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BREA S T CANC E R

Harms

nan nan

Th e h a r m s and d i sadvan t ages o f mamm og ra phy scree n i ng i n cl ud e ov e rd ia gnos i s, FP t es t s, F N t e sts , a nd t h e po ssi b ilit y o f ra d iati on -i ndu ce d br east c ance r . Th e f a c t t ha t m a mm og r aphy scree n i ng h as i n crease d t h e i n ci d e n ce o f l o calize d d i sease w it hou t a s i gn ifica n t c h a ng e i n metastatic d isease at t he time of d i agnos i s sugges t s t ha t t h ere is s o me d e g ree o f ov er d ia gno sis . T he r is k of ove r d i agnos i s i s g r ea test at t h e first scree n i n g a nd v aries wit h p atie n t age, t u m o r t ype, and gr a d e o f d isease . FP s c r een i ng t es t s l ead t o sub sta n tial i n c onv e n ie n ce a nd a nx iet y i n a dd iti on t o unnecessa r y i nvasiv e b i op sies wit h t h eir atte nd a n t c o m p lic a ti ons. I n t he Un it ed S tates , a bou t 10 % o f all w o me n scree n e d f o r br east c ance r a r e ca ll ed back fo r a dd iti on al testi ng, a nd less t h a n h alf o f t h em w ill be d i agnosed w it h b reast ca n ce r T h e ris k o f a FP mamm og r am is gr eater f o r wo m en unde r t he a g e o f 50 . F N t es t s de l ay d i agnos i s and p r ov i d e false reass u ra n ce . T h e y are m o r e c o mm on i n younge r wo m en a nd i n w o me n wit h d e n se b reasts . Certai n h ist o l og i c sub t ypes a r e a l so m o re d i f fic u lt t o see on mamm og ram . M u ci nous and l obu l a r t u m o r s a nd ra p i d l y g r o wi ng t u m o rs te nd t o b le nd in w it h nor m a l b r eas t a r ch it ec t u re . A t yp i ca l sc r een i ng m a mm og ram p r ov i d es a pp r ox imatel y 4 mS v o f r a d iati on. It has been es tim a t ed t h at a nnu al mamm og ra ph ies will ca u se up t o 1 cas e o f b r eas t cance r pe r 1,000 w o me n scree n e d fr o m a g e 40 t o a g e 80 y ea r s . R ad i a ti on exposu r e a t young er a g es ca u ses a g reater ris k o f b reast ca n ce r . T he r e i s a l so conce r n t h at i on izi ng ra d iati on fr o m mamm og ra phies mi gh t d is p r opo rti ona t e l y i nc rease t h e b reast ca n cer ris k f o r w o me n wit h ce r tai n BR C A 1 o r BR C A 2 m u tati on s , b eca u se t h ese g e n es are relate d t o DNA r e pa i r .

BREA S T CANC E R

Recommendations

nan nan

Recommendations

BREA S T CANC E R

Recommendations

W omen at A verage Risk

nan nan

W omen at A verage Risk

BREA S T CANC E R

Recommendations

W omen at A verage Risk

nan nan

Th e A C S and m os t o t he r m edi cal g r oup s rec o mme nd t h at a v era g e ris k wo me n unde r go a CB E eve r y 3 y ears starti ng at a g e 20 a nd t h at w o me n 40 y ea r s of age and ove r shou l d und e r go CBEs a nd scree n i ng mamm og ram s a nnu all y . W o m en shou l d be inf o rme d o f t h e b e n efits , limitati on s , a nd h ar ms ass o ciate d w it h b r eas t cance r s cree n i ng. A mamm og ra phy will no t d etec t all br east c ance r s, and so m e b r ea st ca n cers d etecte d wit h mamm og ra ph ies may still h a ve a poo r p r ognos i s. The h arms ass o ciate d wit h b reast ca n cer sc r ee n i ng a l so i nc l ude t he po te n tial f o r FP res u lts , ca u si ng s ub sta n tial a nx iet y . When abno rm a l fi nd i ng s ca nno t b e res o l v e d wit h a dd iti on al ima g i ng, a b i opsy i s r equ ir ed to r u le ou t t h e po ssi b ilit y o f b reast ca n ce r . A maj or it y o f b i ops i es a r e ben i gn. Fi n all y , s o me b reast ca n cers d etecte d by a mamm og r aphy m ay be b i o l og icall y i ndo le n t , mea n i ng t h e y w ou l d no t have ca u se d a p r ob l e m o r have been d etecte d i n a w o ma n ’ s lifetime h a d s h e not und e r gone a m a mm og r aph y . Th e U SPST F , t he A m e ri can C o lle g e o f P hy sicia n s , a nd t h e Ca n a d ia n T as k F o r ce on t he P e ri od i c H ealt h E x ami n ati on rec o mme nd r ou ti n e sc r ee n i ng beg i nn i ng a t age 50 y ears . F o r w o me n a g e d 40 t o 49 y ear s o f a g e , t h es e g r oups adv i se phys icia n s t o e n ter i n t o a d isc u ssi on wit h t h e p atie n t . T he phys i c i an and pa tie n t s hou l d ta k e i n t o acc oun t i nd i v i du al ri sks a nd c on c e r ns be f o r e dec i d i ng t o scree n . An Adv i so r y Co mmitt ee o n Ca n cer Pre v e n ti on i n t h e E u r op ea n U n i on r ec o mm ends t ha t wo m en be twee n t h e a g es o f 50 a nd 69 y ears b e o ffered mamm og r a m sc r een i ng i n an o r g a n ize d scree n i ng p r og ram wit h qu alit y ass ur a nce T h i s co mmitt ee s a y s w o me n a g e d 40 t o 49 y ears s hou l d b e a dv ise d o f t he po t en ti a l ha rm s o f scree n i ng a nd, if mamm og ra ph ic sc r ee n i ng i s o f f e r ed, it shou l d b e p erf o rme d wit h strict qu alit y sta nd ar d s and doub le read i ng.

BREA S T CANC E R

Recommendations

W omen at High Risk

nan nan

W omen at High Risk

COLON CANCER SCR EE NING

nan nan

C o l or ec ta l cance r sc r een i ng wit h t h e ri g i d si g m o i do sc op e d ates b ac k t o t he late 1960s. T he des ir e t o exam i n e t h e e n tire c o l on le d t o t h e u se o f a b ar ium e n ema a nd t he deve l op m en t o f fecal o cc u lt b l ood tests . W it h t h e d e v el opmen t o f fi be r op ti cs, fle x i b le si g m o i do sc op ies a nd, late r , c o l ono sc op i es we r e e m p l oyed. T od a y , fecal o cc u lt b l ood testi ng (FOBT ), st oo l DNA t es ti ng, fl ex i b l e s i g m o i do sc op ies , c o l ono sc op ies , a nd CT c o l onog r aph i es and, occas i ona ll y , b ari u m e n emas are all u se d i n c o l o rec tal ca n ce r s c r een i ng. MR I co l on osc opy is i n d e v el op me n t . Sc r e en i ng exa mi na ti ons o f t h e c o l on a nd rect u m ca n fi nd ca n cer earl y , bu t als o f i nd p r ecance r ous polyp s . Ra ndo mize d trials h a v e d em on strate d t h at e ndoscop i c po l ypec t o mi es re du ce t h e i n ci d e n ce o f c o l o rectal ca n cer by a bou t 20 % . FOBT was t he fir s t co l o r e ctal scree n i ng test st ud ie d i n a p r o s p ecti v e r a ndo mi zed c li n i ca l tri a l . T he Mi nn es o ta C o l on Ca n cer C on tr o l St udy r a ndo mi zed 46,551 adu lt s t o on e o f t h ree arms: a nnu al FOB T s , b ie nn ial sc r ee n i ng, o r usua l ca r e. A r ehyd rate d gu aiac test was u se d. W it h 13 y ear s of fo ll ow - up, t he annua l sc r een e d arm h a d a 33 % relati v e re du cti on i n c o l or ectal cance r m o rt a lit y co m p are d t o t h e u s u al care g r oup . At 18 y ear s of fo ll ow - up, t he b i enn i a ll y s cree n e d g r oup h a d a 21 % re du cti on i n c o l or ectal cance r m o rt a lit y . T h is st udy w ou l d s ub se qu e n tl y s ho w t h at st ool

COLON CANCER SCR EE NING

nan nan

b l ood te s ti ng was assoc i a t ed wit h a 20 % re du cti on i n c o l on ca n cer i n ci d e n ce T hese r esu lt s we re c on firme d by tw o o t h er ra ndo mize d t r ials . A r educ ti on i n co l on ca n cer – s p ecific m o rtalit y p ersiste d i n t h e Mi nn es o t a tri a l t h r ough 30 yea rs o f f o ll o w- up. O v erall m o rtalit y was not a f f ecte d . Re hyd r a ti on i nc r eases t he s e n siti v it y o f FOBT at t h e e xp e n se o f l ow e r i n g spec ifi c it y . I ndeed, re hyd rate d s p ecime n s h a v e a v er y h i gh F P r ate . Ove r a ll , 1 % t o 5 % o f FOB T s are po siti v e , bu t on l y 2 % t o 10 % o f th ose w it h a pos iti ve F OB T have c a n ce r . F ec a l i mmunochem i ca l t es ts (FIT) are st oo l tests t h at do no t react t o h em og l ob i n i n d i e t a r y p r oduc ts . T h e y a pp ear t o h a v e h i gh er se n siti v it y a nd s p eci f icit y f o r co l o r ec t a l cance r w h e n c o m p are d t o non re hyd rate d FOBT tests F ec a l DN A t es ti ng i s an e me r g i ng m od alit y . T h ese tests l ook f o r DN A se qu e n c es spec ifi c t o co l o r ec t a l po l yp s a nd c o l o rectal ca n ce r . T h e y ma y h a v e i n c reased sens iti v it y and s p ecificit y c o m p are d t o FOB T . Alt hough f ecal D N A t es t s appea r t o fi nd ca n ce r , t h e body o f e v i d e n ce on t h eir a b il ity t o r e du c e co l o r ec t a l cance r m o rtalit y is limite d du e t o a lac k o f st ud y . T his test h as been i n t e rmitt en tl y av aila b le . F lexi b l e s i gmo i doscop i es are , o f c ou rse , limite d t o a n e x ami n ati on o f the r ect u m and s i g m o i d co l on. A pr o s p ecti v e ra ndo mize d trial o f on ce- on l y f le x i b le s i g m o i doscop i es de mo n strate d a 23 % re du cti on i n c o l o rectal ca nce r i n ci d e n ce and a 31 % r educ ti on i n c o l o rectal ca n cer m o rtalit y after a me dian 1 1.2 y ea rs o f f o ll ow - up. I n t h e NCI ’ s Pr o state , L ung, C o l o rectal , a nd Ov a r ia n Cance r S c r een i ng T rial (PLCO) , t h ere was a 21 % re du cti on i n c o l or ectal cance r i nc i dence and a 26 % re du cti on i n c o l o rectal ca n cer m or talit y w it h t wo s i g m o i dos c op ies don e 3 t o 5 y ears a p art c o m p are d w ith t h e u s u al ca r e g r oup a ft e r a me d ia n f o ll o w- up o f 1 1.9 y ears . I n bo t h st ud ies , t he r e was no e f f ec t on p r ox imal lesi on s (i . e ., ri gh t a nd tra n s v erse c o l on) due t o t he limit ed r each o f t h e sc op e . It is estimate d t h at fle x i b le si g m o i doscop i es can fi nd 60% t o 80 % o f ca n cers a nd po l yp s f ound by c o l ono sc op i es .

COLON CANCER SCR EE NING

nan nan

In t wo m e t a - ana l yses o f five ra ndo mize d c on tr o lle d trials o f si g m o i doscop i es, t he r e was an 18 % relati v e re du cti on i n c o l o rectal ca n c e r i n ci d e n ce and a 28 % r e l a ti ve r e du cti on i n c o l o rectal ca n cer m o rtalit y .

COLON CANCER SCR EE NING

nan nan

COLON CANCER SCR EE NING

nan nan

Pa r tici p a n t s r anged i n age fr o m 50 t o 74 y ears . F o ll o w- up ra ng e d fr o m 6 to 13 y ea r s. Th e co l onoscopy has becom e t h e p referre d scree n i ng met hod o f ma n y , alt hough t he r e have been no p r o s p ecti v e , ra ndo mize d trials o f c o l ono sc opy sc r ee n i ng. A pos iti ve F OB T , FI T , fecal DNA test , o r si g m o i do sc opy w a rr a n t s a f o ll ow - up d i agnost ic c o l ono sc op y . Per h a p s t h e b est s uppo rt for c o l ono sc opy sc r een i ng i s i nd irect e v i d e n ce fr o m t h e Mi nn es o ta C o l on Ca n ce r Con tr o l St ud y , wh i ch re qu ire d t h at all p artici p a n ts wit h a po siti ve st oo l b l ood t es t have d i agnos tic ima g i ng o f t h e e n tire c o l on. I n t h e Mi nn es o t a s t ud y , m o r e t han 40 % o f t ho se scree n e d a nnu all y e v e n t u all y r ecei v e d a co l onoscop y . One ca n als o ma k e t h e a r gu me n t t h at t h e si g m o i doscopy s t ud i es i nd ir e ctl y s uppo rt t h e efficac y o f c o l ono sc opy sc r ee n i ng, a lt hough it can be a r gu e d t h at em b r yo l og ic a nd e p i d emi o l og i c e v i d e n ce i nd i ca t e t ha t t he ri gh t a nd left c o l on are b i o l og icall y d isti n ct a nd, t h e r e fore, t he m o rt a lit y bene f i ts fr o m si g m o i do sc op ies do no t c on stit u te proof t ha t a co l onoscopy wou l d similarl y re du ce m o rtalit y fr o m p r ox im al c o l on le s i ons. In st ud i es i nvo l v i ng r epea t c o l ono sc op ies by a sec ond phy sicia n, 21 % o f all a d e n om as we r e mi ssed, i n cl ud i ng 26 % o f 1 t o 5 mm a d e no mas a nd 2% of a d e no m as 10 mm o r m o r e i n le ng t h . Ot h er limitati on s o f c o l ono sc opies i n cl ud e t he i nconven i ence o f th e bo wel p re p arati on a nd t h e ris k o f bo we l p e rfor at ion ( abou t 3 ou t o f 1,000 p r o ce du res , ov erall , wit h n earl y all o f t he r is k am ong pa ti en t s who und e r go c o l ono sc op ic po l yp ect o mies) . T h e c o s t o f t h e pro c edu r e and t he limit ed nu m b er o f phy sicia n s w ho ca n do t h e pro ce du r e a r e a l so o f conce r n. A C T co l onography o r v i rtua l c o l ono sc opy all o ws a phy sicia n t o v is u all y r ep r oduce t he endosc o p ic e x ami n ati on on a c o m pu ter scree n. A C T c o l onog r aphy i nvo l ves t he sa me p re p as a c o l ono sc op y , bu t is less i nv as ive. I t mi gh t have a h i ghe r co m p lia n ce rate . I n e xp erie n ce d h a nd s , t h e se n siti vity of a C T co l onog r aphy f o r t he d etecti on o f po l yp s ≥6 mm a pp ears t o b e

COLON CANCER SCR EE NING

Cur r ent Recommendations

nan nan

Cur r ent Recommendations

COLON CANCER SCR EE NING

Cur r ent Recommendations

nan nan

Th e A C S, t he A m e ri can Co lle g e o f Gastr o e n ter o l og y , t h e America n G ast ro e n t e r o l og i ca l Assoc i a ti on, t h e America n S o ciet y f o r Gastr o i n testi nal Endo sc op y , and t he A m e ri can C o lle g e o f Ra d i o l ogy h a v e iss u e d j o i n t c o l or ectal cance r gu i de li nes. T h ese g r oup s c on si d er FOB T , FI T , ri g i d a nd f le x i b le s i g m o i doscop i es, co lo no sc op ies , a nd CT c o l onog ra ph ies t o all be r eas on a b l e sc r een i ng m e t hodo l og ies . Th e y r eco mm end t he f o ll o wi ng : ( 1 ) Scree n i ng m od alities b e c ho se n b ase d on pe r sona l p r e f e r ence a nd access , a nd ( 2 ) a v era g e ris k a du lts s hould b e g i n c o l o r ec t a l cance r sc r ee ni ng at a g e 50 y ears wit h on e o f t h e f o ll o wi ng op ti on s: 1. Annua l h i gh sens iti v it y FOBT o r FIT 2. A f l ex i b l e s i g m o i doscopy e v er y 5 y ears 3. A c o l onoscopy eve r y 10 y ears 4. A doub l e con tr as t ba ri u m en ema e v er y 5 y ears 5. A C T co l onog r aphy eve r y 5 y ears No t es t i s o f unequ i voca l sup eri o rit y . Patie n t p refere n ces s hou l d b e i n c orpor at ed i n t o sc r een i ng i n o r d er t o i n crease c o m p lia n ce . T h e gu i d eli nes als o st r e ss t ha t a s i ng l e sc r ee ni ng e x ami n ati on is far fr o m op timal a nd t hat p atie n ts s hou l d be i n a p r og r a m o f re gu lar scree n i ng. A lt hough so m e co l o r ec t a l c a n cers are d ia gno se d i n p ers on s und er t h e a g e of 50 yea r s, sc r een i ng pe r son s a g e 40 t o 49 y ears h as l o w y iel d . T he

COLON CANCER SCR EE NING

Cur r ent Recommendations

nan nan

gu i d eli nes a l so s t a t e t ha t pa tie n ts wit h less t h a n a 10 - y ear life e xp ecta n c y s hou l d n o t be sc r eened. Th e U SPSTF i ssued co l o rectal ca n cer scree n i ng gu i d eli n es i n 2008 .

COLON CANCER SCR EE NING

Cur r ent Recommendations

nan nan

COLON CANCER SCR EE NING

Cur r ent Recommendations

nan nan

Th e gu i de li nes we r e based on a s y stematic literat u re re v iew a nd d ecisi o n m od els . The t ask f o r ce conc l ud e d t h at t h ree scree n i ng strate g ies a pp ear t o b e e qu i va l en t f o r adu lt s age 50 t o 75 y ears: 1. An a nnua l F OB T w it h a sen siti v e test 2. A f l ex i b l e s i g m o i doscopy e v er y 5 y ears , wit h a se n siti v e FOBT e v er y 3 y ea rs 3. A c o l onoscopy eve r y 10 y ears Th e t ask f o r ce r eco mm ends t h at p atie n ts a g e 76 t o 85 y ears b e e v al u a ted i nd i v i du all y f o r sc r een i ng. T hey f ound “i n s u f ficie n t e v i d e n ce” t o r ec o mm end C T co l onog r aph i e s o r fecal DNA testi ng.

COLON CANCER SCR EE NING

Cur r ent Recommendations

Patients at Increased Risk of Colorectal Cancer

nan nan

Patients at Increased Risk of Colorectal Cancer

COLON CANCER SCR EE NING

Cur r ent Recommendations

Patients at Increased Risk of Colorectal Cancer

nan nan

Patie n ts can have h i ghe r t han a v era g e ris k o f c o l o rectal ca n cer du e t o f amilial o r he r ed it a r y f ac t o r s a nd cli n ical c ond iti on s s u c h as i n flammat o r y bow el d i sease. T hese pa ti en t s tec hn icall y und er go s u r v eilla n ce a nd no t sc r ee n i ng. Neve rt he l ess, t he r e are few cli n ical st ud ies t o gu i d e r ec o mm enda ti ons. Gu i de li nes h a v e b ee n create d b ase d on p r o fessi on al

COLON CANCER SCR EE NING

Cur r ent Recommendations

nan nan

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

nan nan

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

nan nan

Th e r e a r e no w i de l y accep t ed scree n i ng gu i d eli n es f o r ca n cers o f t h e es oph a gus, s t o m ach, panc r ea s , a nd li v e r . H o we v e r , s u r v eilla n ce is a dvo cate d f o r so m e pa ti en t s at h i gh ris k.

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

Esophageal Cancer Sc r eening

nan nan

Esophageal Cancer Sc r eening

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

Esophageal Cancer Sc r eening

nan nan

E s oph a gea l cance r sc r een i ng h as ce n tere d on e ndo sc op ic e x ami n ati on s f o r t ho se at h i gh ri sk due t o ch r on ic , se v ere g astr o es oph a g eal refl ux d isease .

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

Esophageal Cancer Sc r eening

nan nan

S o me phys i c i ans advoca t e r ou ti n e e ndo sc op ic s u r v eilla n ce o f p atie n ts w ith Ba rr ett esophagus. A t t h i s time , t h ere is no e v i d e n ce t h at s u c h s u r v eilla nce is e f f ecti ve a t r educ i ng cance r m o rtalit y .

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

Gastric Cancer Sc r eening

nan nan

t ho se w i th a h i s t o r y o f spo r ad ic a d e no mas , a nd p atie n ts wit h familial a d e no mat ous po l ypos i s o r her e d itar y nonpo l ypo sis c o l on ca n ce r .

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

Panc r eatic Cancer Sc r eening

nan nan

A t t h is t i m e, t he r e a r e no da t a fr o m p r o s p ecti v e cli n ical trials t o s uppo rt a ro le for panc r ea ti c cance r sc r e e n i ng. S o me p atie n ts wit h a n e x te n si v e fam ily h ist ory have unde r gone pe ri od ic CT sca nn i ng o f t h e a bdo me n, bu t t h is a ppro ach has no t been shown t o re du ce p a n creatic ca n cer m o rtalit y . T h er e is a n ongo i ng sea r ch f o r sc r een i ng b i o mar k ers . T h ere is a n ee d t o f o ll o w la r ge

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

Liver Cancer Sc r eening

nan nan

Sc r ee n i ng f o r li ve r cance r o r he p at o cell u lar carci no ma (HCC) h as f o c u s ed on v e ry h i gh -ri sk i nd i v i dua l s, s u c h as t ho se wit h cirr ho sis . T o d ate , tria l r es u lts ar e un r e li ab l e due t o sm all st udy sizes a nd a lac k o f ra ndo mizati on. Se ru m a l pha -f e t op r o t e i n (AFP) , a fetal-s p ecific g l y c op r o tei n a n ti g e n, is a n H CC t u m o r m a r ke r used i n scree n i ng. It is no t s p ecific t o HCC b eca use it ma y be e l eva t ed i n hepa titis , p re gn a n c y , a nd s o me g erm cell t u m o rs . AFP h as v a r i ab l e sens iti v it y and h as no t b ee n teste d i n a ny ra ndo mize d cli n ic al t r ial w ith a m o rt a lit y end po i n t . In on e p r ospec ti ve, 16 - yea r , popu lati on - b ase d ob ser v ati on al st ud y , sc r ee n i ng was done on 1,487 Alas k a n ati v es wit h c h r on ic h e p atis B v ir us (H B V) i n f ec ti on. T he su r v i va l o f t ho se wit h scree n - d etecte d HCC was c o m p a red w it h a h i s t o ri ca l g r oup o f cli n icall y d ia gno se d HCC p atie n ts .

O THE R CANC E RS OF TH E GAS T ROINTESTINAL TRACT

Liver Cancer Sc r eening

nan nan

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

nan nan

Cervical Cancer Sc r eening

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

nan nan

D r . G e o r ge P apan i co l aou fir s t i n tr odu ce d t h e Pa p smear o r Pa p test i n t h e ea r l y 1940s. T he t es t was w i de l y a dop te d b ase d on its a b ilit y t o i d e n tif y s qu am ous p r e m a li gnanc i es and mali gn a n cies (fr o m t h e ect od ermal cer v i x ) a nd g la ndu l a r dysp l as i a and ad e no carci no mas (fr o m t h e e ndo cer v i x ) . It i s, how e v e r , m o r e sens iti ve a t de tecti ng s qu am ou s lesi on s . Th e P ap t es t was i n tr oduc e d b ef o re t h e a dv e n t o f t h e p r o s p ecti v e , r a ndo mi zed c li n i ca l tri a l and, t h eref o re , h as n e v er b ee n s o teste d. H o wev e r , a nu m be r o f obse r va ti ona l s t u dies ov er t h e p ast 60 y ears s uppo rt t h e e f f ecti veness o f t h i s sc r een i ng test . M u lti p le ec o l og ic st ud ies h a v e s hown a n i nve r se co rr e l a ti on betwee n t h e i n tr odu cti on o f Pa p testi ng i n a g i v e n c oun tr y and r educ ti ons in bo t h cer v ical ca n cer i n ci d e n ce a nd m or talit y . Im po rt an tl y , m o rtalit y re du cti on s i n t h ese st ud ies h a v e b ee n propor ti ona l t o t he i n t ens it y o f scree n i ng. I n on e series , m o re t h a n h alf o f wo me n d i agnosed w it h ce r v ical ca n cer eit h er h a d n e v er h a d a Pa p test o r h a d no t been sc r eened w it h i n 5 y ears o f d ia gno sis Ce rvica l cy t o l ogy has evo lve d ov er t h e y ears . T h e o ri g i n al Pa p smea r u se d a n ec t oce r v i ca l spa t u l a t o a pp l y a s p ecime n (“smear”) t o g lass sli d e s. I t late r i n cl uded an endoce r v i ca l b r u s h. T h e smear was fi x e d, stai n e d, a nd ma nu all y exa mi ned unde r a micr o sc op e . T h at met hod is still u se d t od a y , but a li qu i d-based /t h i n -l aye r sys tem ca p a b le o f b ei ng a n al y ze d by c o m pu ter is g ai n i ng i n popu l a rit y Hu m an pap ill o m av ir us ( HP V) 16 a nd 18 are t h e ca u se o f m o re t h a n 70 % of ce rv i ca l cance r s. T h irt een ot h er HPV s ub t yp es are kno w n t o b e ass o ciate d w it h ce r v i ca l cance r . W it h i n creasi ng und ersta nd i ng o f t h e r o l e o f H P V i n ce r v i ca l d i sease, i n t e rest i n d e v el op i ng tests t o d etermi n e t h e pr ese n c e o f H P V DNA and R NA h as g r o w n. HPV scree n i ng ca n b e u se d al ong w it h cy t o l ogy ( co t es ti n g ) , i n res pon se t o a n a bno rmal c y t o l og ic tes t ( r eflexive t es ti n g ) , o r as a s t and -al on e test . O n e a dv a n ta g e o f t h e li qu i d - b ase d /t h i n -l aye r t es t s ove r t h e o l d er smears is t h at it ma k es refle x i v e test ing easie r t o pe rf o rm . An abno rmal c y t o l ogy scree n ca n b e ob jecti v el y v erifi ed by testi ng f o r t he p r esence o f th e HPV v ir u s wit hou t calli ng t h e p atie n t b ac k.

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

Cytologic T erminology

nan nan

Cytologic T erminology

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

Cytologic T erminology

nan nan

Th e te rm i no l ogy o f t he P ap sm ear h as c h a ng e d ov er time . T h e tra d iti on a l c y t o l og i c ca t ego ri es we r e mil d, m od erate , a nd se v ere dy s p lasia a nd ca r ci noma i n s it u. Mil d co rr e late d wit h cer v ical i n trae p it h elial n e op lasia ( C IN)1 h i s t o l ogy on b i opsy ; m od er a te u s u all y i nd icate d CIN 2 ; a nd seve r e dy s p lasi a i nd i ca t ed C I N3 o r ca rci no ma i n sit u. Th e r e was so m e sub j ec ti v it y a nd s o me ov erla p, es p eciall y i n t h e area o f mil d a nd m ode r a t e dysp l as i a. T h e NCI s pon s o re d t h e d e v el op me n t o f t he Bet h es da sys t e m i n 1988. T h i s s y stem p r ov i d es a n assessme n t o f t h e a d e qu ac y o f t he ce r v i ca l speci me n a nd a wa y o f cate go rizi ng a nd d escri bing t h e Pa p s m ea r fi nd i ngs. It m or e e f fecti v el y a nd un if o rml y c o mm un icates c y t o l ogy r esu lt s fr o m t he l abo rat o r y t o t h e p atie n t care g i v e r . T h e Bet h es da s y stem was m od ifi ed i n 1991 a nd a g ai n i n 2001 . T od a y , m o re t h a n 40 i n te rn ati ona l p r o f ess i ona l soci eties h a v e e ndo rse d t h e Bet h es d a s y stem . Th e Be t hesda sys t e m r ecogn izes bo t h s qu am ou s a nd g la ndu lar c y t o l o g ic a bnor m a liti es. S qu am ous ce ll abno rm a lit i es i n cl ud e:

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

Cytologic T erminology

nan nan

A t yp ical squa m ous ce ll s ( AS C) , w h ic h are cate go rize d as eit h er: Of unde t e rmi ned s i gn ifi c a n ce (ASC-US) Ca nno t exc l ude h i gh - g r a de s qu am ou s i n trae p it h elial lesi on s (ASC- H ) Low-g r ade squa m ous i n tr aep it h elial lesi on (LSIL) , w h ic h c o rrelates wi th h ist o l og i c C I N1 H i gh-g r ade squa m ous i n tr aep it h elial lesi on (HSIL) , w h ic h c o rrelates w ith h ist o l og i c C I N2, C I N3, an d carci no ma i n sit u G la ndu l a r ce ll abno rm a liti e s (feat u res s ugg esti v e o f a d e no carci no ma) i n cl ud e: A t yp ical g l andu l a r ce ll s ( AG C): e ndo cer v ical , e ndo metrial , o r no t o t h e rw i se spec ifi ed AG Cs , f avo r neop l as ti c Endo c e r v i ca l o r no t o t he r w ise s p ecifie d Endo c e r v i ca l adenoca r c i no ma i n sit u (AIS) Ad e noca r c i no m a A SC s d i f f e r fr o m no rm a l c ells bu t do no t meet criteria f o r LSIL o r H S IL. A s m a ll p r opo rti on o f A SC-US smears are fr o m CIN 1 lesi on s; a smalle r pr opo rti on a r e fr o m CIN 2 o r 3. LSILs are u s u all y du e t o a tra n si ent H P V i nfec ti on. H SIL s a r e m o re li k el y t o b e du e t o a p ersiste n t HPV i nf ecti on and a r e m o r e li ke l y t o p r og ress t o cer v ical ca n cer t h a n LSILs . Th e L owe r Anogen it a l S q uam ou s T ermi no l ogy (LAST) p r o ject o f t h e C o lle g e of A m e ri can P a t ho l ogy a nd t h e America n S o ciet y f o r C o l po sc opy a nd Ce rv i ca l P a t ho l ogy has p r opo se d t h at h ist o l og ic cer v ical fi nd i ng s b e d esc r i b e d us i ng t he sa m e t e r m i no l ogy as c y t o l og ic fi nd i ng s . W o m en unde r t he age o f 30 w ho h a v e no t recei v e d t h e HPV v acci n e h a v e a h i gh i nc i dence o f H P V i n fecti o n a nd t h e h i gh est p re v ale n ce o f C IN. Howeve r , t he ove r whe l m i ng maj o rit y o f t h ese HPV i n fecti on s a nd ass o ciate d C I N w ill spon t aneou sl y re g ress D u e t o t h e h i gh re g ressi on r ates , cer v i ca l sc r een i ng and treatme n t i n w o me n a g e d 20 t o 24 y ears a ppea r t o h a v e l ittl e o r no im pac t on t h e i n ci d e n ce o f i nv asi v e cer v ical ca n ce r . I t is estimate d t ha t abou t 6 % o f C IN 1 lesi on s p r og ress t o CIN 3, a nd 10 % t o 20 % of C IN3 l es i ons p r og r ess t o i nv asi v e ca n ce r

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

Cytologic T erminology

nan nan

Th e A t yp i ca l S qua m ous C ells o f U nd etermi n e d Si gn ifica n ce (ASCU S )- LSIL T riage St udy ( A L TS) ev al u ate d w o me n wit h a bno rmal Pa p smears .

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

nan nan

GYNECOLOGIC CANC E R

Cervical Cancer Sc r eening

nan nan

Th e i nv e s ti ga t o r s conc l uded t h at w o me n wit h ASC-US s hou l d b e teste d f o r H P V . Those who a r e H P V po siti v e s hou l d recei v e a c o l po sc op y . I n a dd it ion, b eca u se m os t wo m en w it h LSIL o r HSIL h a d a n HPV i n fecti on, a n imme d i a t e co l poscopy and a b i op s y o f lesi on s was rec o mme nd e d . HP V DNA testi ng i s ve r y sens iti ve f o r i d e n tif y i ng CIN 2 o r w o rse p at ho l og y . A m ong wo m en 30 t o 69 yea r s o f a g e , t h e se n siti v it y o f t h e Pa p test wit h H P V tes t i ng was 95 % co m par e d wit h 55 % f o r t h e Pa p test al on e .

GYNECOLOGIC CANC E R

Sc r eening Recommendations

nan nan

Sc r eening Recommendations

GYNECOLOGIC CANC E R

Sc r eening Recommendations

nan nan

Ce rv ical sc r een i ng, li ke o t he r scree n i ng tests , is ass o ciate d wit h s o me d e gr ee o f ove r d i agnos i s as ev i d e n ce d by t h e ph e no me non o f s pon ta n e ous r e gr essi on ( see p r ev i ous ) and, t h eref o re , po te n tial h arm fr o m ov ertreatm ent, s u c h as c e r v i ca l i nco m pe t enc e , w h ic h ma y re du ce fertilit y a nd t h e a b ilit y to ca rry a p r egnancy t o t e rm . Bec a u se dy s p lasia ta k es y ears t o p r og ress t o ce rv ical cance r , i nc r eas i ng t h e scree n i ng i n ter v al ca n re du ce ov er d ia gno s is a nd e x c ess i ve tr ea tm en t w it hou t d ecreasi ng scree n i ng e f ficac y . In 20 1 2, t he AC S , t he A merica n S o ciet y f o r C o l po sc opy a nd Cer v ica l Pat ho l ogy ( A S CC P) , and t he America n S o ciet y f o r Cli n ical Pat ho l ogy (A SCP ) i ssued j o i n t sc r een i n g gu i d eli n es . T h ese gu i d eli n es rec o mme nd d i f f e r e n t su r ve ill ance s tr a t eg i e s a nd op ti on s b ase d on a w o ma n ’ s a g e , sc r ee n i ng h i s t o r y , ri sk f ac t o r s, a nd c ho ice o f scree n i ng tests . T h e f o ll o wi ng a r e t h e reco mm enda ti ons f o r a w o ma n at a v era g e ris k.

GYNECOLOGIC CANC E R

Sc r eening Recommendations

Screening in Low Resource Countries

nan nan

C y t o l ogy and H P V t es ti ng i s no t wi d el y a v aila b le i n m u c h o f t h e w o rl d. Ce rv ical cance r r e m a i ns a l ead i ng ca u se o f d eat h i n ma ny o f t h ese areas . V is u al i nspec ti on o f t he ce r v i x is a l o w-tec h met hod o f scree n i ng t h at is now r eco gn i zed as hav i ng t he po te n tial t o sa v e t hou sa nd s o f li v es p er y e a r . A cl u ster ed, r ando mi zed tri a l i n I nd ia c o m p are d on e-time cer v ical v is u al i n s p ectio n and imm ed i a t e co l po sc op y , b i op s y , a nd / o r cr yo t h era py (w h er e i nd icated) ve r sus counse li ng on cer v ical ca n cer d eat h s i n w o me n a g e d 30 to 59 y ea r s. A ft e r 7 yea r s o f f o ll o w- up, t h e a g e-sta nd ar d ize d rate o f d eat h due t o ce rv i ca l cance r was 39.6 pe r 100,000 p ers on - y ears i n t h e i n ter v e n ti on group v er sus 56.7 pe r 100,000 p ers on - y ears i n un scree n e d c on tr o ls . This

GYNECOLOGIC CANC E R

Sc r eening Recommendations

Screening in Low Resource Countries

nan nan

w as t h e fir s t p r ospec ti ve r ando mize d cli n ical trial t o e v al u ate cer v ical ca n ce r s c r een i ng.

GYNECOLOGIC CANC E R

Ovarian Cancer Sc r eening

nan nan

Ovarian Cancer Sc r eening

GYNECOLOGIC CANC E R

Ovarian Cancer Sc r eening

nan nan

M od alit ies p r oposed f o r ova ri an ca n cer scree n i ng i n cl ud e t h e b ima nu al p el v ic ex a mi na ti on, se r u m C A- 125 a n ti g e n meas u reme n t , a nd tra n s v a g i nal u lt r as ound (T VU ) . T he b im anu al p el v ic e x ami n ati on is s ub jecti v e a nd not v e ry r e p r oduc i b l e, bu t se r u m C A- 125 ca n b e ob jecti v el y meas u re d. Unfor t una t e l y , CA - 125 i s ne it h er se n siti v e no r s p ecific . It is ele v ate d i n on l y a bou t ha lf o f wo m en w it h ov aria n ca n cer a nd ma y b e ele v ate d i n a nu m b e r o f non m a li gnan t d i sea ses (e .g., d i v ertic u l o sis , e ndo metri o sis , ci rrho si s, no rm a l m ens tr ua ti on, p re gn a n c y , u teri n e fi b r o i d s) . TVU has s hown poo r pe rf o rm ance i n t h e d etecti on o f ov aria n ca n cer i n a v era g e a nd h i gh-r is k wo m en . T he r e i s i n terest i n t h e a n al y sis o f ser u m p r o te o mic p atte rn s , bu t t h i s shou l d be con si d ere d e xp erime n tal . Th e co m b i na ti on o f CA - 125 a nd TVU h as b ee n assesse d i n tw o lar g e , pro s p ecti ve r ando mi zed tri a l s. T h e U . S . trial , t h e Pr o state L ung C o l o rect al a nd Ov a r i an tri a l (PL CO ) , enro lle d 78,216 w o me n o f a v era g e ris k a g e 55 to 74 y ea r s. P a rti c i pan t s we re ra ndo mize d t o recei v e a nnu al e x ami n ati ons w it h C A - 125 ( a t en tr y and t h e n a nnu all y f o r 5 y ears) a nd TVU (at e n tr y and t h e n a nnua ll y f o r 3 yea r s ) ( n = 39,105 ) , o r u s u al care ( n = 39, 1 1 1 ) . Pa r tici p a n t s we r e f o ll owed f or a ma x im u m o f 13 y ears , wit h m o rtalit y fr om ov a r ia n cance r as t he m a i n s t udy ou tc o me . At t h e c on cl u si on o f t h e st ud y , t h e nu m be r o f dea t hs fr o m ova ria n ca n cer was similar i n eac h g r oup. T h er e w e r e 3. 1 ova ri an cance r dea t h s p er 10,000 w o me n y ears i n t h e scree n e d group v er sus 2.6 dea t hs pe r 10,000 w o me n y ears i n t h e c on tr o l g r oup (RR = 1.18 ; 95 % C I , 0.82 t o 1.71 ) Th e U.K. Co ll abo r a ti ve T rial o f O v aria n Ca n cer Scree n i ng (UKC T OC S ) is a r a ndo mi zed tri a l assess i ng t h e efficac y o f CA- 125 a nd TVU i n m o re t h a n 200,000 pos tm enopausa l w o me n. I n t h is trial , CA- 125 is b ei ng u se d as a f i r st - lin e t es t and T VU as a f o ll o w- up test u si ng a ris k o f ov aria n ca n c e r al gor it h m ( ROCA ) T he R OCA meas u res c h a ng es i n CA- 125 ov er ti me

GYNECOLOGIC CANC E R

Ovarian Cancer Sc r eening

nan nan

r at h e r t h a n us i ng a p r ede fi ned c u t po i n t . ROCA is b elie v e d t o im p r ove se n siti v it y f o r s m a ll e r t u m o r s wit hou t meas u ra b l y i n creasi ng t h e FP rate . A m or talit y assess m en t i s expec te d i n 2015 . No o r gan i za ti on cu rr en tl y rec o mme nd s scree n i ng a v era g e ris k w o me n for ov a rian cance r . I n 2012, t h e USPSTF rec o mme nd e d a g ai n st scree n i n g for ov a rian cance r , conc l ud i n g t h at t h ere was “a d e qu ate e v i d e n ce” t h at ( 1 ) a nnu al s c r een i ng w it h T VU and CA- 125 do es no t re du ce ov aria n ca n cer m or talit y and ( 2 ) sc r een i ng f or ov aria n ca n cer ca n lea d t o im po rta n t h ar ms, mai n l y su r g i ca l i n t e r ven ti ons in w o me n wit hou t ov aria n ca n ce r

GYNECOLOGIC CANC E R

Ovarian Cancer Sc r eening

W omen at High Risk for Ovarian Cancer

nan nan

W omen at High Risk for Ovarian Cancer

GYNECOLOGIC CANC E R

Ovarian Cancer Sc r eening

W omen at High Risk for Ovarian Cancer

nan nan

A lt hough no s t udy has shown a m o rtalit y b e n efit f o r ov aria n ca n cer sc r ee n i ng o f h i gh -ri sk i nd i v i du als , a Nati on al I n stit u tes o f Healt h (NIH) c on se n su s pane l conc l uded t h at it was p r ud e n t f o r w o me n wit h a kno w n h e r e d ita ry ova ri an cance r synd r o me , s u c h as BRCA 1 / 2 m u tati on s o r HN PCC , t o have annua l r ec t ov a g i n al p el v ic e x ami n ati on s , CA- 125 d ete r mi na ti ons, and T VU un til c h il db eari ng is c o m p lete d o r at least un ti l a g e 35 y e a r s, a t wh i ch tim e a pr ophy lactic b ilateral oopho rect o m y is r ec o mm ended .

GYNECOLOGIC CANC E R

Endometrial Cancer Sc r eening

nan nan

Endometrial Cancer Sc r eening

GYNECOLOGIC CANC E R

Endometrial Cancer Sc r eening

nan nan

Th e r e is i nsu f fi c i en t ev i dence t o rec o mme nd e ndo metrial ca n cer scree n in g eit h e r fo r wo m en a t ave r age ris k o r f o r t ho se at i n crease d ris k du e t o a h ist ory o f unopposed es tr ogen t h era p y , tam ox ife n t h era p y , late me nop a u s e, nu lli p a r i t y , i n f e rtilit y o r f a il u re t o ovu late , ob esit y , d ia b etes , o r hyp e r te ns i on. T he AC S r ec omme nd s t h at w o me n b e i n f o rme d a bou t t he s y m p t o m s o f endo m e tri a l canc er — i n p artic u la r , v a g i n al b lee d i ng a nd s po tti ng—a ft e r t he onse t o f m e nop a u se . W o me n s hou l d b e e n c ou ra g e d t o imme d i a t e l y r epo rt t hese sy m p t o ms t o t h eir phy sicia n.

GYNECOLOGIC CANC E R

Endometrial Cancer Sc r eening

W omen at High Risk for Endometrial Cancer

nan nan

W omen at High Risk for Endometrial Cancer

LUNG CANC E R SCR EE NING

nan nan

LUNG CANC E R SCR EE NING

LUNG CANC E R SCR EE NING

nan nan

Lung ca nce r sc r een i ng p r og r a ms u si ng c h est ra d i og ra ph s (CXR) a nd s pu t u m cy t o l ogy began i n t he late 1940 s . A n e v al u ati on o f t h ese progr ams showed t ha t sc r een i ng le d t o t h e d ia gno sis o f a n i n crease d nu m be r of ca n cer s, an i nc r eased p r opo rti on o f earl y sta g e ca n cers , a nd a la r g er propor ti on o f sc r een - d i agnos e d p atie n ts s u r v i v i ng m o re t h a n 5 y ears . Th es e fi nd i ngs l ed m any t o a dvo cate f o r mass l ung ca n cer scree n i ng, wh e r eas o t he r s ca ll ed f o r a p r o s p ecti v e , ra ndo mize d trial wit h a l ung ca nce r m or talit y endpo i n t . T he Mayo L ung Pr o ject (MLP) , w h ic h b e g a n i n 1971, w as s u c h a tri a l . Mo r e t han 9,200 male sm ok ers were e n r o lle d a nd r a ndo mi zed t o e it he r have spu t u m c y t o l ogy c o llecte d a nd CXRs don e e v er y 4 m on t hs f o r 6 yea r s o r t o ha ve t h ese same tests p erf o rme d a nnu all y . A t 13 yea r s o f f o ll ow - up, t h ere were m o re earl y sta g e ca n cers i n t h e i n te n si v el y sc r eened a rm ( n = 99 ) t h a n i n t h e c on tr o l arm ( n = 51 ) , bu t t he nu m b e r o f advanced t u m o r s w as n earl y i d e n tical ( 107 v ers u s 109, r es p ecti ve l y ) . Desp it e an i nc rease i n 5 - y ear s u r v i v al ( 35 % v ers u s 15 % ) i n te n si v e sc r een i ng was no t a ss o ciate d wit h a re du cti on i n l ung ca n cer m or talit y ( 3.2 ve r sus 3.0 dea t h s p er 1,000 p ers on - y ears , res p ecti v el y ) . Th e im pac t o f sc r een i ng on ca n cer i n ci d e n ce p ersiste d t h r ough n earl y 20 y ea r s of f o ll ow - up. T he r e we re 585 l ung ca n cers d ia gno se d on t h e i n te nsive sc r ee n i ng a rm ve r sus 500 on t h e c on tr o l arm ( p = 0.009 ) a nd i n te n si v e sc r ee n i ng con ti nued t o be asso ciate d wit h a si gn ifica n t i n crease i n d iseas e -s p eci f ic su r v i va l . Howeve r , a con c o mita n t d ecrease i n l ung -ca n cer m o rta lity d i d no t e m e r ge w it h l ong -t e rm f o ll o w- up ( 4.4 l ung ca n cer d eat h s p er 1,000

LUNG CANC E R SCR EE NING

nan nan

p e r s on-yea r s i n t he i n t ens i ve l y scree n e d arm v ers u s 3.9 p er 1,000 p ers on - y ea r s i n t he con tr o l a rm) T h is s ugg ests t h at s o me l ung ca n cers d ia gnosed by sc r ee n i ng wou l d no t have r es u lte d i n d eat h h a d t h e y no t b ee n d etecte d ( i . e ., ove r d i agnos i s ) . T wo o t he r l a r ge, r ando mi z e d st ud ies o f CXR a nd s pu t u m c y t o l ogy w e r e c ondu cte d i n t he Un it ed St a t e s du ri ng t h e same time p eri od. All t h ree st ud ies eva l ua t ed d i f f e r en t sc ree n i ng sc h e du les rat h er t h a n scree n i ng v er sus no sc r ee n i ng. P a r adox i ca ll y , a meta-a n al y sis o f t h e t h ree st ud ies f ound t hat m or e frequen t sc r een i ng was a ss o ciate d wit h a n i n crease (al b eit no t statistic a ll y s i gn ifi can t) , r a t he r t h a n a d ecrease , i n l ung ca n cer m o rtalit y wh e n c ompa r ed w it h l ess fr equ e n t scree n i ng . A st udy c ondu cte d i n Czec ho s lovak i a i n t he 1980s als o faile d t o s ho w a re du cti on i n l ung ca nce r m or talit y w it h CXR sc r een i ng M ore r ecen tl y , t he NC I condu cte d t h e PLCO trial at 10 sites acr o ss t he Un ite d St a t es. T h i s was a p r osp ecti v e , ra ndo mize d trial o f n earl y 155,000 me n a nd wo m en, aged 55 t o 74 y ears . Partici p a n ts were ra ndo mize d t o r ecei v e annua l , s i ng l e - v i e w , po ster o a n teri o r CXRs f o r 4 y ears v ers u s rou ti n e c a r e. W it h 13 yea r s o f f o ll o w- up, no si gn ifica n t d i f fere n ce i n l ung ca n ce r m o rt a lit y was obse r ved. A t o tal o f 1,213 l ung ca n cer d eat h s o cc ur r ed on t h e i n t e r ven ti on a rm ve r sus 1,230 i n t h e c on tr o l g r oup (RR , 0.99 ; 95% C I, 0.87 t o 1.22 ) . L o w -dose compu t er i zed t o m og r aph y (LDCT) is a n a pp eali ng tec hno l ogy for l ung cance r sc r een i ng. It u ses a n a v era g e o f 1.5 mS v o f ra d iati on t o p e rfor m a l ung scan i n 15 second s . A c onv e n ti on al CT sca n u ses 8 mS v o f r a d iati on and t akes seve r a l min u tes . T h e LDCT ima g e is no t as s h ar p as the c onv e n t iona l im age, bu t sens i t i v it y a nd s p ecificit y f o r t h e d etecti on o f l ung lesi on s a r e s imil a r . A s i n t he ea rl y ches t r ad i og ra ph trials , a nu m b er o f si ng le-arm LDCT st ud ies r e po rt ed a subs t an ti a l in crease i n t h e nu m b er o f earl y sta g e l ung ca n ce r s d i agnosed. T hese s t ud ies als o d em on strate d t h at 5 - y ear s u r v i v al r ates w er e i nc r eased i n sc r een e d c o m p are d t o un scree n e d popu lati on s . Th es e fi nd i ngs l ed t o t he condu ct o f se v eral ra ndo mize d trials o f LD CT for t h e e a rl y de t ec ti on o f l ung ca n ce r . T h e la r g est , l ong est , a nd first t o rep o r t

LUNG CANC E R SCR EE NING

nan nan

a m or talit y end po i n t i s t he N ati on al L ung Scree n i ng T rial (NLST) . I n t h i s t r ial , a pp r ox im a t e l y 53,000 p ers on s were ra ndo mize d t o recei v e t h ree a nnu al LDC T scans o r s i ng l e - v iew po ster o a n teri o r CXRs . Eli g i b le p a r tici pan t s we r e cu rr en t and fo rmer sm ok ers b etwee n 55 a nd 74 y ears o f a g e at t h e tim e o f r ando mi za ti on wit h at least a 30 p ac k - y ear sm ok i ng h ist ory ; f o rm e r s m oke r s we r e eli g i b le if t h e y h a d qu it sm ok i ng wit h i n t he pr e v i ous 15 yea r s. W it h a m ed i an f o ll ow - up o f 6.5 y ears , 13 % m o re l ung ca n cers were d ia gno se d and a 20 % ( 95 % CI, 6.8 t o 26.7 ; p = 0.004 ) relati v e re du cti on in l ung ca nce r m o rt a lit y was ob ser v e d i n t h e LDCT arm c o m p are d t o t h e C X R a r m . Th i s co rr esponds t o r a t e s o f d eat h fr o m l ung ca n cer o f 247 a nd 309 p e r 100,000 pe r son - yea r s, r esp ecti v el y . A no t h er im po rta n t fi nd i ng fr om t h e NL S T was a 6.7 % ( 95 % C I , 1.2 t o 13.6 ; p = 0.02 ) d ecrease i n d eat h fro m a ny cause i n t he L DC T g r oup. NLST pa rti c i pan t s we r e a t h i gh ris k f o r d e v el op i ng l ung ca n cer b ase d on t h ei r sm ok i ng h i s t o r y . I ndeed, 25 % o f all p artici p a n t d eat h s were du e t o l ung ca nce r . A f u rt he r ana l ys is o f t h e NLST s ho ws t h at scree n i ng p re v e nted t h e gr ea tes t nu m be r o f l ung c a n cer d eat h s am ong p artici p a n ts w ho were a t t h e h i ghes t ri sk bu t p r even t ed v er y few d eat h s am ong t ho se at t h e l o wes t r is k. Th e se fi nd i ngs p r ov i de e m p irical s uppo rt f o r ris k - b ase d scree n i ng . LD CT sc r een i ng i s c l ea rl y p r o misi ng, bu t t h ere are s o me no ta b le ca v eats . T he ri sk o f a FP fi nd i ng i n t h e first scree n was 21 % . O v erall , af te r t hr ee CT scans, 39.1 % o f pa rtici p a n ts h a d at least on e po siti v e scree n i ng r es u lt . O f t hose who sc r eened po siti v e , t h e FP rate was 96.4 % i n t h e LDC T group P os iti ve r esu lt s r equ i r e a dd iti on al w o r kup, w h ic h ca n i n cl ud e c onv e n t iona l C T scans, a need le b i op s y , b r on c ho sc op y , me d iasti no sc op y , o r t hor ac o t o m y . T hese d i agnos ti c p r o ce du res are ass o ciate d wit h a nx iet y , e xp e n se , and co m p li ca ti ons (e .g., pn e u m o - o r h em o t ho ra x after a l ung b i op s y). I n t he L DC T s t udy ar m , t h ere were 16 d eat h s wit h i n 60 d a y s o f an i nv asi v e d i agnos ti c p r ocedu r e. Of t h e 16 d eat h s , 6 u ltimatel y d i d no t h a ve ca n ce r . A lt hough it i s no t known w h et h er t h ese d eat h s were d irectl y ca used by t h e i nvas i ve p r ocedu r e, such fi nd i ng s do g i v e p a u se . Alt hough t h e r a d iati on dose fr o m L DC T i s l o w , t h e po ssi b ilit y t h at t h is scree n i ng test

LUNG CANC E R SCR EE NING

nan nan

c ou l d cau se r ad i a ti on -i nduced ca n cers is at least a t h e o retical c on cer n. Th e po ssi b ili ty o f t h i s l ong -t e rm ph e no me non will h a v e t o b e assesse d i n f u tur e a n al y ses . Th e CXR l ung sc r een i ng s t ud ies s ugg este d t h at t h ere is a reser vo ir o f b i o l og ic a ll y i ndo l en t l ung can cer a nd t h at a p erce n ta g e o f scree n - d etecte d l ung ca nce r s r ep r esen t ove r d ia gno sis . T h e estimate d rate o f ov er d ia gno s is i n t h e l ong -t e rm f o ll ow - up o f t h e Ma yo L ung St udy a nd t h e o t h er CXR st ud ies was 17 t o 18.5 % . Similarl y , it is estimate d t h at 18.5 % o f t h e ca n ce r s d i agnosed on t he L D CT arm o f t h e NLST re p rese n te d ov e rd ia gnos i s . Th e r e a r e es tim a t es t ha t w i d es p rea d, h i gh - qu alit y scree n i ng h as t h e po te n tial t o p r even t 12,000 l u n g ca n cer d eat h s p er y ear i n t h e U n ite d States Howeve r , t he N LST was p erf o rme d at 33 ce n ters s p ecificall y c ho se n f or t he ir expe rti se i n t h e scree n i ng, d ia gno sis , a nd treatme n t o f lu ng ca n ce r . It i s no t known whe t h er t h e wi d es p rea d a dop ti on o f LDCT l ung ca n ce r s c r een i ng w ill r esu lt i n h i gh er c o m p licati on rates a nd a less f a vor a b l e ri sk–bene fit r a ti o. A lt hough L DC T l ung canc er scree n i ng s hou l d clearl y b e c on si d ere d f o r t ho se at h i gh ri sk o f t he d i sea se , t ho se at l o wer ris k are e qu all y li k el y t o s u f f e r t h e ha rm s assoc i a t ed w it h scree n i ng bu t less li k el y t o rea p t h e b e n e f its . F o ll ow i ng t he announce me n t o f t h e NLST res u lts , t h e ACS , t h e A me r ic an Co ll ege o f Ches t P hy sicia n s (AACP) , t h e America n S o ciet y o f Cli n ical Onco l ogy ( A S CO ) , and t h e Nati on al C o m p re h e n si v e Ca n cer N et work ( NCCN ) r eco mm end e d t h at cli n icia n s s hou l d i n itiate a d isc u ssi on a bou t l ung cance r sc r een i ng wit h p atie n ts w ho w ou l d h a v e qu alifie d f o r t he t r ial . Tha t i s : Ag e 55 t o 74 yea r s A t least a 30 pack - yea r s m ok i ng h ist o r y C urr e n tl y s m oke o r have qui t wit h i n t h e p ast 15 y ears Relativ e l y good hea lt h

PROS T A TE CANCER SCR EE NING

nan nan

PROS T A TE CANCER SCR EE NING

PROS T A TE CANCER SCR EE NING

nan nan

i n e xp e n si ve. A lt hough PS A sc ree n i ng i n creases t h e d etecti on o f po te n tia lly c ur a b le di sease, t he r e i s subs ta n tial d e b ate a bou t t h e ov erall u tilit y o f t he test . Th i s i s because PS A sc r e e n i ng i n tr odu ces s ub sta n tial lea d time a nd le ng t h b i as as we ll as be i ng as s o ciate d wit h a h i gh FN a nd FP rates a nd h a v i ng a l ow pos iti ve p r ed i c ti v e v al u e . T h e p r o state ca n cer c onund r u m was b est s u mm a ri zed by t he d i s ti ngu is h e d u r o l og ist , W illet W h itm o re w h e n he sai d, “ I s cu r e necessa r y f o r t ho se i n w ho m it is po ssi b le? Is c u re po ssi b l e f o r t ho se i n w ho m it i s necessa r y? Ob ser va ti ona l s t ud i es sugg est t h at t h e p r ob lem o f p r o state ca n cer ov e rd ia gnos i s p r ecedes t he P S A era . I n a la nd mar k a n al y sis wit h 20 - y ear fo ll ow-up, on l y a s m a ll p r opo rti on o f 767 me n, d ia gno se d wit h l o calize d pro state cance r i n t he 1970s and earl y 1980 s a nd f o ll o we d e xp ecta n tl y , died fro m pros t a t e cance r: 4 % t o 7% o f t ho se wit h Gleas on 2 t o 4 t u m o rs , 6 % to 1 1% of those w it h G l eason 5 d isease , a nd 18 % t o 30 % o f me n wit h Gle ason 6 ca n ce r . A lt hough obv i ous l y p r esen t i n t h e p re-PSA era , ov er d ia gno sis i n crea sed s ub sta n ti a ll y a ft e r t he i n tr odu cti on o f PSA scree n i ng. T h is is ill u strate d by a n e x am ina ti on o f t he p r os t a te ca n cer i n ci d e n ce a nd m o rtalit y rates i n W as h i ng t on s t a t e and Connec tic u t . D u e t o t h e earlier up ta k e o f PSA sc r ee n i ng, t he i nc i dence o f p r o state ca n cer i n W as h i ng t on i n crease d t o t wice t h at of Connec ti cu t du ri ng t he 1990 s . H o we v e r , m o rtalit y rates remai n e d simila r thr oughou t t he decade a nd, i n fact , h a v e remai n e d similar t o t h is d a y . The S u r ve ill ance, E p i de mi o l og y , a nd E nd Res u lts (SEER) ca n cer r e g ist r ie s show t ha t , ove r t he l ast 2 d eca d es , a lar g er p r opo rti on o f me n li v i ng i n wes t e r n W ash i ng t on h a v e b ee n d ia gno se d wit h p r o state ca n cer and d e f i n iti v el y tr ea t ed, w it hou t a c on c o mita n t re du cti on i n p r o state ca n cer m or talit y co m pa r ed t o t ha t o f me n li v i ng i n C onn ectic u t . Add iti ona l ev i dence o f t he po te n tial f o r ov er d ia gno sis c o mes fr o m t he un e xp ect ed l y l a r ge nu m be r o f me n d ia gno se d wit h p r o state ca n cer i n t h e P ro state Cance r Pr even ti on T rial (PCPT) . T h e PCPT was a p r o s p ecti v e , r a ndo mi zed, p l acebo - con tr o lle d trial o f fi n asteri d e f o r p r o state ca n cer pr e v e n ti on. Men we r e sc r eened a nnu all y du ri ng t h is trial , a nd t ho se w ho h a d no t been d i agnosed w it h p r o state ca n cer after 7 y ears on -st udy were

PROS T A TE CANCER SCR EE NING

Does P r ostate Cancer T r eatment P r event Deaths?

nan nan

In ord e r f o r sc r een i ng t o wo r k, treatme n t h as t o w o r k. T h e first p r o s p ect ive, r a ndo mi zed s t ud i es show i ng that a ny p r o state ca n cer treatme n t sa v es li v e s w e r e pu bli shed i n t he l a t e 1990 s . T h ese st ud ies d em on strate d a n ov erall

PROS T A TE CANCER SCR EE NING

Does P r ostate Cancer T r eatment P r event Deaths?

nan nan

s urv i v al bene fit f o r t he add itio n o f l ong -term a nd r og e n d e p ri v ati on t o r a d iati on t he r apy i n m en w it h l o call y a dv a n ce d, h i gh -ris k p r o state ca n ce r . Th e va l ue o f su r ge r y f o r l o calize d d isease was assesse d by t h e Sca nd i nav i an Pr os t a t e Cance r Gr oup 4 st udy (SPCG- 4 ) . I n t h is trial , 695 me n w it h c li n i ca ll y l oca li zed p r o state ca n cer were p r o s p ecti v el y r a ndo mi zed t o r ece i ve r ad i ca l p r o statect o m y (RP) o r watc h f u l waiti ng ( W W). In t he expec t an t m anag eme n t g r oup, ho rm on al t h era py was g i v e n at t h e time o f sy m p t o m a ti c m e t a stases . A bou t 60 % o f t ho se e n r o lle d h a d lo w - gr a d e , 23 % had m ode r a t e - g r a de , 5 % h a d h i gh - g ra d e t u m o rs , a nd 12 % had t u m or s o f unknown g r ade. A t a me d ia n f o ll o w- up o f 12.8 y ears , t h e RP group h a d s i gn ifi can tl y l owe r ov erall (RR 0.75 ; p = 0.007 ) a nd p r o state ca n ce r– s pec ifi c m o rt a lit y ( RR 0.62 ; p = 0.01 ) , wit h 14.6 % o f t h e PR g r oup a nd 20.7 % o f t he WW g r oup h a v i ng d ie d o f p r o state ca n ce r . T h e nu m b er n ee d e d to tr ea t o r p r even t one p r o state ca n cer d eat h was 15. T h e s u r v i v a l b e n e f it assoc i a t ed w it h R P wa s similar b ef o re a nd after 9 y ears o f f o ll ow - up a nd for men w it h l ow and h i gh -ris k d isease . H o we v e r , a s ub set a n al y sis s ugg est ed t ha t t he m o rt a lit y b e n efit o f s u r g er y was limite d t o me n less th an 65 y ea r s o f age. An im po rt an t limitati on o f t h is trial is t h at 75 % o f t h e st udy p a r tici pan t s had pa l pab l e d i sea se , on l y 12 % h a d nonp al p a b le d isease , a nd on l y 5% o f t he cance r s had be e n scree n d etecte d. It is , t h eref o re , d i f fic u l t to a pp l y t hese da t a t o t he U S p r o state ca n cer popu lati on, w h ic h is do mi n at ed by nonpa l pab l e, sc r een - de t ec te d d isease . In c on tr as t t o t he SP CG - 4, t h e Pr o state I n ter v e n ti on v ers u s O b ser v ati on T r ial (PI V O T) was conduc t ed i n t h e U n ite d States du ri ng t h e earl y PSA e r a. In t h is st ud y , 731 m en w it h s cree n - d etecte d p r o state ca n cer were r a ndo mi zed t o r ece i ve R P o r W W . Of t h e p artici p a n ts , 50 % h a d nonp al pab l e d i sease and, us i ng esta b lis h e d criteria f o r PSA le v els , g ra d e , a nd t u m o r s t age, 43 % o f m en h a d l o w-ris k, 36 % h a d i n terme d iate-ris k, a nd 21% h a d h i gh -ri sk p r os t a t e can ce r . W it h a me d ia n f o ll o w- up o f 12 y ears , dur i ng w h i ch tim e 48.4 % ( 354 o f 731 ) o f t h e st udy p artici p a n ts h a d d ie d, R P w as assoc i a t ed w it h s t a ti s ticall y i n si gn ifica n t 2.9 % a nd 2.6 % a b s o l u te r e du cti ons i n ove r a ll and p r os tate ca n cer – s p ecific m o rtalit y , res p ecti v el y . S ubgrou p ana l yses sugges t ed m o rtalit y b e n efits f o r me n wit h PSA v al u e s

PROS T A TE CANCER SCR EE NING

Does P r ostate Cancer T r eatment P r event Deaths?

nan nan

gr eate r t han 10 ng /mL and f o r t ho se wit h i n terme d iate- a nd h i gh -ris k d isease

PROS T A TE CANCER SCR EE NING

The P r ospective Randomized Sc r eening T rials

nan nan

The P r ospective Randomized Sc r eening T rials

PROS T A TE CANCER SCR EE NING

The P r ospective Randomized Sc r eening T rials

nan nan

t r eatme n t have con tri bu t ed, a t least i n p art , t o t h e ob ser v e d d ecli n e i n pro state cance r m o rt a lit y . Ano t h er po ssi b le c on tri bu ti ng fact o r ma y b e th e W or l d H ea lt h O r gan i za ti on (WHO) al go rit h m f o r a d j ud icati ng ca u se o f d eat h. A change occu rr ed j us t as m o rtalit y rates b e g a n t o go up i n t h e late 1970 s , a nd WHO changed back t o t h e o l d er al go rit h m i n 1991 w h e n pro state cance r m o rt a lit y beg a n d ecli n i ng i n ma ny c oun tries . All o f t hese f act or s , i nc l ud i ng a bene fi c i a l e f fect fr o m scree n i ng, ma y b e c on tri bu ti ng to t h e d ecl in i ng p r os t a t e cance r m o rtalit y rates i n t h e U n ite d States .

PROS T A TE CANCER SCR EE NING

Sc r eening Recommendations

nan nan

Sc r eening Recommendations

PROS T A TE CANCER SCR EE NING

Sc r eening Recommendations

nan nan

Th e t op ic o f p r os t a t e cance r s cree n i ng te nd s t o e vok e str ong em o ti on al r eacti ons. A lt hough t he i n t u iti v e a pp eal o f earl y d etecti on is und e n ia b le a nd sc r ee n i ng m ay save so m e li ve s , t h e ma gn it ud e o f t h e m o rtalit y re du cti on is r elati v el y s m a ll , whe r eas t he h arms ass o ciate d wit h scree n i ng ca n b e s ub sta n ti a l . Whe t he r t he po t en tial b e n efits ou twei gh t h e kno w n h arms is a qu esti on t ha t each m an m us t an swer f o r h imself b ase d on h is i nd i v i du al pr e f e r e nces. Se v e ra l p r o f ess i ona l o r gani zati on s i n t h e U n ite d States , E u r op e , a nd Ca n a d a have r ecen tl y r ev i ewed t h e scree n i ng d ata a nd iss u e d scree n i ng gu i d eli nes. A ll acknow l edge t h at le g itimate c on cer n s remai n re g ar d i ng t he r is k–b e ne fit r a ti o o f p r os t a t e ca n cer scree n i ng. T h ere is als o g e n eral a gr eeme n t t ha t p r os t a t e cancer scree n i ng s hou l d on l y b e don e i n t h e c ontext of fu ll y i n f o rm ed consen t and t h at me n s hou l d kno w t h at e xp erts do no t a gr ee as t o whe t he r t he bene f i ts o f scree n i ng f o r t h is d isease ou twei gh t he h a r ms . M os t r eco mm end aga i n st mass scree n i ng i n pub lic meeti ng p lace s, malls , ch u r ches, e t c. In 20 0 9, t he A m e ri can U r o l og ical Ass o ciati on (AUA) PSA Best Prac tice Statement was pub li shed, wh ic h state d, “Gi v e n t h e un certai n t y t h at PSA testi ng resu lt s i n m o r e bene fit t h a n h arm , a t hough tf u l a nd b r o a d a pp r o a ch t o PS A is c riti ca l . P a ti en t s ne e d t o b e i n f o rme d o f t h e ris k s a nd t h e b e n ef its of testi ng be f o r e it i s unde rt ak e n. T h e ris k s o f ov e r - d etecti on a nd ov e r -t r eatme n t shou l d be i nc l uded in t h is d isc u ssi on. ”

PROS T A TE CANCER SCR EE NING

Sc r eening Recommendations

nan nan

In 20 1 0, t he AC S upda t ed t h eir gu i d eli n es , stati ng t h at t h e b ala n ce o f b e n e f its and ha rm s r e l a t ed t o pr o state ca n cer earl y d etecti on are un certai n a nd t h e e x i s ti ng ev i dence i s i n s u f ficie n t t o s uppo rt a rec o mme nd ati on f o r o r a g ai n st th e r ou ti ne use o f PS A scree n i ng . T h e ACS calle d f o r d isc u ssi on a nd s h a r e d dec i s i on m ak i ng w it h i n t h e phy sicia n–p atie n t relati on s h i p. Th e m os t r ecen t 2012 U S P STF gu i d eli n es rec o mme nd a g ai n st t h e u s e o f PS A sc reen i ng on t he bas i s t h at t h ere is m od erate certai n t y t h at t h e h ar ms o f PS A testi ng ou t we i gh t he ben efits a nd, on t h at b asis , rec o mme nd e d a g ai nst PS A-b a sed sc r een i ng f o r a ll me n . T h e tas k f o rce d i d ac kno wle dg e t h at s o me me n w ill con ti nue t o r equ est scree n i ng a nd s o me phy sicia n s will c on ti nue t o o f f e r it . Li ke t he ACS a nd AUA , t h e y state t h at scree n i ng unde r s u c h ci rcu m s t ances shou l d r e s p ect p atie n t p refere n ces . In 20 1 3, t he AUA conduc t ed a s y stematic re v iew o f ov er 300 st ud ies . Th e y r e co mm ended aga i ns t sc ree n i ng me n young er t h a n 40 y ears o f a g e , a nd a g ain s t sc r een i ng ave r age -ris k me n a g e 40 t o 54 y ears , m o st me n ov er 70 y ea r s o f age, and m en w it h a life e xp ecta n c y o f less t h a n 10 t o 15 y ear s. Th e y r e co mm end t ha t sc r een in g d ecisi on s b e i nd i v i du alize d f o r h i gh er r isk me n a g es 40 t o 54 yea r s and me n ov er 70 y ears o f a g e w ho are i n e x cell ent h ealt h. T hey p l aced p rim acy on s h are d d ecisi on ma k i ng v ers u s phy sicia n j udg me n t s abou t t he ba l ance of b e n efits a nd h arms at t h e popu lati on le v el . E ven f o r m en aged 55 t o 69 y ears , t h e AUA c on cl ud e d t h at t h e qu alit y o f ev i dence f o r bene fi t s ass o ciate d wit h scree n i ng was m od erate , wh e r eas t he qua lit y o f t he ev i d e n ce f o r h arm was h i gh. T h e y rec o mme nded s h a r e d d e c i s i on m ak i ng f o r t h is g r oup, i n w ho m t h e y h a v e c on cl ud e d t he b e n e f its m ay ou t we i gh t he ha rm .

SKIN CANC E R SCREENING

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A ssessm en t s o f sk i n cance r s cree n i ng h a v e f o c u se d on mela no ma e nd po i n ts w it h ve r y littl e a tt en ti o n t o scree n i ng f o r non mela no ma s k i n ca n c e r . A s y stem a ti c r ev i ew o f sk i n can cer scree n i ng st ud ies e x ami n i ng t h e a v aila b le ev i dence t h r ough mi d 2005 c on cl ud e d t h at d irect e v i d e n ce o f

SKIN CANC E R SCREENING

Recommendations of Experts

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st ud ies . T he AC S r eco mm end s m on t h l y s k i n self-e x ami n ati on s a nd a y ear ly cli n ical s k i n exa mi na ti on as p art o f a r ou ti n e ca n cer-relate d c h ec kup . The U SP ST F fi nds i nsu f fi c i en t ev i d e n ce t o rec o mme nd f o r o r a g ai n st eit h er rou ti n e s k i n cance r sc r een i ng of t h e g e n eral popu lati on by p rimar y care prov i d e r s o r counse li ng pa ti e nts t o p erf o rm p eri od ic s k i n self-e x ami n ati ons. Th e tas k f o r ce does r eco mm e n d t h at cli n icia n s “remai n alert” f o r s k i n lesi on s w it h m a li gnan t f ea t u res w h e n p erf o rmi ng a phy sical e x ami n ati on f o r o t h e r pu r poses, pa rti cu l a rl y i n h i gh -ris k i nd i v i du als . T h e America n A ca d em y o f De rm a t o l ogy r eco mme nd s t h at p ers on s at h i gh est ris k (i . e ., t ho se w i th a s tr ong f a mil y h i sto r y o f mela no ma a nd m u lti p le at yp ical n ev i ) , p e rfor m fr equen t se lf- exa mi n ati on a nd see k a p r o fessi on al e v al u ati on o f the s k i n at le as t once pe r yea r . H i gh -ri sk i nd i v i dua l s a r e pers on s wit h m u lti p le n e v i o r at yp ical m o le s. Th e r e is consensus t hey shou l d b e e du cate d a bou t t h e n ee d f o r fre qu e n t s urv eill ance by a tr a i ned hea lt h -care p r ov i d er b e g i nn i ng at a n earl y a g e . I n t h e Un it ed St a t es, Aus tr a li a, a n d W ester n E u r op e , Ca u casia n me n a g e 50 y ea r s a nd ove r accoun t f o r ne arl y h alf o f all mela no ma cases . T h ere is so me d isc u ssio n t ha t m e l ano m a ea r ly d etecti on eff o rts s hou l d b e f o c u se d on t his popu lati on.

SKIN CANC E R SCREENING

Recommendations of Experts

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Collen M F , Dales LG, Friedman GD, et al. Multiphasic checkup evaluation stud y . 4. Preliminary cost benefit analysis for middle-aged men. P r ev Med 1973;2:236–246. Prorok PC, Kramer BS, Gohagan JK. Screening theory and study design: the basics. In: Kramer B, Prorok P , eds. Cancer Sc r eenin g . New Y ork: Marcel Dekker; 1999:29–53. W elch HG, Black WC. Overdiagnosis in cance r . J Natl Cancer Inst 2010;102:605–613. Y amamoto K, Hayashi Y , Hanada R, et al. Mass screening and age-specific incidence of neuroblastoma in Saitama Prefecture, Japan. J Clin Oncol 1995;13:2033–2038. W oods WG, Gao RN, Shuster JJ, et al. Screening of infants and mortality due to neuroblastoma. N Engl J Med 2002;346:1041–1046. Friedman GD, Collen M F , Fireman BH. Multiphasic Health Checkup Evaluation: a 16-year follow-up. J Ch r onic Dis 1986;39:453–463. Pinsky P F , Miller A, Kramer BS, et al. Evidence of a healthy volunteer e f fect in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Epidemiol 2007;165:874–881. Boyle P , Brawley O W . Prostate cancer: current evidence weighs against population screening. CA Cancer J Clin 2009;59:220–224.

SKIN CANC E R SCREENING

Recommendations of Experts

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Quintero E, Castells A, Bujanda L, et al. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 2012;366:697–706. Murakami R, T sukuma H, Ubukata T , et al. Estimation of validity of mass screening program for gastric cancer in Osaka, Japan. Cancer 1990;65:1255–1260. Kampschoer GH, Fujii A, Masuda Y . Gastric cancer detected by mass surve y . Comparison between mass survey and outpatient detection. Scand J Gast r oente r ol 1989;24:813–817. Stael von Holstein C, Eriksson S, Huldt B, et al. Endoscopic screening during 17 years for gastric stump carcinoma. A prospective clinical trial. Scand J Gast r oente r ol 1991;26:1020–1026. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cance r . N Engl J Med 2013;369: 1 106– 1 1 14. McMahon BJ, Bulkow L, Harpster A, et al. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based stud y . Hepatology 2000;32:842–846. Chalasani N, Horlander JC S r , Said A, et al. Screening for hepatocellular carcinoma in patients with advanced cirrhosis. Am J Gast r oente r ol 1999;94:2988–2993. Sherman M, Peltekian KM, Lee C. Screening for hepatocel l ular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 1995;22:432–438. Dodd GD 3rd, Miller WJ, Baron RL, et al. Detection of malignant tumors in end-stage cirrhotic livers: e f ficacy of sonography as a screening technique. AJR Am J Roentgenol 1992;159:727–733. Laara E, Day NE, Hakama M. T rends in mortality from cervical cancer in the Nordic countries: association with o r ganised screening programmes. Lancet 1987;1:1247–1249. Christopherson WM, Lundin FE J r , Mendez WM, et al. Cervical cancer control: a study of morbidity and mortality trends over a twenty-one-year period. Cancer 1976;38:1357–1366. Janerich D T , Hadjimichael O, Schwartz PE, et al. The screening histories of women with invasive cervical cance r , Connecticut. Am J Public Health 1995;85:791–794. Sawaya G F , McConnell KJ, Kulasingam SL, et al. Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. N Engl J Med 2003;349:1501–1509. Sankaranarayanan R, Nene BM, Shastri SS, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009;360:1385–1394. V esco KK, Whitlock E P , Eder M, et al. In: Sc r eening for Cervical Cancer: A Systematic Evidence Review for the US P r eventive Services T ask Fo r ce . Rockville, MD: Agency for Healthcare Research and Quality; 20 1 1. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytolog y . JAMA 2002;287:2 1 14–2 1 19. Darragh TM, Colgan TJ, Thomas Cox J, et al. The Lower Anogenital Squamous T erminology Standardization project for HP V -associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Patholog y . Int J Gynecol Pathol 2013;32:76– 1 15. Ho G Y , Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338:423–428. Holowaty P , Miller AB, Rohan T , et al. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 1999;91:252–258. Richardson H, Kelsall G, T ellier P , et al. The natural history of type-specific human papillomavirus infections in female university students. Cancer Epidemiol Biomarkers P r ev 2003;12:485–490.

SKIN CANC E R SCREENING

Recommendations of Experts

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Montie JE, Smith JA. Whitmoreisms: memorable quotes from W illet F . Whitmore, J r , M.D. U r ology 2004;63:207–209. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cance r . JAMA 2005;293:2095–2101. Lu- Y ao G, Albertsen PC, Stanford JL, et al. Screening, treatment, and prostate cancer mortality in the Seattle area and Connecticut: fifteen-year follow-up. J Gen Intern Med 2008;23:1809–1814. Thompson IM, Chi C, Ankerst D P , et al. E f fect of finasteride on the sensitivity of PSA for detecting prostate cance r . J Natl Cancer Inst 2006;98: 1 128– 1 133. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per millilite r . N Engl J Med 2004;350:2239–2246. Thompson IM, Ankerst D P , Chi C, et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lowe r . JAMA 2005;294:66–70. W idmark A, Klepp O, Solbe r g A, et al. Endocrine treatment, with or without radiotherap y , in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 2009;373:301–308. Bill-Axelson A, Holmbe r g L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cance r . N Engl J Med 20 1 1;364:1708–1717. W ilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cance r . N Engl J Med 2012;367:203–213. Andriole GL, Crawford ED, Grubb RL 3rd, et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening T rial: mortality results after 13 years of follow-up. J Natl Cancer Inst 2012;104:125–132. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European stud y . N Engl J Med 2009;360:1320–1328. Schroder FH, Hugosson J, Roobol MJ, et al. Prostate-cancer mortality at 1 1 years of follow-up. N Engl J Med 2012;366:981–990. W olters T , Roobol MJ, Steyerbe r g E W , et al. The e f fect of study arm on prostate cancer treatment in the la r ge screening trial ERSPC. Int J Cancer 2010;126:2387–2393. Hugosson J, Carlsson S, Aus G, et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol 2010; 1 1:725–732. Kilpelainen T P , T ammela TL, Malila N, et al. Prostate cancer mortality in the Finnish randomized screening trial. J Natl Cancer Inst 2013;105:719–725. Center MM, Jemal A, Lortet- T ieulent J, et al. International variation in prostate cancer incidence and mortality rates. Eur U r ol 2012;61:1079–1092. Boyle P . Screening for prostate cancer: have you had your cholesterol measured? BJU Int 2003;92:191–199. Greene KL, Albertsen PC, Babaian RJ, et al. Prostate specific antigen best practice statement: 2009 update. J U r ol 2009;182:2232–2241. W olf AM, W ender RC, Etzioni RB, et al. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin 2010;60:70–98. Carter HB. American Urological Association (AUA) guideline on prostate cancer detection: process and rationale. BJU Int 2013; 1 12:543–547. W ol f f T , T ai E, Miller T . Screening for skin cancer: an update of the evidence for the U.S. Preventive Services T ask Force. Ann Intern Med 2009;150:194–198.

SKIN CANC E R SCREENING

Recommendations of Experts

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Katalinic A, W aldmann A, W einstock MA, et al. Does skin cancer screening save lives?: an observational study comparing trends in melanoma mortality in regions with and without screening. Cancer 2012; 1 18:5395–5402. Breitbart E W , W aldmann A, Nolte S, et al. Systematic skin cancer screening in Northern German y . J Am Acad Dermatol 2012;66:201–2 1 1. Smith RA, Brooks D, Cokkinides V , et al. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin 2013;63:88–105. U.S. Preventive Services T ask Force. Screening for skin cancer: U.S. Preventive Services T ask Force recommendation statement. Ann Intern Med 2009;150:188–193.

SKIN CANC E R SCREENING

Recommendations of Experts

Gen e t i c Couns e ling

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Gen e t i c Couns e ling

IN T RODUCTION

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Cli n ical ly based gene ti c t es ti ng h as e vo l v e d fr o m a n un c o mm on a n al y sis ord e r e d f o r t he r a r e he r ed it a r y ca n cer famil y t o a wi d el y a v aila b le t oo l ord e r e d on a r ou ti ne bas i s t o assist i n s u r g ical a nd ra d iati on d ecisi on ma k i ng, che m op r even ti on, and s u r v eilla n ce o f t h e p atie n t wit h ca n ce r , as w ell as m anage m en t o f t he ent ire famil y . T h e e vo l u ti on o f t h is fiel d h as c r eate d a need f o r accu r a t e can cer g e n etic c oun seli ng a nd ris k assessme nt. Ex te n si ve cove r age o f t h i s t op ic by t h e me d ia , i n cl ud i ng A ng eli n a J o lie ’ s pub lic d i sc l osu r e o f he r BR C A 1 + stat u s i n Ma y 2013, a nd wi d es p rea d a dv e r tisi ng by co mm e r c i a l t e sti ng la bo rat o ries h a v e f u rt h er f u ele d t h e d ema nd f o r counse li ng and t es ti ng. Ca n c e r gene ti c counse li ng is a c o mm un icati on p r o cess b etwee n a h ea lth -ca r e profess i ona l and an i nd i v i du al c on cer n i ng ca n cer o cc u rre n ce a nd ri sk i n h is or he r f a mil y . T he p r o cess , w h ic h ma y i n cl ud e t h e e n tire famil y t hrough a b l end o f gene ti c, me d ical , a nd p s y c ho s o cial assessme n ts a nd i n te rv e n ti ons, has been desc ri b e d as a b ri dg e b etwee n t h e fiel d s o f t r a d iti ona l onco l ogy and genet ic c oun seli ng . Th e goa l s o f t h i s p r ocess i n cl ud e p r ov i d i ng t h e clie n t wit h a n assessm ent of i nd i v i dua l cance r ri sk, wh i l e o f feri ng t h e em o ti on al s uppo rt n ee d e d t o und e r sta nd and cope w it h t h i s i n f o rmati on. It als o i nvo l v es d eci ph eri ng wh et h e r t he cance r s i n a f a mi ly are li k el y t o b e ca u se d by a m u tati on i n a ca n ce r g e ne and, if so, wh i ch on e . T h ere are >30 h ere d itar y ca n cer s yndro m es, m any o f wh i ch can b e ca u se d by m u tati on s i n d iffere n t g e n es . Th e r e fo r e, t es ti ng f o r t hese synd r o mes ca n b e c o m p licate d. A dv ertiseme nts

IN T RODUCTION

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by g e n e t i c t es ti ng co m pan i es b ill g e n etic testi ng as a sim p le p r o cess t h at ca n b e c a rri ed ou t by hea lt h - c are p r o fessi on als wit h no trai n i ng i n t h is are a; how e v e r , t he r e a r e m any gene s i nvo l v e d i n ca n ce r , t h e i n ter p retati on o f t he test r es u lt s i s o ft en co m p li ca te d, t h e ris k o f res u lt misi n ter p retati on is g r eat a nd asso c i a t ed w it h po t en ti a l lia b ilit y , a nd t h e em o ti on al a nd p s y c ho l og i cal r ami f icati ons f o r t he pa ti en t a n d famil y ca n b e po werf u l . , A few hou rs o f t r ai n i ng by a co m pany gene r a ti ng a p r o fit fr o m t h e sale o f t h ese tests do e s no t a d e qua t e l y p r epa r e p r ov i d ers t o o f fer t h eir o w n g e n etic c oun seli ng a nd testi ng s e r v i ces F u rt he rm o r e, t h e d ele g ati on o f g e n etic testi ng r es pon sibiliti es t o o f fi ce s t a f f a nd, rece n tl y , mamm og ra phy tec hn icia n s , i s ala r mi ng and li ke l y p r esen t s a hug e lia b ilit y f o r t h ese o r d eri ng phy sicia n s , t h ei r pr acti ces, and t he ir i ns tit u ti on s . P r o vi d ers s hou l d p r o cee d wit h c au ti on be f o r e t ak i ng on t he r o le o f p rim a ry g e n etic c oun sel o r f o r t h eir pa tie n ts . C ou n se li ng abou t he r ed it a r y ca n cers d i f fers fr o m tr ad iti ona l g e n etic c oun seli ng i n seve r a l ways. C lie n ts see k i ng ca n cer g e n etic c oun seli ng ar e r a r el y c once r ned w it h r ep r odu cti v e d ecisi on s , w h ic h are o fte n t h e p rimar y fo c u s i n tr ad iti ona l gene ti c coun seli ng, bu t are i n stea d see k i ng i n f o rmati on a bou t t he ir own and o t he r r e lati v es’ c h a n ces o f d e v el op i ng ca n ce r

IN T RODUCTION

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IN T RODUCTION

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Add iti ona ll y , t he ri sks g i ven a re no t a b s o l u te bu t c h a ng e ov er time as t he f amil y a nd pe r sona l h i s t o r y ch a ng es a nd t h e p atie n t a g es . T h e ris k re du c tion op ti on s ava il ab l e a r e o ft en r ad ical (e .g., c h em op re v e n ti on o r p r ophy lacti c s u r g e ry), and a r e no t app r op riate f o r e v er y p atie n t at e v er y a g e . T h e s urv eill ance and m anage m en t p la n m u st b e tail o re d t o t h e p atie n t ’ s a g e , c h il db ea r i ng s t a t us, m enopau sal stat u s , ris k cate go r y , ease o f scree n i ng, and p e r s on al p r e f e r ences and w ill li k el y c h a ng e ov er time wit h t h e p atie n t . T he u ltimate goa l o f cance r gene tic c oun seli ng is t o h el p t h e p atie n t reac h t he d ecisi on bes t su it ed t o he r pe r son al sit u ati on, n ee d s , a nd circ u msta n ces . Th e r e a r e now a s i gn ifi can t nu m b er o f referral ce n ters acr o ss t h e c ount r y s p eciali z i ng i n cance r gene ti c c oun seli ng, a nd t h e nu m b ers are g r o wi ng. How e v e r , so m e expe rt s i ns i s t t h at t h e on l y wa y t o k ee p up wit h t h e ov e rwhe lmi ng de m and f o r coun seli ng will b e t o e du cate m o re phy sicia ns a nd nurses i n cance r gene ti cs. T h e feasi b ilit y o f a dd i ng a no t h er s p ecialize d

IN T RODUCTION

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a nd tim e - consu mi ng t ask t o t h e cli n ical bu r d e n o f t h ese p r o fessi on als is qu esti on a b l e, pa rti cu l a rl y w it h a v era g e p atie n t e n c oun ters o f 19.5 a nd 21.6 mi nu tes f o r gene r a l p r ac titi on ers a nd gyn ec o l og ists , res p ecti v el y A m o r e pr actica l goa l i s t o be tt e r educ ate cli n icia n s i n t h e area o f ris k assessme nt so t h at t h e y can sc r een t he ir pa ti en t popu lati on s f o r i nd i v i du als at h i gh ris k f o r h e r e d ita ry cance r and r e f e r t h em on t o c o m p re h e n si v e c oun seli ng a nd testi ng p r og r a m s. Access t o gen etic c oun seli ng is no l ong er a n iss u e b eca u se t he r e a r e now i n t e r ne t , phon e , a nd satellite- b ase d teleme d ici n e se rv ices ava il ab l e ( ) , wit h m o st maj o r h ealt h i n s u ra n ce c o m p a nies now cove ri ng t hese ser v ice s a nd se v eral re qu iri ng t h em .

W H O IS A CANDID A TE F O R CANC E R G E NETIC C O UNSELING?

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W H O IS A CANDID A TE F O R CANC E R G E NETIC C O UNSELING?

W H O IS A CANDID A TE F O R CANC E R G E NETIC C O UNSELING?

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On l y 5 % t o 10 % o f m os t can cer is t hough t t o b e ca u se d by si ng le m u tati ons w it h i n a u t oso m a l- do mi nan t in h erite d ca n cer s u sce p ti b ilit y g e n es . T h e key for cli n i c i ans i s t o de t e rmi ne w h ic h p atie n ts are at g reatest ris k t o carr y a h e r e d ita ry m u t a ti on. T he r e a r e se v e n critical ris k fact o rs i n h ere d itar y ca n ce r . T he fir s t is earl y a g e o f ca n cer on set . T h is ris k fact o r , eve n i n t he absence o f a f am il y h ist o r y , h as b ee n s ho w n t o b e ass o ciate d w it h a n i nc r eased fr equency o f g ermli n e m u tati on s i n ma ny t yp es o f ca n ce r s . T he second ri sk f ac t o r is t h e p rese n ce o f t h e same ca n cer i n m u lti p le a f f ec t ed r e l a ti ves on th e same si d e o f t h e p e d i g ree . T h ese ca n cer s do no t need t o be o f s imil a r h ist o l og ic t yp e i n o r d er t o b e ca u se d by a si ngle m u tati on. T he t h ir d ri sk f ac t or is t h e cl u steri ng o f ca n cers kno w n t o b e ca u se d by a s i ng l e gene m u t at i on i n on e famil y (e .g., br east/ ova ri an / panc r ea ti c can cer o r c o l on / u teri n e/ ov aria n ca n cers) . T h e four t h r is k f ac t o r i s t he occu r r e n ce o f m u lti p le p rimar y ca n cers i n on e i nd i v i du al . T h i s i nc l udes m u lti p le p rimar y b reast o r c o l on ca n cers as wel l as a si ng le i nd i v i dua l w it h sepa rate ca n cers kno w n t o b e ca u se d by a si ng le

W H O IS A CANDID A TE F O R CANC E R G E NETIC C O UNSELING?

nan nan

g e n e m u t a ti on ( e.g., b r eas t an d ov aria n ca n cer i n a si ng le i nd i v i du al) . E t hn icit y a l so p l ays a r o l e i n determi n i ng w ho is at g reatest ris k t o carr y a h e r e d ita ry cance r m u t a ti on. I nd i v i du als o f Jewis h a n cestr y are at i n crease d r is k t o carr y t h r ee spec ifi c BRCA 1 / 2 m u tati on s . T h e p rese n ce o f a ca n c e r t h at pr e sen t s unusua ll y— i n t h is case , b reast ca n cer i n a male — re p rese n ts a si x t h r is k f ac t o r and i s im po rta n t e v e n w h e n it is t h e on l y ris k fact o r p re sent. Fi n all y , t he l as t ri sk f ac t o r i s p at ho l og y . Certai n t yp es o f ca n cer are ov e rr e presen t ed i n he r ed it a r y ca n cer families . F o r e x am p le , me du llar y a nd t r i p le n e ga ti ve b r eas t cance r s (w h ere t h e estr og e n, p r og ester on e a nd Her2 r ece p t ors a r e a ll nega ti ve, o fte n a bb re v iate d ER-/PR-/Her 2 ) are ov e rr e presen t ed i n BR C A 1 f am ilies a nd t h e Nati on al C o m p re h e n si v e Ca n ce r Ne t wo r k ( NCCN ) BRC A testi ng gu i d eli n es no w i n cl ud e i nd i v i duals d ia gno se d w it h a tri p l e nega tive b reast ca n cer < a g e 60 y ears . H o we v e r , br east c ance r pa ti en t s w it hou t t h ese p at ho l og ic fi nd i ng s are no t n ecessar ily at l ow e r ri sk t o ca rr y a m u t a ti on. I n c on trast , p atie n ts wit h a bo r d erli n e o r m u ci nous ova ri an ca r c i no m a are at l o wer ris k t o carr y a BRCA 1 o r BRC A2 m u tati o n and m ay i ns t ead c arr y a m u tati on i n a d iffere n t g e n e . It is alre ady w ell - esta b li shed t ha t m edu ll ary t hy r o i d carci no ma , se b ace ou s a d e no ma o r ca r ci noma, ad r enoco rti ca l ca r c i no ma b ef o re t h e a g e o f 25 y ears , a nd m u lti p le adeno m a t ous, ha m a rt o mat ou s , o r j uv e n ile c o l on po l yp s are i nd icati ve o f o t he r r a r e he r ed itar y ca n cer s ynd r o mes . T h ese ris k fact o r s s hou l d b e v i ewed i n t he con t ex t o f t h e e n tire famil y h ist o r y , a nd m u st b e w ei gh e d i n p r opo rti on t o t he nu m b er o f i nd i v i du als w ho h a v e no t d e v el oped ca n ce r . T he ri sk assess m en t is o fte n limite d i n families t h at are small o r h a v e f ew f e m a l e r e l a ti ves ; i n s u c h families , a si ng le ris k fact o r ma y carr y m or e we i gh t . A less co mm on, bu t ex tr em el y im po rta n t , fi nd i ng is t h e p rese n ce o f unu s u al phys i ca l fi nd i ngs o r b irt h d efects t h at are kno w n t o b e ass o ciate d w it h r a re he r ed it a r y cance r synd r o mes . E x am p les i n cl ud e b e n i gn s k i n f i nd i ng s , au ti s m , l a r ge head ci rc u mfere n c a nd t hy r o i d d is o r d ers i n

W H O IS A CANDID A TE F O R CANC E R G E NETIC C O UNSELING?

nan nan

C owd e n synd r o m e, odon t ogen ic k erat o c y sts i n G o rli n s ynd r o me , a nd d esm o i d t u m o r s o r den t a l abn ormalities i n familial a d e no mat ou s po l yposis ( F A P ) T hese and o t he r fi nd i ng s s hou l d p r o m p t f u rt h er i nv esti g ati on o f the p atie n t ’ s f a mil y h i s t o r y and con si d erati on o f a referral t o g e n etic c oun seli ng. In t h is chap t e r , t he b r eas t/ ov aria n ca n cer c oun seli ng sessi on wit h a f emale pa ti en t w ill se r ve as a para d i g m by w h ic h all o t h er sessi on s ma y fo ll ow broad l y .

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

nan nan

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

P r ecounseling Information

nan nan

P r ecounseling Information

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Family History

nan nan

An acc u r a t e f a mil y h i s t o r y i s undoub te d l y on e o f t h e m o st esse n tial c o m ponen t s o f t he cance r gen etic c oun seli ng sessi on. O p timall y , a family h ist ory shou l d i nc l ude a t l eas t t h ree g e n erati on s; ho we v e r , p atie n ts do n o t al w a y s have t h i s i n f o rm a ti on. F o r eac h i nd i v i du al affecte d wit h ca n ce r , i t is im por ta n t t o docu m en t t he ex act d ia gno sis , a g e at d ia gno sis , treatme n t st r ate g ie s, and env ir on m en t a l e xpo s u res (i . e ., o cc up ati on al e xpo s u res , ci g a r ett es, o t he r agen t s ) . T h e c u rre n t a g e o f t h e i nd i v i du al , lateralit y , a nd o cc urr e nce o f any o t he r canc ers m u st als o b e do c u me n te d. Ca n cer d ia gno se s shou l d be con firm ed wit h p at ho l ogy re po rts w h e n e v er po ssi b l e. A st udy by L ove e t a l r eveal e d t h at i nd i v i du als acc u ratel y re po rte d t h e pr ima ry s it e o f cance r on l y 83 % o f t h e time i n t h eir first d e g ree relati v es

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Family History

nan nan

w it h can ce r , and 67 % and 60 % o f t h e time i n sec ond a nd t h ir d d e g ree r elati v es , r espec ti ve l y . It i s com m on f o r p atie n ts t o re po rt a u teri n e ca n c e r as a n ov a r i an cance r , o r a co l on po l yp as a n i nv asi v e c o l o rectal ca n ce r . T h e se d i f f e r e nces, a lt hough see mi n gl y s ub tle t o t h e p atie n t , ca n ma k e a t r eme ndous d i f f e r ence i n ri sk assessme n t . I nd i v i du als s hou l d b e as k e d if t h e r e a re any consangu i neous (i nb re d ) relati on s h i p s i n t h e famil y , if a ny r elati v es we r e bo r n w it h b irt h d efects o r me n tal retar d ati on, a nd w h et h er o t h e r g e ne ti c d i seases r un i n t h e famil y (e .g., Fa n c on i a n emia , C o w d e n s yndro m e ) , because t hese p i e ces o f i n f o rmati on c ou l d p r ov e t o b e im po r tant i n r eac hing a d i agnos i s. Th e m os t co mm on mi sconc e p ti on i n famil y h ist o r y ta k i ng is t h at s o me ho w a m a t e r na l f a mil y h ist o r y o f b reast , ov aria n, o r u teri n e ca n cer i s m or e si gn ifi can t t han a pa t e r n al h ist o r y . C onv ersel y , ma ny still b elie v e th at a p ate rn al h i s t o r y o f p r os t a t e ca n cer is m o re si gn ifica n t t h a n a mater n al h ist or y . F ew cance r genes d i s c ov ere d t hu s far are l o cate d on t h e se x c hro m oso m es and, t he r e f o r e, b o t h mater n al a nd p ater n al h ist o r y are si gn i f ic an t and m us t be exp l o re d t ho r ough l y . It h as als o b ec o me n ecessar y t o elicit t he spouse ’ s pe r sona l a nd famil y h ist o r y o f ca n ce r . T h is h as b ea ring on t h e ca nce r s t a t us o f co mm on c h il d re n, bu t ma y als o d etermi n e if c h il d r en a r e at i nc r eased ri sk f o r a se ri ou s recessi v e g e n etic d isease s u c h as Fa n c oni a n emia Ch il d r en who i nhe rit tw o c op ies o f a BRCA 2 m u tati on ( on e fr om eac h p a ren t) a r e now known t o h a v e t h is seri ou s d is o r d er c h aracterize d by d e f ecti ve DNA r epa ir and h i gh rates o f b irt h d efects , a p lastic a n emia , le uk emi a, and so li d t u m o r s Patie n ts s hou l d b e e n c ou ra g e d t o re po rt c h a ng es i n t he ir f a mil y h i s t o r y ov er time (e .g., n ew ca n cer d ia gno ses , g e n etic tes ti ng r esu lt s i n r e l a t iv es) , b eca u se t h is ma y c h a ng e t h eir ris k assessme n t and counse li ng. A d et a il ed f a mil y h i s t o r y shou l d als o i n cl ud e g e n etic d iseases , b irt h d e f ects , m en t a l r e t a r da ti on, multi p le miscarria g es , a nd i n fa n t d eat h s . A h ist ory o f ce rt a i n r ecess i ve gen etic d iseases (e .g., ata x ia tela ng iectasia , Fa n c on i ane mi a ) can i nd i ca t e t h at h ealt hy famil y mem b ers w ho carr y j ust on e c opy o f t he gene ti c m u t a ti on ma y b e at i n crease d ris k t o d e v el op ca n ce r . O t he r gene ti c d i so r d ers , s u c h as h ere d itar y h em o rr h a g ic

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Family History

nan nan

tela ng ie c t as i a, can be assoc i a te d wit h a h ere d itar y ca n cer s ynd r o me ca u s ed by a m u t a ti on i n t he sa m e gen e — i n t h is case , j uv e n ile po l ypo sis .

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Dysmorphology Sc r eening

nan nan

Dysmorphology Sc r eening

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Risk Assessment

nan nan

Ris k ass ess m en t i s one o f t he m o st c o m p licate d c o m pon e n ts o f t h e g e n e tic c oun seli ng sess i on. It i s c r uc ial t o remem b er t h at ris k assessme n t c h a nges ov e r tim e as t he pe r son ages a nd as t h e h ealt h stat u ses o f t h eir famil y mem b e rs change. R i sk assess me n t ca n b e b r ok e n do w n i n t o t h ree se p arat e c o m ponen t s. Wh at i s t he chance t ha t t he c oun selee will d e v el op t h e ca n cer ob ser v e d in h is/ he r f a mil y ( o r a gene ticall y relate d ca n cer s u c h as ov aria n ca n cer due t o a fa mil y h i s t o r y o f b r ea st ca n cer)? Wh at i s t he chance t ha t t he ca n cers i n t h is famil y are ca u se d by a si ng l e g e n e mu t a ti on? Wh at i s t he chance t ha t we ca n i d e n tif y t h e g e n e m u tati on i n t h is famil y w it h ou r cu rr en t know l edg e a nd la bo rat o r y tec hn i qu es? Ca n ce r c l us t e ri ng i n a f a mil y ma y b e du e t o g e n etic a nd / o r e nv ir on me n t al f act or s , o r m ay be co i nc i den t a l b eca u se s o me ca n cers are v er y c o mm on in t h e g e n e ra l popu l a ti on A lt hough i nh erite d fact o rs ma y b e t h e p rimar y ca u se of cance r s i n so m e f a m i lies , i n o t h ers , ca n cer ma y d e v el op b eca u s e an

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Risk Assessment

nan nan

i nh e r ite d f ac t o r i nc r eases t he ind i v i du al ’ s s u sce p ti b ilit y t o e nv ir on me n ta l ca r ci no g ens. It i s a l so poss i b le t h at mem b ers o f t h e same famil y ma y b e e xpo se d t o s imil a r env ir on m en tal e xpo s u res du e t o s h are d g e og ra phy o r p atte rn s i n behav i o r and d i e t that ma y i n crease t h e ris k o f ca n ce r

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Risk Assessment

nan nan

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Risk Assessment

nan nan

Th e r e fo r e, it i s im po rt an t t o d isti ngu is h t h e d iffere n ce b etwee n a familia l p atte rn o f cance r ( due t o env ir on me n tal fact o rs o r c h a n ce) a nd a h ere d itar y p atte rn o f cance r ( due t o a sh are d g e n etic m u tati on ) . Eme r g i ng researc h i s als o e v al ua ti ng t he r o l e and cl i n ical u tilit y o f m o re c o mm on l o w- p e n etra nce s u sce p ti b ilit y genes and s i ng le nu cle o ti d e po l y m o r ph isms (SNP) t h at m ay acc oun t f o r a p r opo rti on o f f a milial ca n cers . Se v e ra l m ode l s a r e ava il ab le t o calc u late t h e c h a n ce t h at a w o ma n wi ll d e v el op b r eas t cance r , i nc l ud i ng t h e Gail a nd Cla u s m od els . C o m pu t e r - b ase d m ode l s a r e a l so ava il ab le t o h el p d etermi n e t h e c h a n ce t h at a BRC A m u tati on w ill be f ound i n a f a mil y . At first g la n ce , ma ny o f t h ese m odels a pp ea r sim p l e and easy t o use, a nd it ma y b e tem p ti ng t o e x cl u si v el y rel y on t h ese m ode l s t o assess cance r ris k. H o we v e r , eac h m od el h as its stre ng t hs a nd w ea knesses, and t he coun sel o r n ee d s t o und ersta nd t h e limitati on s well a nd know wh i ch a r e va li da t e d , w h ic h are c on si d ere d p r ob lematic , w h e n a m od el w ill no t wo r k on a pa rtic u lar p atie n t , o r w h e n a no t h er g e n etic s yndro m e shou l d be cons i de r ed. F o r e x am p le , non e o f t h e e x isti ng m od e ls a r e a b le t o f ac t o r i n o t he r ri sk s t h at ma y b e esse n tial i n h ere d itar y ris k calc u lati on ( e.g., a s i s t e r who was d ia gno se d wit h b reast ca n cer after r a d iati on tr ea tm en t f o r Hodgk i n d isease) . Th e risk o f a de t ec t ab l e m u tati on will als o v ar y b ase d on ca n cer h ist ory a nd t h e deg r ee o f r e l a ti onsh i p t o a n a f fecte d famil y mem b e r . F o r e x am p l e, f amil y me m be r s w it h ea rl y - o nset b reast ca n cer h a v e a h i gh er li k eli hood o f testi ng pos iti ve t han una f f ec te d famil y mem b ers . T h eref o re , t h e ris k assessme n t p r ocess shou l d i n cl ud e a d isc u ssi on o f w h ic h famil y mem b er is t h e b est cand i da t e f o r t es ti ng.

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

DNA T esting

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

E me r g i ng da t a r evea l t ha t be t w ee n 30 % t o 50 % o f g e n etic tests are o r d er ed i n a pprop ri a t e l y , wh i ch i s p r ob lematic f o r p atie n ts , cli n icia n s , a nd i n s u rer s . – Rece n t da t a de m ons tr a t e t ha t ma ny me d ical p r ov i d ers h a v e d i f fic u lt y i n te rpr et ing even bas i c ped i g rees a nd g e n etic test res u lts . A dd iti on al st ud ies have de m ons tr a t ed t h at a n i n acc u rate i n ter p retati on o f g e n etic testi ng has been shown t o r esu lt i n i n a pp r op riate me d ical ma n a g eme n t r ec o mm enda ti ons, unnecessa r y p r ophy lactic s u r g eries , a massi v e waste o f h ealt h- car e do ll a r s, psychoso cial d istress , a nd false reass u ra n ce f o r p atie n ts . In te rp r e t a ti ons a r e beco mi ng i n creasi ng l y c o m p licate d as m o re tests and g e n e p a ne l s beco m e ava il ab l e. F o r e x am p le , on e st udy d em on strate d t h a t a pprox im a t e l y 25 % o f h i gh -ris k families t h at were BRCA 1 a nd BRCA 2 n e g ati v e by co mm e r c i a ll y av aila b le se qu e n ci ng were f ound t o carr y a d eleti on o r dup li ca ti on i n one o f t h ese g e n es , o r a m u tati on i n a no t h er g e n e Th is i s pa rti cu l a rl y conce rni ng i n a n era i n w h ic h testi ng c o m p a n ies ar e ca nv assi ng phys i c i ans, and no w mamm og ra phy tec hn icia n s , a nd e n c our agi ng t he m t o pe rf o rm t h eir o w n c oun seli ng a nd testi ng. T h e po te n tial im pac t o f t es t r esu lts on t h e p atie n t a nd h is/ h er famil y is g reat and,

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

t h e r e fore, accu r a t e i n t e r p r e t a ti on o f t h e res u lts is p aram oun t . Pr o fessi on a l group s have r ecogn i zed t h i s and h a v e a dop te d sta nd ar d s e n c ou ra g i ng cli n ician s t o r e f e r pa ti en t s t o g e n etics e xp erts t o e n s u re p r op er o r d eri ng and i n te rpr etati on o f gene ti c t es t s. T h e U . S . Pre v e n ti v e Ser v ices T as k F o rce r ec o mm ends t ha t wo m en who se famil y h ist o r y is s ugg esti v e o f a BRCA m u tati on be r e f e rr ed f o r genet ic c oun seli ng b ef o re b ei ng o ffere d g e n etic testi ng . T he A m e ri can Co ll eg e o f S u r g e on s’ C o mmissi on on Ca n cer sta nd a rds i nc l ude “cance r ri sk assessme n t , g e n etic c oun seli ng a nd testi ng se rv ices p r ov i ded t o pa ti en t s eit h er on site o r by referral , by a qu alifie d g e n etics p r o f ess i ona l . ” I n an e f f o rt t o re du ce err o rs , s o me i n s u ra n ce c o m p a nies a r e r equ iri ng gene tic c oun seli ng by a certifie d g e n etic c oun se lo r b e for e t es ti ng f o r he r ed it a r y b reast o r c o l on ca n cer s ynd r o mes . Res u lt s can f a ll i n t o a f ew b r o a d cate go ries . It is im po rta n t t o no te t hat a n e g ati v e t es t r esu lt can ac t ua ll y b e i n ter p rete d i n t h ree d i f fere n t wa y s , d etaile d i n #2, #3, and #4, wh ic h f o ll o ws . 1. D ele te ri ous m u t a ti on “po siti v e . ” W h e n a d eleteri ou s m u tati on i n a we ll - known cance r gene i s d i scov ere d, t h e ca n cer ris k s f o r t h e p atie n t a nd he r f amil y a r e r e l a ti ve l y s tr a i gh tf o rwar d. H o we v e r , wit h t h e d e v el op me n t o f m u lt igene pane l s and t he incl u si on o f ma ny lesser kno w n g e n es , t h e r is k s o f de t ec ti ng a m u t a ti on wit h i n a g e n e w ho se ca n cer ris k s are ill d e f i ned and m ed i ca l m anag eme n t op ti on s unkno w n is m u c h g reate r . Ev e n f o r we ll- known gen es , t h e ris k s are no t p recise a nd s hou l d b e pr es en t ed t o pa ti en t s as a r is k ra ng e . W h e n a tr u e m u tati on is f ound, it is c riti ca l t o t es t bo t h par e n ts (w h e n e v er po ssi b le) t o d etermi n e fr om wh ic h s i de o f t he f a mil y t h e m u tati on is o ri g i n ati ng, e v e n w h e n t h e a n s we r appea r s obv i ous. 2. T ru e ne g a ti ve. An i nd i v i du al do es no t carr y t h e d eleteri ou s m u tati on foun d i n he r f a mil y , wh i ch i d eall y , h as b ee n p r ov e n t o se g re g ate wit h the ca n c e r f a mil y h i s t o r y . I n t h is case , t h e p atie n t ’ s ca n cer ris k s are u s u a lly r e duced t o t he popu l a ti on ris k s . 3. N e g a ti ve. A m u t a ti on was no t d etecte d, a nd t h e ca n cers i n t h e famil y a r e no t li ke l y t o be he r ed it a r y b ase d on t h e p ers on al a nd famil y h ist o r y

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

asses s m en t . F o r exa m p l e, a p atie n t is d ia gno se d wit h b reast ca n cer at a g e 38 yea r s and co m es fr o m a la r g e famil y wit h no o t h er ca n cer d ia gnoses and r e l a ti ves who d ie d at o l d a g es o f o t h er ca u ses . 4. Un i n f o rm a ti ve. A m u t a ti o n ca nno t b e f ound i n a f fecte d famil y mem be r s of a f a mil y i n wh i ch t he can cer p atter n a pp ears t o b e h ere d itar y ; t h er e is li k el y an unde t ec t ab l e m u tati on wit h i n t h e g e n e , o r t h e famil y carries a m u tati on i n a d i f f e r en t gen e . If , f o r e x am p le , t h e p atie n t d e v el op e d br east cance r a t age 38 ye ars , h as a fat h er wit h b reast ca n ce r , a nd h as a p ate rna l aun t who deve l op e d b reast a nd ov aria n ca n cers b ef o re a g e 5 0 y ea rs, a nega ti ve t es t r esu l t w ou l d b e alm o st mea n i ng less . It w ou l d sim p l y m ean t ha t t he f a mil y h as a m u tati on t h at c ou l d no t b e i d e n tifi ed w it h ou r cu rr en t t es ti ng met hod s o r a m u tati on i n a no t h er ca n cer g e ne. Th e en tir e f a mil y wou l d b e f o ll o we d as h i gh ris k. 5. V a r i an t o f unce rt a i n s i g n if i ca n ce . A g e n etic c h a ng e is i d e n tifie d, t h e si gn ifi cance o f wh i ch i s unkno w n. It is po ssi b le t h at t h is c h a ng e is d elet e ri ous o r co m p l e t e l y b e n i gn. It ma y b e h el p f u l t o test o t h er a ffe cted f amil y m e m be r s t o see if t h e m u tati on se g re g ates wit h d isease i n t h e f amil y . If it does no t seg r e gate , t h e v aria n t is less li k el y t o b e si gn ific ant. If it does, t he va ri an t i s m o re li k el y t o b e si gn ifica n t . Ot h er t oo ls , i n cl ud i ng a sp li ce s it e p r ed ict o r , i n c on j un cti on wit h d ata on s p ecies c on s e r va ti on and a mi no ac i d d i f fere n ce sc o res , ca n als o b e h el p f u l i n d ete r mi n i ng t he li ke li hoo d t h at a v aria n t is si gn ifica n t . It is rarel y h el p f u l ( and can be de tri m e n tal) t o test una ffecte d famil y mem b ers f o r s u c h va ri an t s. T he r a t es o f v aria n ts o f un certai n si gn ifica n ce v ar y g r eatly d e p e nd i ng on t he r epo rti ng p r o t o c o ls o f t h e la b a nd t h e g e n es a n al y z ed. C r eati on o f open da t abases t h r ough a n ati on wi d e m ov eme n t calle d Fr ee t h e Da t a w ill li ke l y im p r ov e v aria n t re po rti ng f o r all la bo rat o ries . In or d e r t o p i npo i n t t he m u tati on i n a famil y , a n a f fecte d i nd i v i du al m ost li k el y t o ca rr y t he m u t a ti on shou l d b e teste d first w h e n e v er po ssi b le . T h i s is m o st of te n a pe r son a f f ec t ed wit h t h e ca n cer i n qu esti on at t h e earliest a ge. T est s ub j ec t s shou l d be se l ec te d wit h care , b eca u se it is po ssi b le f o r a p e r s on t o deve l op spo r ad i c can cer i n a h ere d itar y ca n cer famil y . F o r

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

e x am p le, i n an ea rl y - onse t b r e ast ca n cer famil y , it w ou l d no t b e i d eal t o fi r st test a wo m an d i agnosed w it h breast ca n cer at a g e 65 y ears b eca u se s h e may r e pr ese nt a spo r ad i c case. If a mu t a ti on i s de t ec t ed i n a n a f fecte d relati v e , o t h er famil y mem b er s ca n b e te s t ed f o r t he sa m e m u tati on wit h a g reat d e g ree o f acc u rac y . Fa mily mem b e rs who do no t ca rr y t h e m u tati on f ound i n t h eir famil y are d eeme d t ru e n e ga ti ve. T hose who a r e f ound t o carr y t h e m u tati on i n t h eir famil y w ill h a ve m o r e de fi n iti ve i n f or mati on a bou t t h eir ris k s t o d e v el op ca n ce r . Th is i nfo rm a ti on can be c r uc ial i n assisti ng p atie n ts i n d ecisi on ma k i ng r e g a rd i ng su r ve ill ance and ri sk re du cti on. If a mu t a ti on i s no t i den tifie d i n t h e affecte d relati v e , it u s u all y mea ns t h at eit he r t he cance r s i n t he famil y are ( 1 ) no t h ere d itar y , o r ( 2 ) ca u se d by a n und e tec t ab l e m u t a ti on o r a m u tati on i n a d iffere n t g e n e . A caref u l re v i ew of t h e f amil y h i s t o r y and t he r i s k fact o rs will h el p t o d eci ph er w h et h er i n te rpr etati on 1 o r 2 i s m o r e l ik el y . A dd iti on al g e n etic testi ng ma y n ee d to b e ord e red a t t h i s po i n t . I n cas es i n w h ic h t h e ca n cers a pp ear h ere d itar y and no m u tati on i s f ound, DNA bank i ng s hou l d b e o f fere d t o t h e p r ob a nd f o r a time i n t he f u t u r e when im p r ov e d testi ng ma y b ec o me a v aila b le . A letter i nd icati ng exac tl y who i n t he f amil y h as access t o t h e DNA s hou l d acc o m pany t he banked sa m p le . Th e gene ti c counse li ng r esu lt d iscl o s u re sessi on s hou l d als o i n cl ud e a d etaile d d i scuss i on o f wh i ch ot h er famil y mem b ers w ou l d b e n efit fr o m g e n etic c ounse li ng and t es ti n g a nd referral i n f o rmati on. T h is ca n a pp l y not on l y t o fa mili es who have be e n f ound t o carr y a d eleteri ou s m u tati on, b u t ma y als o p r ove use f u l i n o t her families (e .g., test a h i gh er ris k relati v e o r d ete r mi ne seg r ega ti on o f a va ria n t wit h i n a famil y ) . Th e pene tr ance o f m u t a ti on s i n ca n cer s u sce p ti b ilit y g e n es is als o d i f f ic u lt t o i n t e r p r e t . I n iti a l est imates d eri v e d fr o m h i gh -ris k families prov i d e d ve r y h i gh cance r ri sk s f o r BRCA 1 a nd BRCA 2 m u tati on carrier s .

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

M or e r ec en t s t ud i es done on popu lati on s t h at were no t selecte d f o r famil y h ist ory have r evea l ed l owe r p e n etra n ces . Beca u se e x act p e n etra n ce rat es ca nno t be de t e rmi ned f o r i nd ivi du al families at t h is time , a nd b eca u se pr ecise geno t ype / pheno t ype co rrelati on s remai n un clea r , it is p r ud e n t t o

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

DNA T esting

nan nan

prov i d e pa ti en t s w it h a r ange o f ca n cer ris k a nd t o e xp lai n t h at t h eir ris k prob a b l y f a ll s so m ewhe r e w it h i n t h is s p ectr u m . T h is ca n p r ov e c h alle ng i ng for g e n e s t ha t l ack pub li shed l ong -term d ata on ca n cer ass o ciati on s a nd r is k s . Fem a l e ca rri e r s o f BR C A 1 a nd BRCA 2 m u tati on s h a v e a 50 % t o 85 % li f etime ri sk t o deve l op b r eas t ca n cer a nd b etwee n a 15 % t o 60 % lifetim e r is k t o deve l op ova ri an cance r . It is im po rta n t t o no te t h at t h e classi f ic a ti on “ova ri an cance r ” als o i n cl ud es ca n cer o f t h e fall op ia n t ub e s a nd pr im a r y pe rit onea l ca r c i no ma . BRCA 2 carriers als o h a v e a n i n c r ease d lif e tim e ri sk o f m a le b reast ca n ce r , p a n creatic ca n ce r , a nd po ssi b l y , m e l ano m a

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Options for Surveillance, Risk Reduction, and T ailo r ed T r eatment

nan nan

Options for Surveillance, Risk Reduction, and T ailo r ed T r eatment

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Options for Surveillance, Risk Reduction, and T ailo r ed T r eatment

nan nan

Th e ca n c e r ri sk counse li ng ses si on is a f o r u m t o p r ov i d e c oun selees wit h i nfor ma t i on, suppo rt , op ti ons, a nd hop e . M u tati on carriers ca n b e o ffered : ea r lie r a nd m o r e agg r ess i ve su r v eilla n ce , c h em op re v e n ti on, a nd / o r prophy l ac ti c su r ge r y . De t a il ed ma n a g eme n t op ti on s f o r BRCA carriers a re d isc u sse d i n t h i s chap t e r . S urv eill ance r eco mm enda ti on s are e vo l v i ng wit h n ewer tec hn i qu es a nd a dd iti ona l da t a. A t t h i s tim e, it is rec o mme nd e d t h at i nd i v i du als at i n cre ased r is k for b r eas t cance r , pa rti cu l a rl y t ho se w ho carr y a BRCA m u tati on, h a ve a nnu al ma mm og r a m s beg i nn i ng at a g e 25 y ears , wit h a cli n ical b reast ex am by a br ea s t spec i a li s t , a yea rl y b reast ma gn etic res on a n ce ima g i ng (MRI) w it h a c l i n i ca l b r eas t exa m by a b reast s p ecialist , a nd a y earl y cli n ical b r east e x am by a gyneco l og i s t . It is s ugg este d t h at t h e mamm og ram a nd M R I b e s p ac ed ou t a r ound t he ca l e n d ar y ear s o t h at s o me i n ter v e n ti on is p la nned e v e ry 6 m on t hs. Recen t da t a s ugg est t h at MRI ma y b e safer a nd m o re e f f ecti ve i n BR C A ca rri e r s <4 0 y ears o f a g e a nd ma y s o me d a y re p lace mamm og r a m s i n t h i s popu l a t ion . BR C A ca rri e r s m ay t ake a selecti v e estr og e n -rece p t o r m odu lat o r (SE RM ) o r a r o m a t ase i nh i b it o r i n hop es o f re du ci ng t h eir ris k s o f

COMPON E NTS O F TH E CANCER GE NETIC COUNSEL I NG SESSI O N

Options for Surveillance, Risk Reduction, and T ailo r ed T r eatment

nan nan

d e v el oping b r eas t cance r . T h ese me d icati on s h a v e b ee n p r ov e n e f fecti v e in wo me n at i nc r eased ri sk due t o a po siti v e famil y h ist o r y o f b reast ca n ce r – Th e r e a r e limit ed da t a on t h e e f fecti v e n ess o f s u c h me d icati on s i n un a f f ect ed BR C A ca rri e r s ho we v e r , t h ere are s o me d ata t o s ugg est t hat BR C A c a rri e r s t ak i ng t a m ox if en as treatme n t f o r a b reast ca n cer re du ce t hei r r is k of a con tr a l a t e r a l b r eas t can ce r . A dd iti on all y , t h e maj o rit y o f BRC A2 ca rr ie r s who deve l op b r eas t can cer d e v el op a n estr og e n - po siti v e f o rm o f the d isease and it i s hoped t ha t t h is popu lati on will res pond es p eciall y wel l to c h em opreven ti on. F u rt he r s t u dies i n t h is area are n ecessar y b ef o re d rawi ng c on cl u si ons abou t t he e f fi cacy o f c h em op re v e n ti on i n t h is popu lati on. P rophy la c ti c b il a t e r a l m as t ec tom y re du ces t h e ris k o f b reast ca n cer by > 90% i n wo m en a t h i gh -ri sk fo r t h e d isease . Bef o re g e n etic testi ng was a v aila b le , it was no t unco mm on f o r e n tire g e n erati on s o f ca n cer families to h a v e at -r i sk ti ssues r e m oved wit hou t kno wi ng if t h e y were p ers ona lly at i n c r ease d ri sk f o r t he ir f a milial ca n ce r . Fift y p erce n t o f un a f fecte d i nd i v i du al s i n he r ed it a r y canc er families will no t carr y t h e i nh erite d pr e d is pos iti on gene and can b e s p are d p r ophy lactic s u r g er y o r i nv asi v e h i gh-r is k su r ve ill ance r eg im en s . T h eref o re , it is clearl y no t a pp r op riate to o f f e r prophy l ac ti c su r ge r y un t i l a p atie n t is referre d f o r g e n etic c oun seli ng a nd, i f poss i b l e, t es ti ng . W o m en who ca rr y BR C A 1 / 2 m u tati on s are als o at i n crease d ris k t o d e v el op second con tr a l a t e r a l a nd i p silateral p rimaries o f t h e b reast . T hese d ata br i ng i n t o ques ti on t he op ti on o f b reast c on ser v i ng s u r g er y i n w o m en at h i gh r is k t o deve l op a second p rimar y wit h i n t h e same b reast . F o r t h is r eas on, th e BR C A 1 / 2 ca rri e r s tat u s ca n h a v e a p r o f ound im p act on s u r g i cal d ecisi on m ak i ng and m any p atie n ts h a v e g e n etic c oun seli ng a nd testi ng imme d i a t e l y a ft e r d i agnos i s and b ef o re s u r g er y o r ra d iati on t h era p y . T hose p atie n ts w ho t es t pos iti ve and op t f o r p r ophy lactic mastect o m y ca n o fte n be s p a r e d r a d i a ti on and t he r esu l t i ng si d e effects t h at ca n c o m p licate r ec on st ruc ti on. App r ox im a t e l y 30 % t o 60 % o f p re v i ou sl y irra d iate d p ati ents who lat e r op t f o r m as t ec t o m y wit h rec on str u cti on re po rt si gn ifica n t c o m p lic a ti ons o r un f avo r ab l e c o smetic res u lts .