Treatment of HR+, HER2– BC
Endocrine therapy (ET), the therapeutic mainstay of HR+, HER2– BC, blocks endocrine signalling via inhibition of hormone synthesis or targeting of hormone receptors.1
ET may be combined with a variety of biomarker-targeted therapies, depending on the indication. These treatment combinations aim to inhibit multiple pathways simultaneously.2
ETs have evolved through ongoing refinements. Early advances with selective oestrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and first-generation selective oestrogen receptor antagonists and degraders (SERDs) transformed the treatment landscape, while newer oral SERDs aim to address remaining limitations.12
Timeline based on FDA approvals.
Treatment algorithm in HR+, HER2– eBC
In the HR+, HER2– eBC setting, treatment is given with curative intent to prevent early and late recurrences.26
Treatment guidelines recommend tailoring treatment based on tumour stage/biology and menopausal status, with several classes of therapeutic interventions available, including ET, chemotherapy and targeted therapies.26
Note: treatment algorithms are presented as shown in publicly available ESMO treatment guidelines.
a Stage N1 with primary tumour >5 cm, and/or grade 3 and/or Ki67 ≥20%.
b ESMO-MCBS v1.1 was used to calculate scores for new therapies/indications approved by the European Medicines Agency (EMA) or US Food and Drug Administration (FDA). The scores have been calculated and validated by the ESMO-MCBS Working Group and reviewed by the authors.
c If gBRCA1/2 testing is appropriate and feasible.
d Patients with HR+ tumours and non-pCR after neoadjuvant chemotherapy require a CPS + EG score ≥3 to receive olaparib.
e ESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the guideline authors and assisted as needed by the ESMO Translational Research and Precision Medicine Working Group.
f Tamoxifen can be given for lower-risk tumours or if AIs are not tolerated [I, A].
Treatment algorithm in HR+, HER2– mBC
In the mBC setting, patients continue treatment until progression or unacceptable toxicity, at which point they switch to another treatment option. The treatment goal is to improve efficacy and delay the onset of endocrine resistance and to postpone more toxic chemotherapy options.27,28
In the first-line treatment (1L) HR+, HER2– mBC setting, treatment guidelines recommend CDK4/6i + ET for non–biomarker-selected patients, or novel, biomarker-selected combination therapies for eligible patients whose tumours have actionable mutations.27,29
Note: treatment algorithms are presented as shown in publicly available ESMO treatment guidelines.
a Ovarian function suppression if the patient is premenopausal.
b In exceptional cases (e.g. CDK4/6i is not available in first line), ET alone followed by fulvestrant + CDK4/6i upon disease progression may be an option for mBC (de novo or recurring >12 months after the end of adjuvant ET) [I, C].
c ESMO-MCBS v2.0 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS Working Group and reviewed by the authors.
In the second-line or later (2L+) HR+, HER2– mBC setting, treatment guidelines recommend a variety of ET ± biomarker-targeting agents, depending on prior treatment received and presence of actionable biomarkers. For patients who are not eligible for ET, novel ADCs or chemotherapy-based regimens are recommended.27,29
Note: treatment algorithms are presented as shown in publicly available ESMO treatment guidelines.
a ESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the Clinical Practice Guideline authors and validated by the ESMO Precision Oncology Working Group.
b Ovarian function suppression if the patient is pre-menopausal.
c If not previously exposed to fulvestrant ± PI3K inhibitor.
d ESMO-MCBS v2.0 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS Working Group and reviewed by the authors.
e If PIK3CA mutation not targeted before.
f Preferred if the patient has ESR1mut mBC and if not used before.
g If not used before, EMA approved, not FDA approved.
h For HER2-low, trastuzumab deruxtecan can also be given following adjuvant chemotherapy in the setting of fast progression (DESTINY-Breast04/EMA indication).
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