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Minimizing early relapse and maximizing treatment outcomes in hormone-sensitive postmenopausal breast cancer: efficacy review of AI trials.

Markopoulos CJ - Cancer Metastasis Rev. (2010)

Bottom Line: Most early recurrences are distant metastases, which strongly correlate with increased mortality.AIs are better at minimizing risk of early relapse compared with tamoxifen.However, it is not clear if preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC.

View Article: PubMed Central - PubMed

Affiliation: Athens University Medical School, 8, Iassiou str, 11521 Athens, Greece. cmarkop@hol.gr

ABSTRACT
Breast cancer is one of the leading causes of cancer-related deaths in women. Regardless of prognosis, all women with breast cancer are at risk for early recurrence. Nearly 50% of early recurrences occur within 5 years of surgery, and they peak at 2 years after surgery in women treated with adjuvant tamoxifen. Most early recurrences are distant metastases, which strongly correlate with increased mortality. Treatments that mitigate the risk of early distant metastases (DM) are, therefore, likely to improve overall survival in women with early breast cancer (EBC). Aromatase inhibitors (AIs)--anastrozole, letrozole, and exemestane-have been investigated as alternatives to tamoxifen for adjuvant treatment of hormone receptor-positive (HR+) EBC in postmenopausal women (PMW). AIs are better at minimizing risk of early relapse compared with tamoxifen. However, it is not clear if preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC. The ability to subtype HR+ breast cancer on the basis of biomarkers predictive of response to AIs and tamoxifen would likely be key to determining the most beneficial hormonal treatment within patient subpopulations, but this process requires thorough investigation. Until then, adjuvant therapies that provide the greatest reduction in risk of DM should be considered for all PMW with HR+ EBC. This article reviews the clinical trials of AI adjuvant therapies for hormone-sensitive breast cancer, particularly in the context of how they compare with tamoxifen in minimizing the risk of relapse, occurrence of DM, and breast cancer-related deaths.

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Types of adjuvant trials. AI aromatase inhibitor
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Fig2: Types of adjuvant trials. AI aromatase inhibitor

Mentions: Third-generation AIs include anastrozole, letrozole, and exemestane. Anastrozole and letrozole are nonsteroidal drugs that block estrogen synthesis through a competitive inhibition of aromatase, while exemestane is a steroidal AI that blocks estrogen synthesis by irreversibly binding with aromatase and inhibiting its activity [35]. All three AIs almost completely block estrogen synthesis and have been approved by the Food and Drug Administration for the treatment of early-stage breast cancer because of their efficacy and tolerability in a variety of clinical settings [36]. However, there is evidence that letrozole provides a greater suppression of both plasma (residual estradiol (after 6 weeks of AI therapy): 4.8% letrozole vs. 7.2% anastrozole, P = 0.018; residual estrone: 1.2% letrozole vs. 3.7% anastrozole, P = 0.003; residual estrone sulfate: 1.1% letrozole vs. 4.7% anastrozole, P = 0.003) and tissue (residual estradiol (after 16 weeks of AI therapy): 2.4% letrozole vs. 11.0% anastrozole, P = not reported (NR); residual estrone: 9.3% letrozole vs. 16.6% anastrozole, P = NR; residual estrone sulfate: 9.9% letrozole vs. 27.1% anastrozole, P = NR) estrogen levels compared with anastrozole [37]. Clinical trials of adjuvant AIs in PMW with HR+ breast cancer include initial adjuvant, extended adjuvant, switch, and sequential trials (Fig. 2).Fig. 2


Minimizing early relapse and maximizing treatment outcomes in hormone-sensitive postmenopausal breast cancer: efficacy review of AI trials.

Markopoulos CJ - Cancer Metastasis Rev. (2010)

Types of adjuvant trials. AI aromatase inhibitor
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2962795&req=5

Fig2: Types of adjuvant trials. AI aromatase inhibitor
Mentions: Third-generation AIs include anastrozole, letrozole, and exemestane. Anastrozole and letrozole are nonsteroidal drugs that block estrogen synthesis through a competitive inhibition of aromatase, while exemestane is a steroidal AI that blocks estrogen synthesis by irreversibly binding with aromatase and inhibiting its activity [35]. All three AIs almost completely block estrogen synthesis and have been approved by the Food and Drug Administration for the treatment of early-stage breast cancer because of their efficacy and tolerability in a variety of clinical settings [36]. However, there is evidence that letrozole provides a greater suppression of both plasma (residual estradiol (after 6 weeks of AI therapy): 4.8% letrozole vs. 7.2% anastrozole, P = 0.018; residual estrone: 1.2% letrozole vs. 3.7% anastrozole, P = 0.003; residual estrone sulfate: 1.1% letrozole vs. 4.7% anastrozole, P = 0.003) and tissue (residual estradiol (after 16 weeks of AI therapy): 2.4% letrozole vs. 11.0% anastrozole, P = not reported (NR); residual estrone: 9.3% letrozole vs. 16.6% anastrozole, P = NR; residual estrone sulfate: 9.9% letrozole vs. 27.1% anastrozole, P = NR) estrogen levels compared with anastrozole [37]. Clinical trials of adjuvant AIs in PMW with HR+ breast cancer include initial adjuvant, extended adjuvant, switch, and sequential trials (Fig. 2).Fig. 2

Bottom Line: Most early recurrences are distant metastases, which strongly correlate with increased mortality.AIs are better at minimizing risk of early relapse compared with tamoxifen.However, it is not clear if preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC.

View Article: PubMed Central - PubMed

Affiliation: Athens University Medical School, 8, Iassiou str, 11521 Athens, Greece. cmarkop@hol.gr

ABSTRACT
Breast cancer is one of the leading causes of cancer-related deaths in women. Regardless of prognosis, all women with breast cancer are at risk for early recurrence. Nearly 50% of early recurrences occur within 5 years of surgery, and they peak at 2 years after surgery in women treated with adjuvant tamoxifen. Most early recurrences are distant metastases, which strongly correlate with increased mortality. Treatments that mitigate the risk of early distant metastases (DM) are, therefore, likely to improve overall survival in women with early breast cancer (EBC). Aromatase inhibitors (AIs)--anastrozole, letrozole, and exemestane-have been investigated as alternatives to tamoxifen for adjuvant treatment of hormone receptor-positive (HR+) EBC in postmenopausal women (PMW). AIs are better at minimizing risk of early relapse compared with tamoxifen. However, it is not clear if preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC. The ability to subtype HR+ breast cancer on the basis of biomarkers predictive of response to AIs and tamoxifen would likely be key to determining the most beneficial hormonal treatment within patient subpopulations, but this process requires thorough investigation. Until then, adjuvant therapies that provide the greatest reduction in risk of DM should be considered for all PMW with HR+ EBC. This article reviews the clinical trials of AI adjuvant therapies for hormone-sensitive breast cancer, particularly in the context of how they compare with tamoxifen in minimizing the risk of relapse, occurrence of DM, and breast cancer-related deaths.

Show MeSH
Related in: MedlinePlus