Inclusion Criteria:

          -  Patient is male or female 18 years or older

          -  Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer
             not amenable to curative therapy

          -  In case of women, both premenopausal and postmenopausal patients are allowed to be
             included in study; menopausal status is relevant for the requirement of LHRH agonist
             (examples for use in this study include but not limited to goserelin, leuprolide or
             locally available treatment) to be used concomitantly with alpelisib and
             letrozole/fulvestrant

               1. Patient is postmenopausal woman defined as either:

                    -  Prior bilateral oophorectomy or

                    -  Age ≥60 or

                    -  Age <60 and amenorrhea for 12 or more months (in the absence of
                       chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or
                       estradiol in the postmenopausal range per local normal range.

                  If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma
                  estradiol levels should be in post-menopausal range per local normal range.

                  Note: For women using therapy-induced amenorrhea other than ovarian radiation,
                  goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are
                  needed to ensure menopausal status

               2. Patient is premenopausal defined as either:

                    -  Patient had last menstrual period within the last 12 months or

                    -  If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and
                       FSH must be in the premenopausal range per local normal range, or

                    -  In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be
                       in the premenopausal range per local normal range

          -  Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC

          -  Patient has confirmed HER2-negative advanced breast cancer (aBC)

          -  Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient
             has a pathology report confirming PIK3CA mutant status by certified laboratory (using
             validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send
             tumor tissue to Novartis designated central lab for confirmation of mutational status

          -  Patient must have:

               -  Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor
                  combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior
                  to study entry,

               -  AI treatment (either in adjuvant or metastatic setting) and received systemic
                  chemotherapy or ET(as monotherapy or in combination except CDK 4/6i + AI) as last
                  treatment regimen in cohort C

               -  Maintenance therapies, where applicable, must be regarded as part of the main
                  treatment.

               -  No more than two (2) prior anti-cancer therapies for aBC

               -  Received no more than one prior regimen of chemotherapy in the metastatic setting

          -  Patient has either measurable disease per RECIST v1.1 or at least one predominantly
             lytic bone lesion must be present

          -  ECOG performance status ≤ 2

          -  Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated
             hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)

          -  Patient has adequate bone marrow, coagulation, liver and renal function

        Exclusion Criteria:

          -  patient has known hypersensitivity to alpelisib, fulvestrant or letrozole

          -  Patient has received prior treatment with any PI3K inhibitors

          -  Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type
             II

          -  Patient has a concurrent malignancy or malignancy within 3 years of study screening
             period, with the exception of adequately treated, basal or squamous cell carcinoma,
             non-melanoma skin cancer or curatively resected cervical cancer

          -  Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation
             ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from
             related side effects of such therapy

          -  History of acute pancreatitis within 1 year of screening or past medical history of
             pancreatitis

          -  Patients with central nervous system (CNS) involvement unless they meet ALL of the
             following criteria:

               -  At least 4 weeks from prior therapy completion (including radiation and/or
                  surgery) to starting the study treatment

               -  Clinically stable CNS tumor at the time of screening untreated or without
                  evidence of progressions for at least 4 weeks after treatment as determined by
                  clinical examination and brain imaging (MRI or CT) during screening period and
                  stable low dose of steroids for 2 weeks prior to initiating study treatment

          -  Patient with severe liver impairment (Child Pugh score B/C)

          -  Patient has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drugs

          -  Patient has documented pneumonitis/interstitial lung disease which is active and
             requiring treatment

          -  Patient has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome
             (SJS), Erythema Multiforme (EM), Toxic Epidermal Necroloysis (TEN) or Drug Reaction
             with Eosinphilia and Systemic Symptoms (DRESS).

          -  Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must
             be discontinued prior to day one of study treatment.

          -  Subjects with unresolved osteonecrosis of the jaw.