Automated Quantification of Extranuclear Oestrogen Receptor Alpha Using Phosphor-Integrated Dots for Predicting Endocrine Therapy Resistance in Hormone Receptor-Positive HER2-Negative Breast Cancer

1062 Background: Novel endocrine therapies (ETs) and targeted therapeutic regimens have been developed to dramatically improve the outcome of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Since the absence of direct head-to-head comparisons for all regimens, decision-making guidelines are urgently needed for different endocrine sensitivity statuses. This study is to evaluate the efficacy of ET-based regimens in patients with HR+/HER2- MBC and to assess the heterogeneity among different compounds with a particular focus on their ability to improve survival outcomes. Methods: This network meta-analysis of phase II/III randomized controlled trials (RCTs) with at least one ET in HR+/HER2- MBC were enrolled. Based on the endocrine responses, participants were stratified into endocrine therapy sensitivity (ETS) and endocrine therapy resistance (ETR) groups. Primary endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed by bayesian algorithms and primarily measured as surface under the cumulative ranking curve (SUCRA). Results: A total of 42 trials (22917 patients) were included. Regarding PFS, cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) +fulvestrant 500mg (F500) was recommended for the ETS group (SUCRA = 76.92%), while chemotherapy was considered as the most effective option for the ETR group (SUCRA = 73.47%). For visceral metastases, CDK4/6i +aromatase inhibitors (AIs) could provide the extreme efficacy for the ETS group (SUCRA = 63.27%) while the CDK4/6i +F500 (SUCRA = 76.17%) as the prior regimen for the ETR group. For bone-only disease, CDK4/6i+F500 was preferred for both the ETS (SUCRA = 67.04%) and the ETR (SUCRA = 70.24%) group. Concerning OS, CDK4/6i+tamoxifen was estimated as the first-rank regimen for the ETS subgroup (SUCRA = 67.04%) and chemotherapy for the ETR subgroup (SUCRA = 60.02%). Regarding resistance category, abemaciclib +F500 was likely the best option with PFS, for both primary (SUCRA = 69.19%) and secondary ETR (SUCRA = 69.09%) settings, as well as primary ETR associated with OS improvement (SUCRA = 67.67%). Pictilisib +F500 could be the optimal treatment with OS for secondary ETR (SUCRA = 60.50%)group. Conclusions: The results showed that CDK4/6i + F500 was probably the most promising option in ETS, visceral ETR and bone-only disease settings in terms of PFS. OS subgroup analysis showed that different endocrine sensitivity statuses required various optimal treatment strategies.

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The NF-KB pathway and endocrine therapy resistance in breast cancer

Endocrine Related Cancer ◽

10.1530/erc-19-0087 ◽

2019 ◽

Vol 26 (6) ◽

pp. R369-R380 ◽

Cited By ~ 10

Author(s):

Phungern Khongthong ◽

Antonia K Roseweir ◽

Joanne Edwards

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Oestrogen Receptor ◽

Nuclear Factor Kappa B ◽

Treatment Resistance ◽

Therapy Resistance ◽

Nuclear Factor ◽

Mechanisms Of Resistance ◽

Endocrine Therapy Resistance

Breast cancer is a heterogeneous disease, which over time acquires various adaptive changes leading to more aggressive biological characteristics and development of treatment resistance. Several mechanisms of resistance have been established; however, due to the complexity of oestrogen receptor (ER) signalling and its crosstalk with other signalling networks, various areas still need to be investigated. This article focusses on the role of nuclear factor kappa B (NF-KB) as a key link between inflammation and cancer and addresses its emerging role as a key player in endocrine therapy resistance. Understanding the precise mechanism of NF-KB-driven endocrine therapy resistance provides a possible opportunity for therapeutic intervention.

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Faculty Opinions recommendation of Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734467013.793556634 ◽

2019 ◽

Author(s):

Eva Chalas

Keyword(s):

Breast Cancer ◽

Clinical Practice ◽

Endocrine Therapy ◽

Clinical Practice Guideline ◽

Practice Guideline ◽

Hormone Receptor ◽

Adjuvant Endocrine Therapy ◽

Hormone Receptor Positive ◽

Positive Breast Cancer

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Impact of adjuvant endocrine therapy on prognosis in small hormone receptor-positive, HER2-negative early breast cancer

Breast Cancer ◽

10.1007/s12282-021-01245-w ◽

2021 ◽

Author(s):

Yayoi Adachi ◽

Isao Oze ◽

Masataka Sawaki ◽

Masaya Hattori ◽

Akiyo Yoshimura ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Early Breast Cancer ◽

Hormone Receptor ◽

Adjuvant Endocrine Therapy ◽

Hormone Receptor Positive

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Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920987651 ◽

2021 ◽

Vol 13 ◽

pp. 175883592098765

Author(s):

Raffaella Palumbo ◽

Rosalba Torrisi ◽

Federico Sottotetti ◽

Daniele Presti ◽

Anna Rita Gambaro ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Real World ◽

Hormone Receptor ◽

Metastatic Breast ◽

Progression Free Survival ◽

Her2 Receptor ◽

Treatment Line ◽

Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

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Trends in endocrine therapy prescription and survival in patients with non-metastatic hormone receptor positive breast cancer treated with endocrine therapy: A population based-study

The Breast ◽

10.1016/j.breast.2021.06.003 ◽

2021 ◽

Author(s):

Ariane Mamguem Kamga ◽

Oumar Billa ◽

Sylvain Ladoire ◽

Marie-Laure Poillot ◽

Geneviève Jolimoy ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Hormone Receptor ◽

Population Based ◽

Population Based Study ◽

Hormone Receptor Positive ◽

Positive Breast Cancer

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Top 3 abstracts concerning hormone-receptor-positive early breast cancer

memo - Magazine of European Medical Oncology ◽

10.1007/s12254-021-00726-0 ◽

2021 ◽

Author(s):

Simon Peter Gampenrieder ◽

Gabriel Rinnerthaler ◽

Richard Greil

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Endocrine Therapy ◽

Early Breast Cancer ◽

Hormone Receptor ◽

Menopausal Status ◽

Pathologic Complete Response ◽

Oncotype Dx ◽

Hormone Receptor Positive ◽

Her2 Breast Cancer

SummaryThe three top abstracts at the 2020 virtual San Antonio Breast Cancer Symposium regarding hormone-receptor-positive early breast cancer, from our point of view, were the long-awaited results from PenelopeB and RxPONDER as well as the data from the ADAPT trial of the West German Study Group. PenelopeB failed to show any benefit by adjuvant palbociclib when added to standard endocrine therapy in patients without pathologic complete response after neoadjuvant chemotherapy. RxPONDER demonstrated that postmenopausal patients with early hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2−) breast cancer, 1–3 positive lymph nodes and an Oncotype DX Recurrence Score of less than 26 can safely be treated with endocrine therapy alone. In contrast, in premenopausal women with positive nodes, adjuvant chemotherapy plays still a role even in case of low genomic risk. Whether the benefit by chemotherapy is mainly an indirect endocrine effect and if ovarian function suppression would be similarly effective, is still a matter of debate. The HR+/HER2− part of the ADAPT umbrella trial investigated the role of a Ki-67 response to a short endocrine therapy before surgery in addition to Oncotype DX—performed on the pretreatment biopsy—to identify low-risk patients who can safely forgo adjuvant chemotherapy irrespective of menopausal status.

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