cancersCancer

HR-positive / HER2-negative breast cancer

HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs.

Hormone receptor-positive, HER2-negative breast cancer is about 70% of all breast cancers and the archetype of a hormone-driven, slow-evolving disease. Oestrogen receptor signalling drives proliferation, so endocrine therapy has been the backbone since tamoxifen (1977) and aromatase inhibitors (1990s); because recurrences can occur 10-20 years after diagnosis, therapy lasts 5-10 years and adherence is a major real-world determinant of outcome. Gene-expression assays (Oncotype DX, MammaPrint) now spare roughly 70% of node-negative and most postmenopausal node-positive patients chemotherapy, while adjuvant CDK4/6 inhibitors (abemaciclib, ribociclib) reduce recurrence in the high-risk minority.

Metastatic disease is treated as a sequence of endocrine-based combinations. First line is a CDK4/6 inhibitor plus endocrine therapy, with ribociclib and abemaciclib showing overall survival gains that palbociclib did not. Progression is increasingly managed by genotype: ESR1 mutations detected in ctDNA (30-40% after aromatase inhibitors) call for oral SERDs (elacestrant, imlunestrant) or the PROTAC vepdegestrant, and since September 2026 for camizestrant switched in at molecular progression; PIK3CA/AKT1/PTEN alterations (about 50%) call for inavolisib, capivasertib, or alpelisib; gedatolisib (2026) works in PIK3CA-wild-type disease. After endocrine options are exhausted, antibody-drug conjugates precede chemotherapy: T-DXd for the ~60% with HER2-low or ultralow expression, and the TROP2 ADCs sacituzumab govitecan and datopotamab deruxtecan.

Open problems are the evolution of resistance across this long sequence (CDK4/6, then endocrine, then ADC payload resistance), the absence of a validated test for late recurrence, toxicity and adherence over years of therapy, and translating ctDNA-guided decisions into proven survival gains. The near-term pipeline is defined by oral SERDs moving into the adjuvant setting (lidERA positive; CAMBRIA and EMBER-4 pending), CDK4-selective inhibitors, new HER2-low and TROP2 ADCs, and ctDNA-triggered switching, which the FDA endorsed over a negative advisory vote in 2026.

State of the art today

Adjuvant CDK4/6 inhibitors reduce recurrence in high-risk early disease.
ctDNA-guided ESR1 switching and first PROTAC approval (2026).
ADCs before chemotherapy in HER2-low/ultralow disease.
Chemotherapy omission for ~70% of node-negative and most postmenopausal node-positive patients using genomic assays (TAILORx, RxPONDER, MINDACT).
Adjuvant CDK4/6 inhibitors (abemaciclib, ribociclib) cut recurrence in high-risk early disease; the first adjuvant oral SERD (giredestrant, lidERA) is positive and awaiting approval.
Genotype-directed second line: ESR1-mutant → oral SERDs or the first approved PROTAC (vepdegestrant); PIK3CA/AKT/PTEN → inavolisib (OS benefit), capivasertib.
The first ctDNA-triggered treatment switch approved by the FDA (camizestrant, SERENA-6, September 2026), over a negative advisory vote.
ADCs before chemotherapy in endocrine-resistant disease: T-DXd for HER2-low and ultralow (DESTINY-Breast06), TROP2 ADCs for the rest.

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

First-line CDK4/6 + endocrine therapy with median OS beyond five years (MONALEESA-2: 63.9 months).

Who it affects

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

HR-positive disease makes up about 70% of the 2.3 million breast cancers diagnosed each year (roughly 1.6 million), and causes the majority of the 670,000 annual breast cancer deaths because of late recurrence.

Group

breast

Where the cases are

Cases by country · GLOBOCAN 2022

All countries →

Site: Breast (all subtypes) (shared total; subtype split not reported). World: 2,296,840 new cases, 666,103 deaths.

#	Country	New cases	Deaths	Incidence ASR
1	China	357,161	74,986	33.0
2	United States of America	274,375	42,900	95.9
3	India	192,020	98,337	26.6
4	Brazil	94,728	22,189	63.1
5	Japan	91,916	17,638	74.4
6	Russian Federation	78,839	22,115	57.7
7	Germany	74,016	20,601	77.0
8	Indonesia	66,271	22,598	41.8
9	France (metropolitan)	65,659	14,739	105.4
10	United Kingdom	58,756	12,122	94.0

GLOBOCAN reports breast cancer as one site. HR+/HER2- disease is roughly 70% of cases; the figures shown are for all breast cancer.

Standard of care

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Early stage

Surgery, radiation, endocrine therapy 5-10 years; chemotherapy if genomic risk high; abemaciclib or ribociclib adjuvant for high-risk.

NCCN · Category 1, preferred: adjuvant abemaciclib…ESMO-MCBS · A (monarchE); A (NATALEE)

Oncotype DXAbemaciclibRibociclibmonarchE NATALEE

Metastatic first line

CDK4/6 inhibitor + aromatase inhibitor or fulvestrant.

ESMO-MCBS · 4-5 (MONALEESA-2, -3, -7); 2 (PALOMA-2); 2 …

PalbociclibRibociclibAbemaciclib

Metastatic second line

Genotype-directed: capivasertib, inavolisib, alpelisib, everolimus; elacestrant/vepdegestrant if ESR1-mutant; gedatolisib.

ESMO-MCBS · 3 (CAPItello-291); 3 (INAVO120); 3 (EMERALD…

CapivasertibInavolisibElacestrantVepdegestrantGedatolisib

Endocrine-resistant

T-DXd (HER2-low/ultralow) before chemotherapy; sacituzumab govitecan or Dato-DXd after chemotherapy.

ESMO-MCBS · 4 (DESTINY-Breast04); 3 (DESTINY-Breast06);…

DESTINY-Breast06Trastuzumab deruxtecanSacituzumab govitecanDatopotamab deruxtecan

Screening and diagnosis

Mammography ± tomosynthesis; supplemental MRI for dense breasts or high risk; core biopsy with ER/PR/HER2/Ki-67; AI-assisted reading being deployed.

NCCN · Breast Cancer Screening

Mammography & tomosynthesis AI in radiology Histopathology & immunohistochemistry

Early stage, deciding on chemotherapy

Genomic assay (Oncotype DX RS ≤25 node-negative or postmenopausal 1-3 nodes; MammaPrint low risk) → endocrine therapy alone; premenopausal RS 16-25 or high clinical risk → chemotherapy or OFS-based escalation.

NCCN · 1

TAILORx RxPONDER (SWOG S1007)Oncotype DXMammaPrint (70-gene signature)

Early stage, adjuvant endocrine therapy

Postmenopausal: aromatase inhibitor 5-10 years (or tamoxifen → AI switch). Premenopausal: tamoxifen 5-10 years; add OFS (+ AI or tamoxifen) for higher-risk or chemotherapy-treated women (SOFT/TEXT).

NCCN · 1

Letrozole (and other aromatase inhibitors)TamoxifenGoserelin / leuprolide (ovarian function suppression)SOFT & TEXT

Early stage, high risk: adjuvant CDK4/6

Abemaciclib 2 years for node-positive high-risk (monarchE); ribociclib 3 years for stage II-III including node-negative high-risk (NATALEE). Palbociclib not effective (PALLAS/PENELOPE-B). Olaparib 1 year if gBRCA (OlympiA).

NCCN · 1

AbemaciclibRibociclibmonarchE NATALEE PALLAS & PENELOPE-BOlaparib

Early stage, extended and adjuvant SERD (emerging)

Extended AI to 10 years for higher-risk (MA.17R, NSABP B-42); adjuvant giredestrant positive in lidERA (2025, not yet approved); CAMBRIA (camizestrant) and EMBER-4 (imlunestrant) ongoing.

lidERA CAMBRIA-1 & CAMBRIA-2Giredestrant

Metastatic, first line

CDK4/6 inhibitor + aromatase inhibitor (or fulvestrant): ribociclib or abemaciclib preferred where OS data are valued; palbociclib acceptable. Premenopausal: add OFS. For relapse on/within 12 months of adjuvant ET with PIK3CA mutation: inavolisib + palbociclib + fulvestrant (INAVO120).

NCCN · 1, preferredESMO-MCBS · 4 (ribociclib, OS)

MONALEESA-2 MONARCH 3 PALOMA-2 INAVO120RibociclibAbemaciclibPalbociclibInavolisib

Metastatic, molecular progression on first line

Serial ctDNA; on emergent ESR1 mutation before radiographic progression, switch AI → camizestrant and continue the CDK4/6 inhibitor (SERENA-6; accelerated approval 4 Sep 2026).

NCCN · Pending inclusion (approval Sep 2026)

SERENA-6Camizestrant

Metastatic, second line by genotype

ESR1-mutant: elacestrant, imlunestrant (± abemaciclib), or vepdegestrant. PIK3CA/AKT1/PTEN: capivasertib + fulvestrant; alpelisib + fulvestrant. Any genotype after CDK4/6: gedatolisib + palbociclib + fulvestrant (PIK3CA-wild-type, 2026); everolimus + exemestane or giredestrant (filed); abemaciclib switch (postMONARCH, modest).

NCCN · 1 / 2A by agent

EMBER-3 EMERALD VERITAC-2 CAPItello-291 SOLAR-1GedatolisibevERA postMONARCHElacestrantImlunestrantVepdegestrantCapivasertib

Metastatic, endocrine-resistant: ADC before chemotherapy

HER2-low or ultralow (~60%): T-DXd (DESTINY-Breast06 chemotherapy-naive; DESTINY-Breast04 after chemotherapy). HER2-zero: sacituzumab govitecan or Dato-DXd after chemotherapy (TROPiCS-02, TROPION-Breast01).

NCCN · 1 (T-DXd HER2-low)ESMO-MCBS · 4 (DESTINY-Breast04)

DESTINY-Breast06 DESTINY-Breast04 TROPiCS-02 TROPION-Breast01Trastuzumab deruxtecanSacituzumab govitecanDatopotamab deruxtecan

Metastatic, chemotherapy and later lines

Sequential single-agent chemotherapy (capecitabine, taxanes, eribulin, vinorelbine); olaparib/talazoparib if gBRCA; clinical trials; supportive and palliative care integrated early.

Paclitaxel / nab-paclitaxelOlaparibTalazoparib

Bone-predominant disease and survivorship

Bisphosphonate or denosumab for bone metastases and AI-induced bone loss; adjuvant bisphosphonates in postmenopausal women; exercise, cardio-oncology, and adherence support.

Exercise & lifestyle oncology Cardio-oncology

Subtypes & biomarkers

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Subtypes

Luminal A
Luminal B
HER2-low (~60% of HR+)
ESR1-mutant (acquired)
PIK3CA-mutant (~40%)
Luminal A (low proliferation, best prognosis)
Luminal B (higher proliferation, Ki-67 high, benefits more from chemotherapy and CDK4/6)
HER2-low (IHC 1+/2+ ISH-negative, ~60% of HR+) and HER2-ultralow: eligible for T-DXd
ESR1-mutant (acquired under aromatase inhibitors, 30-40%)
PIK3CA-mutant (~40%), AKT1 or PTEN altered (~10%)
Invasive lobular carcinoma (~10-15%; CDH1 loss, often ER+, distinct metastatic pattern)
Endocrine-resistant primary (relapse within 2 years of adjuvant ET) vs secondary
Male breast cancer (>90% ER+)

Biomarkers clinicians test

ER/PR
HER2 IHC 0/1+/2+ (low, ultralow)
Ki-67
Oncotype DX / MammaPrint / Prosigna
PIK3CA/AKT1/PTEN
ESR1 (ctDNA)
gBRCA
ER and PR by IHC (≥1%; 1-10% 'ER-low' behaves like TNBC)
HER2 IHC 0/1+/2+ with the low and ultralow categories for T-DXd eligibility
Ki-67 (≥20% defines high risk for adjuvant abemaciclib, monarchE cohort 2)
Oncotype DX recurrence score, MammaPrint, Prosigna, Breast Cancer Index (late recurrence, extended ET)
PIK3CA, AKT1, PTEN alterations (tissue or ctDNA) for PI3K/AKT-pathway drugs
ESR1 mutation by ctDNA (serial monitoring endorsed by SERENA-6)
gBRCA1/2 (olaparib, OlympiA)
Menopausal status and oestradiol (for AI eligibility, OFS adequacy)
Bone density (AI-induced loss)
CDK4/6 resistance markers under study : RB1 loss, CCNE1, FGFR1 amplification

Target prevalence in this cancer

Target / alteration	Prevalence	Measure	Source
Estrogen receptor (ERα) ~70% of all breast cancers; ESR1 mutation ~30% after AI	100%	ER+ (>=1% IHC), defining	Wikipedia
TROP2	75-90%	IHC, any expression	PMC
HER2	55-65%	HER2-low (IHC 1+ or 2+/ISH-)	Nature
HER3	50-70%	IHC, any expression	Wikipedia
PIK3CA / PI3K-alpha	35-40%	Activating mutation	cBioPortal (TCGA)
CDK4/6 Inhibitors work regardless of amplification	15-20%	Cyclin D1 (CCND1) amplification	cBioPortal (TCGA)
AKT ~50% have PIK3CA/AKT1/PTEN alteration combined	3-5%	AKT1 E17K	cBioPortal (TCGA)
BRCA1 / BRCA2 (HRD) BRCA2 predominant	3-5%	Germline BRCA1/2	Wikipedia

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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1896Beatson removes ovaries to treat breast cancer
First hormonal therapy for cancer.
1896Beatson removes ovaries to treat advanced breast cancer
First hormonal therapy for any cancer.
1958Oestrogen receptor discovered (Jensen)
Basis for predicting hormone responsiveness.
1977Tamoxifen approved
Endocrine therapy (SERMs, AIs, SERDs)
1977Tamoxifen approved
The first targeted cancer drug; later shown to reduce mortality by a third over 15 years.
Tamoxifen
1998Anastrozole and letrozole approved; tamoxifen for prevention
Letrozole (and other aromatase inhibitors)Tamoxifen
2002Fulvestrant: first SERD
Fulvestrant
2004Oncotype DX launched
Gene-expression recurrence score enters practice.
Oncotype DX
2012Everolimus + exemestane (BOLERO-2)
First targeted agent to overcome endocrine resistance.
Everolimus
2014SOFT/TEXT: ovarian suppression in premenopausal women
SOFT & TEXT
2015First CDK4/6 inhibitor (palbociclib)
Palbociclib
2015Palbociclib: first CDK4/6 inhibitor
PalbociclibPALOMA-2
2018TAILORx: most women can skip chemotherapy
Oncotype DX
2018TAILORx: most women can skip chemotherapy
TAILORx
2019Alpelisib: first PI3K inhibitor in breast cancer
AlpelisibSOLAR-1
2020monarchE: adjuvant abemaciclib; PALLAS negative for palbociclib
monarchE PALLAS & PENELOPE-B
2021MONALEESA-2 final OS: ribociclib extends survival by a year
MONALEESA-2
2022HER2-low becomes a treatment category
DESTINY-Breast04
2022HER2-low becomes a treatment category (DESTINY-Breast04)
DESTINY-Breast04
2023Elacestrant (first oral SERD), capivasertib, sacituzumab in HR+
ElacestrantEMERALDCapivasertibCAPItello-291 TROPiCS-02
2024Adjuvant ribociclib (NATALEE); inavolisib approved
NATALEEInavolisibINAVO120
2025Imlunestrant approved; INAVO120 OS benefit; T-DXd in HER2-ultralow; evERA and lidERA positive
ImlunestrantEMBER-3 DESTINY-Breast06 evERA lidERA
2026First PROTAC (vepdegestrant) and gedatolisib approved
VepdegestrantGedatolisib
2026First PROTAC (vepdegestrant), gedatolisib, and the first ctDNA-triggered switch (camizestrant) approved; persevERA fails upfront
VepdegestrantVERITAC-2GedatolisibCamizestrantSERENA-6 persevERA

Pipeline

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ApprovedPROTAC oestrogen receptor degrader

Vepdegestrant · Veppanu

Under reviewADC

Sacituzumab tirumotecan

ApprovedADC

Datopotamab deruxtecan · Datroway

ApprovedAI digital pathology risk test

ArteraAI Breast

Phase 3ADC

Patritumab deruxtecan

ApprovedOral SERD

Camizestrant · Etcamah

Phase 3Oral SERD

Giredestrant

Phase 3Small-molecule CDK4-selective inhibitor

Atirmociclib

ApprovedOral SERD

Imlunestrant · Inluriyo

ApprovedSmall-molecule pan-PI3K/mTOR inhibitor

Gedatolisib · Revtorpyk

CAMBRIA-1 & CAMBRIA-2 FOURLIGHT-1 lidERA evERA Molecular-progression switching beyond ESR1 CDK4-selective inhibitors as the new first-line backbone Intercepting late recurrence with ctDNA surveillance and oral SERDs MRD / molecular residual disease testing

Open problems

Late recurrence (up to 20+ years) with no predictive test.
CDK4/6 resistance mechanisms and sequencing.
Endocrine therapy adherence and toxicity.
Late recurrence: half of relapses occur after year 5 and no test reliably identifies who needs extended or intensified therapy.
Adherence: a third of women stop adjuvant endocrine therapy early because of arthralgia, hot flushes, and sexual side effects.
Sequencing after CDK4/6: no head-to-head trials among oral SERDs, PI3K/AKT agents, everolimus combinations, and ADCs.
Does acting on ctDNA improve survival? SERENA-6 improved PFS; OS and patient-reported outcomes are unresolved, as the ODAC vote showed.
Palbociclib versus ribociclib versus abemaciclib: different survival results without a randomised comparison.
HER2-low scoring reproducibility at IHC 0/1+ determines T-DXd eligibility for millions of patients.
Invasive lobular carcinoma is under-represented in trials despite being 10-15% of cases.
Premenopausal women: whether chemotherapy's benefit in RxPONDER is simply ovarian suppression (NRG-BR009 / OFSET will answer).

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov

HR-positive / HER2-negative breast cancer

condition: hormone receptor positive HER2 negative breast cancer

Open on ClinicalTrials.gov →

within

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Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Gustave RoussyVillejuif, FRNewsweek oncology #6
via Datopotamab deruxtecan, Trastuzumab deruxtecan
The Royal MarsdenLondon, GBNewsweek oncology #7
via Olaparib
National Cancer Center HospitalTokyo, JPNewsweek oncology #13
via Datopotamab deruxtecan, Trastuzumab deruxtecan
Hospital General Universitario Gregorio MarañónMadrid, ESNewsweek oncology #40
via this cancer
Cancer Hospital, Chinese Academy of Medical SciencesBeijing, CNNewsweek oncology #50
via Sacituzumab tirumotecan
Austrian Breast & Colorectal Cancer Study GroupVienna, AT
via this cancer, PALLAS & PENELOPE-B, Palbociclib, Endocrine therapy (SERMs, AIs, SERDs)
Breast Cancer TrialsNewcastle, NSW, AU
via this cancer, SOFT & TEXT, Olaparib, Endocrine therapy (SERMs, AIs, SERDs)
Comprehensive Cancer Center Vienna – Medical University of Vienna / AKHVienna, AT
via this cancer, Palbociclib, Endocrine therapy (SERMs, AIs, SERDs)
ETOP IBCSG Partners FoundationBern, CH
via this cancer, SOFT & TEXT, Endocrine therapy (SERMs, AIs, SERDs)
GEICAM Spanish Breast Cancer GroupMadrid, ES
via this cancer, Palbociclib, Endocrine therapy (SERMs, AIs, SERDs)
Montefiore Einstein Comprehensive Cancer CenterBronx, NY, USNCI comprehensive
via this cancer, TAILORx, Oncotype DX
NSABP FoundationPittsburgh, PA, US
via this cancer, Oncotype DX, Endocrine therapy (SERMs, AIs, SERDs)
SOLTI Cancer Research GroupBarcelona, ES
via this cancer, Ribociclib, Palbociclib
Winship Cancer Institute of Emory UniversityAtlanta, GA, USNCI comprehensive
via this cancer, RxPONDER (SWOG S1007), Oncotype DX
Barbara Ann Karmanos Cancer InstituteDetroit, MI, USNCI comprehensive
via this cancer, Endocrine therapy (SERMs, AIs, SERDs)
Beatson West of Scotland Cancer Centre / CRUK Scotland InstituteGlasgow, GB
via this cancer, Endocrine therapy (SERMs, AIs, SERDs)
Breast International Group (BIG)Brussels, BE
via this cancer, Olaparib
Canadian Cancer Trials Group (CCTG)Kingston, ON, CA
via this cancer, Exercise & lifestyle oncology
Cancer Research UK Cambridge Centre / CRUK Cambridge InstituteCambridge, GB
via this cancer, MRD / molecular residual disease testing
Dan L Duncan Comprehensive Cancer Center, Baylor College of MedicineHouston, TX, USNCI comprehensive
via this cancer, Endocrine therapy (SERMs, AIs, SERDs)
Edinburgh Cancer Centre / CRUK Scotland CentreEdinburgh, GB
via this cancer, Endocrine therapy (SERMs, AIs, SERDs)
Georgetown Lombardi Comprehensive Cancer CenterWashington, DC, USNCI comprehensive
via this cancer, Endocrine therapy (SERMs, AIs, SERDs)
Guy's and St Thomas' NHS Foundation Trust / King's Health Partners Cancer CentreLondon, GB
via this cancer, Olaparib
Hospital de Amor (Barretos Cancer Hospital)Barretos, BR
via this cancer, Mammography & tomosynthesis
INCLIVA Biomedical Research Institute / Hospital Clínico Universitario de ValenciaValencia, ES
via this cancer, MRD / molecular residual disease testing
Institut Jules BordetBrussels, BE
via this cancer, Endocrine therapy (SERMs, AIs, SERDs)
Instituto Alexander FlemingBuenos Aires, AR
via this cancer, Palbociclib
Kaiser Permanente Division of ResearchOakland, CA, US
via this cancer, Mammography & tomosynthesis
Multinational Association of Supportive Care in CancerAurora, ON, CA
via Exercise & lifestyle oncology, Cardio-oncology
National Cancer Center Hospital EastKashiwa, Chiba, JP
via MRD / molecular residual disease testing, Trastuzumab deruxtecan
Sheba Medical CenterRamat Gan, IL
via this cancer, Olaparib
The Institute of Cancer ResearchLondon, GB
via Capivasertib, Olaparib
Tianjin Medical University Cancer Institute and HospitalTianjin, CN
via this cancer, Mammography & tomosynthesis
Tohoku University HospitalSendai, JP
via this cancer, Histopathology & immunohistochemistry
UPMC Hillman Cancer CenterPittsburgh, PA, USNCI comprehensive
via this cancer, Tamoxifen
A.C. Camargo Cancer CenterSão Paulo, BR
via this cancer
Aarhus University HospitalAarhus, DK
via this cancer
Aichi Cancer CenterNagoya, JP
via this cancer
American Society of HematologyWashington, DC, US
via MRD / molecular residual disease testing
Apollo Hospitals (Apollo Cancer Centres)Chennai, IN
via this cancer
ARCAGY-GINECOParis, FR
via Olaparib
Australasian Gastro-Intestinal Trials GroupSydney, AU
via MRD / molecular residual disease testing
BC CancerVancouver, BC, CA
via this cancer
Breast Cancer Research FoundationNew York, US
via this cancer
Butaro Cancer Center of ExcellenceButaro, RW
via this cancer
Cancer Care Alberta (Alberta Health Services)Calgary, AB, CA
via this cancer
Cancer Center Clínica Universidad de Navarra / CIMAPamplona, ES
via MRD / molecular residual disease testing
Cancer Institute (WIA), AdyarChennai, IN
via this cancer
Cancer Institute of Iran, Imam Khomeini Hospital ComplexTehran, IR
via this cancer
Cancer Research UK Manchester InstituteManchester, GB
via MRD / molecular residual disease testing
Centre Antoine LacassagneNice, FR
via this cancer
Centre hospitalier de l'Université de Montréal (CHUM)Montréal, QC, CA
via Olaparib
Centre Léon BérardLyon, FR
via this cancer
Centro Nacional de Investigaciones Oncológicas (CNIO)Madrid, ES
via this cancer
Champalimaud Foundation – Champalimaud Clinical CentreLisbon, PT
via this cancer
Charlotte Maxeke Johannesburg Academic Hospital / University of the WitwatersrandJohannesburg, ZA
via this cancer
Children's Cancer and Leukaemia GroupLeicester, GB
via MRD / molecular residual disease testing
Children's Cancer Hospital Egypt 57357Cairo, EG
via MRD / molecular residual disease testing
Cleveland Clinic Abu DhabiAbu Dhabi, AE
via this cancer
Dharmais National Cancer CenterJakarta, ID
via this cancer
ECOG-ACRIN Cancer Research GroupPhiladelphia, PA, US
via Mammography & tomosynthesis
European Hematology AssociationThe Hague, NL
via MRD / molecular residual disease testing
European Society for Clinical Nutrition and MetabolismLuxembourg, LU
via Exercise & lifestyle oncology
FDA Oncology Center of ExcellenceSilver Spring, MD, US
via MRD / molecular residual disease testing
Fundación Arturo López PérezSantiago, CL
via this cancer
Garvan Institute of Medical Research / Kinghorn Cancer CentreSydney, AU
via this cancer
Geneva University Hospitals (HUG)Geneva, CH
via this cancer
GIMEMARome, IT
via MRD / molecular residual disease testing
Groote Schuur Hospital / University of Cape TownCape Town, ZA
via this cancer
Hacettepe University Cancer InstituteAnkara, TR
via this cancer
Hadassah Medical CenterJerusalem, IL
via this cancer
Hamad Medical Corporation / National Center for Cancer Care and ResearchDoha, QA
via this cancer
Harold C. Simmons Comprehensive Cancer Center, UT SouthwesternDallas, TX, USNCI comprehensive
via this cancer
HealthCare Global EnterprisesBengaluru, IN
via this cancer
Herbert Irving Comprehensive Cancer Center, Columbia UniversityNew York, NY, USNCI comprehensive
via this cancer
Ho Chi Minh City Oncology HospitalHo Chi Minh City, VN
via this cancer
Hospital Clínic de Barcelona / IDIBAPSBarcelona, ES
via this cancer
Hospital de Clínicas de Porto AlegrePorto Alegre, BR
via this cancer
Hospital del Mar / Hospital del Mar Research InstituteBarcelona, ES
via this cancer
Hospital Universitari i Politècnic La FeValencia, ES
via this cancer
Hospital Universitario 12 de OctubreMadrid, ES
via MRD / molecular residual disease testing
HOVONRotterdam, NL
via MRD / molecular residual disease testing
Huntsman Cancer Institute, University of UtahSalt Lake City, UT, USNCI comprehensive
via Talazoparib
HUS Comprehensive Cancer Center, Helsinki University HospitalHelsinki, FI
via this cancer
Institut BergoniéBordeaux, FR
via this cancer
Institut National d'Oncologie, RabatRabat, MA
via this cancer
Institut Paoli-CalmettesMarseille, FR
via this cancer
Institut Salah AzaïezTunis, TN
via this cancer
Institute of Oncology LjubljanaLjubljana, SI
via this cancer
Instituto Nacional de Câncer (INCA)Rio de Janeiro, BR
via this cancer
Instituto Nacional de Cancerología (Colombia)Bogotá, CO
via this cancer
Instituto Nacional de Cancerología (Mexico)Mexico City, MX
via this cancer
Instituto Nacional de Enfermedades NeoplásicasLima, PE
via this cancer
Instituto Português de Oncologia de Lisboa Francisco GentilLisbon, PT
via this cancer
Instituto Português de Oncologia do Porto Francisco GentilPorto, PT
via this cancer
International Association for the Study of Lung CancerDenver, CO, US
via AI in radiology
IRCCS Regina Elena National Cancer InstituteRome, IT
via this cancer
Istanbul University Institute of OncologyIstanbul, TR
via this cancer
Istituto Oncologico Veneto IRCCSPadua, IT
via this cancer
IUCT Oncopole – Institut Universitaire du Cancer de ToulouseToulouse, FR
via MRD / molecular residual disease testing
Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CA
via this cancer
Kenyatta National HospitalNairobi, KE
via this cancer
Kidwai Memorial Institute of OncologyBengaluru, IN
via this cancer
King Faisal Specialist Hospital and Research CentreRiyadh, SA
via this cancer
King Hussein Cancer CenterAmman, JO
via this cancer
Koo Foundation Sun Yat-Sen Cancer CenterTaipei, TW
via this cancer
Korle Bu Teaching HospitalAccra, GH
via this cancer
Lagos University Teaching HospitalLagos, NG
via this cancer
Leeds Cancer Centre, St James's University HospitalLeeds, GB
via Histopathology & immunohistochemistry
Maria Skłodowska-Curie National Research Institute of OncologyWarsaw, PL
via this cancer
Masaryk Memorial Cancer InstituteBrno, CZ
via this cancer
Mays Cancer Center at UT Health San AntonioSan Antonio, TX, USNCI clinical
via this cancer
Medicines and Healthcare products Regulatory AgencyLondon, GB
via AI in radiology
National Cancer Center KoreaGoyang, KR
via Mammography & tomosynthesis
National Cancer Institute, Cairo UniversityCairo, EG
via this cancer
National Institute of Oncology, HungaryBudapest, HU
via this cancer
National University Hospital / National University Cancer Institute, SingaporeSingapore, SG
via this cancer
NRG OncologyPhiladelphia, PA, US
via Olaparib
Ocean Road Cancer InstituteDar es Salaam, TZ
via this cancer
Olivia Newton-John Cancer Wellness and Research CentreMelbourne, AU
via Exercise & lifestyle oncology
Pharmaceuticals and Medical Devices AgencyTokyo, JP
via Trastuzumab deruxtecan
Philippine General HospitalManila, PH
via this cancer
QIMR Berghofer Medical Research InstituteBrisbane, AU
via this cancer
Rajiv Gandhi Cancer Institute and Research CentreNew Delhi, IN
via this cancer
Ramathibodi Hospital, Mahidol UniversityBangkok, TH
via this cancer
Rambam Health Care CampusHaifa, IL
via this cancer
Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityChicago, IL, USNCI comprehensive
via this cancer
Royal Adelaide HospitalAdelaide, AU
via this cancer
Shaare Zedek Medical CenterJerusalem, IL
via this cancer
Siriraj Hospital, Mahidol UniversityBangkok, TH
via this cancer
Skåne University Hospital / Lund University Cancer CentreLund, SE
via this cancer
Society of Surgical OncologyRosemont, IL, US
via this cancer
Stephenson Cancer Center, OU HealthOklahoma City, OK, USNCI clinical
via Olaparib
Sunnybrook Odette Cancer CentreToronto, ON, CA
via this cancer
Sydney Children's Hospitals Network / Children's Cancer InstituteSydney, AU
via MRD / molecular residual disease testing
Sylvester Comprehensive Cancer Center, University of MiamiMiami, FL, USNCI clinical
via MRD / molecular residual disease testing
Tata Medical Center, KolkataKolkata, IN
via this cancer
Tawam HospitalAl Ain, AE
via this cancer
Tel Aviv Sourasky Medical CenterTel Aviv, IL
via this cancer
The Ottawa Hospital Cancer Centre / Ottawa Hospital Research InstituteOttawa, ON, CA
via this cancer
UCLA Jonsson Comprehensive Cancer CenterLos Angeles, USNCI comprehensive
via Palbociclib
Uganda Cancer InstituteKampala, UG
via this cancer
UNC Lineberger Comprehensive Cancer CenterChapel Hill, NC, USNCI comprehensive
via this cancer
University Hospital Basel / Tumour CentreBasel, CH
via this cancer
University of Malaya Medical CentreKuala Lumpur, MY
via this cancer
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensive
via this cancer
Walter and Eliza Hall Institute of Medical ResearchMelbourne, AU
via this cancer
Wilmot Cancer Institute, University of RochesterRochester, NY, USNCI clinical
via Exercise & lifestyle oncology
World Health Organization – Cancer ProgrammeGeneva, CH
via this cancer

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about HR-positive / HER2-negative breast cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 47 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example ER/PR, HER2 IHC 0/1+/2+, Ki-67, Oncotype DX / MammaPrint / Prosigna, PIK3CA/AKT1/PTEN), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include Luminal A, Luminal B, HER2-low.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Early stage

For my situation (early stage), which of the standard options do you recommend and why?
Why: Guideline options include: Surgery, radiation, endocrine therapy 5-10 years; chemotherapy if genomic risk high; abemaciclib or ribociclib adjuvant for high-risk.
Am I a candidate for Oncotype DX, Abemaciclib, Ribociclib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of monarchE and NATALEE apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic first line

For my situation (metastatic first line), which of the standard options do you recommend and why?
Why: Guideline options include: CDK4/6 inhibitor + aromatase inhibitor or fulvestrant.
Am I a candidate for Palbociclib, Ribociclib, Abemaciclib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic second line

For my situation (metastatic second line), which of the standard options do you recommend and why?
Why: Guideline options include: Genotype-directed: capivasertib, inavolisib, alpelisib, everolimus; elacestrant/vepdegestrant if ESR1-mutant; gedatolisib.
Am I a candidate for Capivasertib, Inavolisib, Elacestrant or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Endocrine-resistant

For my situation (endocrine-resistant), which of the standard options do you recommend and why?
Why: Guideline options include: T-DXd (HER2-low/ultralow) before chemotherapy; sacituzumab govitecan or Dato-DXd after chemotherapy.
Am I a candidate for Trastuzumab deruxtecan, Sacituzumab govitecan, Datopotamab deruxtecan, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of DESTINY-Breast06 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Screening and diagnosis

For my situation (screening and diagnosis), which of the standard options do you recommend and why?
Why: Guideline options include: Mammography ± tomosynthesis; supplemental MRI for dense breasts or high risk; core biopsy with ER/PR/HER2/Ki-67; AI-assisted reading being deployed.

Early stage, deciding on chemotherapy

For my situation (early stage, deciding on chemotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: Genomic assay (Oncotype DX RS ≤25 node-negative or postmenopausal 1-3 nodes; MammaPrint low risk) → endocrine therapy alone; premenopausal RS 16-25 or high clinical risk → chemotherapy or OFS-based escalation.
Am I a candidate for Oncotype DX, MammaPrint (70-gene signature), and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of TAILORx and RxPONDER (SWOG S1007) apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Early stage, adjuvant endocrine therapy

For my situation (early stage, adjuvant endocrine therapy), which of the standard options do you recommend and why?
Why: Guideline options include: Postmenopausal: aromatase inhibitor 5-10 years (or tamoxifen → AI switch). Premenopausal: tamoxifen 5-10 years; add OFS (+ AI or tamoxifen) for higher-risk or chemotherapy-treated women (SOFT/TEXT).
Am I a candidate for Letrozole (and other aromatase inhibitors), Tamoxifen, Goserelin / leuprolide (ovarian function suppression), and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of SOFT & TEXT apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Early stage, high risk: adjuvant CDK4/6

For my situation (early stage, high risk: adjuvant cdk4/6), which of the standard options do you recommend and why?
Why: Guideline options include: Abemaciclib 2 years for node-positive high-risk (monarchE); ribociclib 3 years for stage II-III including node-negative high-risk (NATALEE). Palbociclib not effective (PALLAS/PENELOPE-B). Olaparib 1 year if gBRCA (OlympiA).
Am I a candidate for Abemaciclib, Ribociclib, Olaparib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of monarchE and NATALEE apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Early stage, extended and adjuvant SERD (emerging)

For my situation (early stage, extended and adjuvant serd (emerging)), which of the standard options do you recommend and why?
Why: Guideline options include: Extended AI to 10 years for higher-risk (MA.17R, NSABP B-42); adjuvant giredestrant positive in lidERA (2025, not yet approved); CAMBRIA (camizestrant) and EMBER-4 (imlunestrant) ongoing.
Am I a candidate for Giredestrant, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of lidERA and CAMBRIA-1 & CAMBRIA-2 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, first line

For my situation (metastatic, first line), which of the standard options do you recommend and why?
Why: Guideline options include: CDK4/6 inhibitor + aromatase inhibitor (or fulvestrant): ribociclib or abemaciclib preferred where OS data are valued; palbociclib acceptable. Premenopausal: add OFS. For relapse on/within 12 months of adjuvant ET with PIK3CA mutation: inavolisib + palbociclib + fulvestrant (INAVO120).
Am I a candidate for Ribociclib, Abemaciclib, Palbociclib or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of MONALEESA-2 and MONARCH 3 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, molecular progression on first line

For my situation (metastatic, molecular progression on first line), which of the standard options do you recommend and why?
Why: Guideline options include: Serial ctDNA; on emergent ESR1 mutation before radiographic progression, switch AI → camizestrant and continue the CDK4/6 inhibitor (SERENA-6; accelerated approval 4 Sep 2026).
Am I a candidate for Camizestrant, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of SERENA-6 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, second line by genotype

For my situation (metastatic, second line by genotype), which of the standard options do you recommend and why?
Why: Guideline options include: ESR1-mutant: elacestrant, imlunestrant (± abemaciclib), or vepdegestrant. PIK3CA/AKT1/PTEN: capivasertib + fulvestrant; alpelisib + fulvestrant. Any genotype after CDK4/6: gedatolisib + palbociclib + fulvestrant (PIK3CA-wild-type, 2026); everolimus + exemestane or giredestrant (filed); abemaciclib switch (postMONARCH, modest).
Am I a candidate for Gedatolisib, Elacestrant, Imlunestrant or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of EMBER-3 and EMERALD apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, endocrine-resistant: ADC before chemotherapy

For my situation (metastatic, endocrine-resistant: adc before chemotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: HER2-low or ultralow (~60%): T-DXd (DESTINY-Breast06 chemotherapy-naive; DESTINY-Breast04 after chemotherapy). HER2-zero: sacituzumab govitecan or Dato-DXd after chemotherapy (TROPiCS-02, TROPION-Breast01).
Am I a candidate for Trastuzumab deruxtecan, Sacituzumab govitecan, Datopotamab deruxtecan, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of DESTINY-Breast06 and DESTINY-Breast04 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, chemotherapy and later lines

For my situation (metastatic, chemotherapy and later lines), which of the standard options do you recommend and why?
Why: Guideline options include: Sequential single-agent chemotherapy (capecitabine, taxanes, eribulin, vinorelbine); olaparib/talazoparib if gBRCA; clinical trials; supportive and palliative care integrated early.
Am I a candidate for Paclitaxel / nab-paclitaxel, Olaparib, Talazoparib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Bone-predominant disease and survivorship

For my situation (bone-predominant disease and survivorship), which of the standard options do you recommend and why?
Why: Guideline options include: Bisphosphonate or denosumab for bone metastases and AI-induced bone loss; adjuvant bisphosphonates in postmenopausal women; exercise, cardio-oncology, and adherence support.

Any stage

Are there clinical trials I could join, for example of Vepdegestrant, Sacituzumab tirumotecan, Datopotamab deruxtecan, ArteraAI Breast?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “Late recurrence (up to 20+ years) with no predictive test”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “CDK4/6 resistance mechanisms and sequencing”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

institutions

113

pathways

Basement membrane & tissue barriers Fibroblast activation, desmoplasia & matrix stiffness Lipid synthesis, uptake & cholesterol Oestrogen receptor signalling Organ tropism: seed and soil p53 / RB / cell-cycle checkpoint PI3K / AKT / mTOR The cell-cycle engine (cyclins & CDKs)Transcriptional machinery & addiction Tumour dormancy Ubiquitin–proteasome system & protein homeostasis

pairings

Caution: TOP1 ADC immediately after TOP1 ADC CDK4/6 inhibitor + endocrine therapy Gene-expression assay → chemotherapy omission Germline BRCA test → adjuvant PARP inhibitor HER2-low scoring → T-DXd Oral SERD + CDK4/6 inhibitor after ESR1 emergence PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)

roadmaps

ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET

ideas

A blood test for the pre-metastatic niche A dose-finding trial for exercise after cancer A Global Fund for cancer care in low- and middle-income countries A pragmatic trial network for intraoperative margin tools, paid on margin reduction A prevention programme for chemotherapy nerve damage: SARM1 inhibitors, cooling and compression A public fund and label pathway to trial generic drugs against cancer A regulatory endpoint for drugs that block spread, not tumours A short pre-surgery drug window as the default early test of new agents A survivorship research endowment funded by a levy on curative therapy prices After the COMET trial: surveillance pathways and a new name for low-risk DCIS AI quantification of HER2-low and HER2-ultralow AI-first reading for high-volume common cancer diagnoses, pathologist for the exceptions Alpha radioligands after ADC failure Blended finance and a low-cost linac to close the global radiotherapy gap Block the recycling that keeps dormant cells alive Blunt the inflammation that wakes sleeping cancer cells Cancer warnings on alcohol labels, evaluated as a natural experiment Cardiometabolic screening and treatment for survivors on long-term hormone therapy CDK4-selective inhibitors as the new first-line backbone Certified decision aids required for every preference-sensitive cancer decision Cheap perioperative beta-blocker plus anti-inflammatory to blunt surgical stress Circulating tumour cell clearance as the phase 2 gate for anti-metastatic drugs Community health workers trained in cancer triage, navigation and home palliative care Confirm or refute the harm of antioxidant supplements during chemotherapy Decision aids built into the record for every preference-sensitive cancer choice Dose chemotherapy by muscle mass, not body surface area Dual-payload ADCs in first line to prevent resistance Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells Evaluate alcohol minimum unit pricing against cancer incidence Flush dormant cells out of bone marrow, then kill them GLP-1 receptor agonists as adjuvant weight-loss therapy in HR-positive breast cancer Hormone tablets instead of surgery for small breast cancers in the frail over-80s Intercepting late recurrence with ctDNA surveillance and oral SERDs Keep dormant cells asleep instead of trying to kill them Keep them asleep: dormancy maintenance as adjuvant therapy Look for the resistant sub-population before the first dose Low-dose tamoxifen for high-risk women, prescribed by pharmacists and nurses Make one-week radiotherapy the default in overloaded systems Make skipping radiotherapy the default for very low-risk breast cancer Mobile diagnostic units that biopsy, scan and treat on the same visit Molecular indolence classifiers bundled with every screening programme Molecular-progression switching beyond ESR1 Multi-arm, multi-stage trials to answer which order to give approved drugs Nurse-led chemotherapy day units with a doctor on a screen Oncology teams order germline tests; tele-genetic counsellors handle the results One-stop breast clinics: imaging, biopsy and a preliminary answer in a single visit Patient-derived organoids to pick ADC payloads Pay for supervised exercise the way we pay for drugs Pay per course of radiotherapy, not per session, so short courses are not penalised Payer-funded trials that omit surgery or radiotherapy in low-risk patients Payload-class switching as the rule for ADC sequencing Perioperative beta-blocker plus COX-2 inhibitor to reduce metastasis after surgery Pooled coverage-with-evidence for proton therapy across all centres Population germline screening for hereditary cancer genes with cascade testing Pre-consented cohorts that can be randomised to future trials (TwiCs)Prospective arm-volume surveillance to catch and reverse lymphoedema early Public country dashboards for the three WHO breast cancer targets Re-test the metastasis, not the old primary, before every change of treatment Real-time margin assessment and image-guided surgery as the global standard Registry-embedded randomisation of treatment order in routine care Risk-stratified follow-up: low-risk survivors to primary care with fast re-entry Roll out AI-supported mammography nationally as a stepped-wedge trial Rotate between drugs on a fixed schedule instead of waiting for failure Sequential multiple-assignment randomised trials to find the best order of ADCs Set each woman's mammogram interval from her last mammogram, using AI risk Sexual health assessed and treated as a standard toxicity domain Soften the tissue that new metastases need in order to grow Strip the platelet coat off travelling tumour cells in ctDNA-positive patients Structured mentorship so district general surgeons perform common cancer operations safely Tailored screening for second cancers in survivors with known high-risk exposures Take the blood test, and give the drug, at the right time of day Time immunotherapy to the moment targeted drugs make tumours visible Treat insomnia in survivors and measure whether the cancer notices Use a polygenic risk score to set when screening starts Use residual disease tests to decide who needs ten years of hormone therapy What decides which disseminated cells ever colonise?When the blood test is positive, hunt for the lesion with sensitive imaging

collections

Susan G. Komen

bottlenecks

Acquired resistance to every therapy AI that is built but not validated or deployed Biomarkers are not validated or standardised Cold tumours and the immunosuppressive microenvironment Dormant cells and minimal residual disease Inherited risk is mostly unidentified Metastasis is understood least and studied last Misinformation and unproven therapies No incentive to repurpose cheap drugs Overdiagnosis and false alarms Survivorship and late effects are neglected Trial design, endpoints and cost Tumour heterogeneity and clonal evolution Wrong doses

key papers

Alcohol caused an estimated 741,000 cancers worldwide in 2020 DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer IARC verdict: excess body fat causes 13 cancers IBIS-I: five years of tamoxifen keeps preventing breast cancer for at least 20 years MASAI: AI-supported mammography screening finds more cancers with half the radiologist workload monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer PREDIMED: a Mediterranean diet with extra-virgin olive oil and fewer breast cancers PROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival

Key papers

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rctNew England Journal of Medicine 2024changed practice

DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer

Patients with hormone-receptor-positive metastatic breast cancer that has stopped responding to endocrine therapy can be offered trastuzumab deruxtecan as their first chemotherapy-type treatment if the tumour shows any HER2 staining, rather than waiting until after conventional chemotherapy. Whether to use it before or after chemotherapy is now a choice, since overall survival was not shown to differ and the drug carries a risk of lung inflammation.

rctNew England Journal of Medicine 2024changed practice

NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer

Ribociclib is a second adjuvant CDK4/6 option, and the only one with data in node-negative stage II disease. Roughly 3 in 100 patients avoid a relapse or death at three years, so the decision depends heavily on individual risk, tolerance of a three-year oral drug, and cost. Whether the benefit persists after treatment ends, as it did with abemaciclib, needs longer follow-up.

rctJournal of Clinical Oncology 2024

TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival

For hormone-receptor-positive metastatic breast cancer that has already had chemotherapy, Dato-DXd controls the disease for longer with fewer severe side effects than chemotherapy, but does not help patients live longer, so it is not a standard option here. The result is a reminder that progression-free survival is a surrogate; regulators and clinicians should wait for survival data before adopting an ADC in a setting where later therapies are effective.

rctLancet Oncology 2023

MASAI: AI-supported mammography screening finds more cancers with half the radiologist workload

AI can take over one reader's work in double-reading screening programmes while finding more cancers. Whether the extra cancers found are ones that would have harmed women, and whether interval cancers fall, is the question the trial's primary endpoint will answer.

rctNew England Journal of Medicine 2022changed practice

DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group

Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.

observationalLancet Oncology 2021

Alcohol caused an estimated 741,000 cancers worldwide in 2020

There is no safe level of alcohol for cancer risk, and the risk is highest for cancers of the mouth, throat, oesophagus, liver, bowel and breast. Public awareness is low; most people do not know alcohol causes breast cancer. Warning labels and minimum pricing are the policy levers being debated.

rctNew England Journal of Medicine 2021changed practice

OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer

Everyone with HER2-negative early breast cancer that meets high-risk criteria should be offered germline BRCA testing, because a positive result now changes treatment: a year of olaparib after chemotherapy reduces relapse and death. It does not apply to low-risk tumours, HER2-positive disease, or somatic-only BRCA mutations.

rctJournal of Clinical Oncology 2020changed practice

monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer

Women with hormone-receptor-positive, HER2-negative breast cancer that has spread to lymph nodes and has other high-risk features can now be offered two years of abemaciclib alongside their hormone therapy, with a durable reduction in relapse. It does not apply to node-negative or low-risk disease, and the diarrhoea and cost are real trade-offs to discuss.

reviewNew England Journal of Medicine 2016changed practice

IARC verdict: excess body fat causes 13 cancers

Maintaining a healthy weight is now established cancer prevention for over a dozen cancer types. For clinicians and policymakers, obesity belongs alongside tobacco and alcohol in prevention strategy. Whether intentional weight loss in adulthood reverses risk is still being studied, including in trials of GLP-1 drugs.

rctLancet Oncology 2015changed practice

IBIS-I: five years of tamoxifen keeps preventing breast cancer for at least 20 years

For women at raised risk, a 5-year course of tamoxifen offers long-lasting protection against the commonest kind of breast cancer. Uptake is low because of side effects and fear of rare serious harms; low-dose tamoxifen (TAM-01) is now being tested to improve the balance. It has not been shown to save lives.

rctJAMA Internal Medicine 2015

PREDIMED: a Mediterranean diet with extra-virgin olive oil and fewer breast cancers

A Mediterranean dietary pattern rich in olive oil may lower breast cancer risk, and it is safe and good for the heart anyway. The evidence is suggestive, not definitive, because of the small number of cancers; it should not be presented as proven cancer prevention.

observationalJAMA 2010changed practice

PROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers

For women who carry a BRCA mutation, preventive removal of the ovaries and tubes saves lives, and preventive mastectomy almost eliminates breast cancer. These are the strongest prevention effects in oncology, which is why finding carriers before they develop cancer matters so much.