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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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Absolute reduction in overall recurrences and distant metastases in the a Arimidex, Tamoxifen Alone, or Combination trial (hormone receptor-positive patients) at 2.5 years [3] and b Breast International Group 1-98 at 2 years [6]. ANA anastrozole; LET letrozole; TAM tamoxifen
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Fig3: Absolute reduction in overall recurrences and distant metastases in the a Arimidex, Tamoxifen Alone, or Combination trial (hormone receptor-positive patients) at 2.5 years [3] and b Breast International Group 1-98 at 2 years [6]. ANA anastrozole; LET letrozole; TAM tamoxifen

Mentions: Disappointingly, while anastrozole appeared to provide significant benefit with the improvement in DFS, no improvement was seen in survival with more than 9 years of follow-up. OS (HR = 0.97; P = 0.7; 472 anastrozole vs. 477 tamoxifen deaths), deaths after recurrence (HR = 0.90; P = 0.2; 245 anastrozole vs. 269 tamoxifen deaths), and deaths without recurrence (HR = 1.05; P = 0.6; 227 anastrozole vs. 208 tamoxifen deaths) were not significantly different between the two groups [15]. A retrospective analysis of ATAC at 2.5 years, undertaken to better understand the types of early recurrences in the ITT population, indicated fewer locoregional, DM, and contralateral recurrences with anastrozole compared with tamoxifen, but the greatest benefit with anastrozole was in reducing the risk of locoregional and contralateral events with less impact on DM (7% reduction; Fig. 3) [3]. A recently reported retrospective analysis of events at 2 years in the HR+ population of ATAC also reported fewer overall recurrences with anastrozole relative to tamoxifen, but the reduction in DM was not significant (HR = 0.79; 95% CI, 0.58–1.07) [48]. The AEs profile of ATAC displayed a greater incidence of fractures (11% anastrozole vs. 7.7% tamoxifen; P < 0.0001) and arthralgia (35.6% anastrozole vs. 29.4% tamoxifen; P < 0.0001) in anastrozole-treated women in contrast to a greater incidence of endometrial cancer (0.2% anastrozole vs. 0.8% tamoxifen; P = 0.02), venous thromboembolic events (2.8% anastrozole vs. 4.5% tamoxifen; P = 0.0004), and gynecologic abnormalities (i.e., vaginal bleeding, discharge, hot flushes; all P < 0.0001) in tamoxifen-treated women [12].Fig. 3


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

Markopoulos CJ - Cancer Metastasis Rev. (2010)

Absolute reduction in overall recurrences and distant metastases in the a Arimidex, Tamoxifen Alone, or Combination trial (hormone receptor-positive patients) at 2.5 years [3] and b Breast International Group 1-98 at 2 years [6]. ANA anastrozole; LET letrozole; TAM tamoxifen
© Copyright Policy
Related In: Results  -  Collection

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

Fig3: Absolute reduction in overall recurrences and distant metastases in the a Arimidex, Tamoxifen Alone, or Combination trial (hormone receptor-positive patients) at 2.5 years [3] and b Breast International Group 1-98 at 2 years [6]. ANA anastrozole; LET letrozole; TAM tamoxifen
Mentions: Disappointingly, while anastrozole appeared to provide significant benefit with the improvement in DFS, no improvement was seen in survival with more than 9 years of follow-up. OS (HR = 0.97; P = 0.7; 472 anastrozole vs. 477 tamoxifen deaths), deaths after recurrence (HR = 0.90; P = 0.2; 245 anastrozole vs. 269 tamoxifen deaths), and deaths without recurrence (HR = 1.05; P = 0.6; 227 anastrozole vs. 208 tamoxifen deaths) were not significantly different between the two groups [15]. A retrospective analysis of ATAC at 2.5 years, undertaken to better understand the types of early recurrences in the ITT population, indicated fewer locoregional, DM, and contralateral recurrences with anastrozole compared with tamoxifen, but the greatest benefit with anastrozole was in reducing the risk of locoregional and contralateral events with less impact on DM (7% reduction; Fig. 3) [3]. A recently reported retrospective analysis of events at 2 years in the HR+ population of ATAC also reported fewer overall recurrences with anastrozole relative to tamoxifen, but the reduction in DM was not significant (HR = 0.79; 95% CI, 0.58–1.07) [48]. The AEs profile of ATAC displayed a greater incidence of fractures (11% anastrozole vs. 7.7% tamoxifen; P < 0.0001) and arthralgia (35.6% anastrozole vs. 29.4% tamoxifen; P < 0.0001) in anastrozole-treated women in contrast to a greater incidence of endometrial cancer (0.2% anastrozole vs. 0.8% tamoxifen; P = 0.02), venous thromboembolic events (2.8% anastrozole vs. 4.5% tamoxifen; P = 0.0004), and gynecologic abnormalities (i.e., vaginal bleeding, discharge, hot flushes; all P < 0.0001) in tamoxifen-treated women [12].Fig. 3

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