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E42. Global perspectives on lung cancer. Asian perspectives
269
E42. Global perspectives on lung cancer. Asian perspectives Jln Soo Lee National Cancer Center. Korea
Lung cancer i8 the most common cancer and the leading cause of cancer deaths accounting for 12 3°.. of estimated 1~ 1 million new cases of cancer and 17 8°.. of 6 2 million cancer deaths m the year of 2~..~ worldwide [1] In such western countries as the USA and European countries. where the smoking habit was first established and its hazard was recognized earlier, the lung cancer mortalltv rates started to show a downward trend following reductions m the prevalence of smoking after successful antl-smokmg campaigns However. the lung cancer epidemics m Asia take a different direction and its rising trend is expected to continue mto the first half of the 21st centurv m manv Asian countries (-~,'er the last 2 decades, there was more than a 4 5-fold increase m lung cancer mortalltv m Korea [2] while Japan had onlv 1 27-fold mcrease over the same period but 11 6-fold mcrease over the last 5~ years [3] In Chma. where one-fifth of the world population hve. it is estimated that there will be a 26 9°.. increase m the number of new lung cancer cases m men (from 261.839 to 332.286) and 38 4°.. m women (from 119.648 to 165.622) between 2~..~ and 2~.~5 [4] The major portion of this increase m new lung cancer cases is due to the changes in cancer risk m China and a small portion due to the changes in population size and age structure [4] Obviously. high prevalence of cigarette smoking among men. a phenomenon that started in Asia after the end of the 2nd World War. is responsible for the high lung cancer mortalltv rate among men in most Asian countries Howe~r. one of the most unique characteristics of lung c a n c e r epidemics m Asia is that the lung cancer incidence and the mortalltv rate are disproportionately higher m women than what is expected from the smoking prevalence of women In Korea. for example, women's ever-smokmg rate is 6-70.. at most [5] Despite this verv low smoking rate. women account for more than onefourth of all lung cancer cases m Korea Consequently. the majority (..8~O..) of female lung cancer patients had never smoked cigarettes [6]. which is contrarv to the findings m manv Western countries, where self-smoking remams the most Important risk factor for lung cancer, e ~ n in women Obviously. environmental tobacco smoke (ETS) exposure in chlh~lood [7] and also ETS exposure of never-smoker women to spousal smoking are the major potential risk factors for this group of women [8] Recently. a subgroup of non-smoker female lung cancer
patients, for whom adenocarclnoma is the predominant hlstologw, was found to show excellent tumor responses to the molecular-targeted therapy using EGFR tvroslne klnase lnhlbltors such as gefitmlb and erlotmlb Smce the EGFR gene mutations, which were predictive of responses to the EGFR tvroslne kmase lnhlbltors, were more frequently found in female, never-smokers, adenocarcmoma hlstologw. and Oriental ethnlclty, v4e conducted a phase II gefitlnlb therapy for a subset of chemo-na~ve patients with adenocarcmoma of the lung who had never smoked cigarettes [9] We observed 25 169°..) of 36 Korean patients achieved objective responses After a median follow-up of 48 weeks (range 4-7~ weeks), median progression-free survival was 33 weeks and the median survival time has not been reached yet. but the estimated 1-vear survival rate was 73°.. (-~,-erall. approximately 1~O.. of Caucasian and 2~O.. of Oriental lung-cancer patients h a ~ EGFR mutation [1~] In a selected subgroup of Oriental female never-smokers with adenocarcmoma hlstologw, the EGFR mutation rate was as h i g h as 61°.. [11] Fmdlngs of dlstmct EGFR mutations and other mutuallv exclusive KR.-!S and HER2 neu mutations m adenocarcmoma samples from never-smokers [11] suggest that different pathways exist m lung cancer carcinogenesis Since the ETS exposure is a preventable risk factor for lung cancer, smoking is no longer a matter of personal choice Well-orchestrated public efforts for smoMng cessation, ban on smoking in public places, and eventual prohibition of tobacco production and sales are urgently needed to prevent such unwanted disasters as lung cancer and other tobaccorelated cancers in innocent victims
References [1]
P ~ k m E ' M Int_~nlh..nllv~llh..n ,:n...~ene fii,i4.fi3 ~3fi~-4,, [fi] K..rem Nlh..nll 6tlhsh. Ii ,:¢n. e I h e ,:%use ..t E,elth 6tlh~1. ~ In
K,,re~ 6t]tl~l, ~1Ye]rt,,,,,k. E,~_le,,n, K,,re< K,,remN~h,,n~l6t]~l~l, 11 ,:,in.e. l,, G dtltl~-i-l, j ,,i-Jlplrl. dtltl~'il,J lrl,l Int,,rmch,,n E,ept. I'~inl~'i_~J ~_, i'~_t]i'l]~. Mlnl~ry ,,t Helltl~ Lib, ,tlrIrl,l Weltlre [4] -Frog L. Plrkln L,Ni. F ~ h v Z et ~l E~lmcte." ..t . m. ~ in. l.len,e in ,-hlnl t..rZl,,l ~a-!.lpr..le,tl..n."t..r21,15 ,-~a'-!. er Epl.lenn..l Bl..nilrk~." Pr~¢ 211115.14,1,143-5" [5] K,,rem Nltl,,nll 6tlil~l, ~ ,-,]~I,~_ 6ni,,l¢ln~ In Rep,,rt ,,n the 6,,,i],i
[3] \qt~l
[~] Lee l & -fun -FH. H m
l-£ et ~i The etle.t ..t p~ent~l m~..km~ m
, hll,~h,,,,,t ,,n lung, an, ~ rid< t, me-, ,,ntr,,1 ~u, tv Pr,,, Am 6,,, ,-hn ,En,,,l 2,,,,3Z2 ~,,5 ,At,~" 3~4,,,
6 7~
E~ te~.lol .4b "~z~ t"
[7] W m ~ L. Lut,Ln J H . Z h m ~ 6 t L et ~1 L u n ~ , an, ~ m , t errar,,rm~ent~l t,,t,m ,,, ~ i , , k e kn % n,,n-m, t u ~ r l ~ l ar~_~ ,,t ,-hmm Int J ,- m, _~ Z~,,~. 88 1 3 ~ - 4 5 [o] 1_1~ glT411"..rmient~l Pr..te. tl..n A g e n . v IRe ~ l r ~ . . r e h e a l t h erie. t . .t p~lVen]l..lclr~r lung. m._~ m.t..th_~.h~..M_~,Ek4_ml,,~-~lm,l~F, Wz:hLn~t,,n D,- l_l~ EP.4_. ,-,l-'iS_, ~_,,l- R~_3~_tI, h "a-!,i i,_~¢el,,pment ,-,tl~, e , , t H e : l t h m . t Err¢ir..rmient : l .4_~'~'e~'alient. 1 ~ 2 [~] L e e E,H. H m J-K L e e H,3. et ~1 ,3efitinil:. ¢: % ftr~-line t h o r n y ..t : d v m . e.t ..r m e t ~ ' t ~ i . :den... ¢r. m..m% .4 t h e l u n ~ i n n e v ~ - m i . . k ~ " , : l m ,: an. ~ Re~" 2,,,,5.ii,8,, i n press,
[D~] H m 6 ~ . Km~ T]~ H w m g P ' 2 et ~1 Pre, h, t i r e m , t pr,,gn,,~i, m~p~ t ,4 epi, t_~m%l ~,,'~erh tm t,,r re, ept,,r mut,&,,n i n n,,n-cm~ll-, e l l l u n ~ . m. _~ p%tlent~ t r e ~ e . t w l t h gefitmlb J . - l m .in...1 ZI,IS Fet. 14. [Eput. ~he~ut..t print] [11] 6 h l ~ e n l ~ H. T~lc~hz~l~l L N..niur% NL et ~1 6..nl~1. n m t ~ l . . n ~ ,,t t h e H E R / kLnZ:e r , , m ~ l n i n l u n ~ ~ten,,, at, l n , , m z : ,- an, ~ R e s 21,15.~5, 5, 1 ~ 4 2 - ~
E42. Global perspectives on lung cancer. Asian perspectives Jln Soo Lee National Cancer Center. Korea
Lung cancer i8 the most common cancer and the leading cause of cancer deaths accounting for 12 3°.. of estimated 1~ 1 million new cases of cancer and 17 8°.. of 6 2 million cancer deaths m the year of 2~..~ worldwide [1] In such western countries as the USA and European countries. where the smoking habit was first established and its hazard was recognized earlier, the lung cancer mortalltv rates started to show a downward trend following reductions m the prevalence of smoking after successful antl-smokmg campaigns However. the lung cancer epidemics m Asia take a different direction and its rising trend is expected to continue mto the first half of the 21st centurv m manv Asian countries (-~,'er the last 2 decades, there was more than a 4 5-fold increase m lung cancer mortalltv m Korea [2] while Japan had onlv 1 27-fold mcrease over the same period but 11 6-fold mcrease over the last 5~ years [3] In Chma. where one-fifth of the world population hve. it is estimated that there will be a 26 9°.. increase m the number of new lung cancer cases m men (from 261.839 to 332.286) and 38 4°.. m women (from 119.648 to 165.622) between 2~..~ and 2~.~5 [4] The major portion of this increase m new lung cancer cases is due to the changes in cancer risk m China and a small portion due to the changes in population size and age structure [4] Obviously. high prevalence of cigarette smoking among men. a phenomenon that started in Asia after the end of the 2nd World War. is responsible for the high lung cancer mortalltv rate among men in most Asian countries Howe~r. one of the most unique characteristics of lung c a n c e r epidemics m Asia is that the lung cancer incidence and the mortalltv rate are disproportionately higher m women than what is expected from the smoking prevalence of women In Korea. for example, women's ever-smokmg rate is 6-70.. at most [5] Despite this verv low smoking rate. women account for more than onefourth of all lung cancer cases m Korea Consequently. the majority (..8~O..) of female lung cancer patients had never smoked cigarettes [6]. which is contrarv to the findings m manv Western countries, where self-smoking remams the most Important risk factor for lung cancer, e ~ n in women Obviously. environmental tobacco smoke (ETS) exposure in chlh~lood [7] and also ETS exposure of never-smoker women to spousal smoking are the major potential risk factors for this group of women [8] Recently. a subgroup of non-smoker female lung cancer
patients, for whom adenocarclnoma is the predominant hlstologw, was found to show excellent tumor responses to the molecular-targeted therapy using EGFR tvroslne klnase lnhlbltors such as gefitmlb and erlotmlb Smce the EGFR gene mutations, which were predictive of responses to the EGFR tvroslne kmase lnhlbltors, were more frequently found in female, never-smokers, adenocarcmoma hlstologw. and Oriental ethnlclty, v4e conducted a phase II gefitlnlb therapy for a subset of chemo-na~ve patients with adenocarcmoma of the lung who had never smoked cigarettes [9] We observed 25 169°..) of 36 Korean patients achieved objective responses After a median follow-up of 48 weeks (range 4-7~ weeks), median progression-free survival was 33 weeks and the median survival time has not been reached yet. but the estimated 1-vear survival rate was 73°.. (-~,-erall. approximately 1~O.. of Caucasian and 2~O.. of Oriental lung-cancer patients h a ~ EGFR mutation [1~] In a selected subgroup of Oriental female never-smokers with adenocarcmoma hlstologw, the EGFR mutation rate was as h i g h as 61°.. [11] Fmdlngs of dlstmct EGFR mutations and other mutuallv exclusive KR.-!S and HER2 neu mutations m adenocarcmoma samples from never-smokers [11] suggest that different pathways exist m lung cancer carcinogenesis Since the ETS exposure is a preventable risk factor for lung cancer, smoking is no longer a matter of personal choice Well-orchestrated public efforts for smoMng cessation, ban on smoking in public places, and eventual prohibition of tobacco production and sales are urgently needed to prevent such unwanted disasters as lung cancer and other tobaccorelated cancers in innocent victims
References [1]
P ~ k m E ' M Int_~nlh..nllv~llh..n ,:n...~ene fii,i4.fi3 ~3fi~-4,, [fi] K..rem Nlh..nll 6tlhsh. Ii ,:¢n. e I h e ,:%use ..t E,elth 6tlh~1. ~ In
K,,re~ 6t]tl~l, ~1Ye]rt,,,,,k. E,~_le,,n, K,,re< K,,remN~h,,n~l6t]~l~l, 11 ,:,in.e. l,, G dtltl~-i-l, j ,,i-Jlplrl. dtltl~'il,J lrl,l Int,,rmch,,n E,ept. I'~inl~'i_~J ~_, i'~_t]i'l]~. Mlnl~ry ,,t Helltl~ Lib, ,tlrIrl,l Weltlre [4] -Frog L. Plrkln L,Ni. F ~ h v Z et ~l E~lmcte." ..t . m. ~ in. l.len,e in ,-hlnl t..rZl,,l ~a-!.lpr..le,tl..n."t..r21,15 ,-~a'-!. er Epl.lenn..l Bl..nilrk~." Pr~¢ 211115.14,1,143-5" [5] K,,rem Nltl,,nll 6tlil~l, ~ ,-,]~I,~_ 6ni,,l¢ln~ In Rep,,rt ,,n the 6,,,i],i
[3] \qt~l
[~] Lee l & -fun -FH. H m
l-£ et ~i The etle.t ..t p~ent~l m~..km~ m
, hll,~h,,,,,t ,,n lung, an, ~ rid< t, me-, ,,ntr,,1 ~u, tv Pr,,, Am 6,,, ,-hn ,En,,,l 2,,,,3Z2 ~,,5 ,At,~" 3~4,,,
6 7~
E~ te~.lol .4b "~z~ t"
[7] W m ~ L. Lut,Ln J H . Z h m ~ 6 t L et ~1 L u n ~ , an, ~ m , t errar,,rm~ent~l t,,t,m ,,, ~ i , , k e kn % n,,n-m, t u ~ r l ~ l ar~_~ ,,t ,-hmm Int J ,- m, _~ Z~,,~. 88 1 3 ~ - 4 5 [o] 1_1~ glT411"..rmient~l Pr..te. tl..n A g e n . v IRe ~ l r ~ . . r e h e a l t h erie. t . .t p~lVen]l..lclr~r lung. m._~ m.t..th_~.h~..M_~,Ek4_ml,,~-~lm,l~F, Wz:hLn~t,,n D,- l_l~ EP.4_. ,-,l-'iS_, ~_,,l- R~_3~_tI, h "a-!,i i,_~¢el,,pment ,-,tl~, e , , t H e : l t h m . t Err¢ir..rmient : l .4_~'~'e~'alient. 1 ~ 2 [~] L e e E,H. H m J-K L e e H,3. et ~1 ,3efitinil:. ¢: % ftr~-line t h o r n y ..t : d v m . e.t ..r m e t ~ ' t ~ i . :den... ¢r. m..m% .4 t h e l u n ~ i n n e v ~ - m i . . k ~ " , : l m ,: an. ~ Re~" 2,,,,5.ii,8,, i n press,
[D~] H m 6 ~ . Km~ T]~ H w m g P ' 2 et ~1 Pre, h, t i r e m , t pr,,gn,,~i, m~p~ t ,4 epi, t_~m%l ~,,'~erh tm t,,r re, ept,,r mut,&,,n i n n,,n-cm~ll-, e l l l u n ~ . m. _~ p%tlent~ t r e ~ e . t w l t h gefitmlb J . - l m .in...1 ZI,IS Fet. 14. [Eput. ~he~ut..t print] [11] 6 h l ~ e n l ~ H. T~lc~hz~l~l L N..niur% NL et ~1 6..nl~1. n m t ~ l . . n ~ ,,t t h e H E R / kLnZ:e r , , m ~ l n i n l u n ~ ~ten,,, at, l n , , m z : ,- an, ~ R e s 21,15.~5, 5, 1 ~ 4 2 - ~