy Age ≥60 Age <60 and amenorrheic for ≥12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and Follicle-stimulating Hormone (FSH) and estradiol in the postmenopausal range per local normal range 4. Patient has evidence of recurrence or progression during or after AI therapy (i.e. letrozole, anastrozole, exemestane). AI therapy does not need to be the latest treatment regimen. 5. Patient has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory. 6. Patient has adequate bone marrow and organ function as defined by the following laboratory values: 1. Absolute neutrophil count ≥ 1.5 × 1.000.000.000/L 2. Platelets ≥ 100 × 1.000.000.000/L 3. Hemoglobin ≥ 9.0 g/dL 4. Calcium (corrected for serum albumin) within normal limits or ≤ grade 1 according to NCI-CTCAE version 4.03 if judged clinically not significant by the Treating Physician, or corrected with supplements 5. INR ≤ 1.5 6. Creatinine clearance ≥ 35 mL/min using Cockcroft-Gault formula 7. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN. If the patient has liver metastases, ALT and AST ≤ 5 × ULN (elevated AST or ALT values must be stable for 2 weeks, without evidence of biliary obstruction by imaging) 8. Total serum bilirubin < 2 x ULN (any elevated bilirubin should be asymptomatic at enrollment) except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN 9. Potassium within normal limits, or corrected with supplements 10. Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L)* and Glycosylated Hemoglobin (HbA1c) ≤ 6.4% (both have to be met) *For patients with FPG ≥ 100 mg/dL and/or HbA1c ≥5.7% (i.e. threshold for prediabetes), recommend lifestyle changes according to ADA or similar local diabetes guidelines, i.e. dietary advice (e.g. small frequent meals, low carbohydrate content, high fiber, balancing carbohydrate intake over the course of the day, three small meals and 2 small snacks rather than one large meal) and exercise. A consultation with a diabetologist is highly recommended. 11. Fasting Serum amylase ≤ 2 × ULN 12. Fasting Serum lipase ≤ ULN  Patients eligible for this Treatment Plan must not meet any of the following 1. Patient has history of hypersensitivity to any drugs or metabolites of PI3K inhibitor or any of the excipients of alpelisib. 2. Patient with uncontrolled diabetes mellitus type I or not controlled type II (based on FPG and HbA1c, see criterion 6) 3. Patient has a known history of severe cutaneous reactions like Steven Johnson's syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 4. Patient has a known history of Human Immunodeficiency Virus (HIV) infection. 5. Patient has not recovered to grade 1 or better (except for alopecia) from related side effects of prior antineoplastic therapies. 6. Patient has other prior or concurrent malignancy, with the exception of adequately treated basal or squamous cell skin cancer or other in situ cancer, or any other cancer from which the patient has been disease-free for ≥ 3 years. 7. Patient has central nervous system (CNS) involvement, except for patients fulfilling the following 3 1. Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of program treatment and 2. CNS tumor is clinically stable at the start of program treatment and 3. Patient is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases 8. Patient who has other concurrent severe and/or uncontrolled medical conditions that would, in the Treating Physician's judgment, contraindicate administration of alpelisib (e.g. active or uncontrolled severe infection, chronic active hepatitis, immunocompromised, acute or chronic pancreatitis, uncontrolled high blood pressure, intersticial lung disease, severe GI impairment, etc) based on treating physician's discretion 9. Subject has currently documented pneumonitis/interstitial lung disease 10. History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis 11. Patients with unresolved osteonecrosis of the jaw 12. Patient who is concurrently receiving any of the following medications and cannot be discontinued 7 days prior to the start of the treatment: 1. Strong inducers of CYP3A4 2. Inhibitors of BCRP 13. Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to start of program treatment, or who have not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular). 14. Male patient who does not apply highly effective contraception during the treatment with alpelisib and through the duration as defined below after the final dose of alpelisib. Sexually active males should use a condom during intercourse while taking drug and for at least 4 weeks after stopping alpelisib and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. 15. Patient is not able to understand and to comply with treatment instructions and requirements