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Z; 38c?"6@ NNN?NR6L YCosts(2 %  Z) 38c?"6@ NNN?N  ] Mortality (2   ?  Z 38c?"6@ NNN?N g  wEarly Recurrences(2(  H  0޽h ? 33̙33* " ___PPT10 .+0-D' = @B D]' = @BA?%,( < +O%,( < +D' =%(%(D#' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<* D' =+4 8?dCB0-#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<* D' =%(D' =%(DA' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-}6B!strips(upRight)*<3<* +8+0+ > +[L0 2 5(   L 9 /  # M i   C B C DEF1?   @    C B@C DEFjj1????^ @ /   C Bp C@DEF__1???/ ?o @9    C BAC DEF@1?@ ^ ?@@ @ 9 /   C Bp CADEF 1?o @@?/ o @ @9 /   # B C DEFA@? @Diagonali chiare verso il basso* `   c $A ?? Q  Tygֳgֳ ?" 'Aromatase Inhibitors for EBC Recurrence:(($  H     `A))?federico? 2   `1?[   AI Better0 0  hh88>   `1? AI worse > 0  hh88v  NԔٔ8cBc?<v  NfԔٔ8cBc?*<  NԔٔ8cBc?"` ;3 `L 6  # ^ ~   NԔٔ8cBc?. 6~   NfԔٔ8cBc?/ 6  NԔٔ8cBc?"`y < |L  + {   #  <a    NԔٔ8cBc?"` {    NfԔٔ8cBc?"`~ + {   <XnH  :ATAC  <T # ;  9ITA  < lD g  @ ABCSG/ARNO    <$  9IES  <" Md  ]MA.17  <l  ? BIG/FEMTA  H  0޽h ? 33___PPT10i.Ծ0v!+D=' = @B +\L0 2& ((   `L @  # z ~   NԔٔ8cBc?O~   NfԔٔ8cBc?@  NԔٔ8cBc?"` |L  + {   #   {    NԔٔ8cBc?"` {    NfԔٔ8cBc?"`~ + { XB  0DoXB  0DoS S '  Z } 38c?"6@ NNN?N^` _ ATAC BIG 1-98(2  2  N38c?"6@ NNN?N>"  Z# 38c?"6@ NNN?N%  ZARNO IES (2  2  N38c?"6@ NNN?Nu2  ZD~8c?"6@ NNN?N{ SR(2 2  Z8r8c?"6@ NNN?NlP SR(2 (  Z@H 38c?"6@ NNN?N.G `Up-Front (2  &  Z1 38c?"6@ NNN?NGJ ^Switch(2   NԔٔ8cBc?"`.$ |L  + {   # /%  !  NԔٔ8cBc?"` {  "  NfԔٔ8cBc?"`~ + { $ # Z 38c?"6@ NNN?N$NH \ ABCSG VIII (2   2 $ N38c?"6@ NNN?Nz 2 % Z8c?"6@ NNN?N U  SR(2 ( & Zv 38c?"6@ NNN?N r O  `Sequence (2  H  0޽h ? y___PPT10i.,+D=' = @B +1IWL0 % 2// *(   LL D":   # Vt   6Rx"`Z": t   6ffRx"`D $  L     # /`B   0Do?q  `B   0D1?q q `B   0D1?t t `B   0D1?z z `B   0D1?} } `B   0D1?  `B   0D1?     Ht]1?   U00  `B   0D1?w w    H8a1?   U10     He1?  U20     Hi1?  U30     Hlg1?   U40     H\l1?   U50     Ht1?    U60  XB  0Do? % % XB  0D1? $  XB  0D1?, $ , XB  0D1?" $ "   q   # Ci,$D 0`B  0Do?qq `B   0D1?Cp`B   0D1?Cp`B   0D1?D q `B   0D1?D q    Hz1?l  W1.00     H~1?k W0.90   !  HH1?S kM  W0.80   "  H1?s lm  W0.70   # H1?  W1.00   $ H؄1?   W0.90   % H1?   W0.80  B & 0D8c?   ,$D 0B ' 0D8c?   ,$D 0B ( 0D8c?i  ,$D 0 ) HD1?_,$ 0 XHR=10   * H1? |,$0 eHR=0.740  R + BZ1?i$ C,$@0R , BZ1?W RC,$D0 - Hl1? ,$ 0 iHR=0.84 0  R . BZ1?Az,$@ 0 / <d Influence of the Start-Point(f(   H  0޽h ? 3+ +___PPT10*+D'*' = @B D)' = @BA?%,( < +O%,( < +D' =%(D' =%(DE' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*& %(D' =-6B%strips(downRight)*<3<*& D%' =%(D' =%(Du' =4@BBBB%()))D' =1:Bvisible*o3>+B#style.visibility<*' %(D' =-6B%strips(downRight)*<3<*' D ' =%(D' =%(Dg' =4@BB7BB%(D' =1:Bvisible*o3>+B#style.visibility<*, %(D' =+4 8?fCB#ppt_w*0.70BCB#ppt_wB*Y3>B ppt_w<*, D' =+4 8?\CB#ppt_hBCB#ppt_hB*Y3>B ppt_h<*, D' =-g6B fade*<3<*, D' =%(D' =A@BB7BB0B%()))D' =1:Bvisible*o3>+B#style.visibility<** %(D' =+4 8?fCB#ppt_w*0.70BCB#ppt_wB*Y3>B ppt_w<** D' =+4 8?\CB#ppt_hBCB#ppt_hB*Y3>B ppt_h<** D' =-g6B fade*<3<** D' =%(D' =%(DA' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-}6B!strips(upRight)*<3<* D' =%(DE' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*( %(D' =-6B%strips(downRight)*<3<*( D ' =%(D; ' =%(Dg' =4@BB7BB%(D' =1:Bvisible*o3>+B#style.visibility<*+ %(D' =+4 8?fCB#ppt_w*0.70BCB#ppt_wB*Y3>B ppt_w<*+ D' =+4 8?\CB#ppt_hBCB#ppt_hB*Y3>B ppt_h<*+ D' =-g6B fade*<3<*+ Dt' =A@BB7BB0B%(D' =1:Bvisible*o3>+B#style.visibility<*) %(D' =+4 8?fCB#ppt_w*0.70BCB#ppt_wB*Y3>B ppt_w<*) D' =+4 8?\CB#ppt_hBCB#ppt_hB*Y3>B ppt_h<*) D' =-g6B fade*<3<*) D ' =%(D; ' =%(Dg' =4@BB7BB%(D' =1:Bvisible*o3>+B#style.visibility<*. %(D' =+4 8?fCB#ppt_w*0.70BCB#ppt_wB*Y3>B ppt_w<*. D' =+4 8?\CB#ppt_hBCB#ppt_hB*Y3>B ppt_h<*. D' =-g6B fade*<3<*. Dt' =A@BB7BB0B%(D' =1:Bvisible*o3>+B#style.visibility<*- %(D' =+4 8?fCB#ppt_w*0.70BCB#ppt_wB*Y3>B ppt_w<*- D' =+4 8?\CB#ppt_hBCB#ppt_hB*Y3>B ppt_h<*- D' =-g6B fade*<3<*- ++0+)  ++0+*  ++0+-  +9XL0 88 28G U8(     Z3338c?"6@`NNN?NC =B  HDy|?"0@NNN?NL   Z11ȜȜ?  50  Z11ȜȜ? o  685  Zx11ȜȜ?pj 7100RB  @ s *DjJ@@RB  @ s *DjJ z RB  @ s *DjJzXB  @ 0ZDjJ@y  3 BL C DE F8c L @c"$`  ~>  Z11ȜȜ?^ X 624  Z11ȜȜ?^g4X 50  Zd11ȜȜ?^AgX 648  Z11ȜȜ?^DX 660  Z11ȜȜ?@ o:  675RB  @ s *DjJ z   Z11ȜȜ? o  680RB  @ s *DjJ* z*   Z11ȜȜ?^} X 636  Z(11ȜȜ? 3T  Z11ȜȜ?l_@ FT!A$"B  N?D|?"6?@@NNN?ND0DB  N?D|?"6?@@NNN?N0  Z11ȜȜ?^X 672XB  @ 0ZDjJ@yXB  @ 0ZDjJ@yXB  @ 0ZDjJ@F F yXB  @ 0ZDjJ@  yXB  @ 0ZDjJ@{|y  Zh11ȜȜ? Time since surgery (months)> ! Z(11ȜȜ?^X 612XB " @ 0ZDjJ@tty # Z11ȜȜ?o 690RB $ @ s *DjJ z  % Z11ȜȜ?o 695RB & @ s *DjJwzw '  `11ȜȜ?2*$  ;EFS (%)B ( HD8c?"0@NNN?Nw c2 B ) HD8c?"0@NNN?N) c2b   * s 0e0e    ByCDE`F8 @  | 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E||_*6HT*P`Wrckohqu{A|ky@      s " 0e@  `     @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abH B  + s 0e0e    B|CDEFH @  | 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E||$$rz6 ''#:(Z*f.s-~3<HNIJNPTTP%W;Zoblors x{%|!$@          s " 0e@  `     @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abK  , ZH11ȜȜ?kJ  =98.0% - Z11ȜȜ?  B29$" . Z11ȜȜ?  oEvents HR p-value$ / Zl11ȜȜ?  ] 24 1.19 0.5194d 0 Z\11ȜȜ?0?  FT!A$" 1 Z11ȜȜ?0 a First 2 years 2 ZP11ȜȜ?0 3TB 3 ND8c?"0@NNN?NH H 6 4 Z"11ȜȜ?>V Y lTherapy switch$ 5 Z &11ȜȜ?skJ G =98.3%B 6 HD8c?"0@NNN?N@  7 T jJ?"6@`NNN?NGNe F <* U ?ABCSG 08 Trial Event-free survival following surgery (n = 2926):@$f& \    d G Z0 38c?"6@ NNN?N Jakesz et al. SABCS 2005(2B  H  0޽h ? h___PPT10i.P H+D=' = @B +f9YL0 e8]8@26C 7(     Z3338c?"6@`NNN?NC u   Z811ȜȜ?_ Y 50  Z<11ȜȜ?o  685  Zp?11ȜȜ?  7100RB  @ s *DjJ  RB  @ s *DjJ< z< RB  @ s *DjJzXB  @ 0ZDjJ   3 BL C DE F8c L @c"$` 1 ~   ZD11ȜȜ?   624  ZH11ȜȜ? g4 50  Z\K11ȜȜ? Ag 648  Zh 11ȜȜ? D 660  ZR11ȜȜ? o  675RB  @ s *DjJ` z`   ZU11ȜȜ?K oE  680RB  @ s *DjJ z   ZY11ȜȜ? }  636  Z\11ȜȜ? w9  3T  Z|a11ȜȜ? wx  FT!A$"B  N?D|?"6?@@NNN?N| | B  N?D|?"6?@@NNN?N    Ze11ȜȜ?  672XB  @ 0ZDjJ XB  @ 0ZDjJ XB  @ 0ZDjJ F F XB  @ 0ZDjJ   XB  @ 0ZDjJ {|  Zj11ȜȜ?nh Time since surgery (months)>  Zo11ȜȜ?  612XB ! @ 0ZDjJ tt " Z t11ȜȜ?%o 690RB # @ s *DjJz $ ZXx11ȜȜ?o 695RB % @ s *DjJz &  `w11ȜȜ?*$  ;EFS (%)B ' HD8c?"0@NNN?N c2M B ( HD8c?"0@NNN?N c2 B ) ND8c?"0@NNN?NH H  * Z؀11ȜȜ?>V T lTherapy switch$B + HD8c?"0@NNN?N  , Z11ȜȜ?'   B50$" - Z11ȜȜ?' ; 5  oEvents HR p-value$ . Z̎11ȜȜ?' 0   ] 77 0.63 0.0104d / Z11ȜȜ?b"  5A" 0 Z$11ȜȜ?b; . "  ` After switch  1 Z11ȜȜ?b L"  3TB 2 HDy|?"0@NNN?N > V!   3 s 0e0e    BCFDEF @  | 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E||55j!.7+I[Ew@{hKV  r    ; ; O, \[ ? wt }  l   (qb, ,+FFGH@         s " 0e@  `     @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab  4 s 0e0e    BCDEF @  | 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E||..1b ~("?/CWsdV-Gs E4' \C jk p p. ~ ~ h    , ,MB4+hMP@    s " 0e@  `     @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab 5 T jJ?"6@`NNN?N  e B < g ?ABCSG 08 Trial Event-free survival following surgery (n = 2926):@$f& \    d C Z@ 38c?"6@ NNN?N Jakesz et al. SABCS 2005(2B  H  0޽h ? h___PPT10i.P H+D=' = @B +<ZL0 ;;`2<< y;(     Z3338c?"6@`NNN?N=Z B  HDy|?"0@NNN?NVB  HDjJ?"0@NNN?N C e  <( g ?ABCSG 08 Trial Event-free survival following surgery (n = 2926):@$f& \      Z811ȜȜ?   50  Z11ȜȜ?ao[  685  Z11ȜȜ? 7100RB  @ s *DjJ  RB  @ s *DjJzRB  @ s *DjJ9z9XB  @ 0ZDjJ    3 BL C DE F8c L @c"$`  ~   Z$11ȜȜ?   624  Z11ȜȜ? g4 50  Z11ȜȜ? Ag 648  Z811ȜȜ? D 660  Z11ȜȜ? o}  675RB  @ s *DjJ z   Zl11ȜȜ? o  680RB  @ s *DjJm zm   ZD11ȜȜ? }  636  ZD11ȜȜ? 3T  Z11ȜȜ?| FT!A$"B  N?D|?"6?@@NNN?Nm B  N?D|?"6?@@NNN?Nm   Z11ȜȜ?  672XB  @ 0ZDjJ  XB  @ 0ZDjJ  XB  @ 0ZDjJ F F XB  @ 0ZDjJ   XB  @ 0ZDjJ {|  ! ZT11ȜȜ?SM Time since surgery (months)> " Z11ȜȜ?  612XB # @ 0ZDjJ tt  $ Z(11ȜȜ?o 690RB % @ s *DjJLzL & Z11ȜȜ?4o. 695RB ' @ s *DjJz (  `11ȜȜ?u*$E  ;EFS (%)B ) HD8c?"0@NNN?N c2 B * HD8c?"0@NNN?Nl c2 B + ND8c?"0@NNN?NAy  , Z 11ȜȜ?   E0.068$" - Zl%11ȜȜ?   REvents . Z)11ȜȜ?  7101 / ZH$11ȜȜ? N H  Up-value" 0 Z4,11ȜȜ?  3T 1 T jJ?"6@`NNN?NJ 2 Z311ȜȜ?  B79$" 3 ZX811ȜȜ? .  :T!A" 4 Z<11ȜȜ?  ]  L0.76,d&d 5 Z4711ȜȜ? / E  6HR"r  6 s 80e0e    BC@DEF @  | 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| \/n<WYWx^qgs&  4 H i%  }t  ^  'q3,@@AD@s " 0e@  `     @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abDhr  7 s 80e0e    BCDEF @  | 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E|| @"S(P_^rO.VX \ cO  ~i    , ,5|-%FAD@s " 0e@  `     @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abQan 8 Z ?11ȜȜ?x =94.4% 9 ZG11ȜȜ? =92.9%B : HD8c?"0@NNN?N8 B ; HDjJ?"0@NNN?N C d < ZK 38c?"6@ NNN?N Jakesz et al. SABCS 2005(2B  H  0޽h ? h___PPT10i.P H+D=' = @B +$ ^L0 $2(    N38c?"6@ NNN?NH i ,$D 04  # "&<   `gֳgֳ 1d)?C0S" %Q   T L 6~ # N   BFC/DEF&/F/F/@`6eN2  S 1q    S BCDE0F:v @1 hTTfKfKh @` AlB   <v2 @1B Vu x lB   <v2 @1B VC h lB  B <v2 @1VB f     s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B   c     s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B    c ~ `B  0v @12Vex `B  0v @12V3h `B B 0v @1 V2f &  Z 38c?"6@ NNN?Nb  ^Switch(2 (  Z 38c?"6@ NNN?N   `Up-front (2  -  Z 38c?"6@ NNN?N G]  e Better HR (2  $  Z 38c?"6@ NNN?NU   \Toxicity (2  !  Z 38c?"6@ NNN?NR6L YCosts(2 %  Z 38c?"6@ NNN?N  ] Mortality (2   ?  ZM 38c?"6@ NNN?N g  wEarly Recurrences(2(  T  Z5" 8c?"6@ NNN?N tG ,$0 XNo(2 H  0޽h ? 33̙33F>___PPT10.+BD ' = @B Dy ' = @BA?%,( < +O%,( < +D ' =%(%(D ' =%(D' =A@BBBB0B%()))D' =1:Bvisible*o3>+B#style.visibility<*%(D'  =-g6B fade*<3<*)?D'  =+4 8?HCBBCBB*k3>'Bstyle.rotation<*)?D3'  =+4 8?nCB#ppt_x+0.4BCB#ppt_x-0.05B*Y3>B ppt_x<*)?D1'  =+4 8?lCB#ppt_y-0.4BCB#ppt_y+0.1B*Y3>B ppt_y<*)?DK' =+4 8?fCB#ppt_x-0.05BCB#ppt_xB*Y3>B ppt_x<*%( )?DI' =+4 8?dCB#ppt_y+0.1BCB#ppt_yB*Y3>B ppt_y<*%( )?D!' =%(D' =%(Dq' =4@BBBB%()))D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-}6B!strips(upRight)*<3<*+8+0+ +î_L0 ­3 R(       3 r?fv @f?"6?@ `NNN?N/ rl @  "F  :   c T <  #   B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   ZDf11ȜȜ?"0@NNN?N<B  B  `Țff11ȜȜ?"0 NNN?N<  : @  "F f =   gf T <  # f B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   ZDf11ȜȜ?"0@NNN?N<B  B  `ff11ȜȜ?"0 NNN?NL= @     NGf11ȜȜ?C"?_ h  tAnastrozole betterZ$     Zf11ȜȜ?C"?Y0 ` TAM better  XB  @ 0Do^     f@? 11ȜȜ?"6?@`NNN?N  2Non-predefined Adverse events (68 month Follow-up):3(fZ lU 0   # #"B6           0 B   C x4PFжPFж f11ȜȜ?"6@`NNN?N1 < T1.57 f @`>   C xPPFжPFж f11ȜȜ?"6@ NNN?N1< P73 (%)  @`@   C x$MPFжPFж f11ȜȜ?"6@ NNN?N31< R113 (4%)    @`g   C x=PFжPFж f11ȜȜ?"6@ NNN?N013< y Dry mouth    @`B   C xTfPFжPFж f11ȜȜ?"6@`NNN?N  T0.76 f @`A   C xhnPFжPFж f11ȜȜ?"6@ NNN?N S 313 (10%)    @`@   C xPFжPFж f11ȜȜ?"6@ NNN?N3 R244 (8%)    @`   C x$qPFжPFж f11ȜȜ?"6@ NNN?N03 Urinary-tract infection $   @`B   C x?qPFжPFж f11ȜȜ?"6@`NNN?N  T0.55 f @`@   C xHqPFжPFж f11ȜȜ?"6@ NNN?N  R133 (4%)    @`?   C xJqPFжPFж f11ȜȜ?"6@ NNN?N3  Q74 (2%)  @`|   C xLqPFжPFж f11ȜȜ?"6@ NNN?N0 3 Urinary incontinence $  @`B   C xqPFжPFж f11ȜȜ?"6@`NNN?N{  T0.27 f @`@ !  C x0qPFжPFж f11ȜȜ?"6@ NNN?N{   R136 (4%)    @`? "  C x qPFжPFж f11ȜȜ?"6@ NNN?N3{   Q38 (1%)  @`z #  C x:PFжPFж f11ȜȜ?"6@ NNN?N0{ 3  Vaginal moniliasis $  @`B $  C x PFжPFж f11ȜȜ?"6@`NNN?Nq {  T0.25 f @`@ %  C xPFжPFж f11ȜȜ?"6@ NNN?Nq {  R115 (5%)    @`? &  C xPFжPFж f11ȜȜ?"6@ NNN?N3q {  Q30 (1%)  @`b '  C xXPFжPFж f11ȜȜ?"6@ NNN?N0q 3{  t Hysterectomy     @`B (  C xD}PFжPFж f11ȜȜ?"6@`NNN?NQ q  T0.27 f @`A )  C xDPFжPFж f11ȜȜ?"6@ NNN?NQ q  S 324 (10%)    @`? *  C xx PFжPFж f11ȜȜ?"6@ NNN?N3Q q  Q95 (3%)  @`} +  C x PFжPFж f11ȜȜ?"6@ NNN?N0Q 3q  Gynaecological events $ @`B ,  C xPFжPFж f11ȜȜ?"6@`NNN?NG Q  T3.13 f @`B -  C xPFжPFж f11ȜȜ?"6@`NNN?N< G  T3.28 f @`B .  C xPFжPFж f11ȜȜ?"6@`NNN?N' 1 T1.25 f @`B /  C x.PFжPFж f11ȜȜ?"6@`NNN?N ' T1.18 f @`: 0  3 r /PFжPFж f11ȜȜ?"6@ NNN?N  ROR f @`> 1  3 rL@PFжPFж f11ȜȜ?"6@ NNN?N  V    @`? 2  C x@PFжPFж f11ȜȜ?"6@ NNN?NG Q  Q9 (<1%)  @`? 3  C xQPFжPFж f11ȜȜ?"6@ NNN?N3G Q  Q28 (1%)  @`a 4  C x8RPFжPFж f11ȜȜ?"6@ NNN?N0G 3Q  s Dyspareunia     @`s 5  3 rcPFжPFж f11ȜȜ?"6@ NNN?N3 Treatment first received (n[%])    @`< 6  3 rmPFжPFж f11ȜȜ?"6@ NNN?N03 T    @`j 7  3 r(vPFжPFж f11ȜȜ?"6@ NNN?N Tamoxifen (n=3094)$      @`l 8  3 rLPFжPFж f11ȜȜ?"6@ NNN?N3 Anastrozole (n=3092)$      @`< 9  3 r PFжPFж f11ȜȜ?"6@ NNN?N03 T    @`@ :  C xPFжPFж f11ȜȜ?"6@ NNN?N<G  R12 (<1%)    @`? ;  C xhPFжPFж f11ȜȜ?"6@ NNN?N3<G  Q39 (1%)  @`i <  C xPFжPFж f11ȜȜ?"6@ NNN?N0<3G  {Reduction in libido    @`@ =  C xtPFжPFж f11ȜȜ?"6@ NNN?N'1 R216 (7%)    @`@ >  C xPFжPFж f11ȜȜ?"6@ NNN?N3'1 R265 (9%)    @`_ ?  C xPFжPFж f11ȜȜ?"6@ NNN?N0'31 q Diarrhoea     @`A @  C xPFжPFж f11ȜȜ?"6@ NNN?N' S 349 (11%)    @`A A  C x|PFжPFж f11ȜȜ?"6@ NNN?N3' S 402 (13%)    @`b B  C xXPFжPFж f11ȜȜ?"6@ NNN?N03' t Hypertension     @`B C  C xPFжPFжof11ȜȜ?"0@NNN?N03B D  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B E  C xPFжPFжof11ȜȜ?"0@NNN?N00B F  C xPFжPFжof11ȜȜ?"0@NNN?N  B G  C xPFжPFжof11ȜȜ?"0@NNN?N3B H  C xPFжPFжof11ȜȜ?"0@NNN?N00'B I  C xPFжPFжof11ȜȜ?"0@NNN?N  'B J  C xPFжPFжof11ȜȜ?"0@NNN?N0'01B K  C xPFжPFжof11ȜȜ?"0@NNN?N ' 1B L  C xPFжPFжof11ȜȜ?"0@NNN?N010G B M  C xPFжPFжof11ȜȜ?"0@NNN?N 1 G B N  C xPFжPFжof11ȜȜ?"0@NNN?N0G 0B O  C xPFжPFжof11ȜȜ?"0@NNN?N G B P  3 rPFжPFж1 f11ȜȜ?"0@NNN?N3B Q  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B R  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0' 'B S  3 rPFжPFж1 f11ȜȜ?"0@NNN?N01 1B T  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0G G B U  C xPFжPFжof11ȜȜ?"0@NNN?N B V  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0Q Q B W  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0q q B X  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0{ { B Y  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B Z  3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B [  Z1 f11ȜȜ?"0@NNN?N0< <XB \  0o ?u  uXB ]  0o ?u uXB ^  0o ?u 2 uXB _  0o ?u2 ?uRB `  s *Do51 1  a  Z@f11ȜȜ? P 70.2  b  Zf11ȜȜ? P 70.8  c  Z` f11ȜȜ? P 71.0  d  Zf11ȜȜ? P 70.4  e  ZDf11ȜȜ?m O P 70.6  f  Z#f11ȜȜ?e GP 71.2  g  Z-f11ȜȜ?P 77.0  h  Z46f11ȜȜ? P 71.4 RB i  s *D>{{RB j  s *D> k  ZD?f11ȜȜ?P 71.6 RB l  s *D>%% m  Z,If11ȜȜ?P 79.0 RB n  s *DoQ.L T o # T-bB p B TDjJf11ȜȜ?"0@NNN?NTB q B TDjJf11ȜȜ?"0@NNN?NT r  ZRf11ȜȜ?_AP 71.8  s  Z\f11ȜȜ?P 72.0 RB t  s *Do8 =RB u  s *D> RB v  s *D>2 2 RB w  s *D>: : RB x  s *D> RB y  s *D> RB z  s *D>8 8 RB {  s *D> RB |  s *D>5 5 RB }  s *D> RB ~  s *D> RB   s *D>RB   s *D> RB   s *D>,,RB   s *D>RB   s *D> RB   s *D>))RB   s *D>))RB   s *D>}}RB   s *D>RB   s *D>**RB   s *D>**RB   s *D>RB   s *D>RB   s *D>RB   s *D>**RB   s *D>RB   s *D>   ZRB   s *D>55RB   s *D>RB   s *D>RB   s *D>RB   s *D>::RB   s *D>99RB   s *D>RB   s *D>RB   s *D>::RB   s *D>::RB   s *D>RB   s *D>   Zl{f11ȜȜ?hJP 72.4    Z}f11ȜȜ?P 72.6    Zf11ȜȜ?N 72.8    Zf11ȜȜ?rTN 73.0    ZXf11ȜȜ?N 73.2 RB   s *D>"F  &;   S &T <  #  & B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   ZDf11ȜȜ?"0@NNN?N<B  B  ``ff11ȜȜ?"0 NNN?N ;; @  nF x!   vx B   ZDf11ȜȜ?"0@NNN?NB   TZDf11ȜȜ?"0@NNN?N:B   ZDf11ȜȜ?"0@NNN?NxxB  B  `$ff11ȜȜ?"0 NNN?N ! @  T T  # -bB  B TDjJf11ȜȜ?"0@NNN?NTB  B TDjJf11ȜȜ?"0@NNN?NTB   TDf11ȜȜ?"0@NNN?NRxnF d #     d # B   ZDf11ȜȜ?"0@NNN?Nd d B   TZDf11ȜȜ?"0@NNN?Nd 0 B   ZDf11ȜȜ?"0@NNN?N  B  B  `ff11ȜȜ?"0 NNN?N #  @  T T  # - b B  B TDjJf11ȜȜ?"0@NNN?NTB  B TDjJf11ȜȜ?"0@NNN?NTB   TDf11ȜȜ?"0@NNN?NZ  "F   h     * T <  #   8B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   ZDf11ȜȜ?"0@NNN?N<B  B  `<ff11ȜȜ?"0 NNN?N  h @  "F a E Q     a Q % T <  # a y Q B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   ZDf11ȜȜ?"0@NNN?N<B  B  `ff11ȜȜ?"0 NNN?N E  @  "F u [ D    u [ 9 T <  # u [ B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   ZDf11ȜȜ?"0@NNN?N<B  B  `ff11ȜȜ?"0 NNN?N  D @  F $ D    $ DT <  # $ B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   NDf11ȜȜ?"0@NNN?N<B  B  `<ff11ȜȜ?"0 NNN?N{ D @  F   Q     QT <  #   !B   ZDf11ȜȜ?"0@NNN?N<B   TZDf11ȜȜ?"0@NNN?N!!B   NDf11ȜȜ?"0@NNN?N<B  B  `ff11ȜȜ?"0 NNN?N,  Q @  XB   0Do     `d f11ȜȜ?"6@ NNN?N^#  DATAC Trialists Group: Lancet 2006##J  H   0޽h ? 3___PPT10i.a`)+D=' = @B +Я`L0 ϮǮ 3_(     f?fv @f?"6?@ `NNN?N/ rl  Nf11ȜȜ?C"?_  tAnastrozole betterZ$    Z'f11ȜȜ?C"?Y ` TAM better  XB @ 0Do4 a XB  0Do    f0? 11ȜȜ?"6?@`NNN?N  2Non-predefined adverse events (68 month Follow-up):3(f6Z U 0   # #"B6 GHGGH0 B   C xh8PFжPFж f11ȜȜ?"6@`NNN?N  T3.61 f @`?   C x@PFжPFж f11ȜȜ?"6@ NNN?N Q22 (1%)  @`?   C x,JPFжPFж f11ȜȜ?"6@ NNN?N3 Q78 (3%)  @`~   C xJPFжPFж f11ȜȜ?"6@ NNN?N03 Carpal-tunnel syndrome $  @`B  C x0\PFжPFж f11ȜȜ?"6@`NNN?N  T2.73 f @`@  C x\PFжPFж f11ȜȜ?"6@ NNN?N   R108 (3%)    @`@  C xmPFжPFж f11ȜȜ?"6@ NNN?N3   R278 (9%)    @`j  C x$fPFжPFж f11ȜȜ?"6@ NNN?N0 3  |Hypercholesterolemia  @`B  C xPFжPFж f11ȜȜ?"6@`NNN?N  T6.99 f @`?  C xPFжPFж f11ȜȜ?"6@ NNN?N   Q8 (<1%)  @`?  C x8PFжPFж f11ȜȜ?"6@ NNN?N3   Q55 (2%)  @`  C xPFжPFж f11ȜȜ?"6@ NNN?N0 3   Increase in alkaline phosphatase!! 6  @`B  C xPFжPFж f11ȜȜ?"6@`NNN?N  T0.51 f @`?  C xPPFжPFж f11ȜȜ?"6@ NNN?N   Q45 (1%)  @`?  C xPFжPFж f11ȜȜ?"6@ NNN?N3   Q23 (1%)  @`x  C xPFжPFж f11ȜȜ?"6@ NNN?N0 3  Fingal infection $  @`B  C x(PFжPFж f11ȜȜ?"6@`NNN?NB  T0.58 f @`?  C xPPFжPFж f11ȜȜ?"6@ NNN?NB   Q92 (3%)  @`?  C xPFжPFж f11ȜȜ?"6@ NNN?N3B   Q54 (2%)  @`u  C xPFжPFж f11ȜȜ?"6@ NNN?N0B 3   Nail disorder $ @`B  C xxPFжPFж f11ȜȜ?"6@`NNN?N B  T0.70 f @`@  C xD[ PFжPFж f11ȜȜ?"6@ NNN?N B  R159 (5%)    @`@   C xx [ PFжPFж f11ȜȜ?"6@ NNN?N3 B  R113 (4%)    @`] ! C x, [ PFжPFж f11ȜȜ?"6@ NNN?N0 3B  oAnaemia  @`B " C x[ PFжPFж f11ȜȜ?"6@`NNN?N  T0.46 f @`B # C x[ PFжPFж f11ȜȜ?"6@`NNN?N  T1.52 f @`B $ C xp[ PFжPFж f11ȜȜ?"6@`NNN?N<  T0.54 f @`B % C x$[ PFжPFж f11ȜȜ?"6@`NNN?N < T1.49 f @`: & 3 r(%[ PFжPFж f11ȜȜ?"6@ NNN?N  ROR f @`> ' 3 r?[ PFжPFж f11ȜȜ?"6@ NNN?N  V    @`? ( C x\?[ PFжPFж f11ȜȜ?"6@ NNN?N  Q28 (1%)  @`@ ) C xP[ PFжPFж f11ȜȜ?"6@ NNN?N3  R13 (<1%)    @`f * C xt`[ PFжPFж f11ȜȜ?"6@ NNN?N03  xThrombocytopenia  @`s + 3 rb[ PFжPFж f11ȜȜ?"6@ NNN?N3 Treatment first received (n[%])    @`< , 3 rl[ PFжPFж f11ȜȜ?"6@ NNN?N03 T    @`j - 3 r u[ PFжPFж f11ȜȜ?"6@ NNN?N Tamoxifen (n=3094)$      @`l . 3 rD[ PFжPFж f11ȜȜ?"6@ NNN?N3 Anastrozole (n=3092)$      @`< / 3 r[ PFжPFж f11ȜȜ?"6@ NNN?N03 T    @`@ 0 C x[ PFжPFж f11ȜȜ?"6@ NNN?N R145 (5%)    @`@ 1 C x`[ PFжPFж f11ȜȜ?"6@ NNN?N3 R215 (7%)    @`b 2 C xd[ PFжPFж f11ȜȜ?"6@ NNN?N03 t Paresthaesia     @`@ 3 C x[ PFжPFж f11ȜȜ?"6@ NNN?N< R235 (8%)    @`@ 4 C x[ PFжPFж f11ȜȜ?"6@ NNN?N3< R132 (4%)    @`u 5 C x@[ PFжPFж f11ȜȜ?"6@ NNN?N0<3  Muscle cramps $ @`@ 6 C x[ PFжPFж f11ȜȜ?"6@ NNN?N< R226 (7%)    @`A 7 C x8[ PFжPFж f11ȜȜ?"6@ NNN?N3< S 325 (11%)    @` 8 C x[ PFжPFж f11ȜȜ?"6@ NNN?N03< Osteopenia or osteoporosis $   @`B 9 C xPFжPFжof11ȜȜ?"0@NNN?N03B : 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B ; C xPFжPFжof11ȜȜ?"0@NNN?N00B < C xPFжPFжof11ȜȜ?"0@NNN?N  B = C xPFжPFжof11ȜȜ?"0@NNN?N3B > C xPFжPFжof11ȜȜ?"0@NNN?N00<B ? C xPFжPFжof11ȜȜ?"0@NNN?N  <B @ C xPFжPFжof11ȜȜ?"0@NNN?N0<0B A C xPFжPFжof11ȜȜ?"0@NNN?N < B B C xPFжPFжof11ȜȜ?"0@NNN?N00B C C xPFжPFжof11ȜȜ?"0@NNN?N  B D C xPFжPFжof11ȜȜ?"0@NNN?N00 B E C xPFжPFжof11ȜȜ?"0@NNN?N  B F 3 rPFжPFж1 f11ȜȜ?"0@NNN?N3B G 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B H 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0< <B I 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B J 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B K C xPFжPFжof11ȜȜ?"0@NNN?N B L 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B M 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0B B B N 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B O 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B P 3 rPFжPFж1 f11ȜȜ?"0@NNN?N0 B Q Z1 f11ȜȜ?"0@NNN?N0 XB R 0o ?u uXB S 0o ?uU | uXB T 0o ?u|  uRB U s *Do5  V Z$[ f11ȜȜ?-P 76.6 RB W s *D> X Z\ f11ȜȜ?^P 918.56 RB Y s *DoX|L T Z# T.cB [B TDjJf11ȜȜ?"0@NNN?NTB \B TDjJf11ȜȜ?"0@NNN?NT ] Z \ f11ȜȜ? m P 70.8  ^ Z@\ f11ȜȜ? P 71.0  _ Z\ f11ȜȜ?n P P 70.4  ` Z%\ f11ȜȜ? P 71.2  a Z.\ f11ȜȜ?2 P 71.4  b Z7\ f11ȜȜ? P 71.6  c Z@\ f11ȜȜ?S5P 71.8  d ZI\ f11ȜȜ?P 72.0 RB e s *Do ARB f s *D>' ' RB g s *D> RB h s *D> RB i s *D> RB j s *D> RB k s *D> RB l s *D>R R RB m s *D> RB n s *D>E E RB o s *D>n n RB p s *D> RB q s *D> RB r s *D>` ` RB s s *D> RB t s *D>  RB u s *D>66RB v s *D>66RB w s *D>}}RB x s *D>RB y s *D>RB z s *D>RB { s *D>ZZRB | s *D>ZZRB } s *D>RB ~ s *D>RB  s *D>33RB  s *D>33  ZP[\ f11ȜȜ?uXP 72.2 RB  s *D>~~RB  s *D>RB  s *D>RB  s *D>[[RB  s *D>[[RB  s *D>RB  s *D>RB  s *D>RB  s *D>33RB  s *D>~~RB  s *D>~~RB  s *D>RB  s *D>  Zh\ f11ȜȜ? P 72.4   ZHs\ f11ȜȜ?P 72.6   Z|\ f11ȜȜ?6N 72.8   Z܅\ f11ȜȜ?N 73.0   ZD}\ f11ȜȜ?V8N 73.2 RB  s *D>RB  s *D>[[RB  s *D>RB  s *D>RB  s *D>RB  s *D>  ZЗ\ f11ȜȜ?N 73.4   ZH\ f11ȜȜ?dN 73.6 RB  s *D>RB  s *D>  Z\ f11ȜȜ?P 76.8 RB  s *D>44  Z0\ f11ȜȜ? P 70.2   Z\ f11ȜȜ? P 70.6 L < #  -B  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?N FL < #   AB  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?N S ZB  ZDf11ȜȜ?"0@NNN?N  TL T # /dgB B TDjJf11ȜȜ?"0@NNN?NTB B TDjJf11ȜȜ?"0@NNN?NTB  TDf11ȜȜ?"0@NNN?N7\7B  ZDf11ȜȜ?"0@NNN?N##MB  TZDf11ȜȜ?"0@NNN?N2#D2B @ Tff11ȜȜ?"0 NNN?NgL < #  iU B  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?N n L < #  L + B  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?N  D L < #  * k B  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?N n  L < #  M B  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?Nt  j L < # m ~ B  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?NL H L T # TlB B TDjJf11ȜȜ?"0@NNN?NTB B TDjJf11ȜȜ?"0@NNN?NTRB  s *DoB  ZDf11ȜȜ?"0@NNN?Ny && B  TZDf11ȜȜ?"0@NNN?N &D B  NDf11ȜȜ?"0@NNN?Ny  L T # d /d B B TDjJf11ȜȜ?"0@NNN?NTB B TDjJf11ȜȜ?"0@NNN?NTB  TZDf11ȜȜ?"0@NNN?N  L T # d q B B TDjJf11ȜȜ?"0@NNN?NTB B TDjJf11ȜȜ?"0@NNN?NTB  TZDf11ȜȜ?"0@NNN?N [ B @ Tff11ȜȜ?"0 NNN?NX % L < # j1B  ZDf11ȜȜ?"0@NNN?N<B  TZDf11ȜȜ?"0@NNN?N!!B  NDf11ȜȜ?"0@NNN?N<B @ Tff11ȜȜ?"0 NNN?Nl&   `@\  f11ȜȜ?"6@ NNN?N^#  DATAC Trialists Group: Lancet 2006##J  H  0޽h ? 3___PPT10i.a`)+D=' = @B +x+@L0 w*o* /@@ *(      f? 11ȜȜ?"6?@`NNN?N  7ATAC 68-months analysis Annual fracture rates over time*87 fP   Zf11ȜȜ?Z  52RB  @ s *Do6  Zf11ȜȜ?Z O 53RB  @ s *Do6RB  @ s *DoJ6J  Zf11ȜȜ?Z  51   Zlf11ȜȜ?  71.5"   Z|f11ȜȜ? d   Time since randomization (years)!!>    # BCDE FԔ@c"$` C] RB   @ s *Do]6]   Ztf11ȜȜ?    70.5RB  @ s *Do 6 RB  @ s *Do 6   Zf11ȜȜ?? Z   50RB  @ s *Do060XB  @ 0ZDo V V   Zf11ȜȜ?  52XB  @ 0ZDo   Zf11ȜȜ? I  53XB  @ 0ZDo    Zdf11ȜȜ? \  56  Ztf11ȜȜ?z mAnnual rates (%)*$  Z<f11ȜȜ? s 72.54  Zf11ȜȜ?Bd~  (*Calculated using Kaplan-Meier estimates))H      B CDEF Ԕ>" f "  @S" }q   B CDEF fԔ 9Nf  @S" wfc  Zpf11ȜȜ?aT  W Anastrozole    Z|f11ȜȜ? c F  U Tamoxifen  X  0 R B   N?DfԔ?"0?@NNN?NX qX B ! N?DԔ?"0?@NNN?N q l2 " 6f"`UHl # 6"`aZl $ 6"` I l2 % 6f"`rC l & 6"` $l2 ' 6f"`*{ nl ( 6"`#gl2 ) 6f"`al * 6"` 8l2 + 6f"`jl , 6"`Sl2 - 6f"`HQXB . @ 0ZDo   / Zpf11ȜȜ? o  55XB 0 @ 0ZDo   1 Zf11ȜȜ? 4  54XB 2 @ 0ZDo   3 Zpf11ȜȜ? o!  51XB 4 @ 0ZDo BB  5 ZHf11ȜȜ?   50 6 ZDf11ȜȜ? b ? 2 2724 2741   7 Zdf11ȜȜ? : b ? 3 2553 2579   8 ZXf11ȜȜ? Lb = 6 845 846   9 Zf11ȜȜ? `b ? 5 2070 2100   : Zf11ȜȜ? Cb ? 4 2393 2401   ; Zf11ȜȜ? ~b ? 1 2923 2932   < Zx!f11ȜȜ? b ? 0 3092 3094  5 = Z"f11ȜȜ? gZb Years Anastrozole Tamoxifen6 f 6   > Z,f11ȜȜ? g  i Not at risk $l2 ? 6f"`2 .v l @ 6"` . H  0޽h ? 3___PPT10i.a`)+D=' = @B +`3AL0 ..@/TV ).(      f4? 11ȜȜ?"6?@`NNN?N  /Percentage change in BMD over time Lumbar spine*0#$f 6    B CDE Fo @S"  XB  0Do  NC11ȜȜ?e  RStatistically significantly more BMD loss on anastrozole than tamoxifen (p<0.0001) S Sl      pRB  @ s *Doy y   Z TBaseline  # Zf11ȜȜ?-! %Estimated % change (mean and 95% CI)&&6  $ Zf11ȜȜ?. ~CI, confidence intervals ,   % C B CZDEF33ԔZ^n K @"`  ' Z f11ȜȜ?l 6),  W Anastrozole   ( Zf11ȜȜ?$b U Tamoxifen  RB ) s *DjJjjRB * s *DjJvRB + s *DjJ<RB , s *DjJ hRB - s *DjJd dRB . s *DjJ RB / s *DjJ,RB 0 s *DjJRB 1 s *DjJ((RB 2 s *DjJ t RB 3 s *DjJx x RB 4 s *DjJ  RB 5 s *DjJ RB 6 s *DjJ RB 7 s *DjJ RB 8 s *DjJTT RB 9 s *DjJ & RB : s *DjJ&f ; 0"`5x? f < 0"` c f = 0"`  f > 0"`CBf2 ? 0"` DWf2 @ 0"` f2 A 0"`3f2 B 0"`F(R C  `ܛ f11ȜȜ?"6@ NNN?Na Coleman et al ASCO060  B E HDfԔ?"0@NNN?N   B B F HDfԔ?"0@NNN?NF  l  ?T  V  ?T ,$D 0$N  $B  G   ?T ZB H  s *DjJ> ZB I  s *DjJB $B ZB J  s *DjJ$ZB K  s *DjJaoac ZB L  s *DjJ3g g ZB M  s *DjJ3kkZB N  s *DjJ W KZB O  s *DjJ O/ OZB P  s *DjJ S/ Sn Q  0"` % n R  0"`A B S  HDfԔ?"0@NNN?N QB T  HDfԔ?"0@NNN?Nht n U  0"`p / H  0޽h ? 3WO___PPT10/.a`)+/D' = @B D' = @BA?%,( < +O%,( < +D' =%(D' =%(DE' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*V %(D' =-6B%strips(downRight)*<3<*V +$+BL0 #**`/;;$ )(  $  $  f? 11ȜȜ?"6?@`NNN?N  ;KReported Fracture Rates in Adjuvant Aromatase Inhibitor vs Tamoxifen Trials*LK f    $ Z f11ȜȜ?T^  58RB $ @ s *Do0 $ Z$f11ȜȜ?"`\ 612RB $ @ s *Do0RB $ @ s *Do 0  $ Z(f11ȜȜ? T  54  $ Z(,f11ȜȜ? T|  56  $ # BCDE FԔ@c"$` =h RB  $ @ s *Do* 0*   $ ZH0f11ȜȜ? T  52RB  $ @ s *DoO 0O RB $ @ s *Doc 0c  $ Zh4f11ȜȜ? T  50RB $ @ s *Do0 $ Z8f11ȜȜ? H  DBIG 1-98 (51 mo) $ Z<f11ȜȜ?@ 610 $ Tf?"`7;7e  $ T?"`# 84e  $ Tf?"`# T  $ T?"` T  $ Tf?"`51\  $ T?"`P 2. \  $ ZAf11ȜȜ?  ? IES (58 mo)   $ ZFf11ȜȜ? 12 @ ATAC (68 mo)   $ T?"`TX  $  f?f? "6?@`NNN?NO  $ Z@Kf11ȜȜ?P  4Al $ ZCf11ȜȜ?   OTam $ Zf11ȜȜ?"6@ NNN?NH$  $  `R f11ȜȜ?"6@ NNN?N13 611 !$ Zf11ȜȜ?"6@ NNN?NI%  "$  `dV f11ȜȜ?"6@ NNN?N F  77.7 #$ Zf11ȜȜ?"6@ NNN?N,  $$  `xZ f11ȜȜ?"6@ NNN?N 1  77.0 %$ Zf11ȜȜ?"6@ NNN?N1   &$  `9 f11ȜȜ?"6@ NNN?N=   74.9 '$ Zf11ȜȜ?"6@ NNN?N X4 ($  `4b f11ȜȜ?"6@ NNN?N>d 78.6 )$ Zf11ȜȜ?"6@ NNN?N K'  *$  `f f11ȜȜ?"6@ NNN?N =  75.8X +$ 0.   ,$ Tf?"` Z  -$ T?"`) Z  .$ Z|jf11ȜȜ?  @ ARNO (30 mo)   /$ Zf11ȜȜ?"6@ NNN?N} g  0$  `n f11ȜȜ?"6@ NNN?Nw K  72.2 1$ Zf11ȜȜ?"6@ NNN?Ny c  2$  ``m f11ȜȜ?"6@ NNN?Nj >  72.2B 3$  `Df11ȜȜ?"0@NNN?N/ / C `L @ 4$ # ;.~ 5$  NԔٔ8cBc?O~ 6$  NԔٔ8cBc?@`8 {  ;$   7$  NԔٔ8cBc?"` T  + {  8$ #  {  9$  NԔٔ8cBc?"` {  :$  NԔٔ8cBc?"`~ + { H $ 0޽h ? 3___PPT10i.a`)+D=' = @B +& aL0 d\@3(    N38c?"6@ NNN?N i/,$D 04  # "&<   " gֳgֳ 1d)?C0S" %Q  "  T L 6~ # N   BFC/DEF&/F/F/@`6eN2  S 1q    S BCDE0F:v @1 hTTfKfKh @` AlB   <v2 @1B Vu x lB   <v2 @1B VC h lB  B <v2 @1VB f     s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B   c     s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B    c ~ `B  0v @12Vex `B  0v @12V3h `B B 0v @1 V2f &  Z "  38c?"6@ NNN?Nb  ^Switch(2 (  Z"  38c?"6@ NNN?N   `Up-front (2  -  Zx "  38c?"6@ NNN?N G]  e Better HR (2  $  Z*"  38c?"6@ NNN?NU   \Toxicity (2  !  Z4"  38c?"6@ NNN?NR6L YCosts(2 %  Z="  38c?"6@ NNN?N  ] Mortality (2   ?  ZG"  38c?"6@ NNN?N g  wEarly Recurrences(2(     Z R"  8c?"6@ NNN?N tG  XNo(2 l  Z"  8c?"6@ NNN?N.  u ,$0 pMay Be(2( H  0޽h ? 33̙33F>___PPT10.+%D ' = @B Dy ' = @BA?%,( < +O%,( < +D ' =%(%(D ' =%(D' =A@BBBB0B%()))D' =1:Bvisible*o3>+B#style.visibility<*%(D'  =-g6B fade*<3<*)?D'  =+4 8?HCBBCBB*k3>'Bstyle.rotation<*)?D3'  =+4 8?nCB#ppt_x+0.4BCB#ppt_x-0.05B*Y3>B ppt_x<*)?D1'  =+4 8?lCB#ppt_y-0.4BCB#ppt_y+0.1B*Y3>B ppt_y<*)?DK' =+4 8?fCB#ppt_x-0.05BCB#ppt_xB*Y3>B ppt_x<*%( )?DI' =+4 8?dCB#ppt_y+0.1BCB#ppt_yB*Y3>B ppt_y<*%( )?D!' =%(D' =%(Dq' =4@BBBB%()))D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-}6B!strips(upRight)*<3<*+8+0+"  +6 cL0 ..3)),#.(  , , 3 r>Q?f3v @f?"6?@ `NNN?N >   , T38c?"6@ NNN?N' p  ,$D 0P*F k\ , p[ZB ,B s *DjJ /  , ZHQ11ȜȜ?(   50ZB ,B s *DjJ /  , ZPQQ11ȜȜ?H S  620ZB  ,B s *DjJ/  , ZZQ11ȜȜ?Ht 680ZB  ,B s *DjJ/  , Z,2Q11ȜȜ? 7100ZB  ,B s *DjJ_ /_  , ZQ11ȜȜ?H  640ZB ,B s *DjJ/ , Zt]C11ȜȜ?HL 660 ,  `uB11ȜȜ?l  oWomen alive (%)$`B ,B 0ZDjJ `B ,B 0ZDjJ- - `B ,B 0ZDjJb b `B ,B 0ZDjJ  , ZB11ȜȜ? }  51 , Z\B11ȜȜ?O }  52 , Z(B11ȜȜ? o}  50 , ZxB11ȜȜ?  }  53 , ZB11ȜȜ?X  tExemestane Tamoxifen 2$  `B ,B 0ZDjJ    , ZB11ȜȜ? Q}  54`B ,B 0ZDjJH H  , ZdB11ȜȜ? }  55 , ZB11ȜȜ?[mf5 dT = 251 deaths 2B  ,B <D8c?"0@NNN?NM QM B !,B <D8c?"0@NNN?NQ ", Z0B11ȜȜ?[ok8 dE = 210 deaths 2 #, ZB11ȜȜ?^| {  tHR 0.83 (95% CI 0.69-1.00) Log-rank test: p = 0.05 Difference in OS at 2.5 years (E-T) = 0.72% (95% CI-0.41 to 1.85)u ub  $, ZB11ȜȜ?$L| #Oestrogen-receptor-positive/unknown$(2$$ %,  `0e0e    B CDEF @  Ԕ 8c8c     ?A)BCD|E||(( x R 6 L$qdq qddTX XLLTL7DDD44,A'"L d HIL@  # "0e@  `    @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab(H\ &,  n0e0e    B CDEF @  Ԕ 8c8c     ?A)BCD|E||-- l O ` @+x ttPle\$PLp< <&n'$lH  x l `XHHCD@      # "0e@  `    @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `ab$<t ', # BL C DE F8c L @c"$` &zP , (, Z|B11ȜȜ? \  Time since randomisation (years)!!> w ), <B  1The IES Trial Overall survival for Eligible Pts H2f! fn V , 0޽h ?"` hph___PPT10H.B+ D' = @B D' = @BA?%,( < +O%,( < +D!' =%(D' =%(Dq' =4@BBBB%()))D' =1:Bvisible*o3>+B#style.visibility<*,%(D' =-}6B!strips(upRight)*<3<*,D' =%(D' =%(D5' =4@BB*BB%()?)?D' =.Q7 BBBBBcM -4.44444E-6 -1.61887E-6 L -4.44444E-6 0.04255 *3>*B ppt_xB ppt_y=@0BBAApBBBAL<<*,+u3 dL0 t2l23))41(  4 4 3 rP?f3v @f?"6?@ `NNN?N >  /F t` 4 h|  4  X0e0e    B C(DEF @  Ԕ 8c8c     ?A)BCD|E||   ( L =| Do FT LT LK ZD _4 d % v | l e J 8 * ) &4EFLOTTappty|ywhbRLIB<6,$) 4@]^tx}}wtqspiI@4,   $1]xddxGx0++$ppV$X44.3*8 @CLT\\\tu{spxaQHFHD1hT LN"D(9/ 4 4;@HYQ\oylU5X(T((@                                                                # "0e@  `    @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abdm@ ZB 4B s *DjJ / ZB 4B s *DjJn /n ZB 4B s *DjJ/ZB 4B s *DjJ/ZB  4B s *DjJI /I ZB  4B s *DjJ/  4  `4P11ȜȜ?9  BCumulative rate `B  4B 0ZDjJ `B  4B 0ZDjJ- - `B 4B 0ZDjJb b * 4 Zp&P11ȜȜ?~ `  Time since randomisation (years)!!> `B 4B 0ZDjJ  4 Z<2P11ȜȜ?   31 4 Z&P11ȜȜ?S  32 4 Z;P11ȜȜ? l  30 4 Z(3P11ȜȜ?   33 4 ZMP11ȜȜ?X  rExemestane Tamoxifen 2$  `B 4B 0ZDjJ    4 Z8EP11ȜȜ? M  34`B 4B 0ZDjJH H  4 ZjP11ȜȜ?   35B 4B <D8c?"0@NNN?NM QM B 4B <D8c?"0@NNN?NQ 4 ZsP11ȜȜ?t #Oestrogen-receptor-positive/unknown$(2$$ZB 4B s *DjJ/ZB 4B s *DjJ /  4 Z4~P11ȜȜ?   60.00  4 ZtP11ȜȜ?   60.02 !4 Z P11ȜȜ?+ 60.12 "4 ZP11ȜȜ? 60.14 #4 Z|P11ȜȜ?   60.04 $4 ZpP11ȜȜ?N) 60.10 %4 ZaP11ȜȜ?}X 60.08 &4 ZP11ȜȜ?z  60.06  '4  0e0e    B CDE\F, @  Ԕ 8c8c     ?A)BCD|E||    *  ! 8 @ Q j m uy m X A    ) 6y Hl U] dB e0 q# t V:J8EMZ]`eerm}{oH CB<%3.6 =BMQTSUXaer|ttm\LD=4 +15:=?>APIY`be^w@<840,( |tdda` \ XTP L JHHKL9,$<EXZabeesj\PD832(   ))-;UlUHQ9XkuppXH( |gQ<-@                                                                       # "0e@  `    @ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abN 5%  N 5%  N    5%    !"?N@ABC DEFGHIJK5%LMNOPQRSTUWYZ[ \]^_ `abP4  (4 # BL C DE F8c L @c"$` &zP  )4 <P  ;The IES Trial Cumulative Hazard of death for Eligible Pts H<f+ fn V 4 0޽h ?"` h___PPT10i.B+D=' = @B + eL0 3<(  < < 3 r4P?f3v @f?"6?@ `NNN?N^n >  B < H1?"0@NNN?N2B < H1?"0@NNN?N 2 B < H1?"0@NNN?N22 B < H1?"0@NNN?N B < H1?"0@NNN?N 22B < H1?"0@NNN?N B  < H1?"0@NNN?N22B  < H1?"0@NNN?NB  < H1?"0@NNN?N22mB  < H1?"0@NNN?NmB  < H1?"0@NNN?Nm22B < H1?"0@NNN?NmB < H1?"0@NNN?N222B < H1?"0@NNN?N2B < H1?"0@NNN?N222B < H1?"0@NNN?N2B < H1?"0@NNN?N22 B < H1?"0@NNN?N B < H1?"0@NNN?N~B < H1?"0@NNN?N ~ B < H1?"0@NNN?N B < H1?"0@NNN?N B < H1?"0@NNN?N~B < H1?"0@NNN?N B < H1?"0@NNN?N B < H1?"0@NNN?NB < H1?"0@NNN?NB < H1?"0@NNN?NmB < H1?"0@NNN?NmB  < H1?"0@NNN?NmB !< H1?"0@NNN?NmB "< H1?"0@NNN?N2B #< H1?"0@NNN?N2B $< H1?"0@NNN?N2B %< H1?"0@NNN?N2B &< H1?"0@NNN?N B '< H1?"0@NNN?N B (< H1?"0@NNN?N ~ lF 2g$ )< 2$a *< 3 rDPPFPFPFPF 38c?"6@ NNN?N27   y OS (adjusted)  @`> +< 3 rPFPFPFPF 38c?"6@ NNN?N2 7  V   @` ,< 3 rPFPFPFPF 38c?"6@ NNN?N2i   *Age e" 70 years (1153)( b $ @` -< 3 r(PFPFPFPF 38c?"6@ NNN?N2   Previous tam > 2.5 yrs (1838) 6 @`> .< 3 rPFPFPFPF 38c?"6@ NNN?N2  V   @`i /< 3 rPFPFPFPF 38c?"6@`NNN?N2[ No previous CT (3103)   @`> 0< 3 r(PFPFPFPF 38c?"6@ NNN?N2[ V   @`t 1< 3 r )PFPFPFPF 38c?"6@ NNN?N2 i  Age 60-69 years (1969) $ @`s 2< 3 r4;PFPFPFPF 38c?"6@ NNN?N2W   Age < 60 years (1480) $ @`> 3< 3 rEPFPFPFPF 38c?"6@ NNN?N2 W  V   @` 4< 3 rtEPFPFPFPF 38c?"6@ NNN?N2   :Previous tam d" 2.5 yrs (2764)(  b 6 @`d 5< 3 r YPFPFPFPF 38c?"6@ NNN?N2D |ER unknown (560)  @`? 6< 3 rcPFPFPFPF 38c?"6@ NNN?N2D W ER+PgR- (742)  @`@ 7< 3 rkPFPFPFPF 38c?"6@ NNN?N22 XEr+PgR+ (2668)  @`V 8< 3 rtPFPFPFPF 38c?"6@ NNN?N22 n ER+ (4042)    @`> 9< 3 r~PFPFPFPF 38c?"6@ NNN?N2m V   @`^ :< 3 rPFPFPFPF 38c?"6@ NNN?N2m vPrevious CT (1499)   @`Y ;< 3 r$PFPFPFPF 38c?"6@`NNN?N2  q Nodes- (2384)  @`Y << 3 rlPFPFPFPF 38c?"6@ NNN?N2 q Nodes+ (2038)  @`B =< 3 r$PFPFPFPF 38c?"6@ NNN?N2  Z    @`J >< 3 rPFPFPFPF 38c?"6@ NNN?N~7   b0.69  0.99    @`8 ?< 3 rPFPFPFPF 38c?"6@ NNN?N7 ~  P0.83  @`@ @< 3 rPFPFPFPF 38c?"6@ NNN?N~ 7  X   @`@ A< 3 rPFPFPFPF 38c?"6@ NNN?N ~7  X   @`J B< 3 rPFPFPFPF 38c?"6@ NNN?N~i   b0.67  1.22    @`8 C< 3 r PFPFPFPF 38c?"6@ NNN?Ni ~  P0.90  @`J D< 3 rxPFPFPFPF 38c?"6@ NNN?N~   b0.63  1.13    @`8 E< 3 rPFPFPFPF 38c?"6@ NNN?N ~  P0.84  @`@ F< 3 rPFPFPFPF 38c?"6@ NNN?N~  X   @`@ G< 3 r0PFPFPFPF 38c?"6@ NNN?N~  X   @`J H< 3 rPFPFPFPF 38c?"6@`NNN?N~[ b0.67  1.07    @`8 I< 3 rdPFPFPFPF 38c?"6@`NNN?N[~ P0.85  @`@ J< 3 rPFPFPFPF 38c?"6@ NNN?N~[ X   @`@ K< 3 r"PFPFPFPF 38c?"6@ NNN?N~[ X   @`J L< 3 r+PFPFPFPF 38c?"6@ NNN?N~ i  b0.52  0.95    @`8 M< 3 r3PFPFPFPF 38c?"6@ NNN?N ~i  P0.70  @`J N< 3 r3PFPFPFPF 38c?"6@ NNN?N~W   b0.70  1.47    @`8 O< 3 r84PFPFPFPF 38c?"6@ NNN?NW ~  P1.01  @`@ P< 3 rNPFPFPFPF 38c?"6@ NNN?N~ W  X   @`@ Q< 3 r4WPFPFPFPF 38c?"6@ NNN?N ~W  X   @`J R< 3 r_PFPFPFPF 38c?"6@ NNN?N~   b0.65  1.05    @`8 S< 3 rhPFPFPFPF 38c?"6@ NNN?N ~  P0.83  @`J T< 3 rrPFPFPFPF 38c?"6@ NNN?N~D b0.52  1.32    @`8 U< 3 rzPFPFPFPF 38c?"6@ NNN?ND~ P0.83  @`J V< 3 rPFPFPFPF 38c?"6@ NNN?N~D b0.56  1.24    @`8 W< 3 r\PFPFPFPF 38c?"6@ NNN?N~D P0.83  @`J X< 3 rPFPFPFPF 38c?"6@ NNN?N~2 b0.64  1.07    @`8 Y< 3 rhPFPFPFPF 38c?"6@ NNN?N2~ P0.83  @`J Z< 3 rtPFPFPFPF 38c?"6@ NNN?N~2 b0.69  1.02    @`8 [< 3 r8PFPFPFPF 38c?"6@ NNN?N~2 P0.84  @`@ \< 3 rPFPFPFPF 38c?"6@ NNN?N~m X   @`@ ]< 3 rPFPFPFPF 38c?"6@ NNN?Nm~ X   @`J ^< 3 rlPFPFPFPF 38c?"6@ NNN?N~m b0.60  1.09    @`8 _< 3 rPFPFPFPF 38c?"6@ NNN?N~m P0.80  @`J `< 3 rPFPFPFPF 38c?"6@`NNN?N~  b0.61  1.18    @`8 a< 3 rPFPFPFPF 38c?"6@`NNN?N ~ P0.84  @`J b< 3 r<PFPFPFPF 38c?"6@ NNN?N~ b0.60  0.95    @`8 c< 3 rPFPFPFPF 38c?"6@ NNN?N~ P0.75  @`P d< 3 rPFPFPFPF 38c?"6@ NNN?N~  h95% Cl0   @`: e< 3 r PFPFPFPF 38c?"6@ NNN?N~  RHR  @`ZB f< s *DoW f f ZB g< s *D>[e [  h< Zf11ȜȜ?  71.0  i< N %f11ȜȜ? gc rFavours exemestane $  j< N.f11ȜȜ?Wg oFavours tamoxifen $ ZB k< s *DoZZf  l< Zp9f11ȜȜ? * ? HR (95% Cl)    m< NDCf11ȜȜ?Q( $  Xp=0.04 `B n< 0Dorwr`B o<B 0DoHr&rZB p< s *D>e   q< ZLf11ȜȜ?? ! 71.5 ZB r< s *D>p e p  s< ZVf11ȜȜ?  70.6 ZB t< s *D>] e ]  u< ZL0f11ȜȜ?  70.5 ZB v< s *D>je j  w< Zgf11ȜȜ?  71.2 ZB x< s *D>e   y< Zqf11ȜȜ?  70.8 `B z< 0DjJCCf ZB {< s *D> / / ZB |< s *D>    }< T38c?"6@ NNN?NB jD ZB ~< s *D> ZB < s *D>  ZB < s *D>9~ZB < s *D>e //ZB < s *D> ^Q^ZB < s *D> [ [  < T38c?"6@ NNN?N+F Yp ZB < s *D> ZB < s *D> < T38c?"6@ NNN?NW < T38c?"6@ NNN?N  ZB < s *D>2 M  < T38c?"6@ NNN?N'g \  < T38c?"6@ NNN?NR }  < T38c?"6@ NNN?N9r` < T38c?"6@ NNN?N?d < T38c?"6@ NNN?NBz ZB < s *D> xx < T38c?"6@ NNN?N8bb < T38c?"6@ NNN?N4@ZB < s *D>q  < T38c?"6@ NNN?N < T38c?"6@ NNN?NPIwpZB < s *D>A   < T38c?"6@ NNN?N_   < Z 38c?"6@ NNN?N2 HThe IES Trial(20f < Z 38c?"6@ NNN?N!    OS Subgroup Analysis ER+/ERunk >!(2$  ff$Pg < Z 38c?"6@ NNN?N7 Coombs et al. Lancet 2007(2HH < 0޽h ? h___PPT10i.B+D=' = @B +  7L0  0.1b @(   ~  s *AdC0#  d   # lLDd?f3v @f?"6?@ `NNN?NZs i >    ZTGd11ȜȜ? M pMedian follow-up$   Z\Ld11ȜȜ?P{ u Z Hazard ratio  RB  s *DmQRB  s *Dm4 RB  s *DjJ RB  s *DjJ RB  s *DjJ QQ  ZQd11ȜȜ?P ] 51 months  ! ZLVd11ȜȜ? 2  \58 moths  " ZZd11ȜȜ?%   ] 30 months  # ZL^d11ȜȜ?,s uFavors no trastuzumab$  $ Z_d11ȜȜ?,,8 s rFavors trastuzumab$  % Zgd11ȜȜ? X M 51 & Zkd11ȜȜ?#M 52 ' Zod11ȜȜ?M 50 - Z`jd11ȜȜ?T ] 68 months XB 4 0DjJ2 x 5 B3jJ"`O IXB 6 0DjJ 1XB 7 0DjJ0 0 1XB 9 0DjJ  r : <3jJ"`  \ XB ; 0DjJ XB < 0DjJ  XB > 0DjJ x ? B3jJ"` S 3 XB @ 0DjJ & XB A 0DjJ & l H 63jJ"`(/ J <tydg* 8OSv K NԔٔ8cBc?uv L NfԔٔ8cBc?u Q NԔٔ8cBc?"` n |L  + {  R #  n  S  NԔٔ8cBc?"` {  T  NfԔٔ8cBc?"`~ + {  U <~d_F :ATAC W <dX ?  :ARNO X <Ȇd ~v  9IES Z <Ёdw^ ? BIG/FEMTA  R \ T 8c?"6@ NNN?N:R ] T 8c?"6@ NNN?N J XB _ 0DjJ r ` <3jJ"` XB a 0DjJ XB b 0DjJ !H  0޽h ? h___PPT10i.B+D=' = @B +K2 fL0 3D~(  D D N38c?"6@ NNN?N  ,$D 04 D # "&< D  h" gֳgֳ 1d)?C0S" %Q  "  T L 6~ D# N  D BFC/DEF&/F/F/@`6eN2 D S 1q   D S BCDE0F:v @1 hTTfKfKh @` AlB  D <v2 @1B Vu x lB  D <v2 @1B VC h lB  DB <v2 @1VB f    D s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B   c    D s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B    c ~ `B D 0v @12Vex `B D 0v @12V3h `B DB 0v @1 V2f & D Z "  38c?"6@ NNN?Nb  ^Switch(2 ( D Zؒ"  38c?"6@ NNN?N   `Up-front (2  - D Zi"  38c?"6@ NNN?N G]  e Better HR (2  $ D Zd"  38c?"6@ NNN?NU   \Toxicity (2  ! D Z{"  38c?"6@ NNN?NR6L YCosts(2 % D Z"  38c?"6@ NNN?N  ] Mortality (2   ? D Zx"  38c?"6@ NNN?N g  wEarly Recurrences(2(    D ZB  8c?"6@ NNN?N tG  XNo(2 8 D ZlB  8c?"6@ NNN?N[   pMay Be(2( W D Z 8c?"6@ NNN?N  ,$0 [Yes(2 W D Z 8c?"6@ NNN?NF,$0 [Yes(2 H D 0޽h ? 33̙33___PPT10.+D-' = @B D' = @BA?%,( < +O%,( < +D ' =%(%(D ' =%(D' =A@BBBB0B%()))D' =1:Bvisible*o3>+B#style.visibility<*D%(D'  =-g6B fade*<3<*D)?D'  =+4 8?HCBBCBB*k3>'Bstyle.rotation<*D)?D3'  =+4 8?nCB#ppt_x+0.4BCB#ppt_x-0.05B*Y3>B ppt_x<*D)?D1'  =+4 8?lCB#ppt_y-0.4BCB#ppt_y+0.1B*Y3>B ppt_y<*D)?DK' =+4 8?fCB#ppt_x-0.05BCB#ppt_xB*Y3>B ppt_x<*D%( )?DI' =+4 8?dCB#ppt_y+0.1BCB#ppt_yB*Y3>B ppt_y<*D%( )?Dg ' =%(D ' =%(D' =A@BBBB0B%()))D' =1:Bvisible*o3>+B#style.visibility<*D%(D'  =-g6B fade*<3<*D)?D'  =+4 8?HCBBCBB*k3>'Bstyle.rotation<*D)?D3'  =+4 8?nCB#ppt_x+0.4BCB#ppt_x-0.05B*Y3>B ppt_x<*D)?D1'  =+4 8?lCB#ppt_y-0.4BCB#ppt_y+0.1B*Y3>B ppt_y<*D)?DK' =+4 8?fCB#ppt_x-0.05BCB#ppt_xB*Y3>B ppt_x<*D%( )?DI' =+4 8?dCB#ppt_y+0.1BCB#ppt_yB*Y3>B ppt_y<*D%( )?D!' =%(D' =%(Dq' =4@BBBB%()))D' =1:Bvisible*o3>+B#style.visibility<*D%(D' =-}6B!strips(upRight)*<3<*D+p+0+D ++0+D +# kL0 -"%"4..p!(  p .p # lx9?f3v @f?"6?@ `NNN?N i >  x p c $lC0    p <+ 30   a0.5.0    p <  3   a1.0.0    p <h 3X  a1.5.0    p < 3 a2.0.0    p <T" 3}= a2.5.0    p </ 3  Q3.00   :B  p 3 |nAB :B  p@ 3 |9:B  p@ 3 |y9z:B  p 3 | >?   p <<8 3% i  [0*0   :B p 3 |   p <XB 3% :  [1*0   :B p 3 |   p <LL 3%  [2*0   :B p 3 |  p <@V 3% v  [3*0    p <_ 3% O  [4*0   :B p 3 | 78  p <j 3% a  [5*0   :B p 3 |   p <@t 3% 8  [6*0   XB p 0D| 9 :B p 3 |  :B p@ 3 | 9  p 6  3  * vFollow-up time (years)00   R p s *Aox J7 :B p 3 Ԕ $  p 6  iF  v Anastrozole , 0       p 6 [ i  t Tamoxifen , 0     :B !p 3 Ԕ $ :B "p@ 3 | D  #p < 3u i5  _0.0   :B $p@ 3 | 9 :B %p@ 3 |9:B &p@ 3 |7=8| 'p C .BCDE|F4Ԕ .hBAVax5f`F%,9DOQ_moF&+@          S" d  (p C >BTCDEHFxԔRR+{<XM5[$i wzh'J8>I2C6P/](v "<Saooy#)08@5Vwi'+=O]m}!5Igz (Fwzr$p1nJuTv9<@                           S" :Z L )p C B CDEFhԔFF (<Pex''Gg +Kni\OU\c:Qho1Po{hU> 9UqcA!6vKUW8l% 14@                       S" G@  *p C >BC"DEHFxԔRR">Tjx{bI--PTk3 (FwKbmL6  4Kbg{;{h_V[VQ$F7AJ<d6p5|4s:86+)'-)8%Yx J~-Z wB]9<@                           S" @N  +p C BChDEFTԔ77]:GTPSV'SGVgYhhh\+YRVYVSHG!FFPfMJ?81/#(V&2Lfx+V?ES4Y&l'(@                  S" # W  ,p < 33  sAnnual hazard rates (%),0    -p N< ? F  L"0 2b  H p 0޽h ? f̙33y___PPT10Y+D=' = @B +N   i'L0 M E P4` (  `~ ` s *\   : ` B( o?"6@ NNN?NxNU 1 Houghton J et al. Presented at: ESMO 2006, Istanbul, Turkey. Abst #243. 2 Mauriac et al. Ann Oncol. 2007; doi 10.1093/annonc/mdm001: Epub ahead of printX nF* I" * O" " t?          ` 0 b m  ATAC1 No. of events at 2.5 years6! ( @   ` 0& wm "BIG 1-982 No. of events at 2 years6# ( @ ) ` < I  OAIs effectively reduce early recurrences in the first 2-2.5 years after surgery"P!@P& M r `0 ZoA ??\?    `0 ZoA ??\?m    ^2  ` 6y  ` <D'hW Z-17%&   ` <,)Ez Z-30%&   ` <t7 d  a Recurrences "     ` <> `   a Recurrences "   ^2 ` 6CH ` 0޽h ? f3ff3___PPT10i.B$`4+D=' = @B +b  j'L0 aYp4h(  h~ h s * \    h0 NA ? ?\    h0 ZoA ??\?m     h 0b m  ATAC1 No. of events at 2.5 years6! ( @   h 0 J& wm "BIG 1-982 No. of events at 2 years6# ( @ ^2 h 6^2 h 6C  h <W} T-17%    h <E  T-30%  ^2  h 6E^2  h 6%   h <lr<  [-7%&  h < V \-30%&  h < d  a Recurrences "    h < `   a Recurrences "    h <$(   Distant Recurrences" 4   h <2 F  Distant Recurrences" 4  : h BD= o?"6@ NNN?NxNU 1 Houghton J et al. Presented at: ESMO 2006, Istanbul, Turkey. Abst #243. 2 Mauriac et al. Ann Oncol. 2007; doi 10.1093/annonc/mdm001: Epub ahead of printX nF* I" * O" " t?         H h 0޽h ? f3ff3___PPT10i.B$`4+D=' = @B +v% mL0 5y(  4  # "&<   \9gֳgֳ 1d)?C0S" %Q  9 T L 6~ # N   BFC/DEF&/F/F/@`6eN2  S 1q    S BCDE0F:v @1 hTTfKfKh @` AlB   <v2 @1B Vu x lB   <v2 @1B VC h lB  B <v2 @1VB f     s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B   c     s BCDE|Fvd @+b9m/N"c^xMQ~lWG,9]n=@D@`"B    c ~ `B  0v @12Vex `B  0v @12V3h `B B 0v @1 V2f &  ZD{ 38c?"6@ NNN?Nb  ^Switch(2 (  Z{ 38c?"6@ NNN?N   `Up-front (2  -  ZX 38c?"6@ NNN?N G]  e Better HR (2  $  Z{ 38c?"6@ NNN?NU   \Toxicity (2  !  Z 38c?"6@ NNN?NR6L YCosts(2 %  Z 38c?"6@ NNN?N  ] Mortality (2   ?  Z 38c?"6@ NNN?N g  wEarly Recurrences(2(     Z8 8c?"6@ NNN?N tG  XNo(2 8  Z  8c?"6@ NNN?N[   pMay Be(2( #  Z< 8c?"6@ NNN?N   [Yes(2 #  Z 8c?"6@ NNN?NF [Yes(2 K  N9 8c?"6@ NNN?N' n ,$0 [Yes(2 H  0޽h ? 33̙33  ___PPT10 .+D ' = @B DP ' = @BA?%,( < +O%,( < +D ' =%(%(D ' =%(D' =A@BBBB0B%()))D' =1:Bvisible*o3>+B#style.visibility<*%(D'  =-g6B fade*<3<*)?D'  =+4 8?HCBBCBB*k3>'Bstyle.rotation<*)?D3'  =+4 8?nCB#ppt_x+0.4BCB#ppt_x-0.05B*Y3>B ppt_x<*)?D1'  =+4 8?lCB#ppt_y-0.4BCB#ppt_y+0.1B*Y3>B ppt_y<*)?DK' =+4 8?fCB#ppt_x-0.05BCB#ppt_xB*Y3>B ppt_x<*%( )?DI' =+4 8?dCB#ppt_y+0.1BCB#ppt_yB*Y3>B ppt_y<*%( )?+8+0+ + nL0 05(  x  c $BC0 `}  B    `A ?f3ԔPSPS?Us  8 $D0Y  N(1Ȝ? l p,$0 %San Gallen Consensus Conference 2007 &&>    BA ?3 ?" k8 $0  Ht1?  v"De Laurentiis M, Appunti Personali#0 #" H  0޽h ? hum___PPT10M.Bȍ+ W~D' = @B Dt' = @BA?%,( < +O%,( < +D ' =%(%(D' =%(D' =4@BBBB%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?bCB#ppt_x-.2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*D' =-6Bwipe(right)*q3=-B%gradientSize: 0.1<*D ' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?bCB#ppt_x-.2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*D' =-6Bwipe(right)*q3=-B%gradientSize: 0.1<*D' =%(D' =%(Dj' =A@BBBB0B%()))D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-i6B wedge*<3<*+h+0+ ++(+0+w  L0 ~p*"# (     s * C"? `}     <0e0efjJ"`V@  _R A N D O M I Z E0    <Pn Z'h  M00    <hn wD h  M20    <Dn _h  M50  F  _     _ ZB   s *Do  ZB   s *Do _ ZB   s *Do _ ZB   s *Do _ ZB   s *Do _ ZB   s *Do _ ZB   s *Do _   <d _^  QYears0  1  # l?Ԕٔ8cBc?"6?@`NNN?N W Tamoxifen 0   ?   `?pp?"6?@`NNN?NMT q Letrozole* 0    1  # l ?Ԕٔ8cBc?"6?@`NNN?N W Tamoxifen 0   3   `?Ԕ8c?"6?@`NNN?N e Letrozole, 0 B  3   `,?Ԕ8c?"6?@`NNN?N "  e Letrozole, 0 B  1  # l|?Ԕٔ8cBc?"6?@`NNN?N "  W Tamoxifen 0     <D, MA0    <XD,R MB0    <LD, MC0    <! D,  MD0    < > c  Rn=15400    <c Rn=15480    <cT Rn=24630    <"!c Rn=24590  L YJ   # \G f   6oY)J    <L"@ D0   ! 0 "/ T8010 pts 0    " 6" "` *A Initiated 1998, completed May 2003 8028 randomized (18 withdrew consent) Primary analysis compares letrozole vs tamoxifen and excludes events and follow-up beyond switch for C & D    (H  0޽h ? ̙33y___PPT10Y+D=' = @B +   L0   *  (   (   `"?pp?"6?@`NNN?N G:  Z Exemestane 0 "  3  # l| "?Ԕٔ8cBc?"6?@`NNN?NVY  Y Tamoxifen 0 "    s *t$" C"? `}  " (   `|&"?pp?"6?@`NNN?N 0  Z Exemestane 0 "  xB  BDo?"> Xg xB  BDo?"^ OH   T*"wawa1? u N = 9000+< 0 """    </"1?l <Postmenopausal hormone receptor-positive early breast cancer =0 =" =    3"xaxa 3?f1f11?)0<P"6?@`NNN?NIX eRANDOM I ZAT I ON$0( 2"     L8"xaxa 3? 1f11?)0<P"6?@`NNN?N>kv p5 Years of Hormone Treatment$0( P"  H  0޽h ? f̙3fy___PPT10Y+D=' = @B +   L0 * *(   .  C xc? ԔD[D[?"6?@`NNN?N0 H 0    ZD c Ԕ8c? z:  c   H," f?"g+ CGIM3-FATA Design (Firts Adjuvant Trial of All aromatase inhibitors)6D0 ,3 n     n ^   # #"^     fc_ж_жf?#" `v  6TAM 2 yrs ! Exemestane 3yrsD '8   @`    f$c_ж_жf?#" `G v  2TAM 2yrs ! Letrozole 3yrsD '&   @`    f/c_ж_жf?#" `vG  8TAM 2 yrs ! Anastrozole 3yrsD '8   @`<    f9c_ж_жf?"^v Exemestane 5 yrs(   @`;    f;c_ж_жf?"G ^v Letrozole 5 yrs(   @`=    f(Ec_ж_жf?"^G v Anastrazole 5 yrs(   @`B    `_ж_ж1 ?"vvB    `_ж_ж1 ?"G ^G B    `_ж_ж1 ?"^ B    f_ж_жo ?"^ B    f_ж_жo ?"^^B    f_ж_жo ?"^ B    f_ж_жo ?"    HPc f?" ? &L Post-Menopausal, ER+ or Prg+ Chemo allowed N=10,000 Started, March 2006 $M1M   xB  BDo?"XRxB  BDo?"xIb B  TXcf?"Q[  ]R$0  T  < 2޽h ? ̙33y___PPT10Y+D=' = @B +   L0  * (   .  C x$c? ԔD[D[?"6?@`NNN?NX H 0    Zic Ԕ8c? z:  c   Hdc f?"g~G lGIM3-FATA Design$0 ,  n j+  # #"ohj+    foc_ж_жf?#" `@8 + ,TAM 2 yrs ! ExemestaneD ' 0   @`    f$c_ж_жf?#" `U8 @ 4TAM 2yrs ! Letrozole 3 yrsD '0   @`    fc_ж_жf?#" `j8 U :TAM 2 yrs ! Anastrozole 3 yrsD 'B   @`<     fԗc_ж_жff?"@+8  Exemestane 5 yrs(   @`;     fc_ж_жff?"U@8  Letrozole 5 yrs(   @`=     fc_ж_жff?"jU8  Anastrazole 5 yrs(   @`B     `_ж_ж1 ?"j8 +8 B     `_ж_ж1 ?"UUB    `_ж_ж1 ?"@@B    f_ж_жo ?"jjB    f_ж_жo ?"j+B    f_ж_жo ?"++B    f_ж_жo ?"j+  N Ԕٔ8cBc?"`P ] vF f      N0   N Ԕٔ8cBc?"`f     N Ԕٔ8cBc?"`;    N Ԕٔ8cBc?"`U  | vF f       g 5   N Ԕٔ8cBc?"`f     N Ԕٔ8cBc?"`;    N Ԕٔ8cBc?"`b o vF f      ZB   N Ԕٔ8cBc?"`f     N Ԕٔ8cBc?"`;    Hc ?"(CG ZEvaluation of Up-Front AI vs SequencingTAM!AIH.0 i*f&ff@     T  < 2޽h ? ̙33y___PPT10Y+D=' = @B +y  " L0 p+(  (  ( . ( C xc? ԔD[D[?"6?@`NNN?NX H 0   ( Zc Ԕ8c?   c  ( Hlc f?"g~G lGIM3-FATA Design$0 ,  n j+ ( # #"ohj+ (   ftc_ж_жf?#" `@8 + ,TAM 2 yrs ! ExemestaneD ' 0   @` (   fc_ж_жf?#" `U8 @ 4TAM 2yrs ! Letrozole 3 yrsD '0   @` (   fc_ж_жff?#" `j8 U :TAM 2 yrs ! Anastrazole 3 yrsD 'B   @`<  (   fc_ж_жf?"@+8  Exemestane 5 yrs(   @`;  (   fDd_ж_жf?"U@8  Letrozole 5 yrs(   @`=  (   f< d_ж_жff?"jU8  Anastrazole 5 yrs(   @`B  (   `_ж_ж1 ?"j8 +8 B  (   `_ж_ж1 ?"UUB (   `_ж_ж1 ?"@@B (   f_ж_жo ?"jjB (   f_ж_жo ?"j+B (   f_ж_жo ?"++B (   f_ж_жo ?"j+ ( Hd ?" ^G (Face-to-face Evaluation of all three AIs&)0 i)f&%   T ( < 2޽h ? ̙33y___PPT10Y+D=' = @B + UL0 ~v1 (     c $8C0  <$0     \A !|?caosCALMO   BįL "` t ,$D0  con il libro  CAOS CALMO Sandro Veronesi ha vinto il Premio Strega 2006MML H  0޽h ? h"  ___PPT10 .+-KD& ' = @B D' = @BA?%,( < +O%,( < +D' =%(D' =%(D8' =A@BB BB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-g6B fade*<3<* D(' =%(D' =%(D6' =A@BB BB0B%(D' =-g6B fade*<3<* D' =1:Bhidden*o3>+B#style.visibility<* %(D:' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =-i6B wedge*<3<* ++0+  ++0+  ++0+  +(0 '8 8(  8 d 8 c $d0   d 8 s *`ddw , T  d " H 8 0(e ̕ ? ̙3380___PPT10.( 0 ( 8(   d  c $d1   d  s *@ddx V  d " H  0(e ̕ ? 3380___PPT10.Do0 * (   d  c $d/   )  s *\)dy , S  ) " ?  N|)e۲e۲9* CUpdate of Thrlimann et al. J Clin Oncol. 2005;23:6S. Abstract 511.4D0`2    D AAAaaH  0(e ̕ ? 3380___PPT10.200 * (   d  c $d} P   )  s *)dv - U  ) jSPEAKER S NOTES: The Tamoxifen Exemestane Adjuvant Multicenter (TEAM) Trial is a phase 3 adjuvant hormonal study that has accrued >9000 patients, making TEAM the largest 2-arm adjuvant endocrine therapy trial to date. The trial is designed as a collaboration with principal investigators in the United States, the United Kingdom/Ireland, the Netherlands, France, Germany, Belgium, Greece, and Japan. 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