Introduction to Therapies in Oncology PDF

Therapies)in)Oncology Introduction VandeVorst et#al.,#Cancer#Res.,#2019 M2)International,)Therapies)in)Oncology,)TU)n°16 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025  In)France,)cancer)is)the) f...

Therapies)in)Oncology Introduction VandeVorst et#al.,#Cancer#Res.,#2019 M2)International,)Therapies)in)Oncology,)TU)n°16 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025  In)France,)cancer)is)the) first)cause)of)death)in)men)and)the)2nd in)women CHILDS/ADOLESCENTS ADULTS Leukemia)(bone)marrow,) Prostate)/)Breast lymphatic)system) Lung Central)nervous)system Colorectal)(bowel) Lymphoma)(lymphocyte) B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Institut National#du#Cancer,#Panorama#des#cancers#en France,#2023  Organ)of)origin)/)Survival) Prostate Central)nervous) system Melanoma Lung Survival)at)5)years) (2010S15) Breast Liver Cancers)with)bad)prognostic less)than)25)%)survival) at)5)years Colorectal Oesophagus Pancreas Cervix)cancer B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Institut#National#du#Cancer,#Panorama#des#cancers#en#France,#2023  Definitions A neoplasm)/)tumor is)a)type)of)abnormal)and)excessive)growth of)tissue. The)word tumor comes)from)the)Latin)word)for swelling. Neoplasms)/)tumors are)classified)into)four)main)groups: S Benign)neoplasms)(ex:)skin)mole) S In)situ)neoplasms)(potentially)malignant)S still)in)the)place)where)they)started) S Neoplasms)of)unknown)behavior S Malignant)=)cancers)(focus)of)oncology) In)situ invasive circulating micrometastasis metastasis Basal)membrane Connective)tissue Blood)vessel primary)tumor Intravasation circulating'tumor'cells' extravasation secondary)tumor single'or'cluster CTCs dormant' disseminated tumor'cells'0 DTCs Wikipedia B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Figure#20;16,#Molecular Biology of#the#Cell 6th  10)hallmarks)of)cancer Enabling) replicative) immortality Adapted from Hanahan et#Weinberg.#Cell 2000 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Hanahan et#Weinberg.#Cell 2011  ProtoSoncogenes)/)tumor)suppressor)genes stop in)cancer go)on Tumor)suppressor)genes (Rb,)p53,)INK4,)PTEN,)BRCA1…) lost ProtoSoncogenes (EGFR,)HER2,)Ras,)Myc,)Akt,)BRAF,)cSSrc…) activated Viral)proteins)(E6,)E7,)vSSrc…) c0Src :'Nobel'Prize in'Physiology or'Medicine 1989,'J.'Bishop'&'H.'Varmus normal 1)mut 2 mut 3)mut Sporadic) Tumor) Carcinogenesis Cancer) cancer mutational) Multi0step'mutations' cell acquisition Hereditary) burden cancer =)TMB Genomic'instability B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Adapted#from#Ashkenazi#et#al.,#Neoplosia,#2008#  Multistep)carcinogenesis Sporadic) cancer brain'bone'lung'''liver''kidney Hyperplasia Dysplasia (proliferation) (abnormal'cell) B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Liu#et#al.,#Quant#Imaging#Med#Surg,#2015 Clonal)evolution)of)cancer):)intratumoral heterogeneity) therapy S Clonal)expansion S Genetic)diversification) S Clonal)selection Carcinoma)in#situ Metastasis B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Greaves#&#Maley,#Nature,#2012  Ecological)invasion)/)cancerSmetastasis)invasion Invasive)species Cancer)cells B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Neinavaie et#al,#Front.#Eco.#Evo.,#2021#  Intratumoral heterogeneity)/)tumor) microenvironment)(TME)) Primary)site CancerSstem) cells)(CSCs) Tumor) vasculature Functionally) diverse)cancer) cells)(clones) Blood)stream Circulating)tumor) cells)(CTCs) Secondary)site single'or'cluster dormant)disseminated) metastasis):)secondary)tumor tumor)cells)(DTCs) Perivascular'niches Adapted#from#Gonzalez;Silva#et#al,#Trends#in#Cancer,##2020 Ghajar,#Nature#Cancer#Rev.,#2015 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Lambert#et#al.,#Cell,#2016  Intratumoral heterogeneity)/)tumor) microenvironment)(TME)) Primary)site CancerSstem) Cause)of)recurrence)? cells)(CSCs) Tumor) vasculature Functionally) diverse)cancer) cells)(clones) Blood)stream Circulating)tumor) Cause)of)recurrence)? Cause)of)death cells)(CTCs) Secondary)site single'or'cluster dormant)disseminated) metastasis):)secondary)tumor tumor)cells)(DTCs) Perivascular'niches Adapted#from#Gonzalez;Silva#et#al,#Trends#in#Cancer,##2020 Ghajar,#Nature#Cancer#Rev.,#2015 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Lambert#et#al.,#Cell,#2016  Intratumoral heterogeneity)/)tumor) microenvironment)(TME)) ImmunoS suppressive)=) TumorSassociated) CancerSassociated) protumoral macrophages)(TAMs) fibroblasts)(CAFs) protumoral M1,'M2 MyeloidSderived) suppressive)cells) (MDSCs) Regulatory T)lymphocytes) MyeloidSderived) Natural)killer) (Treg) cells)(NKs) suppressive)cells) (MDSCs) cancer)immunity Macrophages Cytotoxic)CD8+ T) antitumoral lymphocytes TumorSinfiltrating) Lymphocyte)T lymphocytes) (TILs) TumorSeducated) Tumor) Dendritic)cells)(DCs) protumoral platelets)(TEPs) vasculature CTCs B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Adapted#from#Gonzalez;Silva#et#al,#Trends#in#Cancer,##2020#  Intratumoral heterogeneity)/)tumor) microenvironment)(TME)) Extracellular)matrix vasculature Lactate,)ROS Drug necrosis Nutrients,)O2,)pH) breast'cancer Adapted#from#Pinto#et#al,#Pharmac.,#2020 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Insua;Rodriguez#et#Oskarsson,#Adv.#Drug#Del.#Rev.,#2016  Intratumoral heterogeneity)/)tumor) microenvironment)(TME)) Tumor)extracellular) vesicles Cancer)and)microbiome Affect)other)tumor)cells Affect)cells)in)the)tumor)environment) Affect)distant)sites):)preSmetastatic)niche initiation,)progression,)and)response)to)therapy Systemic)influence Menck et#al,#Int.#J.#Mol.#Sci.,#2020 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Xavier#et#al.,#Trends#in#cancer,#2020  Intratumoral heterogeneity)/)tumor) microenvironment)(TME)) Cancer)and)nervous) system melatonin /'noradrenaline Neurotransmitters'/'hormones'of'stress Hypothalamic /'adrenaline pituitary)adrenal Central) Local Immunity) neuroendocrine) neuronal) (ex):)melatonin,) system system glucorticoids) Sympatho S Cancer) adrenal)system Proliferation Dissemination (ex):)E/NE) Neurotransmitters)/)hormones)of)stress Hormones)antiSinflammatory B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Magnon &#Hondermarck,#Nat.#Rev.#Cancer,#2023#  Cancer)causes Present)at)birth During)life Inherited)mutation)=)family)cancer)syndrome Oncovirus /)oncogenic)bacteria 0 Retinoblastoma'(RB) 0 Papillomavirus'HPV':'cervical'cancer 0 Li0Fraumeni (p53) 0 Hepatitis'B':'hepatocarcinoma 0 Fanconi anemia'(FANC) 0 Helicobacter'pylori':'gastric'cancer 0 Breast0ovarian'cancer'syndrome'(BRCA1/2) DNA' 0 Lynch'syndrome'(MMR) repair Environmental)(associations)):) 0 Xeroderma pigmentosum (XP) 0 UV'(skin) 0 Tobacco'(lung) Congenital)mutation): 0 Alcohol'(liver)' 0 Trisomy'21'='Down'syndrome'/'leukemia 0 Unhealthy'diet'and'low'physical'activity 0 Retinoblastoma'(13q14'RB) 0 Particle'pollution'in'air 5S10% Breast)cancer 15S20% 70S80% B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://www.ambrygen.com/  Hereditary)cancer)screening)by)oncogenic)test PRÉDISPOSITIONS GÉNÉTIQUES PRINCIPAUX GÈNES ASSOCIÉS SYNDROME SEINS-OVAIRES BRCA1, BRCA2, PALB2, RAD51 SYNDROME DE LYNCH MLH1, MSH2, MSH6, PMS2, EPCAM ADÉNOMES HYPOPHYSAIRES FAMILIAUX AIP ATAXIE-TÉLANGIECTASIE ATM, MRE11A CANCER GASTRIQUE DIFFUS FAMILIAL CDH1 CARCINOME PAPILLAIRE RÉNAL HÉRÉDITAIRE FH, MET HYPERPARATHYROÏDISME CDC73, CASR MALADIE DE COWDEN PTEN, PIK3CA, AKT1 MALADIE DE FANCONI FANC MALADIE DE VON HIPPEL-LINDAU VHL Hereditary)cancer)syndromes MÉLANOME MALIN FAMILIAL CDKN2A, MITF, BAP1, POT1, CDK4 S Often)autosomal)dominant)mutation NÉOPLASIES ENDOCRINIENNES MEN1, RET, CDKN1B S Cancer)in)the)young)age NEUROFIBROMATOSES NF1, NF2, LZTR1, SMARCB1, SPRED1, SMARCE1 S Blood)samples)(saliva,)skin)samples) PHÉOCHROMOCYTOME-PARAGANGLIOME HÉRÉDITAIRE SDH, TMEM127, MAX, EPAS1 POLYPOSES ADÉNOMATEUSES FAMILIALES APC, MUTYH, POLE, POLD1, NTHL1 RÉTINOBLASTOME RB1 SYNDROME DE BIRT-HOGG-DUBÉ FLCN SYNDROME DE BLOOM BLM SYNDROME DE CARNEY PRKAR1A, ARMC5 SYNDROME DE GORLIN PTCH1, PTCH2, SUFU SYNDROME DE LI-FRAUMENI TP53, CHEK2 SYNDROME DE NIJMEGEN NBN SYNDROME DE PEUTZ-JEGHERS STK11 SYNDROME DE POLYPOSE JUVÉNILE BMPR1A, SMAD4 SYNDROME DE WERNER WRN XERODERMA PIGMENTOSUM XP https://www.e;cancer.fr/ https://www.cancer.gov/about0cancer/causes0 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 prevention/genetics/genetic0testing0fact0sheet B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Credit:#WHO  Recommended)cancer)screening DÉPISTA.'Pap'smear'cervix.'HPV'test.'X0ray'picture.'Clinical'/'breast'self0exam Tomography ='smokers DU COL D Earlier'if'family' Organisation du history Dépistage du cancer du col de l’utérus.'Immunological'stool0.'Digital'rectal'exam based'test'for'blood'=.'Prostate0specific'antigen'(PSA) fecal'occult'blood'test test'in'blood (FOBT).'Colonoscopy B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Adpated from#Moffitt#Cancer#Center  Cancer)biomarkers)/)tumor)markers Circulating)tumor)markers):'blood,'urine,'saliva… Tumor)tissue)markers):'biopsy,'surgery PreSdisposition)/)screening Diagnose,)stage)and)/)or)classify)cancer Estimate)prognosis Select)an)appropriate)treatment)/)predictive) Assess)treatment)efficiency)/)monitoring B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Adapted#from#Corcoran,#Nature#Med.,#2020 Tum FDA)(food)&)drug)agency))approved)molecular)biomarkers) (glyco)protein /)carbohydrate) (screening)/)staging /)monitoring) /)DNA) B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Dixit#et#al.,#Royal#Soc.#Chem.,#2015  Others)biomarkers)in)liquid)biopsy)(blood)here) Extracellular) 500'nm'– 5µm vesicles plasma 30'– 100'nm white)blood) cells)+) 1000500'nm platelets red)blood) cells.)Circulating)tumor)cells)(CTCs).)TumorSeducated)cells):.)Tumor)extracellular)vesicles):)exosomes,)microvesicles 0 platelets'(TEPs).)Cell)free)DNA)(cfDNA)):)circulating)tumor)DNA)(ctDNA) 0 macrophages'(TAMs).)Cell)free)RNA)(cfRNA)):)miRNA,)lncRNA,)circulating)tumor)RNA)(ctRNA) Stocklib.fr B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Dang#et#al.,#Cells,#2020  Cancer)imaging Ultrasound Sound'waves'with'frequencies'above'those'humans'can'hear. Magnetic)Resonance)Imaging)(MRI) Radio'waves'in'the'presence'of'a'strong'magnetic'field. XSRay imaging Mammogram.'X0rays A)computed)tomography)scan):)CT)scan Computer0controlled'X0rays to'create'3D'images'of'the'body Molecular)and)nuclear)imaging):)positron)emission)tomography)(PET)) and)single)photon)emission)computed)tomography)(SPECT) Low'doses'of'radioactive'substances'linked'to'compounds'used'by'the' body's'cells'or'compounds'that'attach'to'tumor'cells.'X0rays. Follow'radioactivity'in'real'time B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://imaging.cancer.gov/  Cancer)biopsy ORGANS)OF)ORIGIN (breast,)liver,)kidney,)bones) Cancer)TYPES Adenocarcinoma (epithelial)tissue),)osteosarcoma (connective tissue),)leukemia (bone) marrow,)lymphatic),)lymphoma (lymphocytes),)neuroblastoma (embryonic)tissue)... Cancer)GRADES)written'in'Arabic'numerals'004 Describe)the)level)of)abnormality)of)cancerous)tumor)versus normal)tissue.) Nuclear'and'cytoplasmic'abnormalities,'loss'of'differentiation,'number'of'mitoses,' extension'of'necrosis... Cancer)STAGES)represented'as'Roman'numerals'00IV TNM)classification T:'size'of'the'tumor N:'putative'regional'lymph'node'invasion M:'distant'metastases B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 mskcc.org  Systemic)/)local)treatments systemic systemic local local local systemic systemic B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://www.vectorstock.com/  Most)used)treatments)in)France 1 3 Most'used 2 https://www.vectorstock.com/ B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Institut National#du#Cancer,#Panorama#des#cancers#en France,#2021  Other)treatments LASER)therapy):'light'amplification'by'stimulated'emission'of'radiation Surgical'work Destroy'small'area'by'heat' Activates'light'sensitive'prodrug/therapy'(PDT'photodynamic'therapy) Hyperthermia):' Local'='ablation Radio'waves,'microwaves, Ultrasounds'waves'(histotripsy'FDA'approved'in'liver) Body'surface,'needle'in'the'tumor RFA'(radiofrequency'ablation)':'liver,'kidney,'lung'(5'cm) Regional'='combined'with'chemotherapy,'radiation Organ,'limb,'cavity Regional'perfusion,'peritoneal'perfusion Whole0body'(>'41 C,'metastasis) Prodrug activation)in)tumor)environment Hypoxia,'acidic'pH,'extracellular'matrix'(metalloprotease) B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 American Cancer#Society  Neoadjuvant)and)adjuvant)therapies To'shrink'the'tumor'before'surgery First'line' therapy (primary)'treatment To'prevent'cancer'recurrence B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Cancer#Second#Opinion  SecondSline)treatment First0line treatment : used to treat a cancer after diagnosis (can include more than one treatment method). Second0line treatment : for a disease or condition after the initial treatment has failed, stopped working, or has side effects that aren't tolerated. B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Brulé,#Int J#Cancer#Clin Res,#2016  Cancer)chronobiology Chrono)disruption)by S Environment):)shift)work,)jet)lag,)deregulated)feeding S Pathology):)aging,)diabetes,)obesity,)cancer Circadian)medicine S Normal)tissue)tolerance S Cancer)toxicity (cells)normal/cancer)don’t)have)the)same)cell)cycle)timing) Healthy Tumor 5'FU 5'FU noon noon docetaxel evening docetaxel Optimal)drug) evening toxicity)timing.)Cell)cycle,)apoptosis,)DNA)repair Optimal)healthy).)Drug)metabolism,)detoxification tissue)tolerance).)Angiogenesis timing Ozturk et#al,#Int J.#Mol.#Sci.#2021 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Lee,#Exp Mol Med.,#2021  Complementary)medicine S Reduce)the)side)effects)of)cancer)treatment S Improve)physical)and)emotional)wellSbeing S Improve)recovery)from)cancer.'Nutrition.'Meditation'/'sophrology /'hypnosis'/'art'therapy.'Physiotherapy'/'massage'therapy'/'burn'healer'after'radiation.'Adapted'physical'activity'(yoga,'Tai'chi,'qigong) … QUALITY)OF)LIFE)QUIZ)(QLQSC30))Quality'Of'Life'(QoL) Life)quality)of)cancer)patients):)general,)cancer)specific)or)palliative)care From'European'Organisation for'Research'and'Treatment'of'Cancer'(EORTC) B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025  Aging)&)Cancer 12 Geriatric)oncology Primary#Antagonistic Integrative#hallmarks Lopez;Otin et#al,#Cell,#2023 Lopez;Otin et#al,#Cell#Metabolim,#2023 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025  Prostate)cancers):)screening,)diagnosis)&)treatments Screening):'Digital'rectal'exam,'PSA'test Diagnosis :'Transrectal ultrasound'or'MRI,'biopsy' Metastasis)search)(lung,)bone)):'bone'scan,'MRI,'CT'scan Androgene deprivation)therapy)(ADT) or)cancer)growth)stop no)treatment)until)signs)or)symptoms)appear)or) Surgery)(prostate,)seminal) XSray,)radioactive) change)(old)men) vesicle,)lymph)nodes) capsule Targeted)therapy):)Olaparib (PARP)inhibition) Immunotherapy):)SipuleucelST)(vaccin,)educated) DC)cells) Adapted#from#blog#360.ro# B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://www.cancer.gov/types/prostate rogens Triple)negative)breast)cancers)(TNBC)):) screening,)diagnosis)&)treatments Screening):'clinical'examination,'mammography,'(breast'ultrasound) Diagnosis :'biopsy,'immunohistochemical analysis'of'hormone'receptors':'progesterone'(PR),'estrogen'(ER),'human' epidermal'growth'factor'2'(Her2).'TNBC'='triple'negative'breast'cancer Metastasis)search)(lung,)bone)):'chest'radiograph,'abdominal'ultrasound,'bone'scan,'CT'scan,'PET'scan Hormone)therapy Tamoxifen,'estrogens +'removal'of'the'first'lymph'node Targeted)therapy):)Olaparib (PARP)inhibition) Immunotherapy):))Pembrolizumab (anti)PDS1) Adapted#from#Manjunatj &#Choudhary,#Onco.#Letters,#2021 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://www.cancer.gov/types/breast  Lung)cancers):)screening,)diagnosis)&)treatments Screening):'low0dose'computed'tomography'(LDCT),'chest'X0ray,'(sputum'cytology),'thoracentesis Diagnosis :'biopsy,'bronchoscopy,'molecular'test,'immunohistochemistry'(KRAS,'EGFR) Metastasis)search)(brain,)bone,)liver)):'MRI,'CT'scan,'PET'scan,'bone'scan surgery,)ablative) chemoradiotherapy radiotherapy Non)small) cell)Lung) cancers)NSCL Targeted)therapy):) VEGF,)EGFR,)mTOR chemotherapy)+) chemotherapy)or) immunotherapy immunotherapy Adapted#from#Rudin et#al.,#Nat#Rev#Dis#Primers,#2021 B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://www.cancer.gov/types/lung  Colorectal)cancers):)screening,)diagnosis)&) treatments Screening):'fecal'occult'blood'test'(FOBT),'colonoscopy,'digital'rectal'exam Diagnosis :'colonoscopy,'biopsy,'DNA'stool'test,'CT'scan,'MRI,'CEA'assay'(carcinoembryonic'antigen)' Metastasis)search)(liver,)lung)):'PET'scan,'lymph'node'biopsy FOLFOX':'oxaliplatin +'leucovorin (folinic acid)'+'50FU CapeOX : capecitabine +'oxaliplatin FOLFIRI':'leucovorin (folinic acid)'+'50FU'+'irinotecan Adapted#from# B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://www.cancer.gov/types/colorectal  Rethinking)the)war)on)cancer)? « War)on)cancer”)launched)by)the)US)congress)and)Richard)Nixon)in)1971.'Advances'in'our'knowledge'about'the'nature'and'mechanisms'of'the'disease.'.'Hundreds'of'new'anticancer'drugs':'multiplication'of'weapons.. No'magic'bullets':'adaptive'and'evasive'resistance'of'cancers'under'attack..'Cost–benefit dilemmas. A)cancer)battlespace): need)military)intelligence)to)win)the)war).'Disruption'of'the'several'capabilities'of'the'enemy'(clonal'versatility)..'Neutralization'of'specialized'divisions'of'the'enemy’s'armed'forces'(DTCs)..'Integration'of'the'geographies'of'the'battlefields'(environment). B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 Adapted#from#Hanahan,#The#Lancet,#2014  Prospective)randomized)controlled)clinical)trial Healthy'volunteers Before)becoming)a)blockbuster):)complex,)long,)expensive)and)risked B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://mstrials.org.au/what;are;clinical;trials/  Clinical)trial)parameters Patient)enrollment)S eligibility)criteria)S cohort Treatment)regimen):)dose'escalation,'mode'of'administration Safety):)DLT'(dose'limiting'toxicity) RP2D': recommended'phase'2'dose'='usually'the'highest'dose'with'acceptable'toxicity Tumor)response)visualization) Efficacy)S RECIST)(response'evaluation'criteria'in'solid'tumors'0 CT'scan).'CR'(complete'response).'PR'(partial'response).'SD'(stable'disease).'PD'(progressive'disease) Tolerability)S quality)of)life)(QoL).'Adverse'events'(AE)':'pain','fatigue,'anemia,'digestive'defects,'hair/skin/nail'alteration,' immunity'weakness,'cardiac'toxicity,'fertility'altered,'peripheral'neuropathy'….'Patient0reported'outcome'measures'(PROs)'0 Quality'of'Life'Quiz'(QLQ0C30)' B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 https://www.clinicaltrials.gov/ct2/about;studies/glossary  Precision)medicine)trial B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 West,#Jama#Onco.,#2017  Clinical)trial)endpoints)in)cancer)research:) Overa patien regim Terms)definitions contr progr perso result than'O disea Overa Available#earlier#than#OS#data of'pat Indication#of#disease#control#and#stabilization or'sig gener a'durable,'meaningful'delay'in'disease'progression respo evide perio with'a time'p that't Durat Tangible#proof#that#the#drug#is#working time't Objective)Response)Rate)(ORR)): treatm Measure#the#tumor#burden#(TB#=#given#amount#of#cancer#in#the# sprea body)#after#the#treatment# impro mean oppos B.#BENOIT,#TU#n°16,#Paris#Saclay,#2024;2025 lastin  Overall)survival)in)patients)with)metastatic)breast) cancer)according)to)circulating)tumor)cell)levels)at) baseline)or)first)followSup Arm refers)to)each)group)or)subgroup)of)participants) in)a clinical)trial