Author/Editor		Čufer, Tanja
Title		Aromatase inhibitors versus tamoxifen in early breast cancer
Type		članek
Vol. and No.		Letnik 386, št. 10001
Publication year		2015
Volume		str. 1341-1352
ISSN		0140-6736 - Lancet
Language		eng
Abstract		The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain. METHODS: We undertook meta-analyses of individual data on 31,920 postmenopausal women with oestrogen-receptor-positive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen first-event rate ratios (RRs). FINDINGS: In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0%64, 95% CI 0%52-0%78) and 2-4 (RR 0%80, 0%68-0%93), and non-significantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12%1% vs 14%2%; RR 0%85, 0%75-0%96; 2p=0%009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0%74, 0%62-0%89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0%90, 0%81-0%99; 2p=0%045), though the breast cancer mortality reduction was not significant (RR 0%89, 0%78-1%03; 2p=0%11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 2-4 (RR 0%56, 0%46-0%67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8%7% vs 10%1%; 2p=0%015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments differed (RR 0%70, 0%64-0%77), but not significantly thereafter (RR 0%93, 0%86-1%01; 2p=0%08). Breast cancer mortality was reduced both while treatments differed (RR 0%79, 0%67-0%92), and subsequently (RR 0%89, 0%81-0%99), and for all periods combined (RR 0%86, 0%80-0%94; 2p=0%0005). All-cause mortality was also reduced (RR 0%88, 0%82-0%94; 2p=0%0003). RRs differed little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0%4% vs 1%2%; RR 0%33, 0%21-0%51) but more bone fractures (5-year risk 8%2% vs 5%5%; RR 1%42, 1%28-1%57); non-breast-cancer mortality was similar. INTERPRETATION: Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments differ, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.
Keywords		rak dojke aromatazni zaviralci tamoksifen breast cancer aromatase inhibitors tamoxifen