What changed: HR-positive / HER2-negative breast cancer

When this page itself was last checked or edited.

Accelerated approval (Etcamah)

FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer

HR+/HER2- advanced breast cancer after CDK4/6 inhibitor with palbociclib and fulvestrant (VIKTORIA-1)

ESR1-mutated ER+/HER2- advanced breast cancer after endocrine therapy: first PROTAC approved

FDA clearance: first digital-pathology-based risk stratification tool for early HR+/HER2- breast cancer

ODAC voted 6-3 against (clinical relevance of ctDNA-triggered switch)

persevERA primary endpoint not met

NDA accepted (evERA, ESR1-mutant)

Positive topline phase 2 FOURLIGHT-1

Risk stratification in early-stage HR+/HER2- invasive breast cancer

ER+/HER2- advanced breast cancer with emergent ESR1 mutation, with a CDK4/6 inhibitor; 20 Jul 2026

HR+/HER2- advanced breast cancer with an emergent ESR1 mutation on AI + CDK4/6, with a CDK4/6 inhibitor (accelerated, 4 Sep 2026)

HR+/HER2- advanced breast cancer after CDK4/6 inhibitor (July 2026)

ESR1-mutant ER+/HER2- mBC; 9 Jan 2026

ESR1-mutated ER+/HER2- advanced or metastatic breast cancer after endocrine therapy

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)

PFS improved (HR not yet published in detail).

PFS 33.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

Approved as Inluriyo

NDA based on SERENA-6

OS benefit added to label

NDA submitted (VERITAC-2)

Breakthrough Therapy designation, PIK3CA-wild-type HR+/HER2- breast cancer after CDK4/6

ER+/HER2- ESR1-mutated advanced breast cancer after ≥1 line of endocrine therapy

PIK3CA-mutant ER+/HER2- mBC with palbociclib + fulvestrant; 18 Jul 2025

Weight loss achieved; primary iDFS endpoint not met at first analysis (presented 2025; publication pending, verify).

PFS HR 0.

iDFS ~30% relative reduction (HR ~0.

PFS 16.

PFS HR 0.

A milestone in how this cancer is treated.

PIK3CA-mutant HR+/HER2- endocrine-resistant advanced breast cancer with palbociclib and fulvestrant (INAVO120)

Adjuvant stage II-III HR+/HER2- early breast cancer at high risk (NATALEE)

Fast Track designation

PIK3CA-mutant HR+/HER2- advanced breast cancer with palbociclib and fulvestrant

Adjuvant stage II-III HR+/HER2- breast cancer at high risk of recurrence

PFS HR 0.

PFS HR 0.

Ongoing; the first block results and de-escalation rates were reported from 2024.

PFS 6.

A milestone in how this cancer is treated.

EMA approval

Adjuvant indication broadened to remove Ki-67 requirement

ESR1-mutated ER+/HER2- advanced breast cancer after ≥1 endocrine therapy (EMERALD): first oral SERD

First-line HR-positive, HER2-negative advanced breast cancer with an aromatase inhibitor (DAWNA-2)

ESR1-mutant ER+/HER2- advanced breast cancer after ≥1 endocrine therapy

PFS 15.

5-year local recurrence 2.

Cancer detection 6.

iDFS HR 0.

5-year DFS 86.

PFS HR 0.

A milestone in how this cancer is treated.

To decrease the incidence of febrile neutropenia in adults with non-myeloid malignancies receiving myelosuppressive chemotherapy

PFS HR 0.

OS HR 0.

OS 14.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

Adjuvant high-risk node-positive HR+/HER2- early breast cancer, Ki-67 ≥20% (monarchE)

Adjuvant high-risk node-positive HR+/HER2- early breast cancer

HR-positive, HER2-negative advanced breast cancer with fulvestrant after endocrine therapy (DAWNA-1)

PFS 15.

PFS HR 0.

iDFS HR 0.

A milestone in how this cancer is treated.

RxPONDER extends to 1-3 positive nodes (postmenopausal)

Detection of ER-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer

5-year ipsilateral breast tumour relapse 1.

iDFS HR 0.

PALLAS iDFS HR 0.

Circulating tumour DNA matched tissue genotyping with about 93 percent sensitivity; neratinib (HER2 mutations) and capivasertib plus fulvestrant (AKT1 mutations, receptor-positive) met their response thresholds; extended-dose fulvestrant for ESR1 mutations did not.

No chemo benefit postmenopausal; iDFS HR 0.

A milestone in how this cancer is treated.

PIK3CA-mutant HR+/HER2- advanced breast cancer with fulvestrant after endocrine therapy

10-year ipsilateral breast tumour recurrence 4.

5-year OS 42.

A milestone in how this cancer is treated.

Pre/perimenopausal women and with fulvestrant (MONALEESA-7/-3)

TAILORx results define recurrence score ≤25 as chemotherapy-sparing

With aromatase inhibitor first line (MONARCH 3)

PFS 11.

9-year iDFS 83.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

With fulvestrant after endocrine therapy, and as monotherapy after chemotherapy (MONARCH 2/1)

With aromatase inhibitor, HR+/HER2- advanced breast cancer (MONALEESA-2)

HR+/HER2- advanced breast cancer

First-line HR+ advanced breast cancer (FALCON)

HR+/HER2- advanced breast cancer

5-year local relapse 0.

PFS HR 0.

Multiple graduations (veliparib-carboplatin, neratinib, pembrolizumab, MK-2206, T-DM1 plus pertuzumab, durvalumab plus olaparib, cemiplimab plus fianlimab); pembrolizumab's graduation preceded its approval in early triple-negative breast cancer.

5-year distant metastasis-free survival 94.

OS 63.

PFS HR 0.

10-year overall survival 82.

10-year disease-free survival 82.

10-year local recurrence 9.

A milestone in how this cancer is treated.

A milestone in how this cancer is treated.

Exemestane + OFS: DFS and DRFI improved; no OS difference at 12 years.

A milestone in how this cancer is treated.

Prognosis of distant recurrence in postmenopausal HR+ early breast cancer (510(k))

CE-IVD

First targeted agent to overcome endocrine resistance.

No overall benefit; node-positive 5-year DFS 65.

10-year local-regional relapse 4.

FDA 510(k) clearance for recurrence risk in early breast cancer

Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis or at high risk

Breast cancer events 16.

Adjuvant after 2-3 years of tamoxifen

Launched as a laboratory-developed test

10-year locoregional recurrence 10% (tamoxifen alone) vs 2% (tamoxifen plus radiotherapy); no survival difference.

Gene-expression recurrence score enters practice.

HR+ advanced breast cancer after antioestrogen therapy

A milestone in how this cancer is treated.

Advanced breast cancer after tamoxifen

Risk reduction in high-risk women

A milestone in how this cancer is treated.

Treatment and prevention of postmenopausal osteoporosis

Metastatic breast cancer in postmenopausal women with ER-positive or unknown tumours

82b: 10-year locoregional recurrence 9% vs 32%; overall survival 54% vs 45%.

Tumour-induced hypercalcaemia; prevention of skeletal events in breast cancer with bone metastases (Bondronat)

First-line hormonal treatment of hormone-dependent metastatic breast cancer in postmenopausal women

Advanced breast cancer (goserelin); prostate cancer

Advanced breast cancer

A milestone in how this cancer is treated.

The first targeted cancer drug; later shown to reduce mortality by a third over 15 years.

Basis for predicting hormone responsiveness.

Palliation of androgen-responsive advanced breast cancer in postmenopausal women (historic label)

First hormonal therapy for any cancer.

First hormonal therapy for cancer.