Clinical Review on the Management of Hormone Receptor–Positive Metastatic Breast Cancer

Abstract

The natural history of hormone receptor–positive breast cancer tends to be more favorable than other subtypes such as human epidermal growth factor receptor 2–amplified and triple-negative. In addition, the natural dependence on steroid hormone signaling has allowed for therapeutic targeting of this pathway and significant improvements in survival while maintaining quality of life: the two main goals in management of the disease. The sequential use of endocrine agents including the selective estrogen receptor modulators (tamoxifen), aromatase inhibitors (letrozole, anastrozole, and exemestane) and the selective estrogen receptor degrader fulvestrant has been the backbone of management for years. In the past decade, the introduction of molecularly targeted agents against intracellular targets such as mammalian target of rapamycin (everolimus), cyclin-dependent kinases 4 and 6 (palbociclib, ribociclib, and abemaciclib), and phosphatidylinositol 3-kinase (alpelisib) has offered patients effective nonchemotherapy-based options, which are improving outcomes. Although knowledge gaps still exist in regard to the optimal sequencing of these new regimens, they have expanded our repertoire of options for patients and have shifted the need for cytotoxic chemotherapy and its associated complications to later lines. Still, formatting a plan for these patients includes taking into account traditional prognostic factors such as menopausal status, previous treatments, disease-free interval for those patients with early breast cancer that has recurred, and tumor burden. To assist in developing this treatment plan, we will review the current data with systemic agents in the management of these patients.

The Present and Future of Clinical Management in Metastatic Breast Cancer

“…It is also worth mentioning that in clinical practice, de novo metastatic disease, recurrence after more than 12 months of adjuvant therapy and bone metastasis, fall into the endocrine-sensitive subgroups of patients [40]. Lastly, it is important to note that clinicians should obtain clinical tumor samples before any clinical progression, since the therapeutic decisions depend on Next Generation Sequencing, transcriptomic and mutational characteristics of the tumor [40].…”

CDK 4/6 Inhibitors: Evolution and Revolution in the Management of ER+ Metastatic Breast Cancer

“…The treatment of ER+ MBC will continue to evolve over the next decade—and will likely look very different from the current view as outlined by McAndrew and Finn 1 —as results from several ongoing phase III trials with oral selective estrogen receptor degraders mature, as well as trials with other promising and novel ET agents.…”

“…The advent of novel agents, such as cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors, to overcome common mechanisms of endocrine resistance only reinforces the central role of antiestrogen therapy in estrogen receptor–positive (ER+) metastatic breast cancer (MBC). In the companion to this article, McAndrew and Finn 1 clearly and succinctly highlight the data behind this CDK 4/6 oncologic evolution and how our current management of ER+ MBC must also change as a result.…”

“…McAndrew and Finn 1 also underscore the importance of next-generation sequencing in guiding therapy selection after progression on CDK 4/6 inhibitors given the availability of mammalian target of rapamycin and phosphatidylinositol 3-kinase targeting agents, ie, everolimus and alpelisib. 5,6 Moreover, the results with the potent pan-AKT inhibitor capivasertib are promising.…”

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

“…With more than 2.3 M diagnosed cases and 685 K deaths in 2020, breast cancer is considered the most globally prevalent cancer (World Health Organization, WHO 2021). Breast cancer treatment is mainly based on surgery followed by radiation therapy to the lymph nodes and breast to reduce the probability of recurrence [ 1 , 2 , 3 , 4 , 5 ]. Additionally, several conservative systematic therapies are based on anticancer drugs, including chemotherapy, antibody (targeted biology) therapy, and hormone (endocrine) therapy.…”