Vol 20, No 4 (2024)
Review paper
Published online: 2024-03-07
Wise and skillful utilization of contemporary endocrine therapies for the treatment of ER+/HER2– advanced breast cancer
DOI: 10.5603/ocp.97946
Oncol Clin Pract 2024;20(4):291-301.
Abstract
Endocrine therapy is one of the key and most frequently utilized strategies for breast cancer treatment, both in the early and advanced stages of the disease. Its activity relies on the presence of functional estrogen receptors in cancer cells, which are responsible for stimulating the survival and growth of breast cancer. Over the past four decades, endocrine therapy significantly has progressed not only due to the emergence of new drugs disrupting the estrogen receptor functions but also thanks to the development of new targeted agents that block intracellular mechanisms of hormone resistance.
The large number of endocrine therapies used either as monotherapy or in combination with other agents vary not only in their mechanisms of action but also their safety profiles. This diversity poses a big and continuously growing challenge in planning and conducting an optimal, multi-stage palliative hormonal treatment in clinical practice. This article aims to summarize current knowledge on contemporary endocrine treatment options and highlight the possibilities for making hormone therapies a truly personalized treatment for advanced breast cancer patients.
Keywords: endocrine treatmentestrogen receptoralpelisibCDK4/6imTORPIK3CAbreast cancer
References
- Johnston SJ, Cheung KL. Endocrine Therapy for Breast Cancer: A Model of Hormonal Manipulation. Oncol Ther. 2018; 6(2): 141–156.
- Slamon D, Stroyakovskiy D, Yardley D, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: Primary results from the phase III NATALEE trial. J Clin Oncol. 2023; 41(17_suppl): LBA500–LBA500.
- Im SA, Lu YS, Bardia A, et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019; 381(4): 307–316.
- Sledge GW, Toi M, Neven P, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol. 2020; 6(1): 116–124.
- Neven P, Fasching PA, Chia S, et al. LBA4 Updated overall survival (OS) results from the first-line (1L) population in the phase III MONALEESA-3 trial of postmenopausal patients (PTS) with HR+/HER2− advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL). Ann Oncol. 2022; 33: S194.
- Updated Overall Survival (OS) Results from the First-Line (1L) Population in the Phase III MONALEESA-3 Trial of Postmenopausal Patients (Pts) with... | OncologyPRO. https://oncologypro.esmo.org/meeting-resources/esmo-breast-cancer-congress/updated-overall-survival-os-results-from-the-first-line-1l-population-in-the-phase-iii-monaleesa-3-trial-of-postmenopausal-patients-pts-with (16.12.2022).
- Lu YS, Im SA, Colleoni M, et al. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022; 28(5): 851–859.
- Schwartzberg LS, Wang G, Somer BG, et al. Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Clin Breast Cancer. 2014; 14(1): 13–19.
- Mohammadianpanah M, Ashouri Y, Hoseini S, et al. The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial. Breast Cancer Res Treat. 2012; 132(3): 853–861.
- Belachew EB, Sewasew DT. Molecular Mechanisms of Endocrine Resistance in Estrogen-Positive Breast Cancer. Front Endocrinol (Lausanne). 2021; 12: 599586.
- Montemurro F, Di Cosimo S, Arpino G. Human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive breast cancer: new insights into molecular interactions and clinical implications. Ann Oncol. 2013; 24(11): 2715–2724.
- Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012; 366(6): 520–529.
- André F, Ciruelos E, Rubovszky G, et al. SOLAR-1 Study Group. Alpelisib for -Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019; 380(20): 1929–1940.
- Turner NC, Oliveira M, Howell SJ, et al. CAPItello-291 Study Group. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023; 388(22): 2058–2070.
- Hurvitz SA, Bardia A, Quiroga V, et al. coopERA Breast Cancer study group. Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2023; 24(9): 1029–1041.
- Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022; 40(28): 3246–3256.
- Brufman G, Isacson R, Haim N, et al. Megestrol acetate in advanced breast carcinoma after failure to tamoxifen and/or aminoglutethimide. Oncology. 1994; 51(3): 258–261.
- Bines J, Dienstmann R, Obadia RM, et al. Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial. Ann Oncol. 2014; 25(4): 831–836.
- Hayes DF. Markers of endocrine sensitivity. Breast Cancer Res. 2008; 10 Suppl 4(Suppl 4): S18.
- Li Z, Wei H, Li S, et al. The Role of Progesterone Receptors in Breast Cancer. Drug Des Devel Ther. 2022; 16: 305–314.
- Park S, Koo JaS, Kim MS, et al. Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry. Breast. 2012; 21(1): 50–57.
- Bliss JM, Tovey H, Evans A, et al. POETIC Trialists. Clinico-pathologic relationships with Ki67 and its change with short-term aromatase inhibitor treatment in primary ER + breast cancer: further results from the POETIC trial (CRUK/07/015). Breast Cancer Res. 2023; 25(1): 39.
- Schettini F, Buono G, Cardalesi C, et al. Hormone Receptor/Human Epidermal Growth Factor Receptor 2-positive breast cancer: Where we are now and where we are going. Cancer Treat Rev. 2016; 46: 20–26.
- Luque-Cabal M, García-Teijido P, Fernández-Pérez Y, et al. Mechanisms Behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer and Strategies to Overcome It. Clin Med Insights Oncol. 2016; 10(Suppl 1): 21–30.
- Gutierrez MC, Detre S, Johnston S, et al. Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase. J Clin Oncol. 2005; 23(11): 2469–2476.
- Massarweh S, Osborne CK, Creighton CJ, et al. Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res. 2008; 68(3): 826–833.
- Priedigkeit N, Hartmaier RJ, Chen Y, et al. Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases. JAMA Oncol. 2017; 3(5): 666–671.
- Nayar U, Cohen O, Kapstad C, et al. Acquired HER2 mutations in ER metastatic breast cancer confer resistance to estrogen receptor-directed therapies. Nat Genet. 2019; 51(2): 207–216.
- Wang YC, Morrison G, Gillihan R, et al. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers--role of estrogen receptor and HER2 reactivation. Breast Cancer Res. 2011; 13(6): R121.
- Toy W, Shen Y, Won H, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013; 45(12): 1439–1445.
- Fribbens C, Garcia Murillas I, Beaney M, et al. Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. Ann Oncol. 2018; 29(1): 145–153.
- Turner NC, Swift C, Kilburn L, et al. Mutations and Overall Survival on Fulvestrant versus Exemestane in Advanced Hormone Receptor-Positive Breast Cancer: A Combined Analysis of the Phase III SoFEA and EFECT Trials. Clin Cancer Res. 2020; 26(19): 5172–5177.
- Bidard FC, Hardy-Bessard AC, Dalenc F, et al. PADA-1 investigators. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022; 23(11): 1367–1377.
- Wong N, Yap D, Ong R, et al. Efficacy of Oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups. Ann Oncol. 2023.
- Goetz MP, Bagegni NA, Batist G, et al. Lasofoxifene versus fulvestrant for ER+/HER2− metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial. Ann Oncol. 2023; 34(12): 1141–1151.
- Wysocki PJ, Wierusz-Wysocka B. Obesity, hyperinsulinemia and breast cancer: novel targets and a novel role for metformin. Expert Rev Mol Diagn. 2010; 10(4): 509–519.
- Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-Kinase, Growth Disorders, and Cancer. N Engl J Med. 2018; 379(21): 2052–2062.
- Mollon L, Aguilar A, Anderson E, et al. Abstract 1207: A systematic literature review of the prevalence of PIK3CA mutations and mutation hotspots in HR+/HER2- metastatic breast cancer. Cancer Res. 2018; 78(13_Supplement): 1207–1207.
- Fritsch C, Huang A, Chatenay-Rivauday C, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014; 13(5): 1117–1129.
- André F, Ciruelos E, Rubovszky G, et al. SOLAR-1 Study Group. Alpelisib for -Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019; 380(20): 1929–1940.
- Borrego M, Tolosa P, Blanch S, et al. Abstract PD8-02: Metformin (MET) for the prevention of Alpelisib (ALP)-related Hyperglycemia (HG) in PIK3CA-mutated, Hormone Receptor-Positive (HR[+]) HER2-Negative (HER2[-]) Advanced Breast Cancer (ABC): The METALLICA study. Cancer Res. 2023; 83(5_Supplement): PD8-02-PD8–02.
- Louie CY, DiMaio MA, Matsukuma KE, et al. Idelalisib-associated Enterocolitis: Clinicopathologic Features and Distinction From Other Enterocolitides. Am J Surg Pathol. 2015; 39(12): 1653–1660.
- Rugo HS, Seneviratne L, Beck JT, et al. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial. Lancet Oncol. 2017; 18(5): 654–662.
- Wang DG, Barrios DM, Blinder VS, et al. Dermatologic adverse events related to the PI3Kα inhibitor alpelisib (BYL719) in patients with breast cancer. Breast Cancer Res Treat. 2020; 183(1): 227–237.
- Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020; 31(12): 1623–1649.
- Ramadori G, Cameron S. Effects of systemic chemotherapy on the liver. Ann Hepatol. 2010; 9(2): 133–143.
- Saghir NEl, Yap Y, Eralp Y, et al. Outcomes with first-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs physician’s choice combination chemotherapy (combo CT) by age in pre/perimenopausal patients (pts) with aggressive HR+/HER2− advanced breast cancer (ABC): A subgroup analysis of the RIGHT Choice trial. J Clin Oncol. 2023; 41(16_suppl): 1063–1063.
- Sonke G, Nijhof AV, Wortelboer N, et al. Primary outcome analysis of the phase 3 SONIA trial (BOOG 2017-03) on selecting the optimal position of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). J Clin Oncol. 2023; 41(17_suppl): LBA1000–LBA1000.
- Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375(18): 1738–1748.
- Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017; 35(32): 3638–3646.
- Finn RS, Martin M, Rugo HS, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016; 375(20): 1925–1936.
- Cizkova M, Susini A, Vacher S, et al. PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups. Breast Cancer Res. 2012; 14(1): R28.
- Fillbrunn M, Signorovitch J, André F, et al. PIK3CA mutation status, progression and survival in advanced HR + /HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022; 22(1): 1002.
- Mollon LE, Anderson EJ, Dean JL, et al. A Systematic Literature Review of the Prognostic and Predictive Value of PIK3CA Mutations in HR/HER2 Metastatic Breast Cancer. Clin Breast Cancer. 2020; 20(3): e232–e243.
- Cazzaniga M, Munzone E, Bocci G, et al. Pan-European Expert Meeting on the Use of Metronomic Chemotherapy in Advanced Breast Cancer Patients: The PENELOPE Project. Adv Ther. 2018; 36(2): 381–406.
- Aurilio G, Munzone E, Botteri E, et al. Oral metronomic cyclophosphamide and methotrexate plus fulvestrant in advanced breast cancer patients: a mono-institutional case-cohort report. Breast J. 2012; 18(5): 470–474.
- Rashad N, Abdelhamid T, Shouman S, et al. Capecitabine-Based Chemoendocrine Combination as First-Line Treatment for Metastatic Hormone-Positive Metastatic Breast Cancer: Phase 2 Study. Clin Breast Cancer. 2020; 20(3): 228–237.
- Buda-Nowak A, Kwinta Ł, Potocki P, et al. Metronomic Chemo-Endocrine Therapy (FulVEC) as a Salvage Treatment for Patients with Advanced, Treatment-Refractory ER+/HER2-Breast Cancer-A Retrospective Analysis of Consecutive Patients Data. J Clin Med. 2023; 12(4).