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FEATURE STORY
In Situ Breast Cancer: Is It Really
Cancer?

During a routine clinical exam, Judy Batchelor’s doctor found a small lump in herl e f t b r e a s t . B y t h e t i m e t h e l u m p w a s c h e c k e d w i t h a m a m m o g r a m , i t h a dd i s a p p e a r e d . W h a t t h e m a m m o g r a m d i d s h o w w e r e d e p o s i t s o f c a l c i u m i n t h etissues of the right breast. Batchelor wasn’t particularly concerned, since herm o t h e r ’ s m a m m o g r a m s h a d i d e n t i f i e d c a l c i f i c a t i o n s f o r y e a r s a n d h e r m o t h e r w a sfine. Although most calcifications don’t indicate cancer, the doctor’s office calledthr e e tim es to sc hedule a biopsy becau se o f th e suspicio us pattern of Batchelor’sc a l c i u m d e p o s i t s , b u t B a t c h e l o r a l w a y s t o l d t h e m s h e p r e f e r r e d w a t c h i n g t h ecalcifications for any changes. Then one day the doctor called her personally, telling her that his sister died ofbreast cancer in her early 40s, and asked Batchelor to have the biopsy. It was2004 and Batchelor was 40 at the time. “I gave in,” she recalls. “He soundedge nui ne l y concerned.” T he surgeon wh o p er f o r med the biopsy to ld Batchelor shehad stage 0 breast cancer, also known as ductal carcinoma in situ, or DCIS. Whats h e t h o u g h t w o u l d b e n o b i g d e a l t u r n e d i n t o t w o s u r g e r i e s a n d 3 3 r a d i a t i o nt r e a t m e n t s .
The latin phrase “in situ,” meaning “in place,” is used in the context of cancer tod e s c r i b e a b n o r m a l c e l l s t h a t h a v e n o t e s c a p e d t h e p a r t o f t h e b o d y w h e r e t h e ydeveloped, thus DCIS specifically refers to abnormal cells in the lining of a milkd u c t t h a t h a v e n o t i n v a d e d s u r r o u n d i n g b r e a s t t i s s u e . A l t h o u g h t h e s e c e l l s h a v et h e a p p e a r a n c e o f b e i n g p r e c a n c e r o u s w h e n v i e w e d u n d e r a m i c r o s c o p e , t h e ydon’t have the ability to spread as cancer cells would. Even so, a woman with DCISh a s a n i n c r e a s e d r i s k o f i n v a s i v e b r e a s t c a n c e r , r a n g i n g f r o m t w o t o m o r e t h a ne i g h t t i m e s h i g h e r t h a n t h e r i s k f o u n d i n t h e g e n e r a l p o p u l a t i o n .
View Illustration: Progression of Noninvasive Breast Cancer O f t h e e s t i m a t e d 6 2 , 0 0 0 c a s e s o f i n s i t u b r e a s t d i s e a s e e x p e c t e d i n 2 0 0 6 , a b o u t85 percent will be DCIS. The remainder will have a less common disease known aslobular carcinoma in situ, or LCIS, which refers to abnormal cells contained withinmilk-producing lobules of the breast. Women with LCIS have a three to four timeshigher risk of developing invasive cancer than the general population. Doctors are diagnosing seven times more cases of DCIS than in 1980. Manyb e l i e v e t h i s r i s e o c c u r r e d b e c a u s e o f t h e i n c r e a s i n g u s e o f m a m m o g r a p h y t oscreen for breast cancer, and the growing frequency with which biopsies arep e r f o r m e d o n s u s p i c i o u s l e s i o n s . T h e q u e s t i o n s s u r r o u n d i n g t h i s g r o w i n gp o p u l a t i o n o f p a t i e n t s c o n t i n u o u s l y l e a d s t o d i s a g r e e m e n t a m o n g d o c t o r s a b o u tw h e t h e r t h e s e s u s p i c i o u s l e s i o n s s h o u l d r e a l l y b e c a l l e d c a n c e r a n d w h a t t o d oa b o u t t h e m .
Melvin Silverstein, MD, director of the University of Southern California/NorrisLee Breast Center in Los Angeles, explains that an individual DCIS cell isgenetically abnormal and in that sense, it is cancer. However, a property usuallyassociated with cancer is that the abnormal cells have the ability to spread.
According to Dr. Silverstein, since DCIS is biologically and genetically cancer butdoesn’t have the ability to spread, it could be considered a borderline cancer.
Michael Baum, MD, professor emeritus of surgery at University College London,says it may be more accurate to consider DCIS as a latent lesion that can go in anumber of different directions. Dr. Baum explains that while some cases of DCISp r o g r e s s t o i n v a s i v e c a n c e r , m a n y n e v e r c a u s e a n y t r o u b l e a n d s o m es p o n t a n e o u s l y r e g r e s s .
While doctors agree that not all DCIS cases progress to invasive cancer, it isdifficult to determine which ones will progress since most DCIS lesions aresurgically removed. Long-term follow-up studies of women with low-grade DCISd i a g n o s e d b e f o r e t h e e r a o f w i d e s p r e a d s c r e e n i n g f o u n d t h a t a n y w h e r e f r o m 1 4to 60 percent received a diagnosis of invasive cancer in the same breast wherethe DCIS occurred. Low- and intermediate-grade cells often look similar tonormal cells and may indicate a lower risk of invasive cancer than high-gradecells . The National Comprehensiv e Can cer Network r ecommends that a secondpathologist review a finding of DCIS to confirm that invasive disease is notp r e s e n t .
Despite the debate over whether or not it is cancer, DCIS is distressing to mostwomen. Janice Stuff, a registered dietitian who is employed in the healthcares etti ng , s ays tha t even t hough she un d er st ood that h aving a d iagno sis o f D C IS w asa very low-risk situation, she still panicked when she was diagnosed two yearsago. As Batchelor notes, “Cancer can stir up fears, even when it has a ‘stage 0’attached to it.” However, some women, including 59-year-old Stuff, find a DCISdiagnosis is scarier than it needs to be. “I wish now, in retrospect, that I had beenc a l m e r a b o u t i t . I ’ v e h a d d e n t a l p r o c e d u r e s t h a t h a v e b e e n m o r e t r a u m a t i c t h a nthe lumpectomy,” Stuff recalls. A p e r s i s t e n t d o c t o r l e d J u d y B a t c h e l o r t o f i n d t h a t s h e h a d a f o r m o f noninvasive breast cancer. Photo by Heather Rousseau.
Most experts say that if DCIS is present in only one area and no abnormal cellsa r e f o u n d a t t h e e d g e s o f t h e f i r s t s u r g i c a l e x c i s i o n , t h e p r i m a r y t r e a t m e n to p t i o n s a r e e i t h e r a t o t a l m a s t e c t o m y o r a l u m p e c t o m y f o l l o w e d b y r a d i a t i o n .
Several studies have found that only 1 to 2 percent of women with DCIS later dieo f b r e a s t c a n c e r , r e g a r d l e s s o f w h e t h e r t h e y h a d a m a s t e c t o m y o rb r e a s t - c o n s e r v i n g s u r g e r y . H o w e v e r , m a s t e c t o m y i s u s u a l l y r e c o m m e n d e d o n l y i ft h e m a r g i n s o f t h e t i s s u e r e m o v e d i n a l u m p e c t o m y c o n t a i n a b n o r m a l c e l l s a n dthe DCIS cannot be completely removed with repeat surgery.
M a n y p a t i e n t s t r e a t e d w i t h l u m p e c t o m y a l s o u n d e r g o r a d i a t i o n t h e r a p y t o k i l l a n yremaining abnormal cells in the breast tissue. The National Surgical AdjuvantBreast and Bowel Project B-17 trial tracked 818 women with localized DCIS toc o m p a r e t h e r e s u l t s o f l u m p e c t o m y a l o n e v e r s u s l u m p e c t o m y p l u s r a d i a t i o n . I tf o u n d t h a t a d d i n g r a d i a t i o n r e d u c e d t h e o c c u r r e n c e o f i n v a s i v e b r e a s t c a n c e rfrom 13.4 percent to 3.9 percent. However, since the overall mortality rate forp a t i e n t s i n t h i s s t u d y w a s o n l y 1 p e r c e n t , i t i s t h o u g h t t h a t t h e a d d i t i o n o fradiation may have little effect on overall survival.
While radiation reduces the risk of invasive cancer, it does have side effects. Dr.
Silverstein and his colleagues developed a system called the Van Nuys PrognosticI nd ex, which for the past 10 year s h as h elp ed do ctors identify w hich women havea high risk of recurrence and would be most likely to benefit from radiation afterlumpectomy or mastectomy. This system considers the size of the DCIS, thew i d t h o f n o r m a l t i s s u e a t t h e e d g e s o f t h e r e m o v e d t i s s u e , h o w s e v e r e l y a b n o r m a lthe cells appear and the patient’s age at diagnosis. The higher the score, thegreater the risk of recurrence and the more likely it is that the benefits ofradiation will outweigh the side effects.
Beverley Anderson, RN, who works in the outpatient surgery department of aHouston hospital, has seen the terrible effects of cancer in friends, coworkersand patients. So in 2004 when faced with decisions about treatment for her DCIS,s h e c h o s e a n a g g r e s s i v e c o u r s e o f a c t i o n . H e r d o c t o r s e x p l a i n e d t h e p r o s a n dc o n s o f r a d i a t i o n t r e a t m e n t , a n d s h e c h o s e t o h a v e r a d i a t i o n “ j u s t i n c a s e , ” s h e Although doctors recommend surgery for DCIS, this position is not withoutc o n t r o v e r s y . B e f o r e t h e w i d e s p r e a d u s e o f s c r e e n i n g m a m m o g r a p h y , m o s t c a s e so f D C I S w e r e f o u n d b e c a u s e t h e y c a u s e d s y m p t o m s , s u c h a s a p a l p a b l e m a s s o rserious nipple discharge. Now, most DCIS is discovered by routine mammographya n d h a s n o s y m p t o m s , b u t n o t e v e r y o n e t h i n k s t h a t d i s c o v e r i n g D C I S p r i o r t o t h ed e v e l o p m e n t o f s y m p t o m s i s e n t i r e l y a g o o d t h i n g .
According to Dr. Baum, many women with DCIS have unnecessary mastectomies.
He explains that in around 30 to 40 percent of cases, DCIS is multifocal—meaningit arises in more than one location. When multifocal DCIS is discovered, accordingto current thinking, a surgeon “has no choice but to carry out a mastectomy,” Dr.
Baum says. (The surgeon may suggest a sentinel node biopsy at the time ofsurgery to check for the possibility of invasive cancer.) Invasive breast cancers,on the other hand, are almost always unifocal—they arise in only one location.
This leads to the paradox that the DCIS patient will lose her breast, when, if leftalone, perhaps none of those lesions would have become invasive cancer. If oneof them did become invasive cancer, it would almost certainly be unifocal andt h e r e f o r e t r e a t e d w i t h l u m p e c t o m y .
In contrast, Kent Osborne, MD, director of the Breast Center at Baylor College ofM e d i c i n e i n H o u s t o n , t h i n k s t h a t d o c t o r s m u s t r u n t h e r i s k o f o v e r t r e a t m e n tsince there is currently no way of determining which lesions will lead to invasivecancer, although researchers are actively investigating the biologicalcharacteristics and evolution of precancerous breast lesions. In situ disease is soco mp li cat ed t h at it takes years of exper i ence and training to learn how to sort itall ou t, s o experts advise women to f in d do ctor s they trust and take th eir advice.
T h o u g h t h e r i s k o f r e c u r r e n c e e v e n t u a l l y p l a t e a u s , t h e r e ’ s a b o u t a 1 p e r c e n t p e ry e a r r i s k o f D C I S r e t u r n i n g i n t h e s a m e b r e a s t . S o m e d o c t o r s r e c o m m e n d t h a tpatients with DCIS, particularly those with a family history of breast cancer, takem e d i c a t i o n a f t e r t r e a t m e n t t o p r e v e n t D C I S r e c u r r e n c e a n d t h e d e v e l o p m e n t o finvasive cancer. Many take tamoxifen, which blocks the effects of estrogen in theb r e a s t . R e c e n t d a t a f r o m a l a r g e s t u d y s u g g e s t t h a t c h e m o p r e v e n t i o n w i t ht a m o x i f e n s h o u l d b e r e s e r v e d f o r p o s t m e n o p a u s a l w o m e n w i t h D C I S t h a t i se s t r o g e n r e c e p t o r - p o s i t i v e s i n c e t h e s e t y p e s o f c a n c e r c e l l s n e e d e s t r o g e n t og r o w , a n d t h e y m a y s t o p g r o w i n g w h e n t r e a t e d w i t h d r u g s t h a t b l o c k t h e b i n d i n go f e s t r o g e n .
The Study of Tamoxifen and Raloxifene (STAR) trial compared the effect of thesetwo drugs in healthy women at high risk of developing invasive breast cancer.
Data collected through the end of 2005 indicate that Evista (raloxifene) is aseffective as tamoxifen in reducing the risk of invasive breast cancer. However,unlike tamoxifen, Evista does not reduce the risk of developing DCIS or LCIS. Andthes e d rugs are not without r isks. Tam oxi f en can cause cataracts, a side eff ectnot associated with Evista, and while final data from the STAR trial indicate thatt h e r i s k o f o t h e r c a n c e r s , h e a r t d i s e a s e a n d s t r o k e i s a b o u t t h e s a m e w i t h b o t hd r u g s , a s e p a r a t e s t u d y i n w o m e n a t h i g h r i s k f o r h e a r t p r o b l e m s f o u n d t h a t w h i l e Evista reduced the risk of invasive breast cancer, it raised the risk of blood clotsa n d f a t a l s t r o k e s . T h i s l a t e s t s t u d y p u b l i s h e d i n The New England Journal ofMedicine in July 2006 included an editorial by Marcia Stefanick, PhD, of StanfordUniversity School of Medicine, who said “the moderate benefits” of Evista forbr e as t can cer preventi on “do not seem to ju stif y the risk s.” The best way to solve the disagreement about treatment of in situ breast cancer is tofind a way to identify which lesions will lead to invasive cancer. O t h e r h o r m o n e t h e r a p i e s , s u c h a s A r i m i d e x ( a n a s t r o z o l e ) , A r o m a s i n(exemestane), and Femara (letrozole), are thought to be effective in reducing thechance of cancer coming back, as either another DCIS or an invasive cancer.
T h e s e a r o m a t a s e i n h i b i t o r s a r e b e i n g s t u d i e d f o r p o s t m e n o p a u s a l w o m e n w i t hDCIS that is estrogen receptor positive. Estrogen receptor-negative cells do notn e e d e s t r o g e n t o g r o w , a n d t h e y u s u a l l y d o n o t s t o p g r o w i n g w h e n t r e a t e d w i t hd r u g s t h a t b l o c k e s t r o g e n f r o m b i n d i n g . D r . O s b o r n e e x p l a i n s t h a t r e s e a r c h a b o u ttreating this kind of cell is focusing on identifying the molecular pathways thatc a u s e e s t r o g e n r e c e p t o r - n e g a t i v e t u m o r s t o g r o w a n d f i n d i n g w a y s t o b l o c k t h o s ep a t h w a y s . T h e b e s t w a y t o s o l v e t h e d i s a g r e e m e n t a b o u t t r e a t m e n t o f i n s i t u b r e a s t c a n c e ris to find a way to identify which lesions will lead to invasive cancer. Doctorsanticipate this will be possible in the near future, possibly within five to 10 years,as a result of recent technologies that allow a genetic profile of all the differentgenes in a cancer cell to be generated. Researchers are hopeful that the particulars e t o f g e n e s t h a t c o n t r i b u t e t o t h e f o r m a t i o n o f a t u m o r a l s o d i c t a t e h o waggressive that tumor will be. If so, it may be possible to identify the patterns thatwill allow doctors to predict which lesions will lead to invasive cancer.
Today, Anderson, Stuff and Batchelor are free of DCIS recurrence and invasivedisease. While Batchelor recovered from her surgery, she read everything shecould find about DCIS, but it left her with more questions than answers. “Wouldmy DCIS ever have progressed into an invasive cancer? Was I overtreated? Did In e e d t h e r a d i a t i o n ? ” B a t c h e l o r s a y s s h e w i s h e s s h e h a d t a k e n m o r e t i m e t o l e a r na b o u t D C I S b e f o r e s h e m a d e h e r t r e a t m e n t d e c i s i o n s , b u t s h e d o e s n ’ t k n o w t h a tshe would have done anything differently. “They don’t know whose DCIS willbecome invasive, so they can’t take a chance and do nothing. It’s sad and scaryt h a t w e m a y b e u n d e r g o i n g t r e a t m e n t s t h a t m a y n o t b e n e c e s s a r y . ”

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