7 Tickled PPink 22006

Marilie Gammon, professor ofepidemiology and a Linebergermember, has a serious message forpeople battling their weight: It couldbe a matter of life and death.

That's because excess weightincreases the risk of developingcancers. Estimates from theInternational Agency on Cancer indicate that approximately10 to 40 percent of selected cancers can be attributed toexcess weight, making obesity one of the most importantcauses of cancer, after cigarette smoking.

Postmenopausal breast, colon, endometrial and kidney

cancers, plus esophageal adeno-carcinoma,are most affected by weight, the researchshows.

Breast Cancer & ObesityThe data on the relationship betweenbreast cancer and obesity are particularlyclear, Gammon says. "Women who gain

about 45 pounds after the age of 18 are twice as likely todevelop breast cancer after menopause than those who don't."

Weight gain after age 50 also is linked to about a 70percent increase in the chance of developing

"Today, most medical decisions are based on historical datacompiled from groups of patients who, in general, appear tolook like the patient under consideration for therapy," explainsNeil Hayes, assistant professor of medicine in the division ofhematology/oncology in UNC's School of Medicine. "Wefrequently practice medicine by the law of averages - onaverage a therapy should work for a given patient."

The study of cancer genetics is changing that by allowingphysicians to go directly to more effective therapies for everypatient sooner. And in those cases where no therapy appearslikely to help, researchers can turn their attention earlier to

developing newer and more tailored treatments."Personalized medicine is a movement away from

treatment based on averages, and more based on data derivedfrom the person seeking therapy," continues Hayes, aLineberger member. "This information can assist us in makingmore accurate predictions about what events a patient is atrisk for, such as rapid recurrence versus low likelihood ofrecurrence, specific sites of recurrence, the probability ofresponding to any therapy or to specific therapies. And it canaid in the selection of therapies."

Adds Michael Topal, professor of pathology and bio-chemistry/biophysics and a Linebergermember: "It's medicine that is fine-tunedto the genomic background of theindividual and, in the case of cancer, tothe tumor."

Technological AdvancesIn methods pioneered by Lineberger

member Chuck Perou, “the ability toscreen a high quantity of genes and geneproducts in large patient populationshave revolutionized human genetics -and the way genetics is used in cancerresearch," Topal says.

Dramatic improvements in optics,robotics, microcomputing, and thedissemination of the human genomesequence set the stage for advances inmodern medicine. "These developmentshave allowed for the 'profiling' of tumorsand normal tissues for differentialexpression of genes and proteins, as wellas for specific mutations and othergenetic events," says Hayes.

U N C L i n e b e r g e r C o m p r e h e n s i v e C a n c e r C e n t e rcancer

6

The Cancer Program of UNC-Chapel Hill & UNC Health Care Winter 2007

The GGene GGirls

the

insi

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line

up

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2Profile:Dr. JJohn BBoggess

LINEBERGER COMPREHENSIVECANCER CENTER

N.C. CANCER HOSPITAL

5 Roy WWilliams’ FFastBreak AAgainst CCancer

New Technologies Enable“Personalized” Medicine

continued on page 3

Weight Linked to Cancer Incidence, Survivability

Lines

UNC Lineberger genetic researchers in front of a microarray, a key genetic tool: Drs. Michael Topal; Claire Dees; Chuck Perou; and Neil Hayes.

continued on page 5

February 2007 FINAL.qxp 1/30/2007 10:54 AM Page 2

The UNC Lineberger Comprehensive Cancer Center awarded its 2006Oncology Nursing Excellence Award and Clinical Services Excellence Award tofour staff members. The awards are in recognition of the staff's extraordinaryhard work, care and dedication that they bring to the center each day.

Nurses Linda Fowler, RN, OCN, and Sharon Cush, RN, OCN, won theOncology Nursing Excellence Awards, and Susan Whorley and TonyaThompson won the Clinical Services Excellence Awards.

Fowler has been at UNC since 1987 and is a nurse in the GynecologicOncology chemotherapy infusion room. Cush is a nurse clinician whocoordinates the UNC Neuro-oncology Brain Tumor Clinic. She has been atUNC for 24 years.

Dr. Richard Goldberg, associate director of clinical research and physician-in-chief of NC Cancer Hospital, said that "both of the individuals chosen for thenursing awards are long-term employees who have distinguished themselves inboth patient care and in training and supporting their coworkers."

Susie Whorley has been at UNC for 14 years, the last 3 of which she has beena program assistant for the Multidisciplinary Oncology Programs.

Thompson is a social worker for the in-patient hematology/oncologyservices.

Bobbi Marks, administrative director of UNC Health Care OncologyServices, said, "Susie and Tonya are wonderful representatives of the best incaring attitude. To their patients, families and peers they are attentive to thedetails of the work to be accomplished, displaying a calm, efficient, and caringdemeanor even in the face of urgency and anxiety."

The Oncology Nursing Excellence Awards are in their fifth year at UNC.Winners receive a $1,500 stipend along with the award to be used towardsprofessional education activities. The award was named in memory ofCharmayne S. Gray, an outstanding oncology nurse practitioner who died in anauto accident in 2002. The Clinical Services Excellence Awards are in their thirdyear.•

Front row (left to right): Dr. Richard Goldberg, Tonya Thompson, LindaFowler, Sharon Cush and Susie Whorley. Back row: Bobbi Marks, Dr. Shelley Earp, director,UNC Lineberger, and Dr. Matt Ewend, leader,Neuro-Oncology Program.

P e r s o n a l i z e dmedicine is apopular topic inthe news today.But what does itmean? The vastmajority ofhuman DNA isthe same in all ofus, but the smalldifferences mayimpact how we

respond to certain treatments. As thefield of cancer genetics advances andwe understand genetic patterns andpathways better, we aim to developtailored therapy that will give eachpatient the greatest benefit: what isthe best therapy for an individual,who is more likely to have a toxicreaction to a drug, can we combinetwo therapies in this individual? Thepace of discovery is swift.

UNC is one of the leadinginstitutions for these advances andwe are recognized nationally for ourachievements in this area of research.Two of our faculty, Chuck Perou andNeil Hayes, were recently awarded aprestigious grant from the NationalCancer Institute to UNC Linebergerto participate in the Cancer GenomeAtlas. The Cancer Genome Atlas is alarge-scale collaborative effort tosystematically characterize thegenomic changes that occur incancer. We have become nationalleaders in this type of genomeanalysis and join the likes of Harvard,

MIT, Stanford, and Memorial Sloan-Kettering in this new nationaldiscovery network.

The cover story describes severalUNC research endeavors related topersonalized medicine. Ourphysicians are enrolling patients ontothe TTrial AAssigning IIndividuaLLizedOOptions for Treatment RRx (TAILORx)trial for breast cancer. This study willexamine whether genes that arefrequently associated with risk ofrecurrence for women with early-stage breast cancer can be used toassign patients to the mostappropriate and effective treatment.

In the next issue we will include asecond report on personalizedmedicine highlighting the work ofone of our newest recruits, Dr.Howard McLeod, director of the newUNC Institute on IndividualizedMedicine based in the UNC School ofPharmacy. I am pleased to welcomeHoward to UNC and the LinebergerCenter. You will hear more aboutthese groundbreaking efforts in thefuture.

In this issue, you will also readabout our Cancer Genetics clinicalprogram, led by Jim Evans, as well asa profile of a family who has used andbenefited from this UNC program.The clinical cancer genetics team isan essential part of personalizedmedicine. Once we are able to knowmore about our DNA, we needsomeone to help patients understandwhat it means to them.

On the national scene, the bignews remains the cutback in federalsupport for the National Institutes ofHealth (NIH). This represents amajor threat to biomedical researchin general, and to cancer researchhere at UNC Lineberger and at cancercenters nationwide. In the late1990s, the United States ramped upits investment for discovery andnovel therapies for cancer, puttingour country firmly in the lead. Thatlead is now being eroded by almostfive years of flat and now decreasingfunding. In addition to slowingcurrent discovery of new therapies,these cuts make it difficult for youngfaculty to successfully launch theircareers in cancer research.

In my role as President of theAssociation of American CancerInstitutes, I am working with othercancer research organizations to educate both the administrationand Congress on the amazingopportunities, the economic benefit,and the needs of cancer patients that call for reinvigorating ourinvestment in the NIH. So far, ourhighly competitive Lineberger facultyhave been able to sustain our overallresearch funding. Opportunities lost have been replaced with newgrants, such as the CancerNanotechnology and Genome Atlasgrants, but if we are not able toconvince Congress of the wisdom ofinvesting in what has been andshould be the world's strongestbiomedical research enterprise, weface serious consequences down theroad. •

2 cancerLines Winter 2007

UNC Lineberger is designated aComprehensive Cancer Center bythe National Cancer Institute.

Cancer Lines is a tri-annualpublication of the UNC LinebergerComprehensive Cancer Center, The University of North CarolinaSchool of Medicine at Chapel Hill.

Dr. H. Shelton Earp, III, DirectorDr. Richard M. Goldberg, AssociateDirectorDr. Joseph S.Pagano, Director EmeritusDebbie Dibbert, Director of External AffairsDianne G. Shaw, Director ofCommunications/Executive EditorMargot Carmichael Lestor,ContributorAlyson Newman, Design & Layout

Please remove me from yourmailing list

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Please add the following to theCancer Center’s mailing list.

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City, State, Zip

UNC Lineberger Comprehensive Cancer Center

CB# 7295School of MedicineUniversity of North Carolina at Chapel HillChapel Hill, NC 27599-7295(919) 966-5905http://unclineberger.org

Printed on Recycled Paper

Director’sMessageDirector’sMessage

Dr. H. Shelton Earp, III

LINEBERGER COMPREHENSIVECANCER CENTER

N.C. CANCER HOSPITAL

2006 OOncology EExcellence AAwards

February 2007 FINAL.qxp 1/30/2007 10:54 AM Page 3

BBlluuee CCrroossss BBlluuee SShhiieelldd ooff NNCC 22000066-0077 LLeeaaddeerrsshhiipp PPaarrttnneerr ffoorr UUNNCC LLiinneebbeerrggeerr

Blue Cross Blue Shield of NC has generously supported UNC Lineberger as alead sponsor of major special events this year. We are grateful for theirpartnership and their commitment to cancer care, prevention and research.

In the fall, the Blue Cross and Blue Shield of North Carolina Foundationunveiled its new, interactive Button Chair exhibit, an innovative art displaydesigned to increase awareness of breast cancer, in hopes of saving lives. Thepurpose of the exhibit is to educate visitors about breast cancer, encouragewomen to get mammograms and to deliver messages of hope from survivors whohave overcome the disease.

The new display is a dynamic, interactive experience highlighted by the glassenclosed Button Chair and four hands-on, educational kiosks. The exhibit'sfeatured elements are video stories of hope, as five North Carolina women(representing Asheville, Durham, Greensboro, Raleigh and Wilson) share theirstories of detection, treatment and survival. These uplifting accounts reveal how the disease has touched eachwoman's life, and the lives of their families. One of the stories is told in the survivor's native Spanish and allinformation featured on the touch screens is available in both English and Spanish.

The Button Chair was created in 1998 as a tribute to all women-as well as their families, friends and supportnetworks-who have battled breast cancer in North Carolina. Every button represents a unique story of courageand strength, each having belonged to a breast cancer survivor or someone who lost their battle with thedisease.

The Button Chair is available for display free of charge to North Carolina schools, businesses, hospitals,community groups and other organizations. It can be reserved online at www.bcbsnc.com/foundation/button_chair.html.•

OOuutteerr BBaannkkss MMaarraatthhoonn aanndd BBoonnee MMaarrrrooww DDrriivvee AA HHuuggee SSuucccceessss

Ten members of the UNC Bone Marrow Transplant and Hematologic Malignancy programs traveled to theinaugural Outer Banks Marathon on November 10-12 to hold a Bone Marrow Donor Drive for the NationalMarrow Donor Program (NMDP). With funding from UNC Hospitals and the support of the race organizersand residents of the Outer Banks, the Drive was held in the Dare County Convention Center which also servedas race headquarters.

The Drive and the marathon were both huge successes with enrollment of 226 new donors and nearly 4000participating runners.

UNC has been invited back next year and program members look forward to continuing to work with groupssuch as this to continually expand the donor pool in the NMDP so that all prospective patients who need a donorcan find one.•

Left to right: Dr. Tom Shea, director, the UNC Bone MarrowTransplant and Hematologic Malignancy programs; transplant coordinator Betty Hinshaw;Senator Marc Basnight; UNC physician's assistant John Strader; and transplant coordinators Debbie Covington, andSam Sharf, and Barbara Kok, BMTClinic nurse. Not pictured:BobbiMarks, administrative director, UNCOncology Services.

7cancerLines Winter 2007

The LLoving CCaregiver:A SStory oof FFaith & Courage

Ambrose Dudley and his wife, Alice, have beenloyal supporters of UNC Lineberger since 1998.Ambrose says it best: "where else would you giveyour money but to the place that saved your lifeand made you feel like part of the family?"

Ambrose was diagnosed with Stage 3 multiplemyeloma in 1997 and underwent a bone marrowtransplant seven months later. It was a success,and he has been in remission for 9 years.

Twenty-six months after Ambrose's diagnosis,Alice was in a traffic accident that left her with aclosed-head brain injury and many broken bones.Unconscious for three weeks, she recovered thanksto lots of therapy.

After these two major life-threatening events,they wrote a book sharing their story. Publishedthis fall, The Loving Caregiver is a story of faith,courage and brilliant medicine and how twopeople faced back-to-back crises hand-in-hand.

The Dudleys are sharing the proceeds from the sale of their book with UNC Lineberger. To purchase a copy of their heart-warming story, contact Ambrose directly atadudley002@nc.rr.com.•

Ambrose andAlice Dudley of Raleigh,NC onvacation inthe CanadianRockies.

TTiicckklleedd PPiinnkk iinn TTrriipplliiccaattee!!

Tickled Pink 2006 was a series of three totally pinkevents to benefit women's cancers. This pastOctober, women of all ages attended two fun andfunky, all pink luncheons, which were held for thethird consecutive year at Squid's Restaurant inChapel Hill and for the second year at GallowayRidge in Fearrington. Everything in sight was pink,from the creative decorations, right down to thedressing on the salads.

A third event, "Tickled Pink at Twilight," wasintroduced at Top of The Hill Restaurant indowntown Chapel Hill. This totally pink co-edevent complete with feather boas and pink drinkswas a fun way to bring men and women of all agesout to support research for women’s cancers.

Tickled Pink 2006 raised $63,000 and had over 530 people in attendance. The total money raised forwomen's cancers at UNC Lineberger since Tickled Pink's creative beginning three years ago is $161,000.

Our thanks go out to all of our sponsors, our wonderful committee members, Squid's/Chapel HillRestaurant Group, Top of The Hill and Galloway Ridge in Fearrington.•

Dr. Paola Gehrig, Associate Professor of Obstetrics andGynecology, Tickled Pink co-chairs Margie Haber and MissyJulian-Fox, and Dr. Carolyn Sartor, Professor, Co-Chair of theUNC Breast Center, and newly appointed Chair of RadiationOncology.

UNC Women's Basketball Coach Sylvia Hatchell receivedthe 2006 UNC Lineberger Outstanding Service Award. Shewas cited for her work to raise awareness of gynecologiccancers and for her fundraising, including proceeds from herblueberry patch near Black Mountain, NC. Dr. ShelleyEarp, Director, UNC Lineberger Comprehensive CancerCenter, presented the award at the Lineberger Board ofVisitors meeting in September.

February 2007 FINAL.qxp 1/30/2007 10:54 AM Page 4

DDrruugg CCoommbbiinnaattiioonn SSlloowwssTTrreeaattmmeenntt-RReessiissttaanntt BBoonneeMMaarrrrooww CCaanncceerrCombining a newly formulated drug with aproven standard treatment slows the progressionof multiple myeloma, an advanced cancer of thebone marrow cells, according to a clinical trialled by Robert Orlowski, Lenvel Lee Rothrockassociate professor in the division ofhematology/oncology at the School of Medicine,and Lineberger member. Orlowski reported hisfindings at the annual meeting of the AmericanSociety of Hematology in December 2006.

The phase III trial included 646 patients withrelapsed or refractory multiple myeloma, acondition in which cancerous cells continue tomultiply despite treatment. Patients in the trialwere randomly assigned to receive the drugbortezomib (Velcade), standard therapy forrelapsed multiple myeloma, or a combination ofVelcade and Doxil, a chemotherapy drug(doxorubicin) delivered via liposomes, ormicroscopic fat bubbles.

An interim analysis revealed that participantsreceiving the combined treatment had a 9.3-month median time to progression - the timeinterval between the response to treatment andthe time the disease starts to show evidence of

growing or recurring. Thoseon Velcade alone progressedafter 6.5 months. The interimanalysis also showed an earlytrend toward increasedsurvival for patients takingthe combination treatment.

"It does provide someadded hope for patients and

their families," Orlowski says.

NNeeww LLuunngg TTuummoorr SSuubbttyyppeessIIddeennttiiffiieedd iinn DDNNAA PPrrooffiilliinngg SSttuuddyyA new study led by researchers at UNCLineberger identified three subtypes of non-small-cell lung cancer tumors. The discoverymay provide valuable clinical information aboutpatient survival in early- or late-stage disease,how likely the cancer is to spread and whetherthe tumor will prove resistant to chemotherapy.

"We are frequently surprised with the range ofresponses that our patients' non-small-cellcarcinomas have. Some are very responsive totreatment, some metastasize early, and we haveno way of sorting this out up front," explainsstudy lead author David Neil Hayes, assistantprofessor of medicine in the division ofhematology/oncology in UNC's School ofMedicine and a Lineberger member. The studyresults were published in the November issue ofthe Journal of Clinical Oncology.

Hayes and his colleagues used a relatively newtechnology, DNA microarray analysis, whichallows researchers to identify a tumor's geneticpattern. "We see evidence that these geneticpatterns are associated with significantdifferences in tumor behavior, which could notbe anticipated by any conventional testingmethod," he says.

The tumor subtypes, named bronchioid,squamoid and magnoid, according to theirgenetic pattern, also correlated with clinicallyrelevant events, such as stage-specific survivaland metastatic pattern. "If we can pigeonholethese tumors right from the start, then we canbecome much more rational in our decisionmaking for treatment and our ability to tellpatients what to anticipate in terms of their risk,likelihood of recurrence and response totherapy," Hayes says. "That's the goal."

TTuummoorr SSuupppprreessssoorr GGeenneeiiss KKeeyy ttoo CCeelllluuaarr AAggiinnggA gene that suppresses tumor cell growth alsoplays a key role in aging, according to NormanSharpless, assistant professor of medicine andgenetics at the UNC School of Medicine and aUNC Lineberger member. Researchers from theUNC-Chapel Hill, University of Michigan andHarvard University found increasingconcentration, or expression, of the genep16INK4a in older pancreatic islet cells and brainand blood stem cells. An author or co-author onall three studies, Sharpless' results were publishedin the September 2006 issue of Nature.

The findings indicate that disparate cell typesshare a common aging mechanism and suggestthat aging-related diseases such as diabetes resultfrom a failure of cell growth. "The studiesindicate that certain stem cells lose their abilityto divide and replace themselves with age as theexpression of p16INK4a increases," Sharplesssays. "This suggests that if we could attenuatep16INK4a expression in some way in humans, itcould lead to enhanced islet re-growth in adultsand a possible new treatment for diabetes."•

Leslie H. Lang contributed to this section.

BriefsBriefs

Even as a child, John Boggess wanted to teach. "SoI'm living the dream," says the associate professor ofobstetrics and gynecology. But his secret passion ismovie production and special effects.

"If I weren't doing this, I'd make movies withGeorge Lucas," he quips. "I'd be knocking his doordown. 'You wouldn't have to pay me.'" He createsdigital special effects on his home computer, just incase Lucas is hiring.

Boggess is one of those lucky people for whomvocation and avocation meet. By practicing leading-edge medicine, he teaches others and uses videoproduction techniques to spread his educationalreach. And the Newport Beach, Calif., native gets towork with one super high-tech toy that would makeeven the creator of Star Wars green with envy: theda Vinci Surgical System, a robotic "surgicalassistant" manufactured by Intuitive Surgical.

Leading-Edge TechnologyPurchased in February 2005 to support the UrologyOncology program, the da Vinci System givessurgeons better dexterity and allows more controlthan open surgery. It also allows high-resolution 3-D visuals that improve precision and reducetrauma to surrounding tissue. And it's all donethrough quarter- to half-inch incisions.

Impressed, Boggess wantedto explore its use ingynecologic oncology. "Therewas no description of how todo that," he recalls. "So westarted blazing a new trail. Wewere the first people todocument robotic procedures

for cervical and uterine cancer." (UNC Hospitalspurchased a newer version of the robot, the onlyone of its kind in the state, for the Women'sHospital in July 2006.)

While the technology is exciting, the real valueof robotics is improved patient outcomes."Robotics improves quality of life," he notes. "Usingthe robot, there's much less blood loss and patientsget faster recovery times. Most of our patientshaving any type of hysterectomy (radical forcervical cancer, endometrial staging, large fibroids

or simple hysterectomy) go home in less than 24hours with no IV pain meds. This compares to 3-4 days for open procedures. As importantly, wehave never transfused a patient for a robotichystectomy and have done now over 130 of them.The average recovery is only 1-2 weeks to feel 90percent normal compared with 8-12 weeks withopen surgery. We are doing a better canceroperation and this translates into better survival."

Big Ideas Boggess came to UNC after completing his residencyat the University of Washington in 1994. "One of myinterests is in developing new ideas," he says. He wasattracted by the opportunity to do fellowshiptraining in less-invasive surgical techniques, likelaparoscopy. "The program at UNC suited me."

Three years later, he joined the faculty andstarted the minimally invasive surgery program. "It'sa privilege to be exposed to robotics at the righttime and be able to run with it," he says.

"I'm very proud of our hospital staff andleadership, particularly the nurses and the ORtechs," he continues. "I'm involved with people whoare overwhelmingly talented; it's humbling to workwith them. Everyone took to this with a lot ofenthusiasm, so we've had more success. What we'vedone in a year and half has blown me away. Wereally followed through on this mission and it haspaid off for our patients."

John's wife, Dr. Kim Boggess, is an associateprofessor of maternal- fetal medicine, and they livein Chapel Hill with their two children, Emma, age8, and Mason, age 9.•

4 cancerLines Winter 2007

ProfileProfile

Dr. John Boggess

February 2007 FINAL.qxp 1/30/2007 10:54 AM Page 5

what doWe want to know your thoughts about

cancerLines.Do you find this newsletter useful? Whether you’re a new

or longtime reader, please share your opinions by completing the brief online survey by March 9, 2007 at

http://unclineberger.org/lcccnewsletter

Roy Williams' 2nd Annual Fast Break Against Cancer was held on the floor of theDean E. Smith Center on Friday, October 13th. There were 400 people inattendance at this year's lively event, which raised over $200,000 for cancerresearch - doubling the goal of $100,000! This seated breakfast benefited UNCLineberger Comprehensive Cancer Center and the American Cancer Society.

This year's event was a "who's who" of Carolina basketball. Coach Williamsand his entire coaching staff, former Coaches Dean Smith and Bill Guthridgewere in attendance, as were many former players including several from the1957 National Championship team. Guest speaker and former Tar Heel playerMichael Norwood, shared his family's personal experience with cancer at theevent (see side story).

Coach Williams and "Voice of the Tar Heels" Woody Durham closed theevent with a very spirited auction. By far, the hottest item was the chance to siton the bench with Coach Williams and the team during a non-conference game- truly a once in a lifetime experience! Coach also personally donated two itemsautographed by former Tar Heel great Michael Jordan and Coach Williams.

Special thanks to presenting sponsor, PPD and our other lead sponsors:Atlantic Corporation, Blue Cross Blue Shield of North Carolina, Curtis MediaGroup, GlaxoSmithKline and Long Beverage, Inc.

Next year's Fast Break Against Cancer is scheduled for Friday, October 12.Mark your calendars now!•

Coach Roy Williamsand Emcee WoodyDurham help JohnMorgan, a cancersurvivor fromHillsborough, NC,celebrate his 13thbirthday while all400 attendees sang“Happy Birthday”!

5cancerLines Winter 2007

postmenopausal breast cancer. "Thus, as a breastcancer risk reduction strategy, it is never too late towatch your weight," she adds.

Decreased SurvivabilityA recent study, led by former UNC School ofPublic Health graduate student Page Abrahamson,found that excess abdominal fat can affect breastcancer survival by tracking 1,254 women ages 20to 54 who were diagnosed with invasive breastcancer between 1990 and 1992. Those with waist-to-hip ratios higher than 0.80, an indicator oflarger concentrations of abdominal fat, were 52percent more likely to die of breast cancer in thenext nine years.

The research also noted that obesity (a bodymass index of 30 or higher) adversely affectssurvival rates for breast cancer patients. Study

participants with BMIsover 30 were 48 percentmore likely to die duringthe nine-year studyperiod than women ofideal weight. Even morestartling: Women en-rolled in the study whowere both overweight (aBMI greater than 25) andhad waist-to-hip ratiosover 0.80 increased theirrisk of dying from breast cancer by 92 percent.

"We don't know whether weight loss can reallyreduce your risk of developing breast cancer,"Gammon admits. "However, weight maintenance -in other words, avoidance of weight gain - will helpwomen to avoid the increased risk in developingbreast cancer, or the increased risk of dying oncediagnosed, that has been associated with adultweight gain." •

Weightcontinued from page 1

Running tthe NNumbersLooking for more data besides what your scale tells you?

Ask your doctor or check out these online resources:

A waist-to-hip ratio calculator is available atwww.healthcalculators.org/calculators/waist_hip.asp

The Centers for Disease Control and Prevention offers a bodymass index calculator for adults and children at

www.cdc.gov/nccdphp/dnpa/bmi/index.htm

Professor of EpidemiologyMarilie Gammon

Remembering NellThe guest speaker at this year's Fast Break AgainstCancer event was former Tar Heel basketballplayer Michael Norwood. Michael shared hisfamily's personal experience with cancer and theimportance of ongoing support for cancerresearch. Michael and Caroline Norwood'syoung daughter Nell was diagnosed withrhabdomyosarcoma when she was 2 ½.

Nell endured 14 months of treatment,spending long hours, days and sometimesweeks in the hospital. To keep Nell busy, herparents would bring crafts to the hospital forNell to work on to pass the time. Stringing

beads became a wonderful way for Nell to interact with family andfriends while she was in the hospital-and a wonderful way to help Nellcontinue working on her shapes and colors.

In the summer of 2002, Michael and Caroline Norwood were toldNell would not survive her illness. She had lost her sight to the diseaseand her illness was advancing rapidly. Nell was taken home to be withher family and friends. Her family hosted a small jewelry making partyfor Nell after she returned home from the hospital. As it turned out, thejewelry party was the last day Nell was full of zest, and she passed awayless than a week later.

Shortly after Nell's death, a friend of the Norwoods from church askedif she and other church members could make beaded jewelry to sell at achurch festival. The Norwoods agreed to the idea. "Nell's jewelry" cannow be found in stores and at events in the eastern part of the state. Themoney raised has exceeded $10,000 and is used to help other families inneed. Caroline Norwood continues to make "Nell's jewelry" and can bereached at cpnorwood@suddenlink.net.•

FFast BBreeak Event DDoubles SSupport ffor CCancer RResearch

Charles and MeMe Briley graciously hosted a Linebergerevent at The Cypress of Charlotte last December. Dr. ShelleyEarp spoke to a group of about 60 people on the increasingpersonalization of cancer care. The Brileys (left) and Dr.Earp (right) are pictured here with Alice Lineberger Harney,member of the UNC Lineberger Board of Visitors.

you think?

February 2007 FINAL.qxp 1/30/2007 10:54 AM Page 6

The GGene GGirlsFor Rivka From and her daughtersCarlye and Courtney, genetic testingat UNC provided them with "anopportunity to live an amazing life,"Rivka says.

A Raleigh-based life coach, Fromwas diagnosed with an aggressive formof breast cancer in 2004. Because hermother had died of ovarian cancer,doctors recommended a test for theBRCA mutation before beginning treatment.

"If I tested negative, the treatment would be chemo or radiation," Rivka recalls."If it came back positive, they suggested a mastectomy. When the test came backpositive, I had a bilateral mastectomy and oophorectomy. Cleaned me right out."

But the result did more than impact her treatment. "It was a no-brainer for mydaughters," she says. "We had to get them tested." Both have the mutation.

"Screening for the BRCA mutation was, in my mind, mandatory for me," saysCourtney, who also lives in Raleigh. "I want to know what is going on with mybody to be able to take careful preventative actions. My mother and grandmothersdid not have the opportunity for testing and all developed cancer - fortunately

Mom is alive and thriving today but I was never blessed with the opportunity tomeet my grandmothers as they passed in their 40s."

For Carlye, a student at Meredith College, the results helped her take actionthat will help improve her overall health - and lower her cancer risk. In additionto regular screening and exams with her doctor, Carlye made some lifestylechanges.

"I eat organic foods at home and choose healthier options when I'm at school,"she says. "I have changed my 'college lifestyle' of socially drinking every weekendto an occasional drink once a month. I have started exercising regularly with afriend and using the workout facilities on campus. I started a low dose birthcontrol because it reduces my risk of developing ovarian cancer. Since the test Ihave also been focused on minimizing the amount of stress in my life. I use thistest as a wake-up call to make overall healthy choices for myself."

The Froms have become activists for genetic cancer screening, callingthemselves The Gene Girls. They speak at events and find any opportunity tospread the word.

"To live with the not-knowing for us would be far more painful than the actualknowing of it," Rivka says. "Honey, if we're on this earth we've all got something -some genetic mutations. We are blessed to know about this vulnerability. If youknow, you can go about taking care of yourself.

"It's not always happy stuff that you hear," Rivka notes, "but it really matters ifyou want to live. And bottom line honey, I want to live."•

Technological advances that helpscientists understand the genetics ofcancer have made it possible forphysicians to better predict patients'susceptibility.

It's been recognized for 2,000years that we've been missing asignificant component of medicine,"says Jim Evans, director of ClinicalCancer Genetics and The BrysonProgram in Human Genetics at UNC,and a Lineberger member. "It's onlyrecently that we've begun to acquirethe tools to figure out why if you havetwo people who smoked for 20 years,one gets lung cancer and anotherdoesn't. We are finally accruing thetools to begin to solve that equation."

Right now, most doctors don't treat people, theytreat diseases, Evans says. "We give the samemedicine and doses to everyone and hope it workswell ….and doesn't cause adverse affects."Knowing who has genetic predispositions fordeveloping cancer allows physicians to offerpatients better options and treatments. "We'restarting to guide our choice and dosing of drugs byone's genetic constitution," he continues. "Theimpact of that could be profound."

Genetic TestingGenetic testing is a catch-all phrase for tests thatdirectly or indirectly uncover a patient's particularand unique genetic status. Sequencing DNA is themost common genetic test. Sequencing allowsresearchers to determine the exact order of thebase pairs in a segment of DNA for comparisonwith others. This helps identify anomalies ormutations that could lead to higher susceptibility.

"It's startlingly simple at its most basic," Evanssays. "DNA is a digital code - and that's not ametaphor. Our ability to analyze that code and doso cheaply has given us an emerging ability to getprodigious amounts of data on lots of individuals inlots of health states and correlate that information."

Breast CancerThe most common genetic tests currently are

for breast cancer. Two of the genes that areassociated with familial breast and ovarian cancers,BRCA1 and BRCA2 can beanalyzed with DNAsequencing. UNC's High-Risk Breast Cancer Clinicoffers this kind of testing toabout 650 patients a year.Lineberger funds have beenused to offer tests to patientswho cannot afford to pay.

"Genetic testing forcancer predisposition is notsomething offered to allpatients at this point,"explains certified geneticcounselor Lisa Susswein."But all individuals can havetheir personal and familyhistory assessed by a geneticcounselor to see if testing isindicated."

If a mutation is found,doctors and the patients cantake preventative action.

Susswein explains: "A woman who is diagnosed withbreast cancer might be a candidate for lumpectomy(breast conserving therapy). However, if she isfound to carry a gene mutation that puts her atgreatly increased risk for another cancer, she has theopportunity to choose bilateral mastectomy instead.Women who have not had cancer also have thechoice to have preventive mastectomies.Furthermore, all women with a BRCA mutation areadvised to have their ovaries removed since ovariancancer is difficult to detect."

Other CancersThere are several other genes associated withcancers in other organs. "Colon cancer, forexample, can be due to alterations or mutations inso-called mismatch repair genes," explainsassistant professor Cecile Skrzynia, who also is acertified genetic counselor. "Testing is available forfamilies that show familial clustering of coloncancer and specific other cancers such asendometrial and gastric."

Other genes associated with more rare cancers,such as thyroid or renal cancers can also be tested."Our team consults with any person concernedabout cancer in their family," she continues."Frequently we can be reassuring as to the possibility

of an inherited pre-dispositionto developing cancer. In manyother cases we are able topinpoint the exact change inthe gene of interest andprovide valuable informationfor the family and the treatingphysicians."

The breadth of geneticcounseling services availableat UNC is rare, Evans says."We are one of the few centersthat provides integrated care,"he says. "We have medicalgeneticists, a team ofcounselors and an integratedlab to evaluate patients fromthe get-go. We can decide onwhether to test, do the testand help navigate insurance.From the basic science to theclinic, UNC is at theforefront."•

Cancer GeneticsProgram membersstudy a family tree, one of the tools theyuse to assess the risk of developing cancer.Pictured (left to right):Lisa Susswein; Dr. JimEvans, programdirector; and CecileSkrzynia.

6 cancerLines Winter 2007

Genetics HHelps DDoctors, PPatients Understand SSusceptibility

Should You Consider GGeenneettiicc TTeessttiinngg??The likelihood that breast cancer isassociated with BRCA1 or BRCA2 ishighest in families with a history of:

Breast cancer under age 50Multiple cases of breast cancer

Ovarian cancerMale breast cancer

Ashkenazi Jewish heritage

If you meet any of these criteria, youshould consider working with agenetic counselor to determinewhether genetic testing is right foryou. For more information, contactthe Genetics Clinic at 919-843-8724.

Carlyle, Rivka and Courtney From

February 2007 FINAL.qxp 1/30/2007 10:54 AM Page 7

cancerLines Winter 2007 3

DNA microarray analysis is one of the mostpowerful tools scientists use to learn more aboutcancer genes.

"Knowledge of how a patient's many genes, orgenome, respond to disease and therapy providesa profile or fingerprint for correlation with clinicaloutcomes," Topal explains. "This knowledge alsoprovides us with information about which geneticpathways are turned on or off in response tostimulus such as disease or treatment. That, inturn, enables comparisons between differentpatients and how they respond to therapeuticregimens both clinically and genomically."

Thanks to these technological breakthroughs,more effective diagnostics, preventives andtherapies for cancer are possible as researcherslearn not only how cancer works, but how itdiffers among patients.

Hayes and Topal are co-principal investigatorswith principal investigator Chuck Perou of a newlyfunded genome characterization center, one ofseven grants awarded by the National CancerInstitute and the National Human GenomeResearch Institute. Perou is associate professor ofgenetics and pathology, and a Lineberger member.

The UNC team is part of the Cancer GenomeAtlas project, a national effort to characterize andchart the molecular changes in specific types ofcancer. The Cancer Genome Atlas is a collaborativethree-year, $100 million pilot project to test usinglarge-scale genome analysis technologies toidentify important genetic changes involved incancer. Launched in December 2005, the canceratlas will map the genomic changes associatedwith lung, brain and ovarian cancers. The sevengenome characterization centers will operate as anetwork, with each center using advanced genomeanalysis technologies to identify major changes inthe genomes of these cancers. Read more aboutthis at http://www.unc.edu/news/archives/oct06/genome101606.htm.

Lung Cancer GeneticsThe ability to look into the genetic make-up ofcancer cells is changing the treatments given topatients with certain types of lung cancer.

Currently, lung cancer treatment is basedmostly on the size and location of the tumor, andwhether it has metastasized. Almost 80 percent areidentified as non-small-cell carcinoma (NSCLC), acatch-all diagnosis. Some patients respond well totreatment, while others metastasize early. Noexisting technology gives any meaningful insightinto why patients have such different outcomes.

But DNA microarray analysis enabled Hayes andthe research team to look at the genetic pattern ofspecific tumors. The result: The scientistsdiscovered three subtypes of adenocarcinoma,where only one type was observed before. Theirfindings were published in the 11/01/06 Journal ofClinical Oncology (see Briefs page 4).

"In patients who have tumors that look similarunder a microscope, there are dramaticallydifferent gene expression patterns," Hayes says."There is evidence that these patterns areassociated with significant differences in tumorbehavior that couldn't be anticipated by anyconventional testing method."

Categorizing the tumors early enables doctors tomore accurately target treatments, improvingpatient outcomes.

Breast CancerGeneticsThe development of newbiomarkers, and genomicanalyses using gene expression,genetic variation singlenucleotide polymorphisms,help Lineberger researchersunderstand breast cancerbetter.

"We know that breastcancer isn't one disease, butseveral," explains Perou. "Wehope this will enable us to givepatients more specifictherapies that are targeted totheir tumor biology. This willincrease efficacy."

It also decreases toxicity."We tend to over-prescribe tobe safe," he says. "But we'relearning to be more precise inwhat we give. Knowing whichdrugs they need and whichthey don't, toxicity will godown and their survival willgo up."

For example, breast cancerpatients who over-express theHER2 protein represent 20 to 25 percent of all breast cancer patients. Theyrespond particularly well toHerceptin®, a drug thatinhibits the activity of theHER2 protein, while thosewith other tumor types do notrespond.

"If you give Herceptin® toeveryone, it 'fails'," he says."But if you give it just to thosewho have the target, it adds asurvival benefit. We are developing morediagnostics that will help identify these patients sothey will get this particular treatment."

Looking AheadWhile more personalized therapies mean betterpatient outcomes, Perou is cautiously optimistic.

"It's a double-edged sword," he admits. "Newdiagnostics and drugs are quite promising, but westill need to be patient and to properly evaluatethem. That just takes time and patientparticipation in clinical trials. That's the mostcritical thing patients can to do help advance

treatment. Without clinical trials and money, noneof these things will get implemented."

The effort is worth it. "Personalized diagnosticsand therapies offer the promise of earlier detectionof cancers because of greater knowledge of the riskfactors for that patient," Topal says. "Earlierdetection offers treatment at a time when thecancer is more susceptible to therapy. In addition,knowledge of the genomic background of thepatient and the cancer will mean greater ability todesign the most effective therapy against theparticular cancer in that patient. This will meanmore effective screening, more effective therapy,and at a lower cost for society."•

Personalized Medicinecontinued from page 1

UNC Lineberger clinical researchers are participating in a new treatmenttrial investigating individualized therapy and designed for women withnode-negative estrogen-receptor positive, HER 2 negative breast cancers.In this study, patients are randomized to receive chemotherapy or notbased on a recurrence score calculated from the expression of genes intheir particular tumor.

Called TAILORx (Trial Assigning IndividuaLized Options forTreatment Rx), the study is part of the NCI-sponsored Program for theAssessment of Clinical Cancer Tests (PACCT) and is designed todetermine whether adjuvant hormonal therapy with chemotherapy isbetter than adjuvant hormonal therapy alone in a particular group ofpatients who have intermediate risk of recurrence. Over 4,000 patientswill be randomized in this study at cancer centers all over NorthAmerica.

"Oncotype DX™ is a new assay which looks at the expression of 21genes in a person's tumor and from that expression pattern calculates arisk score," explains Claire Dees, MD, assistant professor of medicine inthe Division of Hematology and Oncology, and leader of theDevelopmental Therapeutics Working Group at UNC Lineberger. "Thisstudy will investigate whether adding chemotherapy helps people whoserecurrence risk scores are in a middle range. Patients whose tumors havea score between 11 and 25 are randomized to be treated with eitherendocrine therapy only or with endocrine therapy plus the adjuvantchemotherapy that they and their oncologist have planned." About 44percent of node-negative ER positive breast cancer patients have arecurrence score in this range.

The findings will help personalize breast cancer treatment further bygiving doctors patient-specific information that will help them optimizecare plans for each patient.

"Current guidelines and practice patterns include use ofchemotherapy in great numbers of node negative patients, many ofwhom may not benefit from it," Dees explains. "This is a way to try tomake better individualized judgments about which patients in thisgroup will benefit from chemotherapy in addition to endocrine therapy."

Patients who think they might be eligible and are interested inknowing more should call the Clinical Protocol Office at 919-966-4432or visit http://unclineberger.org/ct/ or http://www.cancer.gov.•

Personalized MMedicine TToday

Surf’s up for the 2007 UNC Lineberger Beach Ball!Join us for an evening of fun and dancing with East Coast favorite LIQUID PLEASURE

Saturday, April 14, 2007 • 9 pm - 1 am University Mall • Chapel Hill, NC

For more information visit www.unclineberger.orgor contact Mary Seagroves at 919-966-5905.

A fundraiser to benefit the cancer treatment, research and prevention programs at UNC Lineberger Comprehensive Cancer Center

February 2007 FINAL.qxp 1/30/2007 10:54 AM Page 8

This photograph taken by Morganton, NC, resident Anne Wilson,the mother of UNC cancer patient Katherine Wilson, won anational award and a monetary prize of $10,000 for cancerresearch at the UNC Lineberger Comprehensive Cancer Center.The prize was presented by Eli Lilly and Company in partnershipwith the National Coalition for Cancer Survivorship (NCCS) at anawards finale in New York City in December 2006. Anne and JohnWilson and thoracic oncology program nurse coordinator AnnSteagall attended the event hosted by Regis and Joy Philbin.

Anne Wilson took the award-winning picture of Katherine andher father, John, and titled it "This Is Not A Dress Rehearsal."

Judges for the contest, called Lilly Oncology on Canvas: Expressionsof a Cancer Journey International Art Competition, selected Wilson'sphoto as Best of the United States 2006 from over 490 entries. Thepicture shows Katherine and her father, John, standing side by side,hats in hands and both sporting bald heads, Katherine's due tocancer therapy, and her father's due to his head shave in support ofher. Katherine died in 2005 of small cell lung cancer.

Said Wilson, "One of Katherine's greatest concerns was thetremendous need for more cancer research, especially lung cancerresearch. This wonderful gift from Lilly to the UNC LinebergerComprehensive Cancer Center can make a difference in this muchneeded research."

Shown left to right: Dr. John C. Lechleiter, president and COO of Eli Lilly and Company,Regis and Joy Philbin, Anne Wilson, and Michael Bergin, COO of the National Coalitionfor Cancer Survivorship.

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8 cancerLines Winter 2007

calendarof eventsA P R I L 2 0 0 7

14th Fourth Annual Beach Ball,University Mall, Chapel Hill, NC

20th UNC Lineberger Board ofVisitors Meeting, Chapel Hill, NC

24-25th 31st AnnualScientific Symposium. Chapel Hill, NC

J U N E 2 0 0 7

9th Komen Race for the CureNC Triangle Affiliate, Raleigh, NC

UNC Lineberger Comprehensive Cancer CenterCB# 7295School of MedicineUniversity of North Carolina at Chapel HillChapel Hill, NC 27599-7295(919) 966-5905http://unclineberger.org

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