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

2021 ◽  
Author(s):  
Nicholas P. McAndrew ◽  
Richard S. Finn
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Hormone Receptor ◽  
Treatment Plan ◽  
Menopausal Status ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Current Data ◽  
Hormone Receptor Positive

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.

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).

scholarly journals Outcomes of Older Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer Treated With a CDK4/6 Inhibitor and an Aromatase Inhibitor: An FDA Pooled Analysis

2019 ◽  
Vol 37 (36) ◽  
pp. 3475-3483 ◽  
Author(s):  
Lynn J. Howie ◽  
Harpreet Singh ◽  
Erik Bloomquist ◽  
Suparna Wedam ◽  
Laleh Amiri-Kordestani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Epidermal Growth Factor ◽  
Older Women ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Human Epidermal Growth Factor ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

PURPOSE Many older women will be treated with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and an aromatase inhibitor (AI), given US Food and Drug Administration approval of three agents in this class. The current pooled analysis examines the efficacy and safety of this combination in older women. PATIENTS AND METHODS We pooled data from three randomized controlled studies (N = 1,827) of different CDK4/6 inhibitors in combination with an AI for initial treatment of postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. The effect of age on progression-free survival was evaluated using Kaplan-Meier estimates and a Cox proportional hazards regression model. RESULTS For patients age 75 years or older (n = 198) who were treated with a CDK4/6 inhibitor and an AI, hazard ratio was 0.49 (95% CI, 0.31 to 0.76) with an estimated median progression-free survival of 31.1 months (95% CI, 20.2 months to not reached) versus 13.7 months (95% CI, 10.9 months to 24.9 months) for those treated with an AI. Incidence of grade 3 to 4 adverse events was 88.8% in patients age 75 years and older and 73.4% in patients younger than age 75 years. Patients age 75 years or older reported a decline in quality-of-life measures using the EQ-5D regardless of treatment with AI alone or with the addition of a CDK4/6 inhibitor. CONCLUSION There was similar efficacy with a CDK4/6 inhibitor in combination with an AI compared with AI alone for first-line treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer in older women compared with younger patients. Patients older than age 75 years experienced higher rates of toxicity, dose modifications, and a decrease from baseline in quality-of-life measures.

Trastuzumab Plus Anastrozole Versus Anastrozole Alone for the Treatment of Postmenopausal Women With Human Epidermal Growth Factor Receptor 2–Positive, Hormone Receptor–Positive Metastatic Breast Cancer: Results From the Randomized Phase III TAnDEM Study

2009 ◽  
Vol 27 (33) ◽  
pp. 5529-5537 ◽  
Author(s):  
Bella Kaufman ◽  
John R. Mackey ◽  
Michael R. Clemens ◽  
Poonamalle P. Bapsy ◽  
Ashok Vaid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

Purpose TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor–copositive metastatic breast cancer (MBC). Patients and Methods Postmenopausal women with HER2/hormone receptor–copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Results Overall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor–positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure. Conclusion Trastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor–copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.

Treatment Algorithms for Hormone Receptor-Positive Advanced Breast Cancer: Applying the Results from Recent Clinical Trials into Daily Practice—Insights, Limitations, and Moving Forward

2013 ◽  
pp. e20-e27
Author(s):  
Sheridan Wilson ◽  
Stephen K. Chia
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Acquired Resistance ◽  
Mammalian Target Of Rapamycin ◽  
Real Life ◽  
Metastatic Breast ◽  
Predictive Biomarkers ◽  
Endocrine Treatment ◽  
First Line ◽  
Hormone Receptor Positive

Hormone receptor–positive (HR+) breast cancer is the most prevalent subtype of breast cancer in both early- and advanced-stage disease. Thus, the treatment of HR+ breast cancer has had the greatest global influence in improving clinical outcomes overall. Although the first-line metastatic breast cancer (MBC) trials comparing a third-generation aromatase inhibitor (AI) to tamoxifen have favored the AI, one of the challenges in translating these findings into clinical practice stems from the influence of prior adjuvant endocrine therapy, particularly the increasing use of adjuvant AIs today, on the choice of endocrine agent in the advanced setting because of the development of acquired resistance. Because the majority of patients enrolled into these studies were either endocrine-treatment naïve or exposed to tamoxifen only, the “real-life” applicability of the evidence is unclear. Because a superior dose of the selective estrogen receptor (ER) downregulator fulvestrant has now been established, its role as first-line therapy is being re-established. We are now starting to see the promise realized with blocking cross-talking growth factor pathways in addition to the ER pathway. The greatest efficacy is seen with the mammalian target of rapamycin (mTOR) inhibitor everolimus in combination with exemestane and, perhaps to a lesser extent, anti-HER2–directed therapy in combination with an AI. Future gains will likely involve a greater understanding of the redundancy and compensation induced by blocking these pathways, trials involving blocking multiple pathways in addition to hormonal agents, and the molecular interrogation of the individual's tumor in search of predictive biomarkers and “actionable” genomic aberrations.

scholarly journals Everolimus in the Treatment of Metastatic Breast Cancer

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S29268 ◽  
Author(s):  
Melanie E. Royce ◽  
Diaa Osman
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Vital Role ◽  
Hormone Receptor Positive ◽  
Cancer Pathogenesis ◽  
New Research

The discovery of the mammalian target of rapamycin (mTOR) molecular pathway has brought insight into its vital role in breast cancer pathogenesis. Several clinical trials have shown that the mTOR inhibitor everolimus could improve patient outcomes in several subtypes of breast cancer, including hormone receptor–positive, human epidermal growth factor receptor–negative metastatic disease that has progressed after prior endocrine therapy. This review summarizes findings from clinical trials that have demonstrated the benefit of everolimus in metastatic breast cancer and highlights some new research directions utilizing everolimus.

scholarly journals A Case of Disease Improvement after Treatment with Everolimus plus Exemestane in a Patient with Hormone Receptor-Positive Metastatic Breast Cancer with Bone Metastases

2015 ◽  
Vol 8 (1) ◽  
pp. 101-105 ◽  
Author(s):  
J. Thaddeus Beck ◽  
Ryan Mantooth
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Lobular Carcinoma ◽  
Mammalian Target Of Rapamycin ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Mtor Inhibitors ◽  
Hormone Receptor Positive ◽  
Nonsteroidal Aromatase Inhibitors

Breast cancer is one of the most frequently diagnosed cancers and a leading cause of death in women worldwide. Despite significant advances in the treatment of hormone receptor-positive breast cancer, tumor metastasis occurs frequently and is associated with poor long-term prognosis. The mammalian target of rapamycin (mTOR) pathway plays a central role in cancer cell growth, proliferation, and resistance to endocrine therapies. Therefore, mTOR inhibitors such as everolimus in combination with nonsteroidal aromatase inhibitors might reverse endocrine resistance and improve clinical outcomes in patients. Here, we report on a case of infiltrating lobular carcinoma of the breast with metastases to the bone. Histopathologic analysis showed that the patient was estrogen and progesterone receptor positive and human epidermal growth factor-2 negative. This case represents the clinical spectrum of complications caused by metastasis: the patient experienced a considerable amount of skeletal-related complications, had previously received chemotherapy, and experienced disease progression while taking nonsteroidal aromatase inhibitors. After treatment with oral everolimus 10 mg daily plus oral exemestane 25 mg daily, the patient's disease was ameliorated. Combination therapy was well tolerated, with minimal adverse effects that were manageable with concomitant medications. Although further analyses in larger populations are necessary, the addition of everolimus to exemestane might provide an effective new treatment option for patients with bone metastasis.

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