Limits...
Delaying Chemotherapy in the Treatment of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

Brufsky AM - Clin Med Insights Oncol (2015)

Bottom Line: Global guidelines for the management of locally advanced or metastatic hormone receptor-positive (HR-positive), human epidermal growth factor 2-negative (HER2-negative) breast cancer recommend endocrine therapy as first-line treatment for all patients, regardless of age or postmenopausal status.Given that chemotherapy is associated with increased toxicity and reduced quality of life (QOL) compared with endocrine therapy, prolonging the duration of response obtained with endocrine therapy may help delay chemotherapy and its attendant toxicities.Several strategies to delay or overcome endocrine resistance and thereby postpone chemotherapy have been explored, including the use of second-line endocrine agents with different mechanisms of action, adding targeted agents that inhibit specific resistance pathways, and adding agents that act in complementary or synergistic ways to inhibit tumor cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Professor of Medicine, Associate Division Chief of Hematology/Oncology, Medical Director of Women's Cancer Center at Magee-Womens Hospital, Codirector of Comprehensive Breast Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

ABSTRACT
Global guidelines for the management of locally advanced or metastatic hormone receptor-positive (HR-positive), human epidermal growth factor 2-negative (HER2-negative) breast cancer recommend endocrine therapy as first-line treatment for all patients, regardless of age or postmenopausal status. However, current practice patterns in the United States and Europe suggest that these modes of therapy are not being used as recommended, and many patients with advanced HR-positive, HER2-negative disease are being treated first-line with chemotherapy or switched to chemotherapy after a single endocrine therapy. Given that chemotherapy is associated with increased toxicity and reduced quality of life (QOL) compared with endocrine therapy, prolonging the duration of response obtained with endocrine therapy may help delay chemotherapy and its attendant toxicities. Several strategies to delay or overcome endocrine resistance and thereby postpone chemotherapy have been explored, including the use of second-line endocrine agents with different mechanisms of action, adding targeted agents that inhibit specific resistance pathways, and adding agents that act in complementary or synergistic ways to inhibit tumor cell proliferation. This review analyzes the different therapy options available to HR-positive, HER2-negative patients with advanced breast cancer that can be used to delay chemotherapy and enhance QOL.

No MeSH data available.


Related in: MedlinePlus

Emerging targeted agents against breast cancer under clinical development. Reprinted with permission from Ref 36.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4697769&req=5

f1-cmo-9-2015-137: Emerging targeted agents against breast cancer under clinical development. Reprinted with permission from Ref 36.

Mentions: Agents that inhibit multiple signaling pathways and targets are in various stages of development, and identifying different subtypes of breast cancer allows for targeted treatment (Fig. 1).7,34–36 A major mechanism of endocrine resistance is the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) intracellular signaling pathway. mTOR inhibitors have subsequently been developed to overcome resistance, with promising results observed in patients with advanced HR-positive, HER2-negative breast cancer. Indeed, studies have shown that adding the mTOR inhibitor everolimus to exemestane significantly improves PFS versus exemestane alone in postmenopausal patients with HR-positive breast cancer who experienced recurrence or progression while receiving NSAI therapy.37 In the phase 3 BOLERO-2 trial, 724 patients were randomly assigned 2:1 to treatment with everolimus plus exemestane or exemestane plus placebo.38 In the final PFS analysis, median PFS (assessed by the investigator) was 7.8 months with everolimus plus exemestane versus 3.2 months with exemestane plus placebo (hazard ratio for progression or death, 0.45; 95% CI, 0.38–0.54; log rank P < 0.0001).38 Median PFS (determined via central assessment) was 11.0 months versus 4.1 months for everolimus plus exemestane versus exemestane plus placebo, respectively (hazard ratio, 0.38; 95% CI, 0.31–0.48; log rank P < 0.0001).38 PFS was improved in both elderly and younger patients.39 However, everolimus plus exemestane did not significantly reduce the risk of death.40 Median OS was 31.0 months for everolimus plus exemestane versus 26.6 months for exemestane plus placebo (hazard ratio, 0.89; 95% CI, 0.73–1.10; P = 0.14).40 Poststudy treatments were received by 84% of patients in the everolimus plus exemestane arm versus 90% of patients in the exemestane plus placebo arm.40 In patients who had previously received only neoadjuvant treatment, everolimus plus exemestane nearly tripled PFS (as assessed by the investigator) to 11.5 months versus 4.1 months (hazard ratio, 0.39; 95% CI, 0.25–0.62).41 Adding everolimus to exemestane increased median PFS by 4 months in patients with HR-positive, HER2-negative advanced breast cancer, regardless of the presence of visceral metastases.42 In the everolimus plus exemestane treatment arm, bone marker levels decreased after 6 and 12 weeks, whereas in the exemestane plus placebo arm, bone marker levels increased.43 The everolimus plus exemestane arm also had a lower cumulative incidence rate of progressive bone disease than the exemestane plus placebo arm (13.0% vs 18.8%; P = 0.04, Gray’s test), despite the less frequent use of bisphosphonates in the everolimus plus exemestane (43.9%) versus the exemestane plus placebo arm (54.0%).41


Delaying Chemotherapy in the Treatment of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

Brufsky AM - Clin Med Insights Oncol (2015)

Emerging targeted agents against breast cancer under clinical development. Reprinted with permission from Ref 36.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4697769&req=5

f1-cmo-9-2015-137: Emerging targeted agents against breast cancer under clinical development. Reprinted with permission from Ref 36.
Mentions: Agents that inhibit multiple signaling pathways and targets are in various stages of development, and identifying different subtypes of breast cancer allows for targeted treatment (Fig. 1).7,34–36 A major mechanism of endocrine resistance is the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) intracellular signaling pathway. mTOR inhibitors have subsequently been developed to overcome resistance, with promising results observed in patients with advanced HR-positive, HER2-negative breast cancer. Indeed, studies have shown that adding the mTOR inhibitor everolimus to exemestane significantly improves PFS versus exemestane alone in postmenopausal patients with HR-positive breast cancer who experienced recurrence or progression while receiving NSAI therapy.37 In the phase 3 BOLERO-2 trial, 724 patients were randomly assigned 2:1 to treatment with everolimus plus exemestane or exemestane plus placebo.38 In the final PFS analysis, median PFS (assessed by the investigator) was 7.8 months with everolimus plus exemestane versus 3.2 months with exemestane plus placebo (hazard ratio for progression or death, 0.45; 95% CI, 0.38–0.54; log rank P < 0.0001).38 Median PFS (determined via central assessment) was 11.0 months versus 4.1 months for everolimus plus exemestane versus exemestane plus placebo, respectively (hazard ratio, 0.38; 95% CI, 0.31–0.48; log rank P < 0.0001).38 PFS was improved in both elderly and younger patients.39 However, everolimus plus exemestane did not significantly reduce the risk of death.40 Median OS was 31.0 months for everolimus plus exemestane versus 26.6 months for exemestane plus placebo (hazard ratio, 0.89; 95% CI, 0.73–1.10; P = 0.14).40 Poststudy treatments were received by 84% of patients in the everolimus plus exemestane arm versus 90% of patients in the exemestane plus placebo arm.40 In patients who had previously received only neoadjuvant treatment, everolimus plus exemestane nearly tripled PFS (as assessed by the investigator) to 11.5 months versus 4.1 months (hazard ratio, 0.39; 95% CI, 0.25–0.62).41 Adding everolimus to exemestane increased median PFS by 4 months in patients with HR-positive, HER2-negative advanced breast cancer, regardless of the presence of visceral metastases.42 In the everolimus plus exemestane treatment arm, bone marker levels decreased after 6 and 12 weeks, whereas in the exemestane plus placebo arm, bone marker levels increased.43 The everolimus plus exemestane arm also had a lower cumulative incidence rate of progressive bone disease than the exemestane plus placebo arm (13.0% vs 18.8%; P = 0.04, Gray’s test), despite the less frequent use of bisphosphonates in the everolimus plus exemestane (43.9%) versus the exemestane plus placebo arm (54.0%).41

Bottom Line: Global guidelines for the management of locally advanced or metastatic hormone receptor-positive (HR-positive), human epidermal growth factor 2-negative (HER2-negative) breast cancer recommend endocrine therapy as first-line treatment for all patients, regardless of age or postmenopausal status.Given that chemotherapy is associated with increased toxicity and reduced quality of life (QOL) compared with endocrine therapy, prolonging the duration of response obtained with endocrine therapy may help delay chemotherapy and its attendant toxicities.Several strategies to delay or overcome endocrine resistance and thereby postpone chemotherapy have been explored, including the use of second-line endocrine agents with different mechanisms of action, adding targeted agents that inhibit specific resistance pathways, and adding agents that act in complementary or synergistic ways to inhibit tumor cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Professor of Medicine, Associate Division Chief of Hematology/Oncology, Medical Director of Women's Cancer Center at Magee-Womens Hospital, Codirector of Comprehensive Breast Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

ABSTRACT
Global guidelines for the management of locally advanced or metastatic hormone receptor-positive (HR-positive), human epidermal growth factor 2-negative (HER2-negative) breast cancer recommend endocrine therapy as first-line treatment for all patients, regardless of age or postmenopausal status. However, current practice patterns in the United States and Europe suggest that these modes of therapy are not being used as recommended, and many patients with advanced HR-positive, HER2-negative disease are being treated first-line with chemotherapy or switched to chemotherapy after a single endocrine therapy. Given that chemotherapy is associated with increased toxicity and reduced quality of life (QOL) compared with endocrine therapy, prolonging the duration of response obtained with endocrine therapy may help delay chemotherapy and its attendant toxicities. Several strategies to delay or overcome endocrine resistance and thereby postpone chemotherapy have been explored, including the use of second-line endocrine agents with different mechanisms of action, adding targeted agents that inhibit specific resistance pathways, and adding agents that act in complementary or synergistic ways to inhibit tumor cell proliferation. This review analyzes the different therapy options available to HR-positive, HER2-negative patients with advanced breast cancer that can be used to delay chemotherapy and enhance QOL.

No MeSH data available.


Related in: MedlinePlus