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Inclusion Criteria: * Patient with a diagnosis of breast cancer Exclusion Criteria: \-

Inclusion Criteria: 1. Written informed consent 2. Age 18 - 65 years inclusive at surgery 3. IMC \> 35 4. Subject qualified for bariatric surgery (sleeve gastrectomy or gastric bypass) 5. Specific criteria : * Type 2 diabetes group (D) (90 patients) : type 2 diabetes according to ADA criteria * Insulin resistance non diabetes group (IR) (80 patients) : HOMA-IR criteria ≥ 3 * Insulin Sensitivity non diabetes group (N) (100 patients) : N1.HOMA-IR criteria \< 3 Non inclusion Criteria: 1. Vulnerability according to article L1121-6 of the Public Health Code 2. Protected adult or unability to give consent according to article L1121-8 of the Public Health Code 3. Unability to understand the design and aims of the study or to communicate with the investigator 4. Non affiliation to a social security system 5. Prior bariatric surgery (except lap-band procedure) 6. Serologic profile indicating hepatitis B, hepatitis C or HIV infection 7. Inflammatory, infectious or autoimmune disease (current or in the previous 3 month) 8. Malignancies within 5 years prior to inclusion or not considered as treated curatively 9. Concomitant use of steroids or NSAI or use in the 8 days before surgery 10. alcohol abuse/addiction 11. Anticipated poor compliance to study procedures 12. Other type of diabetes than type 2 Exclusion Criteria : 1. Cancelled bariatric surgery 2. Tissue collection not possible during the bariatric surgery

Inclusion Criteria: * Women with histologically proven breast cancer * Aged 18 to 38 years old * Planned adjuvant chemotherapy * No prior chemotherapy * Affiliated to a public health insurance program * Informed consent signed by the patient Exclusion Criteria: * Metastatic breast cancer * Planned neo-adjuvant chemotherapy * Hysterectomy * Exclusive adjuvant hormonotherapy * Positive serology for syphilis, hepatitis B or C, or VIH * Contraindication related to use of r-FSH * Pregnant or breastfeeding patients

Inclusion Criteria: 1. Type-2 diabetes for at least six months, 2. ≥ 18 years of age, men or female, 3. Written informed consent to participate in the study and ability to comply with all requirements. Exclusion Criteria: 1. History of hypersensitivity to any of the investigated drugs as well as known or suspected contraindications to the study drugs or previous history of intolerance to high dose of RAS-Antagonist or Beta-blocker in the absence of any other blood pressure lowering drugs. 2. Patients already on maximum dose of RAS-antagonist or beta-blocker. 3. Creatinine \> 2.5mg/dl. 4. Symptomatic hypotension and/or systolic blood pressure (SBP) \< 100 mmHg at Visit 1. 5. Symptomatic bradycardia and/or heart rate (HR) \< 60 bpm at Visit 1 6. Signs of cardiac disease in the ECG such as atrial fibrillation; ST-T abnormalities or any bundle branch block / higher degree atrioventricular (AV) block. 7. Abnormal echocardiography, defined as low ejection fraction \< 50%; wall motion abnormalities suggesting coronary artery disease (CAD), significant valve dysfunction \> grade I or other significant alteration. 8. Coronary artery disease, defined by a history of myocardial infarction, known coronary stenosis \> 70% detected either by angiography or by CT-scan, significant defects in myocardial scintigraphy or positive stress-test echocardiography. 9. A disease other than T2DM lowering the patient's life expectancy to less than two years. 10. Chronic infections or malignancies. 11. Systemic treatment with corticosteroids. 12. Renal replacement therapy. 13. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels \> 40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception (implantable, patch, and oral), and double-barrier methods (if accepted by local regulatory authority and ethics committee). Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test (\> 5 U/ml). 15. History of noncompliance to medical regimes and patients who are considered potentially unreliable. 16. Current double blind treatment in diabetic trials. 17. Participation in an investigational drug study at the time of enrollment or within the past 90 days. Eligibility criteria for eye-substudy: Inclusion criteria: 1. Participation in the PONTIAC 2 Study 2. Written informed consent to participate in the eye-study Exclusion criteria: 1. Media opacities like cataract or vitreous hemorrhage 2. Active intraocular inflammation (grade trace or above) in either eye like infectious conjunctivitis, keratitis, scleritis, endophthalmitis as well as idiopathic or autoimmune-associated uveitis in either eye 3. Structural damage to the center of macula in the study eye 4. Atrophy of retinal pigment epithelium, subretinal fibrosis, laser scar within foveal avascular zone (FAZ) or organized hard exudate plaques 5. Ocular disorders in the study eye including retinal vascular occlusion, retinal detachment, macular hole, choroidal neovascularization, macula dystrophies 6. Intraocular surgery (including cataract surgery, Yttrium-Aluminium-Granat (YAG) laser capsulotomy) in the study eye within 3 months preceding Day 0 7. Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication) 8. History of glaucoma filtration surgery, corneal transplantation in the study eye 9. Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded 10. History of epilepsy

Inclusion Criteria: * Subjects with at least 1 lesion of tumor of the breast * Subjects must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Subjects who have been treated with radiation therapy on the chest. * Has had previous sentinel lymph node biopsy * Has a known hypersensitivity to ICG, methylene blue and 99mTc-colloid.

Inclusion Criteria: * Women and men with stage III adenocarcinoma of the breast harboring signs of a breast cancer with features of homologous recombination deficiency (HRD) * Age of 18-65 years * The tumor must be HER2-negative * Treatment must start within 8 weeks after the last surgical resection * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria: * Previous radiation therapy * Previous chemotherapy * Any previous treatment with a PARP-inhibitor, including olaparib * Pre-existing neuropathy from any cause in excess of Grade 1 * Chronic concomitant use of known strong or moderate CYP3A inducers

Inclusion Criteria: * Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including Screening evaluations. * Females, ≥18 years at time of study entry. * HLA-A2 positive by deoxyribonucleic acid (DNA) sequence analysis (by history or as part of this study). * Histopathological diagnosis of triple negative breast cancer(TNBC) (ductal, lobular, mixed or metaplastic), defined as estrogen receptor (ER)\<1%, progesterone receptor (PR)\<1%, and Human Epidermal growth factor Receptor 2 (HER2) negative according to American Society of Clinical Oncology/College of American Pathologists guidelines by local testing according to institutional standards. For tumors with equivocal interpretation of receptor status (e.g. "weak" or "faint" staining, the Principal Investigator will have final determination of triple negative status. * Completed all planned therapy for Stage II or III TNBC (American Joint Committee on Cancer, 7th Edition) meeting the following guidelines: * received neoadjuvant chemotherapy with residual invasive disease at surgery and/or completed adjuvant chemotherapy with or without radiation. (The patient may have had adjuvant and/or neoadjuvant chemotherapy for their disease). Adjuvant/neoadjuvant chemotherapy regimens must include at least 4 cycles of a standard chemotherapy regimen, and generally this should include one of the generally accepted standard regimens (including but not limited to: Adriamycin/Cytoxan-Taxol, Taxotere/Cytoxan, Adriamycin/Cytoxan, or Cytoxan/Methotrexate/Fluorouracil). For patients who received their standard chemotherapy as part of a clinical trial, the regimen should include at least 4 cycles of therapy. * All planned radiation therapy surgery for the treatment of the current cancer should be complete (not including plastic or reconstructive surgery). * Patients with local-regional recurrence without evidence of distant metastases (no definite stage IV disease) who are treated with curative intent may be eligible following completion of all surgery and/or chemotherapy and/or radiotherapy. Such patients must have no evidence of residual disease by standard clinical and radiological examination (per Investigator discretion) following completion of curative intent treatment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix B). * Adequate normal organ and marrow function as defined below: * Hemoglobin ≥9.0 g/dL. * absolute neutrophil count (ANC) ≥1.5 109/L (≥1500 per mm3). * Platelet count ≥100 109/L (\>100,000 per mm3). * Serum bilirubin ≤1.5 institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology). * aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 ULN. * gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), and alkaline phosphatase ≤2.5 ULN. * Serum creatinine clearance \>40 mL/min by the Cockcroft-Gault formula 72 or by 24-hour urine collection for determination of creatinine clearance: Females: Creatinine Clearance (mL/min) = Weight (kg) x (140 - Age) 0.85 72 x serum creatinine (mg/dL) * Negative virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B (surface antigen), and hepatitis C. * Female patients must either be of non-reproductive potential (i.e. post-menopausal by history of age ≥60 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test (β-human chorionic gonadotropin (HCG)) at the Screening visit. (If Screening visit pregnancy test was completed within 7 days of first treatment visit it does not need to be repeated. Patients with a negative pregnancy test at Screening beyond 7 days prior to treatment, but who otherwise meet all other criteria, may be registered to study but must have a repeat negative serum pregnancy test within 7 days of treatment and such testing may be done on day of first treatment prior to administration). * If not postmenopausal or surgically sterile, study patients must be willing to practice at least one of the following methods of birth control for at least a menstrual cycle before and after study drug administration: (1) Total abstinence from sexual intercourse with a male; (2) Sexual intercourse with vasectomized male partner; (3) Other acceptable forms of birth control (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicide or cream); (4) Use of an intrauterine contraceptive device. * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Exclusion Criteria: * Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). * Previous enrollment in the present study. * Receipt of the last dose or treatment of anti-cancer therapy for the current cancer (chemotherapy, radiotherapy, surgery, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤4 weeks (6 weeks for nitrosoureas or mitomycin C) or \>6 months prior to first dose of study drug. * Any unresolved clinically significant treatment related toxicity of ≥Grade 1 intensity, as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), from previous anti-cancer therapy. Patients with irreversible toxicity (eg, hearing loss, peripherally neuropathy) or reversible toxicity (eg, alopecia) that is not reasonably expected to be exacerbated by the investigational product and is not expected to interfere with study participation may be included. * Participation in another clinical study with an investigational product during the previous 4 weeks. * Any previous treatment with a programmed cell death protein 1 (PD1) or PD-L1 inhibitor, including durvalumab. * Stage IV disease, confirmed by biopsy or unequivocal radiographic evidence (note: staging scans are not required, but should be performed at treating physician discretion in accordance with standard guidelines). * Mucinous or tubal histology or other good prognosis histology. * Ongoing or planned systemic anti-cancer therapy or radiation therapy. * Pregnant or nursing. * Known hypersensitivity to any component of the investigational product (PVX-410, durvalumab, or any excipient). * Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction. * Active or prior documented active autoimmune disease that has required systemic treatment. Note: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. * Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic (oral or iv) corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. * Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis). * History of primary immunodeficiency. * History of allogeneic organ transplant. * Uncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have evidence of acute or chronic hepatitis B, hepatitis C or HIV) * Psychiatric

Eligibility criteria 1. True resistant hypertension (≥ 3 antihypertensive drugs including a diuretic, if tolerated, and each prescribed at optimal doses) and uncontrolled blood pressure confirmed by 24-hour ambulatory blood pressure monitoring. The 24-hour ambulatory blood pressure monitoring is performed after nurse-administered medication and blood pressure measurements are performed hourly. If the average 24-hour ambulatory systolic blood pressure is ≥ 130 mmHg the patient can be evaluated for renal artery stenosis. 2. Hypertension and intolerance or side effects of the antihypertensive treatment. Hypertension is confirmed by 24-hour ambulatory blood pressure monitoring. The 24-hour ambulatory blood pressure monitoring is performed after nurse-administered medication and blood pressure measurements are performed hourly. If the average 24-hour ambulatory systolic blood pressure is ≥ 130 mmHg the patient can be evaluated for renal artery stenosis. 3. Progressive renal insufficiency (a reduction in eGFR \> 5 ml/min/1,73 m2 per year) in patients with bilateral renal artery stenosis or in patients with renal artery stenosis and only one kidney. 4. Recurrent heart failure/pulmonary edema and resistant hypertension (≥ 3 antihypertensive drugs including a diuretic, if tolerated, and each prescribed at optimal doses) that may not be attributed to non-compliance, reduced left heart ventricular ejection fraction/heart valve disease or other obvious explanations (atrial fibrillation, fever, hyperthyroidism etc.). If the average 24-hour ambulatory systolic blood pressure is ≥ 130 mmHg after nurse-administered medication the patient can be evaluated for renal artery stenosis. 5. Younger patients (\< 40 years) with hypertension (24-hour ambulatory blood pressure monitoring ≥ 130/80 mmHg after nurse-administered medication ) Inclusion Criteria: All of the following: 1. At least one of the above eligibility criteria 2. Duplex doppler ultrasonography or renography investigations consistent with hemodynamically significant renal artery stenosis 3. CT angiography or renal arteriography with angiographic renal artery stenosis of ≥ 70 % reduction of the luminal diameter in at least one projection Exclusion Criteria: 1. If angiography/arteriography, ultrasonography or renography is consistent with bilateral significant renal artery stenosis and only one side is treated with PTRA 2. PTRA of a renal artery supplying a kidney which pre-PTRA handles ≤ 10% of the total kidney function (with no blockage of the renin-angiotensin system) and has a kidney size \< 7 cm (length)

Inclusion Criteria for Women with Stage I - III Breast Cancer: * Stage I-III female breast cancer (including inflammatory and newly diagnosed or locally recurrent breast cancer) but not metastatic breast cancer being treated with curative intent * \> 18 years old * Scheduled to receive chemotherapy and/or estrogen antagonist aromatase inhibitors (anastrozole \[Arimidex\], letrozole \[Femara\], exemestane \[Aromasin\]). * Able to hold breath for 10 seconds * ECOG performance status 0 -2 * Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting * Able to exercise on a treadmill or stationary cycle * Participants in other ongoing clinical trials are eligible for this study Exclusion Criteria for Women with Stage I-III Breast Cancer: * Those with ferromagnetic cerebral aneurysm clips or other intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted non-compatible MRI devices (patients with tissue expanders will not be excluded) * If previously measured, known LVEF \<50% * Symptomatic claustrophobia * Unable to provide informed consent * At the beginning of the study, pregnant women and women who are breast-feeding will not be enrolled. * Severe pulmonary hypertension * Within the past 6 months: * Acute pulmonary embolus * Deep vein thrombosis * Within the past month: * Heart attack * Unstable or stable angina (cardiac chest pain) * Left main coronary artery disease * Symptomatic heart failure * Uncontrolled hypertension (SBP \> 180 mm Hg or DBP \> 120 mm Hg) * Severe valvular heart disease * Uncontrolled metabolic disease (diabetes with fasting BS \>300 mg/dl, thyrotoxicosis, myxedema) * Aortic aneurism (\>45 mm diameter) or aortic dissection * Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise * Hypertrophic obstructive cardiomyopathy * Patient does not understand English Inclusion Criteria for Women Free of Cancer for Comparison: * Healthy female without known coronary artery disease \> 18 years old * Able to hold breath 10 seconds * ECOG performance status = 0 or 1 * Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting * Able to exercise on a treadmill or stationary cycle * No personal history of cancer other than superficial skin cancers * Has never received chemotherapy, radiation therapy, immunotherapy, or had breast cancer related surgery * If previously measured, LVEF ≥ 50% Exclusion Criteria for Women Free of Cancer for Comparison: * Inflammatory conditions such as lupus or inflammatory bowel disease * Overt coronary artery disease or heart failure * Those with ferromagnetic cerebral aneurysm clips or other intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted non-compatible MRI devices * Symptomatic claustrophobia * Unable to provide informed consent * At the beginning of the study, pregnant women or women who are breast feeding will not be enrolled. * Severe pulmonary hypertension * Within the past 6 months: * Acute pulmonary embolus * Deep vein thrombosis * Within the past month: * Heart attack * Unstable or stable angina (cardiac chest pain) * Left main coronary artery disease * Symptomatic heart failure * Uncontrolled hypertension (SBP \> 180 mm Hg or DBP \> 120 mm Hg) * Severe valvular heart disease * Uncontrolled metabolic disease (diabetes with fasting BS \>300 mg/dl, thyrotoxicosis, myxedema) * Aortic aneurism (\>45 mm diameter) or aortic dissection * Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise * Hypertrophic obstructive cardiomyopathy * Patient does not understand English

Inclusion Criteria: Be willing and able to provide written informed consent/assent for the trial. * Be 18 years of age on day of signing informed consent. * HER2-negative breast cancer (defined by immunohistochemistry (IHC) 0-1 (or) IHC 2 and in situ hybridization (ISH) HER2 / centromere on chromosome 17 (CEP17) \< 2.0); * ER and PR-negative breast cancer (defined by IHC\<1%); * Measurable metastatic or unresectable disease based on response evaluation criteria in solid tumours (RECIST) 1.1. * Indicated for treatment with either weekly paclitaxel or oral capecitabine, as first or second-line chemotherapy in the metastatic/unresectable setting (as determined by the consenting investigator); * Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained during screening. Archival tissue is acceptable if no intervening anti-neoplastic therapy has been administered, and if sufficient material is available for analysis (see section 8.0 for requirements); * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Demonstrate adequate organ function as defined by protocol defined lab values * Female subjects of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female subjects of childbearing potential must avoid becoming pregnant while on treatment. Men must avoid fathering a child while on treatment. Exclusion Criteria: * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. * Has a known history of active TB (Bacillus Tuberculosis) * Hypersensitivity to pembrolizumab or any of its excipients. * Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study, Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Denosumab is allowed. * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy and alopecia are an exception to this criterion and may qualify for the study. * Has received the assigned chemotherapy regimen previously in the metastatic setting, or has received the assigned chemotherapy regimen previously in the (neo)adjuvant setting within 12 months of consent; * If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Has a known additional malignancy that progressed or required active treatment in the last 5 years. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has history of/active pneumonitis requiring treatment with steroids or history of/active interstitial lung disease. * Has an active infection requiring systemic therapy. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. * Has received prior therapy with an anti-programmed death 1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), or anti-programmed death ligand 2 (anti-PD-L2) agent or has participated in a Merck-sponsored pembrolizumab study. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B or Hepatitis C. * Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Inclusion Criteria: * Have a diagnosis of HR+, HER2- breast cancer. Although not required as a protocol procedure, metastatic disease should be considered for biopsy whenever possible to reassess hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status if clinically indicated. * To fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least 1 of the HRs (estrogen receptor \[ER\], progesterone receptor \[PgR\]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. * To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined in the relevant ASCO/CAP guidelines. * Meet either Inclusion Criterion (2a) or Inclusion Criterion (2b). Participants meeting Inclusion Criterion 2a will be enrolled in Cohort A and participants meeting Inclusion Criterion 2b will be enrolled in Cohort B. * (2a) Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease. * Relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and have received no prior endocrine therapy for locoregionally recurrent or metastatic disease (Note: prior adjuvant endocrine therapy for localized disease may have included, but is not limited to, anti-estrogens or aromatase inhibitors. In addition, a participant may be enrolled if she has received ≤2 weeks of NSAI in this disease setting immediately preceding screening and agrees to discontinue NSAI until study treatment initiation.) OR * Presented with de novo metastatic breast cancer (mBC) and not received any prior endocrine therapy. OR * Relapsed with radiologic evidence of progression less than 1 year from completion of or while receiving adjuvant endocrine therapy (except for letrozole or anastrozole) and have received no prior endocrine therapy for locoregionally recurrent or metastatic disease. * (2b) Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease. * Relapsed with radiologic evidence of progression while receiving neoadjuvant or adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression OR * Relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression OR * Relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as firstline endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease OR * Presented with de novo metastatic disease and then relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease. * Have postmenopausal status defined as meeting at least 1 of the following: * Prior bilateral oophorectomy * Age ≥60 years * Age \<60 years and amenorrheic for at least 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone (FSH) and estradiol levels in the postmenopausal range. * Have 1 of the following, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: * Measurable disease * Nonmeasurable bone-only disease. Nonmeasurable bone-only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft tissue component, or mixed lytic-blastic bone lesions without a measurable soft tissue component. * Have a performance status (PS) of ≤1 on the Eastern Cooperative Oncology (ECOG) scale. * Have adequate organ function, including: * Hematologic: absolute neutrophil count (ANC) ≥1.5 × 109/Liter (L), platelets ≥100 × 109/L, and hemoglobin ≥8 g/deciliter (dL). Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after the erythrocyte transfusion. * Hepatic: Total bilirubin ≤1.5 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 times ULN (or ALT and AST ≤5 times ULN if liver metastases are present). * Renal: serum creatinine ≤1.5 times ULN. * Have discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture at least 2 weeks prior to randomization and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy. * Are able to swallow capsules. * Are reliable, willing to be available for the duration of the study, and willing to follow study procedures. Exclusion Criteria: * Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis. Visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease. * Have inflammatory breast cancer. * Have clinical evidence or a history of central nervous system (CNS) metastasis. Screening test is not required for enrollment. * Are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer. (Note: Participants may be enrolled if they received prior \[neo\]adjuvant chemotherapy for localized disease.) * Have received prior treatment with everolimus or fulvestrant (for Cohort B only). * Have received prior treatment with any cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) inhibitor (or participated in any CDK4 and CDK6 inhibitor clinical trial for which treatment assignment is still blinded). * Have initiated bisphosphonates or approved Receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents \<7 days prior to randomization. * Are currently enrolled in a clinical trial involving an investigational product (IP) or non-approved use of a drug or device (other than the IP/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. If a participant is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and Eli Lilly and Company (Lilly) clinical research physician (CRP) is required to establish eligibility. * Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively. * Have had major surgery within 14 days prior to randomization to allow for post-operative healing of the surgical wound and site(s). * Have received recent (within 28 days prior to randomization) live attenuated vaccines such as yellow fever vaccine. * Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (eg, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis). * Have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular

Inclusion Criteria: 1. Participants male and female aged 8 years old and older. 2. Participants have no smoking history. 3. For participants with CF and asthma, a clinical diagnosis is necessary and they should be at their baseline level of symptom control based on history. 4. Participants should have a FEV1%pred value greater than 40%. 5. Participant understands the study procedures and is willing to participate in the study as indicated by signature on the informed consent or assent. 6. Participant must be able to perform a breath hold for 20s or less. 7. Participant able to perform reproducible pulmonary function tests (i.e., the 3 best acceptable spirograms have FEV1 values that do not vary more than 5% of the largest value or more than 100 ml, whichever is greater). For the PEx sub-cohort, admission to the Hospital for Sick Children for a pulmonary exacerbation (based on clinical or pulmonary function assessment). Children who will be admitted and then discharged on home IV antibiotics may also be included in this study. Exclusion Criteria: 1. Participant is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent/assent from being obtained, or cannot read or understand the written material. 2. Participant has a history of cardiovascular disorders including coronary insufficiency, cardiac arrhythmias, severe hypertension. 3. Other than for the PEx sub-cohort, participant has had a cold or respiratory infection in the last four weeks. 4. Participant requires supplemental oxygen or has a daytime room air oxygen saturation ≤ 95%. 5. Participant is unable to perform spirometry or plethysmography maneuvers. 6. Participant is pregnant or lactating. 7. In the investigator's opinion, participant suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia. 8. Participant has an MRI incompatible device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bio prosthetic, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants). \-

Inclusion Criteria: * Histologically-confirmed primary invasive breast cancer within 5 years of study entry * Qualifying risk status, at diagnosis utilizing receptor testing by ASCO/CAP guidelines, meeting at least one of the following: * Pathologically-confirmed invasive breast cancer in axillary lymph nodes, regardless of receptors * Primary tumor with triple negative subtype: estrogen receptor (ER) \< 10%, progesterone receptor (PR) \< 10% and negative Her2-overexpression by ASCO-CAP guidelines * Primary tumor that is ER+/Her2 negative/Lymph node negative with a Breast Cancer Recurrence Score of ≥ 25 per the Genomic Health Oncotype DX breast cancer test and/or HighRisk MammaPrint * Evidence of residual disease in the breast on pathologic assessment after neoadjuvant chemotherapy * Completed all primary therapy (surgery, (neo)adjuvant chemotherapy, adjuvant radiation, and/or Her2-directed therapy) for the index malignancy at least 4 weeks prior to study entry. Concurrent receipt of adjuvant endocrine therapy and bone modifying agents is allowed per standard of care. However, tamoxifen is not allowed on recurrence prevention trials that use Hydroxychloroquine. Patients on tamoxifen may still be enrolled on Penn-Surmount as long as the treating physician is aware and tamoxifen can be stopped if patient is DTC positive. * No evidence of local or distant recurrent disease by physical examination, blood tests (CBC, LFTs, Alk Phos), or symptom-directed imaging, per NCCN guidelines. * Adequate bone marrow function as shown by: ANC \>/= 1.5x10\^9/L, Platelets \>/= 100x10\^9/L, Hb \> 9 g/dL * Adequate liver function as shown by: Serum bilirubin \</= 1.5 x ULN, ALT and AST \</= 2.5 x ULN, and INR \</= 1.5 * Normal coagulation studies: PT and PTT ≤ 1.5 x upper limit of normal per institutional laboratory range * Anti-coagulation is allowed if target INR \</= 1.5 on a stable dose of warfarin or on a stable dose of anticoagulant for \>2 weeks at time of enrollment. For patients on therapeutic anti-coagulants, medication must be clinically held peri-procedure (bone marrow aspirate) per standard clinical management. * Adequate renal function: serum creatinine \</= 1.5 x ULN * Willing to undergo bone marrow aspiration and blood specimen collection per protocol specifications * Age 18 or over and able to give informed consent Exclusion Criteria: * Concurrent enrollment on another investigational therapy * Patients receiving chronic, high dose systemic treatment with corticosteroids defined as: chronic use of cortisone \>50mg; hydrocortisone \>40mg, prednisone \>10mg, methylprednisone \>8mg or dexamethasone \>1.5mg; or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed. * EKG demonstrating QTC \> 480 ms * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * History or evidence of increased cardiovascular risk including any of the following: (i) current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation, (ii) History of acute coronary syndromes (including myocardial infarction and unstable angina, coronary angioplasty, or stenting within 6 months prior to enrollment, (iii) Current \>/= Class II congestive heart failure as defined by New York Heart Association * History of pneumonitis/interstitial lung disease or severely impaired lung function with a previously documented spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air * Uncontrolled diabetes * Active (acute or chronic) or uncontrolled severe infections * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis * A known history of HIV seropositivity as reported by the patient * History of major surgical resection involving the stomach or small bowel, or pre-existing impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, Crohn's disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) * Patients with an active, bleeding diathesis * History of retinopathy or retinal vein occlusion * Female patients who are pregnant or breast feeding. Women of childbearing potential must have a negative urine or serum pregnancy test. * Patients who have received prior treatment with a CDK4/6 inhibitor * Patients with a known hypersensitivity to Hydroxychloroquine or any of its derivatives * Patients with prior hydroxychloroquine exposure for a duration of \> 1 month since the completion of the patient's primary therapy (definitive surgery, (neo)adjuvant chemotherapy, adjuvant radiation, and/or Her2-directed therapy) for the index malignancy * Patients who have initiated bone modifying agents within 3 months prior to study enrollment * A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.

The study population for Step 1 must meet the following eligibility criteria: Inclusion Criteria: * Stage 1, 2 or 3 invasive breast cancer which is triple negative. Triple negative breast cancer is defined as ER \<1, PR \<1 and HER2 0 or 1+ or FISH not amplified if IHC 2+. * AR testing may be performed while patient is undergoing other adjuvant therapy (i.e., surgery, chemotherapy, radiation). * Willing and able to provide informed consent. Woman at least 18 years of age. * Patient is a candidate for treatment of their early stage breast cancer. The study population for Step 2 will meet the eligibility criteria: Inclusion Criteria: * Stage 1, 2 or 3 invasive breast cancer which is triple negative. Triple negative breast cancer is defined as ER \<1%, PR \<1% and HER2 0 or 1+ or FISH not amplified if IHC 2+. * AR(+), defined as ≥1% nuclear staining by IHC testing. The assessment of AR expression may have been performed any time in the past and is not limited to participation in Step 1. * Any neoadjuvant or adjuvant chemotherapy regimen is permitted. Prior chemotherapy for the treatment of this breast cancer is not required. * At least 4 weeks from end of surgery, chemotherapy, or radiotherapy with resolution of any toxicity to Grade 1 or less, excluding alopecia. * Patients are eligible to participate within 6 months of completion of therapy for their breast cancer. This includes prior radiation therapy if needed. * ECOG performance status of 0 or 1. * Willing and able to provide informed consent. * Woman at least 18 years of age. * Able to swallow study drug and comply with study requirements. * Women of childbearing potential must have a negative pregnancy test and must agree to use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. * Is not breastfeeding at screening and will not breastfeed throughout the study period and for at least 3 months after final drug administration. Exclusion Criteria: Each patient eligible to participate in this study must NOT meet any of the following exclusion criteria. * Any severe concurrent disease, infection or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator or interferes with the patient's ability to participate in the study requirements. * Evidence of metastatic/Stage 4 breast cancer * History of another invasive cancer within 5 years with the exceptions of nonmelanoma skin cancers and AJCC Stage 0 or 1 cancers that have a remote probability of recurrence in the opinion of the investigator * Absolute neutrophil count \< 1500/μL, platelet count \< 75,000/μL, or hemoglobin \< 9 g/dL (5.6 mmol/L). * Total bilirubin \> 1.5 times upper limit of normal (ULN) unless an alternate nonmalignant etiology exists (eg, Gilbert's disease). Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times ULN. * Creatinine \> 1.5 times ULN or an estimated creatinine clearance \< 50 mL/minute calculated using the Cockcroft-Gault equation. * History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past. Also, history of loss of consciousness or transient ischemic attack within 12 months before day 1 * An active gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer disease, uncontrolled celiac) * Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole and butylated hydroxytoluene.

Inclusion Criteria: * Histological diagnosis of invasive or in-situ ductal carcinoma (DCIS) * Treated by breast conserving surgery with axillary node dissection (with a minimum of 6 nodes sampled) or sentinel lymph node biopsy * Surgical margins clear for invasive carcinoma (no tumor at ink margin) or superior or equal to 2 mm for in-situ ductal carcinoma (DCIS) * A maximum tumor size of 3 cm * Age ≥50 years old * Informed consent signed if participating in the Registry Exclusion Criteria: * No previous cancer unless in remission for more than 2 years. * Active auto immune disorder with severe vasculitis component * Uncontrolled and complicated insulin-dependent diabetes * Pregnancy * Cosmetic breast implants * Psychiatric or addictive disorder that would preclude attending follow-up * Post-operative breast infection requiring prolonged antibiotic therapy * Lobular features on histology (pure or mixed) or sarcoma histology * Node macroscopically positive on axillary dissection or in the sentinel lymph node biopsy * Extensive in- situ carcinoma * Multicentric disease (in more than one quadrant or separated by 2 cm or more) * Paget's disease of the nipple * Metastases * Patients presenting with a large post-surgical fluid cavity as determined on the planning Ultrasound (US), resistant to the application of hot compresses for 4 weeks * Clear delineation of the target volume on Computerized Tomography (CT) is not possible * Volume to be implanted over 150cc * Target volume too close to skin such that the 90% isodose overlaps the skin surface

Inclusion Criteria: * American Society Anesthesiology (ASA) Scale I and II patients * Patients submitted to breast cancer * informed consent signature Exclusion Criteria: * Patients with chronic pain * Local anesthesia reaction/allergy

Inclusion Criteria: 1. Enrolled in the Women in Recovery (WIR) program and reporting problems with: 1. Anxiety and/or depressive symptoms 2. Trauma-related symptoms 3. Problems related to substance use 4. Problems related to eating behavior 2. Screened positive for problems in (1) as indicated by: 1. Patient Health Questionnaire (PHQ-9) ≥ 10 and/or Overall Anxiety Severity and Impairment Scale (OASIS) ≥ 8. 2. PTSD Checklist (PCL) ≥30 3. Drug Abuse Screening Test (DAST-10) score \> 2 4. Eating Disorder Screen (SCOFF) score ≥ 2 3. Have a body mass index between 17 to 38 kg/m² 4. Able to provide written informed consent. 5. Have sufficient proficiency in English language to understand and complete interviews, questionnaires, and all other study procedures. Exclusion Criteria: 1. No telephone or easy access to telephone. 2. Has a history of unstable liver or renal insufficiency; glaucoma; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbance; or any other condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments. 3. A positive test for drugs of abuse, including alcohol (breath test), cocaine, marijuana, opiates, amphetamines, methamphetamines, phencyclidine, benzodiazepines, barbiturates, methadone, and oxycodone. 4. Has any of the following Diagnostic and Statistical Manual (DSM-V) disorders: 1. Schizophrenia Spectrum and Other Psychotic Disorders 2. Bipolar and Related Disorders 3. Obsessive-Compulsive and Related Disorders 5. Moderate to severe traumatic brain injury or other neurocognitive disorder 6. Active suicidal ideation with intent or plan. 7. Change in the dose or prescription of a medication within the 6 weeks before enrolling in the study that could affect brain functioning 8. Prescription of a medication outside of the accepted range, as determined by the best clinical practices and current research. 9. Taking drugs that affect the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, excessive caffeine intake \> 1000 mg/day) 10. MRI contraindications 11. Unwillingness or inability to complete any of the major aspects of the study protocol Non-correctable vision or hearing problems

Inclusion Criteria: * Pregnant women Exclusion Criteria: * Pre-existing diabetes before the index pregnancy

Inclusion Criteria: A patient will be eligible for androgen receptor expression testing (STEP 1) if the following criteria are met: * Female * Pathologically confirmed invasive cancer of the breast * ER/PR status (ER or PR defined as positive if ≥1%; ER/PR is defined as negative if \<1%): * Phase I: Patients may have ER/PR(-) breast cancer. * HER2 normal (IHC 0-1; FISH \< 2.0) * Non-measurable or measurable, metastatic disease * Available tissue for AR testing for research purposes A patient will be eligible for participation in the therapeutic trial (STEP 2) if the following criteria are met: * Androgen receptor expression testing confirms that the patient's tumor is AR (+). AR is considered positive if ≥1% of cell nuclei are immunoreactive using the Dako antibody (clone AR441). Receptor testing may be performed on either primary tumor specimen or tissue from a metastatic site. Local testing permitted for eligibility but will require confirmation at MSKCC. * There is no limit to the number of prior chemotherapy or endocrine therapy regimens allowed. Patients with ER(+) AR(+) breast cancer must have had at least 1 prior line of endocrine therapy to be eligible for the phase I portion of the trial. * At least 2 weeks since last cytotoxic chemotherapy, hormonal therapy, or radiotherapy. Toxicities related to prior therapy must either have returned to grade 1, or baseline (excluding alopecia) * Patient may receive bisphosphonates/denosumab for the palliation of bone metastases * If patient has a history of brain metastases or leptomeningeal disease, lesions must be stable for at least 3 months (as documented by either head CT or brain MRI) * Prior treatment with bicalutamide will not be allowed * At least 3 weeks from major surgery with full recovery * ECOG performance status 0-2 * Age 18 years or greater * Postmenopausal. Use of LHRH agonist permitted. * Patients must not have another, non-breast, active malignancy that requires treatment. * The effects of palbociclib on the developing human fetus at the recommended therapeutic dose are unknown. Women of child-bearing potential must agree to use adequate contraception (barrier method of birth control; abstinence). Women must not breast feed while on study. * Ability to understand and the willingness to sign a written informed consent document. * Ability to swallow intact palbociclib capsules and bicalutamide tablets. * Adequate organ and marrow function as defined below (ULN indicates institutional upper limit of normal): * Absolute neutrophil count ≥ 1.5 10\^9/ * Hemoglobin ≥ 9.0 g/dL * WBC ≥ 3.0 10\^9/L * Platelets ≥ 100 10\^9/L * Total bilirubin ≤ 1.5 ULN except for patients with known Gilbert syndrome * AST(SGOT)/ALT(SGPT) ≤ 3 institutional ULN * Plasma creatinine ≤ 1.5 ULN or Creatinine Clearance \> 50 mL/min (calculated by Cockcroft-Gault method) * QTc interval ≤ 470 msec Exclusion Criteria: * Patients who have not recovered from adverse events of prior therapy to ≤ NCI CTCAEv4.0 Grade 1. * Patients receiving any other investigational anti-cancer agents. * Patients who have received prior treatment with a selective CDK4/6 inhibitor * Patients who have received prior anti-androgen therapy * History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib. * Uncontrolled intercurrent illness including, but not limited to, known ongoing or active infection, including HIV, active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (specifically, uncontrolled atrial fibrillation or ventricular dysrhythmias except ventricular premature contractions), or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women and women who are breast-feeding. * Patients with a history of long-QT syndrome or documented family history of long-QT syndrome. Patients who must remain on drugs that prolong the QT interval. * Palbociclib is a substrate of CYP3A. Caution should be exercised when dosing palbociclib concurrently with CYP3A inducers or inhibitors. Furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk.

Inclusion Criteria: 1. Written informed consent 2. Female or male patients with breast cancer confirmed by histology 3. Tumor and blood samples available. Luminal B type confirmed by immunohistochemistry or, preferably, genomic profiling using Next-Generation Sequencingwith ER ≥120% and Ki67 ≥20% and not HER2 amplified, or, if aged 40 or younger and/or verified lymph node metastases, luminal A type, defined as ER and PR positive ≥20% and the proliferation marker Ki 67 \<20% and not HER2 amplified. Any luminal B, Luminal A with verified lymph node metastases and/or aged 40 or younger 4. Age 18 years or older. Elderly patients in condition adequate for planned therapy 5. Primary breast cancer \>20mm in diameter and/or verified regional lymph node metastases 6. Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders 7. LVEF \>55% 8. ECOG performance status 0-1 9. Primary breast cancer as defined in p. 5 plus at most 2 morphologically characterized well-defined distant metastases accessible for stereotactic radiotherapy, provided that this treatment is available Exclusion Criteria: 1. Distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum 2. Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix 3. Patients in child-bearing age without adequate contraception 4. Pregnancy or lactation 5. Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders