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Inclusion Criteria: * Pregnant women visiting a trial facility up to the end of the 28th week of gestation * Women who are planning to remain within the five study districts until at least one-month post-partum OR women whose mothers reside in the selected districts Exclusion Criteria: • Women coming to the trial facility for a non-routine ANC visit (for example, to get a laboratory investigation, to collect a report or her medicine)

Inclusion Criteria: 1. Ages 12 years and older 2. Ability to provide informed consent 3. Ability to perform pulmonary function tests 4. Female participants of childbearing potential must have a negative urine pregnancy test upon study entry 5. Female participants with reproductive potential must agree to use FDA-approved methods of birth control for the duration of the study2 6. Participant-reported physician or licensed medical practitioner diagnosis of asthma 7. Treatment with medium to high dose ICS (400 mcg to maximum of 2000 mcg per day of fluticasone propionate or equivalent) for at least 3 months with a stable dose ≥1 month prior to screening OR used a biologic medication for asthma within the past 8 weeks 8. History of asthma exacerbation in the past year An exacerbation is an asthma attack for which a clinician prescribed a course of systemic (oral, IV, IM) steroids whether or not the patient took the steroids OR An increase of \>50% of baseline inhaled corticosteroid dose for ≥3 days OR An unscheduled visit for acute asthma attack (licensed medical practitioner/nurse office, urgent care intervention, emergency department, or hospitalization) Exclusion Criteria: 1. Chronic lung disease other than asthma, which may impair lung function 2. Current smoker or cessation of smoking ≤6 months prior to Visit 0 screening 3. Current use of any electronic (e) "vaping" device (e.g., e-cigarette, e-cig, mod, vape pen, JUUL, e-cigar, e-hookah, e-pipe, vape pods) or cessation ≤ 6 months prior to screening 4. Pregnant or breast feeding 5. Any other condition or abnormality that, in the opinion of the Principal Investigator, would compromise the safety of the patient or quality of data 6. Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures 7. Planning to relocate away from the clinical center area before study completion 8. Currently participating in an investigational drug trial or participated in one within 30 days before screening 9. Currently being treated with immunosuppressive/immunomodulatory or other investigational agents or biologics for conditions other than asthma, or used a biologic for a non-asthma indication within the past 6 months 10. History of respiratory illness requiring antibiotics or systemic corticosteroids, including asthma exacerbations, within the past 4 weeks (evaluated at time of screening visit) 11. History of alcohol or illicit substance abuse within 6 months of screening 12. Neutropenia (\<1,000/mm3) or thrombocytopenia (\<100,000/mm3) or hemoglobin \< 100 g/L (10 g/dL) or blood eosinophils \> 1500/mm3 at screening 13. Administration of a live vaccine within 4 weeks of screening 14. Currently receiving allergen immunotherapy (food or aeroallergen) other than an established maintenance regimen implemented continuously for a minimum of 2 months. Individuals receiving aeroallergen immunotherapy must be willing to stay on it for the duration of the study.

Inclusion Criteria: * Has a localized invasive breast ductal adenocarcinoma, confirmed by the local pathologist, that includes either T1c-T2 (tumor size ≥2 cm), clinical node stage (cN)1-cN2, or T3-T4, cN0-cN2. Note: Inflammatory breast cancer is allowed. * Has centrally confirmed ER+/HER2-, Grade 3 breast cancer of ductal histology, according to the most recent American Society of Clinical Oncology/College of American Pathologist guidelines. * Provides a new or recently obtained core needle biopsy, consisting of multiple cores, taken from the primary breast tumor(s) for central determination of HR status (ER and progesterone receptor), HER2, grade, and PD-L1 status. Note: Sponsor agreement is required for formalin-fixed paraffin-embedded (FFPE) tumor tissue sample or slides that were obtained greater than 60 days prior to the date that the documented informed consent was obtained. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment. * Male participants must agree to use contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment and refrain from donating sperm during this period. * Female participants must agree to use effective contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment with pembrolizumab or placebo. * Has adequate organ function. Exclusion Criteria: * Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis. * Has breast cancer with lobular histology. * Has bilateral invasive breast cancer. * Has metastatic (Stage IV) breast cancer. * Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast). * Has any of the following clinical lymph node staging per current American Joint Committee on Cancer (AJCC) staging criteria for breast cancer staging based on radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c. * Has ER-, progesterone receptor positive breast cancer. * Has undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment. * Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal breast carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. * Has an 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) Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Has a known history of active tuberculosis (Bacillus tuberculosis). * Has an active infection requiring systemic therapy. * Has left ventricular ejection fraction (LVEF) of \<50% or below the institution limit of normal, as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening. * Has other significant cardiac disease, such as: 1) History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months. or 2) Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV. * Has a known history of human immunodeficiency virus (HIV) infection. * Has a known history of hepatitis B or known active hepatitis C virus infection. * Has received prior treatment for breast cancer. * Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX 40, CD137). * Has received a live vaccine within 30 days prior to the first dose of study treatment. * Has severe hypersensitivity (≥Grade 3) to any of the components or excipients used in the study treatments. * Is/was enrolled in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks (12 months for an investigational agent or device with anticancer or antiproliferative properties) prior to the first dose of study treatment. * Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment.

Inclusion Criteria: * Have histologically confirmed new diagnosis of breast cancer according to biopsy or surgery Exclusion Criteria: * Patients who are not mentally capable of giving written informed consent * Serum samples doesn't qualified * Patients who refuse follow-up on their conditions * Patients with prior cancer history * Patients with a diagnosis of other severe acute or chronic medical may increase the risk associated with study participation or may interfere with the interpretation of the study results and, in the judgement of the Investigator, would make the patient inappropriate for enrollment in this study

Inclusion Criteria: * Men and women older than 18 years-old; * Suffering from a Mood Depressive Episode ( according to DSM IV criteria), and-or Mood Depressive recurrent depression (unipolar or bipolar) (\<at stage 3 of Thase and Rush). Treatment resistance will be assessed using Thase an Rush Classification and measured with Maudsley Staging Method (Fekadu et al., 2009); * MADRS score 15; * Capacity for the patient to receive information on protocol; * Patient who gave their consent to the protocol. Exclusion Criteria: * Contra-indication to MRI * Patients under social protection or hospitalized without their consent * Patients suffering from a psychiatric comorbidity such as: schizophrenia, schizo-affective disorder, personality disorder, actual addiction, anorexia-bulimia, obsessive-compulsive disorder; * Patients suffering from severe intercurrent disease with health prognosis engaged; * Patients suffering from neurological comorbidity such as: any neurodegenerative disorder (Alzheimer disease, Parkinson disease, Lewy's body disease, multiple sclerosis), any intracranial expansive process. * Patients with an history of severe cranial injury (with coma); * Patients with abnormal cerebral MRI.

Inclusion Criteria: * Patient - 1. Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures. 2. Is aged ≥ 18 years 3. Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following: 1. Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition 2. Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit 3. Malignancy has relapsed after standard therapy 4. Malignancy for which there is no standard therapy that improves survival by at least 3 months 4. Has evaluable tumor(s) by standard radiological and/or laboratory assessments as applicable to their malignancy - in Part 3, patients with solid tumors must have least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 criteria, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI). In the case of patients with glioblastoma multiforme (GBM) or other central nervous system (CNS) tumors, the tumor must be measurable, defined as a clearly enhancing tumor with at two perpendicular diameters at entry equal or superior to 1cm. 5. Has laboratory function within specified parameters (may be repeated): 1. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/mL 2. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN 3. Adequate renal function: creatinine clearance ≥ 60 mL/min (Cockcroft and Gault) 4. Adequate blood coagulation: international normalized ratio (INR) ≤ 2.3 5. Serum amylase and lipase ≤ 1.5 x ULN 6. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG) PS 0-2 7. Has received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug (unless in the opinion of the investigator and the study medical coordinator the treatments/ procedures will not compromise patient safety or interfere with study conduct and with IDMC agreement): * Chemotherapy, immunotherapy, or systemic radiation therapy - 14 days or ≥ 5 half-lives (whichever is shorter) * Focal radiation therapy - 7 days * Systemic and topical corticosteroids - 7 days * Surgery with general anesthesia - 7 days * Surgery with local anesthesia - 3 days 8. May continue endocrine therapies (e.g. for breast or prostate cancer) and/or anti-human epidermal growth factor (Her2) therapies while on this study 9. Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal or barrier method of birth control, or true abstinence) for the duration of study participation and in the following 90 days after discontinuation of study treatment 10. Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 90 days after discontinuation of study treatment and use appropriate barrier contraception or true abstinence 11. Must not be receiving any other investigational medicinal product Exclusion Criteria: * Patient - 1. Is pregnant or lactating 2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation 3. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as ≤ Grade 2 CTCAE Version 4.03 4. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening 5. Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator or study medical coordinator 6. Has known symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Patients with stable asymptomatic brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug 7. Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major) 8. Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation 9. Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial 10. Has a current active malignancy other than the target cancer 11. Is considered to be a member of a vulnerable population (for example, prisoners) Part 3 ARMB Inclusion Criteria: Patient - 1. Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures 2. Is aged ≥ 18 years 3. Has pathologically confirmed metastatic pancreatic cancer AND is previously untreated with systemic agents in the recurrence/metastatic setting. 4. Must have at least 1 measurable lesion per RECIST v1.1, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI) 5. Has laboratory function within specified parameters (may be repeated): e. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 75,000/mL f. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤ 10 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN Adequate renal function: creatinine clearance ≥ 30 mL/min (Cockcroft and Gault) 6. Has Eastern Co-operative Oncology Group (ECOG) PS 0 or 1 7. Has received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug: * Focal radiation therapy - 7 days * Surgery with general anesthesia - 7 days * Surgery with local anesthesia - 3 days 8. May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment 9. May have received neoadjuvant chemotherapy with FOLFIRINOX if last dose given at least 6 months before study enrollment 10. May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if last

Inclusion Criteria: Infants will be eligible for this study if their mother, father, or an older sibling has a self-reported history of at least one of the following conditions: * asthma, * eczema/atopic dermatitis, * hay fever/ allergic rhinitis or * food allergy Exclusion Criteria: infants with any of the following will be excluded: * A parent who has a known hypersensitivity to any of the ingredients of EpiCeram™ will be excluded, as it would be difficult for these parents to apply EpiCeram™ to their infant, and there is likely to be an increased risk of the infant reacting to the cream. * Multiple births (twins, triplets etc.) will be excluded, due to the difficulty in randomising individual twins and because of the clustering effect of multiple children from the same family which would reduce the effective sample size of the study. * Who are born premature (\<36 weeks) as the effect of the intervention may be different in premature infants. * Who have major birth or early life medical complications that require admission into a special care nursery, as it will be difficult for parents to comply with the study requirements. * Whose parents do not have sufficient English language skills to be able to answer questions. * Whose parents are not able to comply with all protocol required visits and procedures

1. Woman or man, with or without cancer, carrying a deleterious BRCA1/BRCA2 mutation, aged 18 years and over. 1. Woman with or without breast cancer or ovarian cancer at baseline. 2. Man with or without breast cancer at baseline. 2. Signed consent to participation 3. Affiliation to a social security regimen, or beneficiary of such a regimen. Exclusion Criteria: 1. A person of legal age subject to a legal protection measure, or unable to express consent. 2. Impossibility to submit to the follow-up of the test for geographical, social or psychological reasons

Inclusion Criteria: * Newborn has newborn screening in North Carolina * Newborn lives in North Carolina or South Carolina * Newborn is less than 31 days old * Person giving consent must have legal custody of the newborn. When the mother retains custody, they must be the person to give consent. * Person giving consent must be able to interact with the online permission portal (available in English and Spanish) and give permission online Exclusion Criteria: * A newborn screening (NBS) sample is unavailable for the newborn * Insufficient NBS sample remains to conduct the screening

Cohort 1: Children, Adolescents and Young Adults (Cohort 1) Inclusion: Individuals must meet all the following criteria to be eligible for this study. 1. Patient, parent, or legal guardian must have given written informed consent. For patients ≥ 168 years of age who are developmentally able, assent or affirmation will be obtained. 2. Age 8-24, inclusive, at time of consent. 3. Diagnosed with Systemic Sclerosis (SSc) at the age of ≤19. 4. Failure to respond, specifically no improvement or progression of disease, to at least 2 disease-modifying antirheumatic drugs (DMARDS) within 12 months of consent with any of the following conditions: 1. Progression of skin thickening over the past 6 months or Modified Rodnan skin score (mRSS) ≥ 20 2. Progression of ILD within 18 months prior to consent. Progression to be determined by either of the following: * CT scan showing increased ground glass opacities or reticulations OR * Pulmonary function testing (PFTs) showing a decrease in FVC% or DLCO% predicted value of ≥10%. 3. Myositis - CPK \> 2x upper limit of normal or MRI consistent with myositis 4. Childhood Myositis Assessment Score \< 30 5. Arthritis 6. Digital tip ulcerations 5. Cardiology clearance to undergo stem cell transplantation (documented in subject's medical chart) 6. Negative for human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, all confirmed by PCR testing. 7. Negative pregnancy test for females. who have reached menarche. 87\. All females of childbearing potential and sexually active males must agree to use an FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect. Exclusion: Individuals who meet any of these criteria are not eligible for this study. 1. FVC \<35%, determined by pulmonary function tests for those able to complete spirometry adequately (per investigator's determination) 2. O2 sat \<92% at rest in room air 3. Estimated CrCl \<40 mL/min,using Cockcroft-Gault formula based on actual body weight. 4. Active, untreated SSc renal crisis at the time of consent. 5. ALT \> 4x upper limit of normal. 6. Active, uncontrolled infection that would be a contraindication to safe use of high-dose immunosuppressive therapy or cyclophosphamide. 7. Hematologic abnormalities as defined by any of the following peripheral blood counts: 1. ANC \< 1500 cell/µL. 2. Platelets \< 100,000 cells/ µL. 3. Hemoglobin \< 9.0 g/dL. 8. Malignancy within 2 years prior to enrollment, excluding adequately treated squamous cell cancer, basal cell carcinoma or carcinoma in situ. Treatment should have been completed with cure/remission status documented for at least 2 years. 9. Past or current medical problems or findings from medical history, physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. Cohort 2 for Adults Inclusion: Individuals must meet all the following criteria to be eligible for this study. 1. Patient, parent, or legal guardian must have given written informed consent. For patients ≥ 16 years of age who are developmentally able, assent or affirmation will be obtained. 2. Age 1618-705560, inclusive, at time of consent. Patients up to age 24, diagnosed with SSc at age ≤ 19, will be included in Cohort 1 and evaluated according to the Pediatric and Young Adult criteria listed in sections 3.1.1 and 3.1.2. 3. Diagnosed with Systemic Sclerosis (SSc), according to the 2013 ACR/EULAR criteria (van den Hoogen et al., 2013). 4. All patients must meet either the following skin or ILD criteria. Disease duration is defined as time from first non-Raynaud symptom. Skin Criteria: Diffuse SSc, defined by presence of proximal skin thickening and: A. If disease duration is of \<2 years, patients must have a calculated mortality risk prediction score which places them in the intermediate or high- risk category (Domsic et al., 2016). Refer to Appendix 5 for calculation criteria. B. If disease duration is of \>2 years, patients must have evidence of active cutaneous disease based upon 1) a worsening Modified Rodnan Skin Score (MRSS) in the preceding three months or 2) the presence of palpable tendon friction rubs. ILD Criteria: A. The presence of recognized fibrosis on imaging of \<2 years AND either \> 10% of lung involvement by CT scan or FVC% pred \<80% or B. Fibrosis on imaging of any duration with a decline in FVC% pred of ≥10% over the preceding 12-18 months. 5. Negative for human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, all confirmed by PCR testing. 6. Negative pregnancy test for females. 7. All females of childbearing potential and sexually active males must agree to use an FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect. Exclusion Criteria Individuals who meet any of these criteria are not eligible for this study. 1. Moderate to severe cardiac involvement defined by any of the following: 1. New York Heart Association classification of heart failure ≥3. 2. Left ventricular ejection fraction (LVEF) \<50% as determined by cardiac MRI. 3. Significant pulmonary hypertension, for subjects ≥ 18 years of age, defined as mean PASP ≥30 mmHg determined by right heart catheterization, or for subjects ≤ 17 years of age, defined as mean PASP \>45 mmHg, determined by echocardiogram. 4. Atrial tachycardia, atrial fibrillation or atrial flutter of ≥1-minute duration, determined by electrocardiogram (EKG) or, cardiac event monitor and/or implanted loop recorder (if applicable), or on anti-arrhythmic therapy for the arrhythmias listed above. 5. Ventricular tachycardia of ≥6 beats at rate of ≥100 beats per minute, determined by EKG or, cardiac event monitor and/or implanted loop recorder (if applicable), or on an anti-arrhythmic therapy for any ventricular arrhythmia. 6. Left bundle branch block, bifascicular heart block, Mobitz 2 heart block, complete heart block or infarction pattern as determined by EKG or, cardiac event monitor and/or implanted loop recorder 7. Presence of pacemaker or implantable cardioverter defibrillator. 2. Moderate to severe pulmonary involvement defined by any of the following: 1. Hemoglobin-corrected DLCO \<45%, determined by pulmonary function tests. 2. FVC \<45%, determined by pulmonary function tests. 3. pO2 \<70 mmHg, determined by an arterial blood gas (not applicable for subjects ≤17 years of age). 4. pCO2 ≥45 without supplemental O2 determined by an arterial blood gas (not applicable for subjects ≤17 years of age). 5. O2 sat \<92% at rest without supplemental O2, determined by an arterial blood gas (not applicable for subjects ≤17 years of age). 6. Six-minute walk (6MW) results \<400 feet. 3. Steroid therapy defined by either of the following: 1. Subjects who received \> 10 mg/day prednisone or equivalent within 30 days prior to start of conditioning regimen on Day -21. 2. Subjects who have been treated for concurrent illnesses (eg, asthma) with the equivalent of prednisone 1 mg/kg/day or its equivalent for \> 5 days on \> 2 occasions during the previous 12 months (prior to conditioning) or \> 1 occasion in the prior 6 months (prior to conditioning). 4. Estimated CrCl \<40 mL/min,using Cockcroft-Gault formula based on actual body weight. 5. Serum creatinine \>2.0 mg/dL. 6. Active, untreated SSc renal crisis at the time of consent. 7. Dependence on nutritional supplementation/hyperalimentation. 8. Active gastric antral vascular ectasia

Inclusion Criteria: * ECOG performance status of 0-1; * Metastatic or locally advanced unresectable HER2-negative breast cancer (by NCCN criteria); * Triple Negative Breast Cancer tumors will require confirmation of androgen-receptor (AR) positivity at screening (refer to laboratory manual for guidelines). Local testing permitted for eligibility if reviewed by a designated study pathologist; * RECIST1.1 measurable disease; * Participants must be willing (if clinically feasible) to provide a fresh tumor biopsy (or archived tissue). For archived tissue, a tissue block from the most recent biopsy is acceptable if no intervening anti-neoplastic therapies have been administered since the time of biopsy. * Previous systemic chemotherapy: no greater than one line of previous chemotherapy in non-curative setting; subjects with metastatic progression within 1 year following completion of curative-intent chemotherapy are eligible if they have not received any additional lines of systemic therapy in the non-curative setting. * Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal patient care. * Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study * Adequate hematologic and liver function (using CTCAE v4). (All baseline laboratory requirements will be assessed and should be obtained within 14 days prior to enrollment): WBC≥2000/μL; Neutrophils≥1500/μL; Platelets≥100 × 103/μL; Hemoglobin ≥9.0 g/dL; AST≤3 × ULN; ALT ≤3 × ULN; Total bilirubin ≤1.5 × ULN (except in participants with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL). Subjects with elevations in LFTs related to underlying hepatic cancer involvement may be considered for enrollment (after discussion with lead PI) if ALT/AST is ≤5 x ULN and Total bilirubin ≤3 × ULN. * Female and Age ≥18 years. (Men are excluded because of potential confounding effects of sex on correlative analyses) * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment. * Women must not be breastfeeding * Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of birth regulation for the duration of treatment with study treatment(s) for a total of 5 months post-treatment completion. Exclusion Criteria: * Active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI except where contraindicated in which CT scan is acceptable) evidence of progression for at least 2 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. Cases must be discussed with the lead PI, Dr. Page. Brain lesions are not considered measurable disease. * Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix. Subjects with prior history of unrelated breast cancer not requiring active therapy may be considered for enrollment, but require discussion with and approval of PI; * Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results. * Participants must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before enrollment. * Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. * Uncontrolled adrenal insufficiency. * New York Heart Association (NYHA) Functional Classification of Heart Failure: Class III or Class IV * All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. Participants with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy grade 2 or less, are permitted to enroll * Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit obtaining informed consent or compliance with study requirements. * Participants who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation. * Participants with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. * Has known active hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA is detected); * History of allergy or hypersensitivity to study drug components * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody in the metastatic setting, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Previous treatment with anti-PD-1/L1 in the curative setting is allowed if subjects have not received such therapy within one year of screening. * Prior treatment with bicalutamide, enzalutamide, or any other androgen receptor blocker. * Use of an investigational agent within 4 weeks of Day 1 visit

Inclusion Criteria: * Patients must have histologically and/or cytologically confirmed diagnosis of breast cancer, that is advanced/metastatic/recurrent or unresectable, for which no curative therapy exists, either: * Negative for ER, PR and HER2 by ASCO/CAP criteria (COHORT 1) OR * Positive for ER and or PR and negative for HER2 AND * loss or mutation of PTEN, as assessed by IHC assay (COHORT 2) OR * No loss or mutation of PTEN, as assessed by IHC assay (COHORT 3) For the patients entered on the PK/safety component only, results of the PTEN status may be documented after enrollment * Only female patients will be enrolled. * All patients must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block. Biopsies are optional but strongly encouraged for patients with accessible disease suitable for biopsy. The timing of tumour biopsies for patients who provide informed consent and willing is prior to treatment (after enrollment), and again between cycle 2 day 15- day 22. An additional biopsy at the time of progression in patients with clinical benefit is also encouraged. Lesions planned for biopsy may not be the only target lesion. * Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 21 days prior to enrollment (within 28 days if negative). * All patients must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows: Chest x-ray ≥ 20 mm CT scan (with slice thickness of 5 mm) ≥ 10 mm --\> longest diameter Physical exam (using calipers) ≥ 10 mm Lymph nodes by CT scan ≥ 15 mm --\> measured in short axis * Patients must be ≥ 18 years of age. * Patients must have an ECOG performance status of 0 or 1. * Patients must have a life expectancy of 3 months or longer. * Laboratory Requirements (must be done within 7 days prior to enrollment) Absolute neutrophils ≥ 1.5 x 10\^9/L Platelets ≥ 100 x 10\^9/L Bilirubin ≤ 1.5 x ULN (upper limit of normal) AST and ALT ≤ 2.5 x ULN; ≤ 4.0 x ULN if patient has liver metastases Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 50 mL/min * Patients must be able to swallow oral medications and have no known gastrointestinal disorders that may interfere with absorption (such as malabsorption). * Patients must have had at least 1 prior line of cytotoxic chemotherapy for breast cancer, in any setting, which must have included an anthracycline and a taxane (unless contraindicated). Select patients that have not received both anthracycline and taxane therapy may be considered eligible after discussion with CCTG. There is no limit to the number of prior chemotherapy regimens * Patients may have received other therapies including endocrine therapy, immunotherapy, and/or targeted therapies (including CDK4/6 inhibitors). * Patients must have recovered (to at least grade 0 or 1) from all reversible toxicity related to prior chemotherapy or systemic therapy and have adequate washout as follows: * Longest of one of the following: * Two weeks, * 5 half-lives for investigational agents * Standard cycle length of standard therapies. * Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of enrollment. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiotherapy is not permitted. * Previous surgery is permitted provided that a minimum of 21 days (3 weeks) have elapsed between any major surgery and date of enrollment and that wound healing has occurred. * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. * Patients must be accessible for treatment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. * In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment. * Women of childbearing potential must have agreed to use a highly effective contraceptive method Exclusion Criteria: * Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \> 2 years and which do not require ongoing treatment. * Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. * Patients are not eligible if they have a known hypersensitivity to the study drug(s) or their components. * Patients with HER2 positive breast cancer (based on the most recent assessment). * Patients with significant cardiac (including uncontrolled hypertension) or pulmonary disease, or active CNS disease or infection. Patients should have a LVEF ≥ 50%. * Patients may not receive concurrent treatment with other anti-cancer therapy (other than bone-targeted therapy, if already taking and stable) or investigational agents while on protocol therapy. * Patients who have received growth factors within 28 days prior to initiation of dosing of CFI-400945 or who will require treatment with growth factors throughout the duration of the trial. * Pregnant or breastfeeding women. * Patients being treated with drugs listed in Appendix V Table 1 are excluded. Patients being treated with drugs listed in Appendix V Table 2 may be enrolled, but should be monitored carefully for toxicities resulting from potential interactions between CFI-400945m and these drugs. In addition, patients must avoid consumption of the fruit or juice of Seville oranges (e.g. marmalade), grapefruit, pomelos and star fruit from 7 days before the first dose of study drug and during the entire study due to potential CYP3A4 interaction with the study drug. Regular orange juice is allowed. * Patients with history of central nervous system metastases or spinal cord compression unless they have received definitive treatment, are clinically stable and do not require corticosteroids. * Patients with any medical condition that would impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled nausea or vomiting. * Patients being treated with full dose warfarin. Patients with history of deep vein thrombosis or pulmonary embolus who are being treated with therapeutic doses of low molecular weight heparin, direct factor Xa inhibitors or prophylactic dose anticoagulants may be enrolled

Inclusion Criteria: 1. Age of ≥ 18 years 2. Female 3. Life expectancy of a least 12 weeks 4. Body weight above 35kg 5. The locally recurrent or metastatic relapse must be histologically confirmed TNBC in patients not previously treated with systemic treatment and which cannot be treated with curative intent. Newly diagnosed patients with de-novo metastatic disease are eligible 6. Estrogen receptor (ER) and progesterone receptor (PR) negativity (\< 1% positive staining cells in the invasive tumour) determined locally using IHC per ASCO/CAP criteria 7. Human epidermal growth factor receptor 2 (HER2) negativity (negative IHC staining \[score 0 or 1\] or negative fluorescence in situ hybridization \[FISH\] based on the ASCO/CAP guidelines and recommendations) and determined locally59 Note: patients initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer OR de novo metastatic patients with a primary tumor hormone receptor-positive (weak positivity or ER negativity and PR positivity) considered as non-clinically relevant are eligible if the tumor biopsy obtained from a local recurrence or distant metastasis site confirms the TNBC disease. 8. Confirmed tumour PD-L1 and CD73 IHC assessment as documented through central testing of a representative tumour tissue specimen for stratification purposes (only for phase II) 9. Provision of recurrence/metastatic tissue samples from resections, core-needle biopsies or excisional, incisional, punch, or forceps biopsies: * at least 1 FFPE \[Formalin-Fixed paraffin-embedded\] tumour tissue and 1 frozen core as a priority, if feasible 2 additional fresh tumour tissue cores should be collected too) * Fine-needle aspiration (FNA) (defined as samples that do not preserve tissue architecture and yield cell suspension and/or smears), brushing, and cell pellets from cytology samples are not acceptable. Note 1: If the patient has just performed a metastatic lesion biopsy, she is eligible only if an archived FFPE tissue sample (or at least 20 unstained slides, freshly cut for the purposes of the study) of the metastatic lesion is available. In this situation only, frozen/fresh cores are not mandatory. Note 2: In case of a de-novo metastatic disease, if a biopsy of a metastatic lesion is not feasible, the patient is eligible if a biopsy of the primary lesion is available. 10. Provision of an archived FFPE diagnostic biopsy or surgical primary breast tumour sample (or at least 20 unstained slides, freshly cut for the purposes of the study). Note: In case of neoadjuvant treatment (before surgery), the diagnostic biopsy is preferable. 11. At least 6 months elapsed between the completion of treatment with curative intent (e.g., the date of primary breast tumour surgery or the date of last adjuvant chemotherapy administration, whichever occurred last) and first documented local or distant disease recurrence (NOTE: not applicable for de-novo metastatic disease) 12. At least one measurable disease based on RECIST v1.1. Tumour lesions in a previously irradiated area are considered measurable, if progression has been demonstrated in such lesions 13. Adequate organ function: 1. Absolute neutrophil count (ANC) ≥ 1500/μl (without the addition of growth factors) 2. Platelets \[PLT\] ≥ 100000/μl (without the addition of growth factors/prior transfusions) 3. Hemoglobin (Hb) ≥ 10 g/dl (without the addition of growth factors/prior transfusions) 4. Creatinine ≤ 1.5 x upper limit of normal (ULN) OR estimated glomerular filtration rate (eGFR) ≥ 60 ml/min as calculated using the method standard for the institution. If eGFR is lower than 60 ml/min, a 24-hour urine creatinine clearance can be performed to rule out an underestimation of the eGFR. 5. Total serum bilirubin (TBL) ≤ 1.5 x ULN unless the subject has documented Gilbert syndrome in which case up to 3 x ULN is acceptable 6. Aspartate and alanine aminotransferase (AST/ALT) ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤ 5 x ULN 7. International Normalized Ratio (INR) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as INR and activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants 14. Performance status (PS) of 0 or 1 on the ECOG Performance scale 15. Female subjects of childbearing potential (FSCP) must be willing to use one highly effective method of contraception (detailed at protocol section 6.6.) for the course of the study through 6 months after the last study drug administration. FSCP must have a negative serum pregnancy test done within the 28 days before treatment start. FSCP are those who have not been surgically sterilized or have not been free of menses for at least 1 year. 16. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 17. Absence of any concurrent illness that would preclude the evaluation of safety 18. Agreement to provide tissue and blood samples for research purposes 19. Written informed consent must be given according to ICH/GCP, and national/local regulations before patient enrolment 20. Applicable to France only: Affiliated to the French Social Security System Exclusion Criteria: 1. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: 1. Patients with vitiligo or alopecia 2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement 3. Any chronic skin condition that does not require systemic therapy 4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician 5. Patients with celiac disease controlled by diet alone 2. Current or prior treatment with immunosuppressive medication within 14 days prior to enrolment. The following are exceptions to this criterion: 1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) 2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent 3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication 3. Any live, attenuated vaccine administered within 28 days prior to enrolment or anticipation that such a live attenuated vaccine will be required during the study 4. Chronic daily treatment with non-steroidal anti-inflammatory drug (NSAID) (occasional use for the symptomatic relief of medical conditions, for example, headache, fever is allowed) 5. Active infection including 1. Tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice) 2. Hepatitis B (known positive HBV surface antigen (HBsAg) result). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. 3. Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 4. Human immunodeficiency virus (positive HIV 1/2 antibodies). 6. Treatment with systemic immunostimulatory agents, including but not limited to, interferon (IFN)-alpha, IFN-beta, interleukin (IL)-2, conjugated IL-2 cytokines within 42 days or five half-lives of the drug, whichever is longer, prior to screening 7. Previous treatment with immune checkpoint inhibitors

Inclusion Criteria: 1. Signed written informed consent. 2. \>= 18 years 3. Any menopausal status: 1. Pre-menopausal women must have commenced treatment with an LHRH agonist at least 4 weeks prior to starting AZD9833 (± combination IMP(s)) and must be willing to continue to receive LHRH agonist therapy for the duration of the study 2. Post-menopausal defined according to standard criteria in the protocol. 4. Histological or cytological confirmation of adenocarcinoma of the breast 5. Documented positive oestrogen receptor status of primary or metastatic tumour tissue, according to the local laboratory parameters.HER-2 negative. 6. Metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit 7. Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP 8. Prior chemotherapy, endocrine therapy and other therapy as follows: 1. No more than 2 lines of chemotherapy for advanced disease 2. Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting 3. There is no limit on the number of lines of prior endocrine therapies 4. Prior treatment with CDK4/6 inhibitors is permitted 9. Women of childbearing potential must agree to use a highly effective contraceptive measure, must not be breast feeding, and must have a negative pregnancy test prior to the start of dosing. 10. At least one lesion (measurable and/or non-measurable, as per RECIST 1.1 that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, or plain X-ray; or clinical examination. Blastic-only lesions in bone are not considered assessable. 11. ECOG/ WHO performance status 0 to 1, with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks Inclusion criteria for the paired tumour biopsy research: Inclusion criteria for the paired tumour biopsy research 12. Disease suitable for paired baseline and on-study tumour biopsies 13. Washout from prior fulvestrant: 6 months 14. Washout from prior tamoxifen: 4 months 15. Signed written informed consent for tumour biopsies Exclusion Criteria 1. Intervention with any of the following 1. Any cytotoxic chemotherapy, investigational agents/other anti-cancer drugs for the treatment of advanced breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of IMP 2. Concomitant medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5, sensitive CYP2B6 substrates, and drugs which are sensitive substrates of CYP2C9 and/or CYP2C19, and which have a narrow therapeutic index. In addition: Parts E and F will exclude the concomitant use of moderate CYP3A4 and/or Pgp inhibitors; Parts G H, I, J, K and L will exclude the concomitant use of moderate CYP3A4/5 inhibitors and inducers; Parts I and J will exclude concomitant use of sensitive substrates of CYP3A4 and/or CYP2D6 with a narrow therapeutic index." 3. Drugs known to prolong QT and known risk of Torsades de Pointes 4. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP, except patients receiving radiotherapy to more than 30% of the bone marrow/a wide field of radiation within 4 weeks of the first dose of IMP 5. Major surgical procedure/significant traumatic injury, as judged by the investigator, within 4 weeks of the first dose of IMP, or an anticipated need for major surgery and/or any surgery requiring general anaesthesia during the study. 2. Any unresolved toxicities from prior therapy \> CTCAE Grade 1 at the time of starting IMP, with the exception of alopecia. 3. Presence of life-threatening metastatic visceral disease, as judged by the investigator, uncontrolled CNS metastatic disease. Patients with spinal cord compression and/or brain metastases may be enrolled if definitively treated (eg, surgery or radiotherapy) and stable off steroids for at least 4 weeks prior to start of IMP 4. Past medical history of ILD (Parts E, F, K and L only) 5. Currently symptomatic radiotherapy-induced pneumonitis (Parts E, F, K and L only) 6. Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) 7. Any of the following cardiac criteria 1. Mean resting QTcF \>470 msec obtained from a triplicate ECG (≥450 msec for Parts K and L) 2. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, second- and third-degree heart block), or clinically significant sinus pause. Patients with controlled atrial fibrillation can be enrolled c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome, or unexplained sudden death at \<40 years of age. Hypertrophic cardiomyopathy and clinically significant stenotic valve disease (d) LVEF \<50% and/or experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade ≥2, cerebrovascular accident, or transient ischaemic attack. (e) Uncontrolled hypertension. Hypertensive patients may be eligible but blood pressure must be adequately controlled at baseline. (f) Uncontrolled hypotension - SBP \<90 mmHg and/or DBP \<50 mmHg for parts I \&J 8. Inadequate bone marrow reserve/organ function as demonstrated by any of the following lab values 1. ANC \<1.5 × 109/L 2. Platelet count \<100 × 109/L 3. Haemoglobin \<90 g/L 4. ALT \>2.5 × ULN 5. AST \>2.5 × ULN 6. TBL \>1.5 × ULN or \>3 × ULN in the presence of documented Gilbert's Syndrome 7. GFR \<50 mL/min 9. Clinically significant abnormalities of glucose metabolism, as defined by any of the following at screening (Parts I and J only): 1. Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment. 2. HbA1c ≥8.0% (63.9 mmol/mol).

Inclusion Criteria: * Member of a Seventh-day Adventist church \>30 years of age Ability to read English Live in the US or Canada Exclusion Criteria: * Less than 30 years of age * Church members who did not complete the baseline questionnaire. * Incarcerated or institutionalized people * Non-English speakers

Inclusion Criteria: * The study will be based on female volunteers between the ages of 18 and 35 of all ethnic backgrounds. Exclusion Criteria: * Patients with breast cancer treatment, removal of non-malignant masses, trauma, burns or dermatological diagnoses involving the breast are excluded from the study.

Inclusion Criteria: • If you are an adult between the ages of 18-40 year old Exclusion Criteria: * Evidence of cardiovascular, pulmonary, renal, hepatic, cerebral, or metabolic disease * Evidence of pregnancy * Using medications that affect vascular tone (i.e., nitrates, etc.) * Use of any anticoagulants (i.e. aspirin) * Anemia * If you are postmenopausal * If you have uncontrolled hypertension (treated resting SBP \>140 mm Hg or DBP \>90 mm Hg)

Inclusion Criteria: * Previously or currently prescribed antihypertensive therapy * Average office BP ≥ 140/90 mmHg \<180/120 mmHg while stable for at least 4 weeks on 0-2 classes of antihypertensive medication * Documented daytime ABP ≥ 135/85 mmHg and \< 170/105 mmHg after 4-week washout/run-in period Exclusion Criteria: * Lacks appropriate renal artery anatomy for treatment * Known, uncorrected causes of secondary hypertension other than sleep apnea * Type I diabetes mellitus or uncontrolled Type II diabetes * eGFR of \<40 * Brachial circumference ≥ 42 cm * Any history of cerebrovascular event or severe cardiovascular event, or history of stable or unstable angina within 12 months prior to consent * Repeat (\>1) hospitalization for hypertensive crisis within 12 months prior to screening period, or any hospitalization for hypertensive crisis within 3 months prior to screening period * Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea * Primary pulmonary hypertension * Night shift workers * Pregnant, nursing or planning to become pregnant

Inclusion Criteria: * Diagnosed with de novo or recurrent advanced breast cancer since 2007 * Diagnosed with or treated for advanced breast cancer in one of the participating hospitals * Participating hospitals (period of inclusion): Maastricht UMC+ (2007-2025), Zuyderland hospitals Sittard/Heerlen (2007-2025), Amphia Hospital Breda (2013-2025), Catharina Hospital Eindhoven (2007-2025), Elkerliek Hospital Helmond (2010-2025), Maxima Medical Center Veldhoven/Eindhoven (2007-2025), Jeroen Bosch Hospital Den Bosch (2013-2025), Laurentius Hospital Roermond (2007-2025), St. Annaziekenhuis Geldrop (2007-2025), St. Elisabeth Hospital Tilburg (2007-2009), St. Jans Gasthuis Weert (2007-2025), VieCuri Medical Center Venlo/Venray (2013-2025), all in the Netherlands. * Hospitals (and periods) were eligible for inclusion if (distant) registration from Maastricht UMC+ was possible. * The inclusion period may be prolonged after 2025. Exclusion Criteria: none

Inclusion Criteria: Women who satisfy all of the following conditions will be eligible for this study. 1 DCIS or invasive ductal, medullary, papillary, mucinous (colloid), lobular,or tubular histologies. 2\. Age ≥ 18 years. 3. ECOG Performance status 0-2. 4. Women of child-bearing potential must agree to use adequate contraception (barrier method of birth control- condom or diaphragm and spermicidal foam; intrauterine device, prescription birth control pills, or abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 4.1. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 5\. Appropriate staging studies identifying as AJCC stage Tis, or T1-T2, N0 (N0i+). The tumor size must be 3 cm or less. 6\. Surgical treatment of the breast with lumpectomy with histologically confirmed margins free of tumor (no ink on margin) for invasive disease, and at least 2mm for Ductal Carcinoma In Situ.. (Re-excision of margins is permitted). 7\. Gross disease within the breast must be unifocal. (Patients with microscopic multifocality are eligible as long as the total extent of tumor, gross and microscopic, occupies a volume with greatest dimension extent of 3 cm or less (regarding the largest diameter of volume occupying space). 8\. Patients with invasive disease are required to have axillary staging including: sentinel node biopsy or axillary dissection. If patients are over age 65, axillary staging is at the discretion of the physician. Patients with DCIS are not required to have axillary staging. 9\. Lymphovascular invasion is allowed if limited or focal. 10\. Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: 1. Men are not eligible for this study. 2. T2(\>3.0 cm), T3, N1, stage III, or stage IV breast cancer 3. Evidence by physical examination or mammography of other suspicious masses, densities, or microcalcifications in either breast, unless biopsied and found to be benign. 4. Patients with non-epithelial breast malignancies such as sarcoma or lymphoma are excluded. 5. Paget's disease of the nipple. 6. Previous thoracic or breast radiation on ipsilateral side. Contralateral breast radiation is not excluded. 7. Treatment plan that includes ipsilateral whole breast or ipsilateral regional nodal irradiation. 8. Any prior treatment with radiation, or chemotherapy (in the neoadjuvant setting) for currently diagnosed breast cancer prior to GammaPod treatment- adjuvant chemotherapy is acceptable. 9. Patients with active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or active skin rash, systemic lupus erythematosis, or scleroderma, or no other exclusions. 10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppressed patients or psychiatric illness/social situations that would limit compliance with study requirements. 11. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. 12. If the lumpectomy cavity is completely outside of the vacuum assisted breast cup, then patient should not be treated on the GammaPod secondary to concerns of reproducibility. 13. Transplant patients or any patients on immunosuppressive therapy. 14. Breast size that is too large for the breast cup immobilization device.