Relationship between endocrine resistance and the periods of adjuvant endocrine treatment for hormone receptor-positive, HER2-negative breast cancer

2021 ◽  
pp. 1-6
Author(s):  
Jun Yamamura ◽  
Yukiko Miyamura ◽  
Shunji Kamigaki ◽  
Junya Fujita ◽  
Hiroki Osato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Endocrine Resistance ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Endocrine Treatment ◽  
First Year ◽  
Hormone Receptor Positive ◽  
First Recurrence ◽  
The Relationship

BACKGROUND: Current guidelines define primary and secondary endocrine resistance according to the periods of adjuvant endocrine therapy (adj-ET); however, the relationship between adj-ET period and endocrine resistance remains unclear. OBJECTIVE: We examined progression-free survival (PFS) after primary ET for recurrent hormone receptor-positive/HER2-negative breast cancer, and evaluated the relationship between endocrine resistance and the periods of adj-ET. METHODS: We assessed PFS among 183 patients who received ET as primary treatment for the first recurrence, according to the period of adj-ET (adj-ET < 1 year, 1–2 years, ≥2 years, and completion). RESULTS: Patients who relapsed during the first year of adj-ET had the significantly shortest PFS. PFS did not significantly differ between patients who relapsed at 1–2 years of adj-ET and patients who relapsed while on adj-ET but after the first 2 years. CONCLUSIONS: Relapse at 1–2 years after adj-ET initiation might be better classified as secondary endocrine resistance rather than primary endocrine resistance.

scholarly journals Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: A potential role for Liquid Biopsies?

Tumor Biology ◽  
2017 ◽  
Vol 39 (11) ◽  
pp. 101042831773151 ◽  
Author(s):  
Florian Reinhardt ◽  
André Franken ◽  
Tanja Fehm ◽  
Hans Neubauer
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Potential Role ◽  
Endocrine Resistance ◽  
Resistance Mechanisms ◽  
Intratumoral Heterogeneity ◽  
Endocrine Treatment ◽  
Liquid Biopsies ◽  
Hormone Receptor Positive

The majority of breast cancers are hormone receptor positive due to the expression of the estrogen and/or progesterone receptors. Endocrine therapy is a major treatment option for all disease stages of hormone receptor–positive breast cancer and improves overall survival. However, endocrine therapy is limited by de novo and acquired resistance. Several factors have been proposed for endocrine therapy failures, which include molecular alterations in the estrogen receptor pathway, altered expression of cell-cycle regulators, autophagy, and epithelial-to-mesenchymal transition as a consequence of tumor progression and selection pressure. It is essential to reveal and monitor intra- and intertumoral alterations in breast cancer to allow optimal therapy outcome. Endocrine therapy navigation by molecular profiling of tissue biopsies is the current gold standard but limited in many reasons. “Liquid biopsies” such as circulating-tumor cells and circulating-tumor DNA offer hope to fill that gap in allowing non-invasive serial assessment of biomarkers predicting success of endocrine therapy regimen. In this context, this review will provide an overview on inter- and intratumoral heterogeneity of endocrine resistance mechanisms and discuss the potential role of “liquid biopsies” as navigators to personalize treatment methods and prevent endocrine treatment resistance in breast cancer.

scholarly journals Targeted Therapies Overcoming Endocrine Resistance in Hormone Receptor-Positive Breast Cancer

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 168-172 ◽  
Author(s):  
Katrin Almstedt ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Hormone Receptor ◽  
Endocrine Resistance ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Study Results ◽  
Er Positive ◽  
Positive Breast Cancer

Breast cancer is a heterogeneous disease with different molecular subtypes. Most tumours are hormone receptor positive (luminal subtype) with potential endocrine responsiveness. Endocrine therapy is commonly used in these patients. Disease progression caused by endocrine resistance represents a significant challenge in the treatment of breast cancer. To understand the mechanisms of resistance of long-term oestrogen-deprived breast cancer cells, it is important to focus on cross-talk between steroid receptor signalling and other growth factor receptors and intracellular pathways. (Pre-)clinical trials showed that co-targeting these pathways can restore endocrine sensitivity. The focus of the current review is on the intracellular PI3K/AKT/mTOR signalling pathway and cyclin-dependant kinases (CDKs) in oestrogen receptor (ER)-positive breast cancer. Study results clearly show that both inhibition of the PI3K/AKT/mTOR pathway and CDK4/6 are promising ways to improve the efficacy of endocrine treatment in ER-positive breast cancer patients with comparably few side effects. Further clinical trials are needed to identify the patient population who would benefit most from a dual inhibition.

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations

2020 ◽  
Author(s):  
Athanasios Mavratzas ◽  
Frederik Marmé
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Pik3ca Mutations ◽  
Hormone Receptor Positive ◽  
Fda Approval

Since the US FDA approval of everolimus/exemestane in July 2012, and of the first CDK 4/6 inhibitor, palbociclib, combined with endocrine treatment in February 2015, a third class of therapeutic compounds, the PI3K inhibitors, has been introduced to the arsenal of targeted therapies overcoming endocrine resistance in hormone receptor-positive metastatic breast cancer. Alpelisib (PIQRAY®) is the first of these novel agents yielding promising clinical results, giving an impetus to further development of tailored endocrine anticancer treatments. Herein, we review its pharmacodynamic and pharmacokinetic properties, safety and efficacy data, as well as Phase III SOLAR-1 trial, prompting FDA approval of alpelisib in hormone receptor-positive metastatic breast cancer harboring PIK3CA mutations. Furthermore, implications for clinical use and current research will also be discussed.

scholarly journals 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

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.

Advances in Adjuvant Endocrine Therapy for Postmenopausal Women

2008 ◽  
Vol 26 (5) ◽  
pp. 798-805 ◽  
Author(s):  
Nancy U. Lin ◽  
Eric P. Winer
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Diagnosis ◽  
Endocrine Treatment ◽  
Future Research ◽  
Sequential Approach ◽  
Hormone Receptor Positive

Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity.

scholarly journals Epirubicin and docetaxel as neoadjuvant treatment of hormone receptor positive, HER-2 negative breast cancer: findings from two successive phase II studies

2013 ◽  
Vol 47 (1) ◽  
pp. 57-62
Author(s):  
Alessandro Tuzi ◽  
Davide Lombardi ◽  
Diana Crivellari ◽  
Loredana Militello ◽  
Tiziana Perin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Progression Free Survival ◽  
Preoperative Treatment ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
In Series ◽  
Her 2

Abstract Background. We report on the activity of the combination of epirubicin and docetaxel given in neoadjuvant setting for 4 and 8 cycles respectively in 2 successive series of patients with large operable or locally advanced, hormone receptor positive, HER-2 negative breast cancer. Patients and methods. Patients were treated from 2002 to 2006 with epirubicin 90 mg/m2 and docetaxel 75 mg/ m2 intravenously, every 3 weeks for 4 cycles before and 4 cycles after surgery (Series I - 13 patients), and from 2006 to 2010 with the same regimen administered for 8 cycles preoperatively (Series II - 37 patients), plus hormonal therapy for 5 years and radiation therapy if indicated. All Series I and 32 Series II patients were able to complete the preoperative chemotherapy. Results. A complete response was found in 1 patient from Series I and 13 patients from Series II and the partial remission in 10 patients from Series I and 21 patients from Series II. Two Series I and 3 Series II patients did not respond clinically. Response rate (Series I/Series II) was 84/92%. All 50 patients underwent surgery. In Series I patients, 3 pCR occurred in the breast and the axilla was histologically negative in 2 cases. No evidence of disease both in the breast and in the axilla was achieved in 7.6% (1/13) of patients. In Series II patients, 8 pCR occurred in the breast and axilla was histologically negative in 15 patients. No evidence of disease both in the breast and in the axilla occurred in 10.8% (4/37) of patients. G3-G4 toxicity included myelosuppression in 3 patients from Series I and all patients from Series II, and mucositis in 1 patient from Series I and 4 patients from series II. No other G3-4 toxicities or toxic deaths occurred. Five-year progression free survival was 38% and 90% in Series I and Series II patients respectively. Conclusions. The incidence of pathologic complete remissions was lower in our patient population, compared to reported data. A longer duration of the preoperative treatment might be associated with a longer progression-free survival.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

2020 ◽  
Vol 20 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Jonathan Wilkie ◽  
M. Alexandra Schickli ◽  
Michael J. Berger ◽  
Maryam Lustberg ◽  
Raquel Reinbolt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hormone Receptor Positive
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