scholarly journals Systemic treatment approaches in her2-negative advanced breast cancer—guidance on the guidelines

2015 ◽  
Vol 22 ◽  
pp. 29 ◽  
Author(s):  
A.A. Joy ◽  
M. Ghosh ◽  
R. Fernandes ◽  
M.J. Clemons
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
De Novo ◽  
Treatment Guidelines ◽  
Early Stage ◽  
Symptom Control ◽  
Growth Factor Receptor ◽  
Disease Recurrence ◽  
Primary Treatment ◽  
Advanced Breast

Despite advancements in the treatment of early-stage breast cancer, many patients still develop disease recurrence; others present with de novo metastatic disease. For most patients with advanced breast cancer, the primary treatment intent is noncurative—that is, palliative—in nature. The goals of treatment should therefore focus on maximizing symptom control and extending survival. Treatments should be evaluated on an individualized basis in terms of evidence, but also with full respect for the wishes of the patient in terms of acceptable toxicity. Given the availability of extensive reviews on the roles of endocrine therapy and her2 (human epidermal growth factor receptor 2)–targeted therapies for advanced disease, we focus here mainly on treatment guidelines for the non-endocrine management of her2-negative advanced breast cancer in a Canadian health care context.

scholarly journals CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 332
Author(s):  
Michela Roberto ◽  
Antonio Astone ◽  
Andrea Botticelli ◽  
Luisa Carbognin ◽  
Alessandra Cassano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Hormone Receptor ◽  
Molecular Mechanisms ◽  
Breast Cancer Subtype ◽  
Endocrine Resistance ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Disease Recurrence ◽  
Advanced Breast

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2−, ABC.

scholarly journals Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial

2017 ◽  
Vol 168 (1) ◽  
pp. 127-134 ◽  
Author(s):  
Joyce O’Shaughnessy ◽  
Katarina Petrakova ◽  
Gabe S. Sonke ◽  
Pierfranco Conte ◽  
Carlos L. Arteaga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
De Novo ◽  
Advanced Breast

Endocrine Resistance: What Do We Know?

2013 ◽  
pp. e37-e42 ◽  
Author(s):  
Todd W. Miller
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Tyrosine Kinases ◽  
De Novo ◽  
Early Stage ◽  
Effective Means ◽  
Endocrine Resistance ◽  
Large Body ◽  
Growth Factor Receptor ◽  
Oncogenic Signaling

Adjuvant therapy with antiestrogens targeting estrogen receptor α (ER) signaling prevents disease recurrence in many patients with early-stage ER+ breast cancer. However, a significant number of cases exhibit de novo or acquired endocrine resistance. While other clinical subtypes of breast cancer (HER2+, triple-negative) have disproportionately higher rates of mortality, ER+ breast cancer is responsible for at least as many deaths because it is the most common subtype. Therefore, identifying mechanisms that drive endocrine resistance is a high clinical priority. A large body of experimental evidence indicates that oncogenic signaling pathways underlie endocrine resistance, including growth factor receptor tyrosine kinases (HER2, epidermal growth factor receptor [EGFR], fibroblast growth factor receptor 1/2 [FGFR], insulin-like growth factor-1 receptor [IGF-1R]/ insulin receptor [InsR]), PI3K/AKT/ mTOR, MAPK/ERK, Src, CDK4/CDK6, and ER itself. Combined targeting of ER and such pathways may be the most effective means to combat antiestrogen resistance, and clinical trials testing such strategies show promising results. Herein, we discuss pathways associated with endocrine resistance, biomarkers that may be useful to predict response to targeted agents, and avenues for further exploration to identify strategies for the treatment of patients with endocrine-resistant disease.

Characterization of patients who received prior chemotherapy for advanced breast cancer (ABC) in BOLERO-2.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 151-151
Author(s):  
Denise Aysel Yardley ◽  
Mario Campone ◽  
Fabienne Lebrun ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Symptom Control ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Disease Recurrence ◽  
Tumor Burden ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Study Entry

151 Background: In patients with hormone receptor–positive (HR+) breast cancer, endocrine therapy is the standard of care both in the adjuvant setting and as front-line therapy for ABC. Chemotherapy (CT) is commonly used for HR+ ABC patients if disease burden is high and rapid symptom control is required (Barrios CH. GAMO. 2010). In the phase III BOLERO-2 study (NCT00863655), first-line of prior CT in the ABC setting was allowed. This subset analysis examined disease characteristics and the efficacy of everolimus (EVE) + exemestane (EXE) in patients who received CT for ABC prior to BOLERO-2 study entry. Methods: In BOLERO-2, 724 patients with HR+, human epidermal growth factor receptor 2–negative (HER2–) ABC whose disease recurred or progressed during/after a nonsteroidal aromatase inhibitor were randomized 2:1 to EVE (10 mg/d) + EXE (25 mg/d) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local investigator review (confirmed by blinded independent central review). Results: A total of 186 patients (26%) received prior CT for ABC (125 in the EVE + EXE group and 61 in PBO + EXE). In this subset, 54% (67 of 125) of EVE+ EXE patients received prior CT in the advanced setting only while 46% (58 of 125) of EVE + EXE patients received prior CT in both the neoadjuvant/adjuvant and advanced settings. Visceral metastases (67% vs. 56%), multiple metastases (79% vs. 66%), and ≥ 4 metastatic sites (18% vs. 15%) were more frequent in ABC patients with prior CT for ABC at study entry compared with those with no prior CT for ABC. History of disease recurrence <6 months from initial diagnosis was recorded in 32% (n = 60) of prior CT patients versus 17% (n = 93) of patients with no prior CT. Median PFS (by local assessment) in patients who received prior CT for ABC was substantially longer with EVE + EXE versus PBO + EXE (6.1 vs. 2.7 mo; hazard ratio = 0.38; 95% CI, 0.27-0.53). PFS by central review showed similar results (7.1 vs. 2.8 mo, respectively; hazard ratio = 0.42; 95% CI, 0.27-0.65). Conclusions: These results demonstrate that patients with HR+, HER2 ABC who received previous CT in the advanced setting had a higher tumor burden but derived significant and clinically meaningful benefit from combination therapy with EVE + EXE. Clinical trial information: NCT00863655.

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