>> WE'LL GET GOING. IT'S A RAINY OCTOBER DAY, AND WE HAVE ONE ANNOUNCEMENT, THAT BEING NEXT MONDAY, WE DO TRACO AGAIN AT 4-6:00. BUT MONDAY AT 3:00 WE HAVE THE COURSE. IF YOU HAVEN'T SIGNED UP YOU CAN JUST SEND ME AN E-MAIL. THE SECOND LECTURE TODAY WE HAVE STEFAN AMBS TALKING ABOUT CANCER DISPARITY. OUR FIRST SPEAKER IS FARAH ZIA, SHE'S A MEDICAL OFFICER WITH CANCER TREATMENT AND DIAGNOSIS AT THE NCI. HER TITLE, OVERVIEW OF BREAST CANCER. FARAH. >> THANK YOU. >> ALL RIGHT, TERRY THANK YOU. I JUST WANT TO START BY SAYING IT'S A VERY APPROPRIATE MONTH TO HAVE A BREAST CANCER LECTURE. AS MOST OF YOU ARE PROBABLY AWARE, IT IS BREAST CANCER AWARENESS MONTH, AND I HOPE FOR YOU TO TAKE AWAY FROM THIS LECTURE SOME CLINICAL KNOWLEDGE, SOME RESEARCH KNOWLEDGE AND MAYBE SOME PERSONAL KNOWLEDGE THAT WILL HELP FAMILY AND FRIENDS. OKAY. SO I THOUGHT IT WOULD BE INTERESTING TO START BY TALKING ABOUT BREAST CANCER YESTERDAY. WAY BACK THEN. I THINK THAT WILL GIVE YOU AN IDEA OF THE ADVANCES THAT WE HAVE MADE IN BREAST CANCER RESEARCH OVER 35 YEARS. SO GOING BACK TO 1975, THE INCIDENCE RATE FOR FEMALE BREAST CANCER IN THE UNITED STATES WAS 105 NEW CASES DIAGNOSED FOR EVERY HUNDRED THOUSAND WOMEN IN THE POPULATION. THE MORTALITY RATE WAS ONE FOR EVERY 30,000 WOMEN. FROM 1975 TO 1977, OF THOSE PEOPLE WHO WERE DIAGNOSED WITH BREAST CANCER, ABOUT 75% SURVIVED THEIR DISEASE ABOUT FIVE YEARS. AND AMONG THE WHITE FEMALES, THE RELATIVE SURVIVAL RATE WAS 76% AND AMONG AFRICAN AMERICANS, IT WAS 62%. IN 1975, MASS -- MASTECTOMY WAS -- SEVERAL OTHER TRIALS JOINED NIH AMERICAN CANCER SOCIETY OF BREAST CANCER DETECTION DEMONSTRATION PROJECTS WERE JUST BEGINNING. CHEMO USING MULTIPLE DRUGS WITH DIFFERENT MECHANISMS OF ACTION AND THERAPY POST SURGICAL TREATMENT FOR BREAST CANCER WAS AT ITS EARLIEST STAGES. IN THE MID 1970'S, CLINICAL EVALUATION OF THE DRUG TAMOXIFEN THAT WE KNOW SO WELL NOW AS A HORMONAL TREATMENT FOR BREAST CANCER WAS BEGINNING. IN 1970'S NO GENES ASSOCIATED WITH RISK OF BREAST CANCER HAD OF YET BEEN IDENTIFIED. SO TODAY, IN 2007 FOR THE LAST YEAR WE ACTUALLY HAVE COMPILED STATISTICS FROM THE -- PROGRAM, INCIDENT RATE FOR FEMALE BREAST CANCER WAS 175 NEW CASES FOR EVERY 100,000 WOMEN. THE MORTALITY RATE WAS 23 DEBTS FOR EVERY 100,000. IF YOU NOTICE, YES, THAT IS HIGHER THAN 1975, BUT IT ACTUALLY PEAKED AT A MUCH HIGHER RATE AND IT'S BEEN DECLINING SINCE 1998. THE BREAST CANCER DEATH RATE ALSO CALLED MORTALITY IN THE U.S. HAS BEEN DECLINING STEADILY SINCE 1989 WHEN I SAID WHEN IT SPEAKED AT A RATE OF 33 DEATHS FOR EVERY HUNDRED THOUSAND WOMEN. THERE WERE 24 DEATHS FOR EVERY 100,000 WOMEN. 90% WERE EXPECTED TO SURVIVE THEIR DISEASE AT LEAST FIVE YEARS. AMONG WHITE WOMEN, THE FIVE YEAR RELATIVE SURVIVAL RATE WAS 91% AND AMONG AFRICAN AMERICAN WOMEN IT WAS 78%. SO THE INCREASE IN BREAST CANCER SURVIVAL THAT'S BEEN SEEN SINCE THE MID 1970'S HAD BEEN ATTRIBUTED TO BOTH SCREENING AND IMPROVED TREATMENT. THIS IS A GRAPH SHOWING YOU THE INCIDENCE RATE GOING BACK TO 1975, FROM WHEN WE ACTUALLY STARTED COMPILING THIS DATA. I DON'T HAVE THE DATA FOR 2007. YOU CAN SEE WHAT I WAS JUST TALKING ABOUT FOR WHITE FEMALES, IT PEAKED VERY HIGH AT 141 BACK AROUND 1998 AND NOW IT'S COMING DOWN, IT'S PLATEAUED OVER THE LAST COUPLE YEARS. FOR AFRICAN AMERICAN WOMEN IT WAS A STEEP RIDE UNTIL THE MID 90'S BUT NOW IT'S PLATEAUED. THIS IS LIKE I SAID THE INCIDENCE. SO WHAT IS BREAST CANCER? IT'S CANCER THAT FORMS IN THE TISSUES OF THE BREAST, USUALLY EITHER THE DUCTS OR THE LOBULES AND IT OCCURS IN MEN AND WOMEN ALTHOUGH IN MEN IT'S RARE. A LITTLE BIT ABOUT THE STRUCTURE OF THE BREAST. IT'S COMPOSED MAINLY OF FATTY TISSUES AND HAS A NETWORK OF LOBES WHICH ARE BROKEN UP INTO LOBULES AND THE LOBULES, THEY CONTAIN THE MILK GLANDS AND ALL OF THESE ARE CONNECTED BY DUCTS. THEY RUN THROUGHOUT AND ABOUT 90% OF ALL BREAST CANCERS ACTUALLY START IN THE DUCT OR THE LOBES OF THE BREAST. SO STAGING IS IMPORTANT. IT'S A WAY OF DESCRIBING CANCER SUCH AS THE SIZE OF A TUMOR, AND IF IT HAS SPREAD AND WHERE IT HAS SPREAD. IT'S THE MOST IMPORTANT TOOL THAT WE HAVE TO DETERMINE A PATIENT'S PROGNOSIS, AND IT'S ALSO THE ONCOLOGISTS WILL DETERMINE THE TREATMENT DEPENDING ON THE STAGE OF THE CANCER. YOU MAY HAVE IS AN SOMETHING CANCER'S DESCRIBED ACCORDING TO A TMM SYSTEM. IT'S A SYSTEM THAT DESCRIBES THE EXTENT OF CANCER IN A PATIENT'S BODY. HE DESCRIBES THE SIZE OF THE TUMOR AND WHETHER IT'S ACTUALLY INVADED OTHER TISSUES THAT ARE NEARBY. THE END WILL DESCRIBE THE REGIONAL LYMPH NODES THAT ARE INVOLVED AND THE M WILL TELL YOU IF THERE'S A METASTASES. I GUESS WE CAN GO THROUGH THIS QUICKLY. I HAVE A LOT OF SLIDES BUT I THINK STAGE ZERO BREAST CANCER IS CANCERS INSIGHTS YOU. SO THE CANCER HAS ACTUALLY NOT SPREAD PAST THE DUCT TO THE LOBE TO THE BREAST. AND IT'S ALSO CALLED A NON-INVASIVE CANCER. STAGE ONE BREAST CANCER, IT'S A VERY SMALL TUMOR, LESS THAN 2 CENTIMETERS AND IT HAS NOT SPREAD TO THE LYMPH NODES. STAGE 2A BREAST CANCER IS EITHER A LESS THAN 2 SEND METERS AND IT ACTUALLY HAS GONE TO THE LYMPH NODES OR IT'S A LITTLE BIT LARGER, GREAT THAN TWO BUT LESS THAN FIVE AND IT HAS NOT SPREAD THROUGH LYMPH NODES. STAGE 2A MAY ALSO DESCRIBE A CANCER IN THE AXILLARY NODES BUT IT'S NOT YET, YOU CAN'T SEE ANY EVIDENCE IN THE BREAST ITSELF. STAGE 2B DESCRIBES SOME LESION THAT'S MORE THAN 2 CENTIMETERS BUT LESS THAN 5 CENTIMETERS BUT IT HAS NOT SPREAD TO THE AXILLARY LYMPH NODES. AND STAGE 2B MAY DESCRIBE A LODGER TUMOR WHICH IS GREATER OR EQUAL TO 5 CENTIMETERS THAT HAS NOT SPREAD TO THE AXILLARY LYMPH NODES. STAGE 3A DESCRIBES ANY SIDE TUMOR AS LONG AS IT'S IN THE LIMB -- LYMPH NODES AT THIS POINT. STAGE 3B, THE MOST IMPORTANT THING IS EITHER THE SKIN IS US -- ULCERATED, GOES THROUGH THE SKIN AND INVADES THE CHEST WALL. INFLAMMATORY CHEST CANCER WHICH I WILL TALK IN A LITTLE BIT IS STAGE 3D. 3C IS THE CANCER THAT HAS STRED TO THE DISTANT LYMPH NODES. SO THE AXILLARY LYMPH NODES ARE CLOSER IN BUT THE DISTANT LYMPH NODES ARE LIKE B, ABOVE THE COLLAR BONE OR THE MEDIAL STEINEM LYMPH NODES. THE CANCER CAN BE ANY SIZE BUT IT HAS SPREAD TO OTHER ORGANS IN THE BODY. FOR BREAST CANCER MAINLY IT GOES TO THE BRAIN, THE LUNGS, THE BONE, THE LIVER AND THE CHEST WALL. IT RUNS THROUGHOUT THE BODY AND CARRIES FLUID CELLS AND OTHER MATERIALS WHICH ARE COLLECT IT WASLY KNOWN AS LYMPH AND ALL OF THIS RUNS TO THE LYMPH NODES THAT ACT AS FILTERS FOR THE IMMUNE SYSTEM. WHAT ARE THE LYMPH NODES THAT ARE IMPORTANT IN BREAST CANCER? SO MAINLY IT IS THE AXILLARY CHAIN OF LYMPH NODES AS YOU CAN SEE HERE. HOWEVER, IF YOU HAVE A PRIMARY TUMOR THAT'S IN THE INNER QUADRANT THEN THE MAMMARY NODES CAN BE INVOLVED AND THE CLAVICLE CAN BE INVOLVED. YOU PROBABLY HEARD OF AXILLARY NODE LEVELS. THEY ARE DIVIDE INTO THREE LEVELS. ONE LEVEL IS CLOSEST TO THE ARM PITS AND IT RECEIVES MOST ON THE DRAINAGE FROM THE CHEST WALL AND THE BREAST AND TRAINAGE MOVES ON TO LEVEL TO AND LEVEL THREE. ARE SO THIS PROCEDURE FOR STAGING PRESS CANCER INVOLVES REMOVING BETWEEN 10 AND 30 LYMPH NODES IN THE ARM PITS THAT ARE CLOSEST TO THE TUMOR. AND THE BENEFITS OF TAKING BETWEEN 10 AND 30 LYMPH NODES ARE ALL OF THE LYMPH NODES CAN BE EXAMINED FOR CANCER. AND THIS GIVES YOU A RELIABLE DETERMINATION WHETHER CANCER IS ACTUALLY SPREADING. BUT THE DRAW BACKS OF THIS PROCEDURE ARE, A LOT OF POST SURGICAL COMPLICATIONS, ONE OF WHICH IS LYMPHODINA WHICH IS SWELLING ON THE ARM ON THE SIDE WHERE THE AXILLARY NODES HAVE BEEN TAKEN OUT. BECAUSE THE LYMPH IS ACTUALLY NOT DRAINING ADEQUATELY AT THIS POINTED. THIS CAN RUPT IN INFECTION AND THE SURGERY ITSELF CAN ACTUALLY CAUSE NERVE DAMAGE. THERE'S A LOT OF MORBIDITY ASSOCIATED WITH THIS SURGICAL PROCEDURE FOR THE PATIENTS. YOU MAY HAVE HEARD ABOUT THE -- NODES. THE WORD -- IT PASSES THROUGH A GROUP AVENUE -- GROUP OF LYMPH NODES. IT PROTECTS IT FROM HARMFUL MATERIAL. WHAT IS A SENTINEL NODE BIOPSY -- FEWER COMPLICATIONS. DURING SHARYJ THE SURGEON WILL INDEX A BLUE DYE AND MAY USE RADIOACTIVITY AND IT'S INJECTED NEAR THE TUMOR OR UNDER THE NIPPLE. SO THE TRACER AND THE FLUIDS, THE LYMPH FLUIDS THAT TRAVEL TO THE LYMPH NODES AND THE SENTINEL NODE IS ACTUALLY THE FIRST NOID THAT WOULD RECEIVE THIS DRAINAGE. THE SENTINEL NODE IS REMOVED. IT'S SENT FOR PATHOLOGICAL REVIEW. IF CANCER IS PRESENT, WHAT WE HAVE BEEN DOING IS TAKING MORE LYMPH NODES. AND IF THERE'S NO CANCER THAN NO MORE LYMPH NODES ARE TAKEN. BUT THE QUESTION IS, SO WE KNOW THAT LYMPH NODES WILL DETECT EARLY BREAST CANCER BUT IT HAS NOT BEEN CLEAR WHETHER FURTHER NODAL SECTION AFFECTS SURVIVAL. THROUGHOUT THIS TALK YOU'RE GOING TO HEAR ABOUT SURVIVAL BECAUSE FOR THE ONCOLOGIST THIS IS REALLY THE STANDARD WHETHER IT'S TREATMENT WITH CHEMOTHERAPY OR A SURGICAL PROCEDURE. YOU WANT TO KNOW WHETHER SOMETHING IS IMPROVING A PATIENT'S SURVIVAL. SO THERE WAS A STUDY THAT WAS JUST RELEASED FEBRUARY 9TH, 2011. IT WAS A RANDOMIZED CLINICAL TRIAL. IT WAS CONDUCTED TO DETERMINE THE EFFECT OF COMPLETE AXILLARY DISSECTION ON SURVIVAL OF PATIENTS WITH SENTINEL LYMPH NODES. IT WAS OPENED AT 115 SITES AND ENROLLED FROM MAY 9 TO DECEMBER 2004. THE MEASURES HAD INVASIVE BREAST CANCER. THEY DIDN'T HAVE ANY PALPABLE -- AND THIS WAS IDENTIFIED BY FROZEN SECTION -- ON PERMANENT SECTIONS. SO THESE PATIENTS, THEY RECEIVED LUMPECTOMY AND WHOLE BREAST IRRADIATION. THOSE PATIENTS WHO HAD SENTINEL LYMPH NODE METASTASES THEY WERE DIVIDED INTO TWO GROUPS. ONE GROUP ACTUALLY RECEIVED AN AXILLARY LYMPH NODE DISSECTION BETWEEN 10 AND 30 NODES AND THE OTHER GROUP DID NOT RECEIVE ANY FURTHER AXILLARY TREATMENT. SO OUR PRIMARY END POINT OF THE STUDY WAS OVERALL SURVIVAL AND THE SECONDARY END POINT WAS FREE SURVIVAL WHICH ARE YOUR TYPICAL END POINTS FOR A PHASE THREE STUDY. THE RESULTS, VERY SURPRISINGLY SHOW A FOLLOW UP AT 6.3 YEARS, THE FIVE YEAR OVERALL SURVIVAL WAS 91.8% WITH AXILLARY LYMPH NODE DISSECTION AND 92.5% WITH JUST TAKING THE SENTINEL NODE ALONE. AND THE FIVE-YEAR DISEASE FREE SURVIVAL WAS 82.2% WITH THE FULL AXILLARY DISSECTION AND 83.9 WITH JUST A SENTINEL NODE ALONE. AND THE RESULTS WERE ACTUALLY STATISTICALLY SIGNIFICANT. SO THE CONCLUSION FROM THIS VERY IMPORTANT STUDY WAS THAT AMONG PATIENTS WITH LIMITED SENTINEL LYMPH NODE METASTASES, BREAST CANCER TREATED WITH BREAST CONSERVATION AND SYSTEMIC THERAPY WHICH IS CHEMOTHERAPY, THE USE OF JUST TAKING THE SENTINEL LYMPH NODE ALONE COMPARED WITH AXILLARY FULL DISSECTION DID NOT RESULT IN INFERIOR SURVIVAL. SO I GUESS IT IS SOMETHING THAT WE CAN PRESENT TO THE PATIENTS. THIS IS DONE BY SURGERY AND NOT MEDICAL ONCOLOGY. BUT RESULTS LIKE THIS, WE PRESENTED THE PATIENTS, WE TELL THEM THAT, YOU KNOW, STUDIES ARE SHOWING THAT THIS SECTION DOES NOT HAVE TO BE DONE. BUT OFTEN TIMES THE PATIENTS WILL CHOOSE TO BE MORE CONSERVATIVE, AND THEY WOULD LIKE TO HAVE THE MAXIMUM THEY CAN GET. SO THAT'S THE PATIENT'S CHOICE. TYPES OF BREAST CANCER. WE'LL FLIP THROUGH THIS QUICKLY. JUST TO GIVE YOU AN IDEA OF THE TERMINOLOGY. CARCINOMA INSIGHTS YOU, DCIF IS THE MOST COMMON TYPE OF INVASIVE BREAST CANCER. THE CANCER IS ONLY IN THE DUCTS AND HAD NOT PRESIDENT THROUGH THE WALLS OF THE DUCTS INTO THE TISSUE OF BREAST. NEARLY ALL WOMEN WITH CANCER AT THIS STAGE CAN BE CURED. THAT'S VERY IMPORTANT. IT'S THE BEST FORM OF EARLY DETECTION AT THIS STAGE IS A MAMMOGRAM BECAUSE DCIS IS NON-PALPABLE, YOU CANNOT FEEL IT. THIS IS WHAT WE'RE SEEING WITH OUR EARLY DETECTION METHODS, MUCH MORE DCIS. LCIS, THIS CONDITION BEGINS IN THE MILK DPLANDZ, IT DOES NOT GO THROUGH THE WALLS OF THE LOB ANNUALS LIKE DCIS. IT'S NOT A TRUE CANCER. IT INCREASES WOMAN'S RISK OF DEVELOPING CANCER LATER IN LIFE. IT IS IMPORTANT THAT WOMEN WITH LCIS HAVE REGULAR MAMMOGRAMS MANY THAT PUTS YOU IN A HIGH RISK CATEGORY. INVASIVE CARCINOMA, THIS IS THE MOST COMMON TYPE OF BREAST CANCER. IT ACCOUNTS FOR EIGHT OUT OF TEN INVASIVE BREAST CANCERS. STARTS IN THE DUCT, BREAKS THROUGH THE DUCT WALLS AND INVASIVE SURROUNDING TISSUES. IT MAY ENTER THE LYMPHATIC AND OTHER PARTS OF THE BODY. SAME IDEA, BREAKS INTO THE WALL, GETS INTO THE BREAST TISSUE. BUT IT'S RARE. IT ONLY ACCOUNTS FOR ONE OUT OF TEN INVASIVE CANCERS. INFLAMMATORY BREAST CANCER. THIS SECTION DESERVES A TALK OF ITS OWN, IN FACT. BUT IT'S RARE. REPRESENTS ABOUT ONE TO FIVE% OF CASTERS, THE BREAST CANCER IN THE U.S. IT IS THE MOST AGGRESSIVE FORM OF BREAST CANCERS. IT IS A CLINICAL DIAGNOSIS SO A PATIENT COMES TO YOU, YOU SEE DIFFUSED ERYTHEMA INVOLVE ON IT, YOU SEE -- THERE'S NO PALPABLE MASS FOR THE MAJORITY OF PATIENTS. AND THIS TYPE OF CANCER HAS A SIGNIFICANT LOWERKgF OVERALL SURVIVAL THAN NON-IBC. WHAT IS THE CAUSE OF THE APPEARANCE. THE CELLS INFILTRATE AND CLOG THE LYMPHATIC VESSELS IN THE SKIN OF THE BREAST CALLED THE DERMAL LYMPHATICS. THE BLOCKAGE CAUSES THE RED SWOLLEN APPEARANCE WE OFTEN SEE. I JUST PUT THIS HERE. IT'S NOT INFLAMMATORY BREAST CANCER, I JUST WANT TO MAKE A POINT, IT'S NOT A PATHOLOGICAL DIAGNOSIS. IT'S ACTUALLY A CLINICAL DIAGNOSIS. BUT ON THE PATHOLOGY, YOU OFTEN WILL SEE DERMAL LYMPHATIC INVASION. BUT IT'S A CLINICAL DIAGNOSIS. THIS IS AN EXAMPLE OF, I THINK YOU CAN SEE IT SURROUNDING THE BREAST. IT CAN TAKE MANY, IT LOOKS DIFFERENT IN ALL WOMEN. IT REALLY LOOKS DIFFERENT. OFTEN TIMES THESE PATIENTS WILL BE DIAGNOSED WITH MASS TITUS. SOMETIMES THIS HAPPENS RIGHT AFTER A CHILD IS BORN AND THE BABY'S NURSING AND THE MOTHER WILL THINK AND EVEN THE PHYSICIAN WILL THINK THIS IS MAYBE AN INFECTION. AND IT GETS TREATED WITH ANTIBIOTICS. I'VE SEEN UNFORTUNATE ME TOO MANY CASES LIKE THIS. SO PRIMARY CARE PHYSICIANS, THEY NEED TO BE MORE EDUCATED INTO THINKING ABOUT SOMETHING LIKE THIS, ESPECIALLY POST PREGNANCY WHEN WE DO SOMETIMES SEE A LOT OF BREAST CANCERS COME UP. BUT A WIDE VARIETY OF HOW IT LOOKS IN DIFFERENT PEOPLE. SO PRECISELY WHY DOES A WOMAN DEVELOP PRESS CANCER? WE STILL, WE DON'T KNOW. YES? >> [INDISCERNIBLE] >> LIKE I SAID IT'S A CLINICAL DIAGNOSIS SO PATIENTS DO GET ANTIBIOTICS. BUT IF YOU'RE CONCERNED, YOU SHOULD TAKE A BIOPSY. IF IT SHOWS DERMAL LYMPHATIC AND SOME OF THE CLASSIC THINGS THAT'S FINE, YOU HAVE THE DIAGNOSIS. BUT IF YOU HAVE A CLINICAL SITUATION AND YOU'RE STILL NOT SEEING DERMAL LYMPHATIC INVASION ON THE BIOPSY, YOU STILL HAVE TO THINK ABOUT INFLAMMATORY BREAST CANCER. YES. I MEAN, YES, RIGHT. SO, BREAST CANCER CAUSES GENETIC, A COMBINATION OF GENETIC, ENVIRONMENTAL AND LIFE-STYLE FACTORS. THERE'S A LINK BETWEEN HE IS GEN LEVELS AND THE RISK OF DEVELOPING BREAST CANCER. BREAST CANCER RISK FACTORS, WELL AGE. 80% OF BREAST CANCERS OCCUR IN POST MENOPAUSAL WOMEN. IF YOU'VE HAD A PRIOR RISK CANCER THAT'S A RISK FOR DEVELOPING ANOTHER. IF YOU HAD A HISTORY OF LCIS WHICH IS NOT A TRUE CANCER BUT IT PUTS YOU IN A HIGH RISK SITUATION. IF YOU HAVE A HISTORY OF ATYPICAL DUCT TILE HYPERPLASIA WHICH IS ATYPICAL CELLS WHICH IS NOT A CANCER BUT IT PUTS YOU AT A HIGH RISK SITUATION. YOU HAVE EXOGENOUS HORMONES IN SITUATIONS LIKE EARLY OR LATE MENOPAUSE OR IF YOU TAKE HORMONE REPLACEMENT THERAPY POST MENOPAUSALLY. IF YOUR FIRST CHILD IS AT AN AGE GREATER THAN 35, THAT ALSO SUPPOSEDLY PUTS YOU AT A HIGHER RISK OF BREAST CANCER. PATIENTS WHO HAVE A HISTORY OF MULTIPLE BREAST BIOPSIES FOR WHATEVER REASONS. WE SEE THEY ARE AT AN INCREASED RISK. IF YOU HAVE A RADIATION EXPOSURE BEFORE THE AGE OF 40. AN EXAMPLE IS A LOT OF YOUNG WOMEN WHO HAVE HODGKINS LYMPHOMA, THEY GET RADIATION. TO THE CHEST AREA FOR THEIR TREATMENT. WE HAVE SEEN A LOT OF BREAST CANCERS DEVELOP IN THIS POPULATION OF PATIENTS POST RADIATION. AND WE SEE THAT PATIENTS WHO HAVE VERY DENSE BREASTS ON MAMMOGRAMS, THEY SEEM TO BE AT A HIGHER RISK FOR DEVELOPING INVASIVE BREAST CANCER. LIFE-STYLE FACTORS, ALCOHOL, LACK OF EXERCISE. THAT ALL LEADS TO OBESITY WHICH INCREASES THE ESTROGEN EXPOSURE FOR YOUR BODY. FAMILY HISTORY IS A VERY VERY IMPORTANT RISK FACTOR FOR BREAST CANCER. IF YOUR MOTHER, SISTER OR DAUGHTER HAS DEVELOPED BREAST CANCER BEFORE MENOPAUSE, YOU ARE THREE TIMES MORE LIKELY TO DEVELOP THE DISEASE. IF TWO OR MORE CLOSE RELEVANTIVES SUCH AS COUSINS, AUNTS, GRANDMOTHERS HAVE HAD BREAST CANCER, YOU ARE STILL AT AN INCREASED RISK ALSO. AGAIN, WE KNOW THAT PEOPLE WHO HAVE FAMILIAL BREAST CANCERS, THERE ARE MUTATIONS IN THE BRCA1. YOU WILL NOT SEE ANY FAMILIAL BREAST CANCERS. BRCA IS ASSOCIATED WITH OVARIAN CANCERS. BR CA2 IS ASSOCIATED WITH BOTH MALE AND FEMALE BREAST CANCERS. P53, THEY ARE ALSO SEEN IN BREAST CANCERS AND MUTATIONS IN THE ONCOGENES ALSO HAPPEN IN BREAST CANCERS. WHAT ARE THE A NORMAL SIGNS AND SYMPTOMS WE ALL NEED TO BE AWARE OF? IT'S INTERESTING. THESE THINGS SEEM LIKE VERY OBVIOUS BUT IN THE CLINIC, I'VE HAD PATIENTS WHO ACTUALLY COME TO ME WITH SWOLLEN BREASTS, BIG BREASTS, THINGS THAT ARE I WOULD I IS A OFF -- IS OBVIOUS AND THEY SAY TO ME I DIDN'T REALIZE I HAD BREAST CANCER AND THEY WERE IGNORING IT FOR MONTHS AT A TIME. IT MAY BE OBVIOUS BUT I HAVE SEEN A LOT OF THINGS IN THE CLINIC SO WE ALL NEED TO BE COGNIZANT OF THESE CHANGES AND SYMPTOMS. SO CHANGE IN BREAST SIZE, PAIN OR TENDERNESS, REDNESS, CHANGE IN NIPPLE POSITION, SCALING AROUND THE NIPPLES. AND SCALING AROUND THAT COULD BE SOMETHING PEOPLE WILL IGNORE. SORE BREASTS THAT DOES NOT HEAL. SICKENING OF SKIP OR LUMP OR RETRACTIVE NIPPLE. WHAT ARE THE METHODS OF DETECTION. CLINICAL EXAM BY A PHYSICIAN OR TRAINED NURSE. MAMMOGRAPHY AND BREAST SELF EXAM. SO THE AMERICAN CANCER SOCIETY GUIDELINES FOR EARLY DETECTION OF BREAST CANCER SAY YOU NEED AN ANNUAL MAMMOGRAM STARTING AT THE AGE OF 40 AND CONTINUING AS LONG AS THE WOMAN IS IN GOOD HEALTH. A CLINICAL BREAST EXAM EVERY THREE YEARS FOR WOMEN IN THEIR 20'S AND 30'S AND ANNUALLY AFTER 40. AND A BREAST SELF EXAM IS AN OPTION FOR WOMEN STARTING IN THEIR 20'S. THE REASON I SAY OPTION IS IN THIS SLIDE. IN 2002, THE U.S. PREVENTIVE SERVICE TASK FORCE WHICH IS A PANEL OF INTERESTS IN SPECIFIC AREAS. THEY GET TOGETHER, THEY LOOK AT ALL THE EVIDENCE THAT'S OUT THERE, THE RESEARCH EVIDENCE AND THEN THEY MAKE A RECOMMENDATION ON VARIOUS THINGS. AND I'M SURE YOU PROBABLY HEARD THEIR MAMMOGRAM RECOMMENDATION THIS PAST YEAR. THAT CREATED QUITE A STIR. BUT THIS TOPIC, IN 2002, THEY ACTUALLY RECOMMENDED AGAINST TEACHING SELF BREAST COMPASSION BASED ON EVIDENCE INDICATING THAT IT DID NOT REDUCE BREAST CANCER MORTALITY. AND THE DECISION WAS LARGELY BASED ON ONE TRIAL SHOWING THAT THERE WAS NO DIFFERENCE IN BREAST CANCER MORTALITY AFTER 10 YEARS. AND THESE WOMEN THERAPY STUD -- THEY WERE STUDYING IN THE FAX TREE WHETHER THEY RECEIVED THE TRAINING OR NOT. PEOPLE WHO WERE DOING SELF BREAST EXAMS ACTUALLY, THEY WERE ENDING UP HAVING MORE BREAST BIOPSIS AND DIAGNOSIS OF BENIGN LESIONS. SO THEY WERE SUBJECT THEMSELVES TO A LOT OF UNNECESSARY PROCEDURES. SO BASED ON THAT. THIS IS THE RECOMMENDATION BUT I HAVE TO SAY A LOT OF PHYSICIANS DO STILL RECOMMEND IT. AND THEY DO SPEND THE TIME TEACHING THE PATIENT WHEN THEY DO THE EXAM THEY TEACH THE PATIENT HOW TO DO A SELF BREAST EXAM. RECOMMENDATION CLINICAL EXAM SHOULD BE PERFORMED BY A DOCTOR OR TRAINED NURSE PRACTITIONER AND THE CLINICAL BREAST EXAM, THE DIFFERENCE BETWEEN A SELF BREAST EXAM AND CLINICAL BREAST EXAM IS DONE BY A PHYSICIAN OR A TRAINED NURSE PRACTITIONER. AND THIS IS ACTUALLY BEEN SHOWN TO DECREASE MORTALITY. AND THERE'S EVIDENCE FROM THE CANADIAN NATIONAL BREAST CANCER TRAINING STUDY. SO MA'AM DPRAMS -- MAMMOGRAMS CAN BE USED FOR WOMEN WHO ARE HAVING SYMPTOMS -- IT'S A DOUBLE ANGLE EXTRA OF THE BREAST. THE X-RAYS, THEY COME FROM HERE AND THEN THIS LITTLE THING HERE, YOU CAN ANGLE THE BREAST IN DIFFERENT WAYS TO GET DIFFERENT PICTURES OF THE BREAST. BREAST CANCER SCREENING MAMMOGRAPHY REDUCES MORTALITY 26% IN AGE 16 TO 44 AND WOMEN 40-49. WHAT WERE THE OTHER MODALITIES OF SCREENING IN OTHER HIGH RISK WOMEN. THERE'S DIGITAL MAMMOGRAPHY WHICH WAS APPROVED IN JANUARY OF 2000. IT USES X-RAYS JUST LIKE A MAMMOGRAM TO PRODUCE A BREAST IMAGE BUT IT'S JUST AN ELECTRONIC IMAGE THAT'S STORED IN THE COMPUTER. IT'S A COMPUTER FILE YOU CAN ENHANCE IT AND LOOK AT LESIONS MORE CLOSELY. BASICALLY A STUDY WAS DONE THAT SHOWED THAT IT HAS BETTER ACCURACY IN PEOPLE WHO ARE LESS THAN 50 YEARS OLD AND FOR THOSE PATIENTS WHO HAVE AN INCREASED MAMMOGRAMMIC DENSITY AND THOSE PATIENTS WHO ARE PRE OR PERI MENOPAUSAL. THE SENSITIVITY FOR MRI IS HIGHER THAN MAMMAL. BUT THE SPECIFICITY FOR MRI IS LOWER THAN MAMMAL MEANING YOU SEE A LOT MORE FALSE POSITIVES AND THAT LEADS TO MORE BIOPSIES, UNNECESSARY BIOPSIES. THIS IS SOMETHING STILL IN RESEARCH. IT'S A PROMISING TECHNIQUE BUT CLINICAL TRIALS ARE LOOKING AT THIS STILL. SO A BREAST SELF EXAMINATION IS AN OPPORTUNITY FOR A WOMAN TO BECOME FAMILIAR WITH HER OWN BODY SO IF THERE IS A CHANGE IT CAN BE DETECTED QUICKLY. I ALREADY TOLD YOU WHAT THE TASK FORCE HAS SAID BUT PERSONALLY I STILL RECOMMEND PEOPLE TO BE AWARE OF WHAT'S GOING ON. THE RECOMMENDATION BEGAN AT AGE 20 AND CONTINUE MONTHLY. IT IS AN EXAM OF THE BREAST, AN UNDER ARM AREA. JUST REALLY QUICKLY, THE FIRST STEP, YOU LOOK AT YOURSELF IN FRONT OF A MIRROR, YOU KEEP YOUR SHOULDERS STRAIGHT, HANDS ON THE HIPS. LOOK FOR ANY CHANGES THAT I TALKED ABOUT PREVIOUSLY. YOU PUT YOUR ARMS UP TO LOOK FOR ANY CHANGES THAT I SPOKE ABOUT PREVIOUSLY. YOU WANT TO LIE DOWN BECAUSE SOMETIMES LESIONS ARE ACTUALLY BETTER WHEN YOU'RE LYING DOWN YOU WANT TO USE THE FIRST THREE FINGERS OF YOUR HANDS, THE PADS ACTUALLY AND USE A FIRM TOUCH. AND FEEL IT ALL DIFFERENT LEVELS. YOU WANT TO USE SOME SORT OF A PATTERN SO YOU MAKE SURE YOU COVER THE ENTIRE AREA. AND THEN THE OTHER PART IS YOU WANT TO STAND UP AGAIN AND USE THE CIRCULAR MOTIONS ONCE AGAIN TO FEEL FOR ANY LESIONS. SO THE FIRST TIME YOU'RE DOING THIS, YOU'RE ACTUALLY JUST LOOKING AT CHANGES. THE SECOND TIME YOU'RE FEELING FOR CHANGES. SO HOW IS BREAST CANCER DIAGNOSED? BIOPSY IS NECESSARY TO CONFIRM A DIAGNOSIS OF CANCER AND INVOLVES REMOVING EXAMPLE OF BREAST TISSUE TO DETERMINE WHETHER THE LESION IS CANCEROUS OR BENIGN. THERE'S ACTUALLY MANY METHODS OF BREAST BIOPSY THESE DAYS. THE APPROPRIATE METHOD REALLY DEPENDS ON DIFFERENT THINGS, DIFFERENT CHARACTERISTICS OF THE LESION. PATIENT CHARACTERISTICS, A VARIETY OF FACTORS. THIS IS FOR BREAST BIOPSY. THE FIRST THING I HAVE TO SAY DESPITE WHICH ONE YOU USE, IF YOU CAN NOT FEEL THE LESION, IF IT'S IN THE BREAST, THE BIOPSY HAS TO BE DONE UNDER SOME SORT OF GUIDANCE AND THE WE HAVE A STEREO -- WHICH IS UNDER MAMMOGRAMMIC GUIDANCE WHICH IS BASICALLY A MAMMOGRAM AND THE OTHER ONE IS THE -- IT'S USUALLY DONE FOR CYSTS. IF THE FLUID LOOKS BLOODY MORE THAN LIKELY IT'S CANCER. IF THE FLUID IS YELLOW OR STRAW COLORED MORE THAN LIKELY IT'S BENIGN. A COURT NEEDLE BIOPSY, IT'S LIKE A GUN THAT SHOOTS AND YOU HAVE TO DO MULTIPLE TIMES. IT'S LIKE 10 TO 20 TIMES YOU HAVE TO DO THIS PROCEDURE. SO IT'S NOT THE MOST COMFORTABLE PROCEDURE. THE VACUUM BIOPSY, ANOTHER NAME THAT YOU MIGHT BE FAMILIAR WITH IS MAMA CHROME BIOPSY, A NEW -- TO GET AN EVALUATION WITH ONE SHOT. SO THERE'S MINIMAL PROBLEMS FOR THE PATIENT -- IT'S ACTUALLY ABLE IN ONE SHOT TO BE ABLE TO PICK UP MICRO CALCIFICATIONS WHICH ARE ACTUALLY SEEN ON THE MAMMOGRAM. AND MICRO CALCIFICATIONS ARE ACTUALLY THE EARLIEST FORMS, THE EARLIEST SIGN I HAVE TO SAY OF BREAST CANCER. YOU SEE MICRO CALCIFICATIONS ON THE MAMMOGRAM. YOU DEFINITELY WANT TO GET THAT AREA OF BIOPSY, THAT AREA TO MAKE SURE THERE'S NO MALIGNANCY THERE. ADDI IS BASICALLY A LARGE CORE BIOPSY AND IT AWE DEMONSTRATES TO TAKE THE ENTIRE LESION OUT WITHOUT DOING AN OPEN SURGICAL BIOPSY. AND THEN THE FINAL ONE IS THE OPEN SURGICAL BIOPSY. THIS IS A PICTURE OF THE MAMMATOMORROW. THIS IS JUST A PICTURE OF A CYST SOMETIMES YOU PICK UP THINGS ON A MAMMOGRAM YOU LOOK AT MORE CAREFULLY AND THAT'S WHY A MAMMOGRAM IS FOLLOWED WITH AN ULTRASOUND. THIS IS AN ULTRASOUND GUIDED FOR BIOPSY. THE NEEDLE IS GOING IN. THIS IS WHAT THEY'RE LOOKING AT AND THEY KNOW EXACTLY WHERE THEY'RE GOING. ALL RIGHT. LET'S TALK ABOUT SYSTEMIC THERAPY. ENDOCRINE DIRECTED. IT CAN BE CHEMOTHERAPY AND YOU CAN HAVE BIOLOGIC AGENTS AND SYSTEMIC THERAPY IS BASICALLY CHEMOTHERAPY. LOOKING AT HORMONE THERAPY, ESTROGEN, WE KNOW ESTROGEN IS A GROSS FACTOR FOR BREAST CANCER CELLS SO IT'S A VERY ATTRACTIVE WAY TO FOR PREVENTION PURPOSES, TO TARGET THIS PATHWAY. IT'S VERY LUCRATIVE FOR BOTH PREVENTION AND FOR TREATMENTS. THERE'S TWO WAYS YOU CAN TARGET THE PATHWAY. YOU CAN BLOCK THE RECEPT USING TAU MOSQUE FIN -- THESE ARE RECEPT MODULATORS. OR IF YOU DON'T BLOCK THE RECEPTOR YOU CAN DECREASE THE LIGAND. INHIBITORS, IN POST MENOPAUSAL WOMEN, THE MAJORITY OF I -- ESTROGEN WAS PRODUCED IN THE ADRENAL GLANDS. TESTOSTERONE ARE ACTUALLY CONVERTED TO ES TROGIAL. YOU CAN ACTUALLY INHIBIT THE ENZYMES FOR THE PRODUCTION HOW FAR LIGANDS. ACTUALLY TAKING OUT THE OVARIES, INCREASING THE LIGAND AND AGAIN GOING TO RELEASING HORMONE ANALOGS WILL ALSO DECREASE THE AMOUNT OF ESTROGEN PLASMA LEVELS OF ESTROGEN. SO THIS IS A STUDY THAT WAS JUST RECENTLY CAME OUT IN THIS JOURNAL OF CLINICAL ONCOLOGY IN MAY OF 2011. SO ALTHOUGH STUDIES HAVE SHOWN THAT TAMOXIFEN AND -- CAN BOTH BE USED IN HIGH RISK WOMAN THE DRUGS CAN CAUSE ADVERSE SIDE EFFECTS. TAMOXIFEN CAN CAUSE THE UTERINE CANCER. IT ACTUALLY STIMULATES THE ESTROGEN RECEPTORS IN THE UTERUS. IT CAN CAUSE BLOOD CLOTS, IT CAN CAUSE CATARACTS. SO THERE ARE SIDE EFFECTS TO THESE MEDICATIONS THAT HAVE TO BE KEPT IN MIND. BUT FOR WOMEN WHO ARE ADD HIGH RISK OF DEVELOPING A BREAST CANCER, THEY WANT TO KNOW WHAT THEIR OPTIONS ARE. SO WOMEN AND THEIR PHYSICIANS MUST DECIDE WHETHER THE POTENTIAL BENEFITS OF EITHER ONE OR THE OTHER DRUG OUTWEIGH THE RISKS OF ANY SITUATION. SO RESEARCHERS RIGHT HERE FROM THE NCI AND NC -- FROM WHICH THEY HAVE DEVELOPED A BENEFIT RIRI INDEX TO HELP GUIDE CONDITIONS ON WHETHER POST MENOPAUSAL WOMEN THE INCREASED RISK TO TAKE EITHER -- OR TAMOXIFEN. THE RESEARCHERS USE DATA FROM PREVIOUS PREVENTION STUDIES WHICH IS THE WOMEN'S HEALTH INITIATIVE, THE BREAST CANCER PREVENTION TRIAL AND THE STAR TRIAL WHICH WAS THE ONE LOOKING AT [INDISCERNIBLE] THEY CONSIDER POSSIBLE ADVERSE HEALTH OUTCOMES SUCH AS BONE FRACTURES WHICH ARE INCREASED WITH TAMOXIFEN. BLOOD CLOTS, STROKE AND ENDOMETRIAL CANCER, RATES OF WHICH WERE POTENTIALLY INCREASED OR DECREASED BY TAMOXIFEN OR [INDISCERNIBLE] THEN THEY ASSIGNED A WROTE TO EACH POSSIBLE ADVERSE EFFECT. AND TO INVASIVE INCITES YOUR BREAST CANCER. THEY'RE ASSIGNING A WAY TO EACH WOMAN'S RISK AND ALSO FOR THE SIDE EFFECTS PROFILE FOR THAT PATIENT. AND THEY CALCULATED THE PROBABILITY THAT A WOMAN WITH VARIOUS RISK FACTORS WILL HAVE EACH OUTCOME IN FIVE YEARS WITH AND WITHOUT -- OR TAMOXIFEN. THEN THEY USED -- TO USE A COLOR CODED TABLE FOR EACH DRUG THAT SHOWED FOR EACH AGE GROUP AND FIVE YEAR PROJECTED RISK OF INVASIVE CANCER WHETHER THIS IS STRONG OR MODERATE EVIDENCE IF THEY RISK OUTWEIGH THE BENEFITS FOR EACH PARTICULAR PATIENT. >> I JUST WANT TO SAY, THIS GIVES WOMEN THE OPTION OF DISCUSSING WITH THEIR PHYSICIANS WHAT WE KNOW THEY CAN DO FOR BREAST CANCER PREVENTION. LOOKING AT TAMOXIFEN THIS IS FROM THE EARLY BREAST CANCER TRIAL DATA. IT'S SHOWING THAT TAMOXIFEN AND REDUCE FOR OCCURRENCE AND BREAST CANCER MORTALITY. NOTES OF THE EFFECT OF RECURRENCE ACTUALLY COMES FROM THE FIRST FIVE YEARS WHEREAS THE EFFECT OF MORTALITY IS MORE PERSISTENT WITH TIME. THIS IS REPORTED BACK IN 2009 BUT IT'S STILL UNDER RESEARCH. TAMOXIFEN PHARMACOGENETICS. WE KNOW THAT THE GROWTH INHIBITORY EFFECT OF TAMOXIFEN IS MEDIATES BY ITS METABOLIZE FOR TAMOXIFEN -- THE FORMATION OF THESE IS ACTUALLY CATALYZED BY THE -- THERE IS A VARIANCE WITH THIS PARTICULAR ENZYME. PEOPLE WE THOUGHT BENEFITING FROM TAMOXIFEN IN THE PAST, THERE WAS A GROUP THAT NEVER BENEFITED FROM IT. THEY WERE NOT ABLE TO METABOLIZE TAMOXIFEN. WE SEE PEOPLE WHO HAVE NORMAL ACTIVITY FOR THIS ENZYME, REDUCED ACTIVITY, NO ACTIVITY OR HIGH ACTIVITY. SO IT CAN BE CALCULATED THAT GENOTYPE FOR THE RESPONSE TO TAMOXIFEN. THIS STUDY SHOWS BASICALLY THOSE WHO WERE -- WE HAD A RECURRENCE RATE OF THE NINE YEAR FOLLOW UP AND PEOPLE WHO WERE EXTENSIVE METABOLIZERS TO THE METABOLITES, THEIR OCCURRENCE RATE WERE MUCH LOWER THAN 14.9%. WE ALREADY MENTIONED THE -- INHIBITORS THAT ARE USED IN POST MENOPAUSAL WOMEN BECAUSE THE ESTROGEN IN POST MENOPAUSAL WOMEN FOR THE MOST PART PRODUCING THE ADRENAL GLANDS. THEY INHIBIT AROMATASE ENZYME -- TO ESTROGEN AND THIS REACTION CAN TAKE PLACE IN THE FAT AND MUSCLE AND THE BREAST. THERE'S THREE APPROVED AROMATASE INHIBITORS ON THE MARKET NOW. THIS WAS THE -- IT WAS PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE ON JUNE 23RD, 2011. BASICALLY THE RESULTS OF THE COLLECTIVE TRIAL WERE ALSO REVEALED THIS PAST ASCO. IT WAS BIG NEWS. EXEMESTANE SUBSTANTIALLY REDUCED THE RISK OF INVASIVE BREAST CANCER IN POST MENOPAUSAL WOMEN. FOR POST MENOPAUSAL WOMEN THERE'S ANOTHER OPTION FOR BREAST CANCER PROVISION THAT HAPPENS LESS SIDE EFFECTS AND TOXICITY. IT I'M ROLLED 4,560 WOMEN WITH INCREASED RISK OF DEVELOPING BREAST CANCER. A HIGH RISK DETERMINATION WAS MADE BASED ON SOME OF THE RISK FACTORS, COMMON RISK FACTORS AGE GREATER THAN 60. NORMAL BREAST GROSS HISTORY OF BPIS AND ELEVATED MODEL WHICH IS I HAVEN'T TALKED ABOUT THAT BUT IT'S BREAST CANCER RISK MODEL THAT'S VERY WELL-KNOWN. SO THE PATIENTS. >> -- 11 WOMEN DEVELOPED INVASIVE CANCER COMPARED TO THE WOMEN IN THE PLACEBO. WOMEN WHO TOOK -- WERE 65% LESS LIKELY THAN THE WOMEN WHO TO GO PLACEBO. THIS IS THE LARGEST REDUCTION IN ANY OF THE FOUR LARGE BREAST CANCER PREVENTION TRIALS THAT HAVE BEEN CONDUCTED TO DATE AND THAT'S THE TWO TRIALS WHERE THE BCPT AND THE STAR TRIAL. IN PREVIOUS TRIALS DAILY USE OF TAMOXIFEN REDUCED BREAST CANCER BY 50% AND 38% AS COMPARED TO 65% HERE. AND THAT WAS A FIVE YEAR FOLLOW UP. THIS IS A THREE-YEAR FOLLOW UP BUT IT'S GOING TO KEEP GOING. THAT'S WHAT WE DO WITH ONCOLOGY FOR A CERTAIN NUMBER OF YEARS BUT IT'S LOOK LOOK VERY VERY PROMISING. JUST BRIEFLY ON SYSTEMIC -- CHEMO. POLY CHEMO THERAPY THAT'S THE NAME OF THE GAME WHEN YOU'RE TALKING ABOUT ADJUVANT -- THAT CREATES THE BEST SURVIVAL. THIS IS FROM THE -- AND IT SHOWS FOR PATIENTS, THIS IS PATIENTS AGE LESS THAN 50. THIS IS RECURRENCE HERE, MORTALITY HERE, POLY CHEMOTHERAPY, DEFINITELY. FOR THE YOUNGER GROUP THERE'S A MUCH BIGGER DIFFERENCE IN THE CURVE FOR THE 50-59. IT DEFINITELY REDUCES OCCURRENCE AND MORTALITY POLY CHEMOTHERAPY. I'M GOING TO SKIP THIS SLIDE IT'S BASICALLY SHOWING THE SAME THING. POLY CHEMOTHERAPY IS MORE EFFECTIVE THAN SINGLE AGENTS. -- MEN MASSACHUSETTSAL STATUS iWHICH IS A PARTICULAR TYPE OF CHEMOTHERAPY PRODUCED IN ABSOLUTE BENEFIT OF 4% IN THE RECURRENCE AND SURVIVAL. DIFFERENT AGENTS THAT CAN BE USED. THESE ARE FIRST LINE. THESE ARE SOME OF THE OPTIONS. WE OFTEN GIVE OUR CHEMOTHERAPY IN THE LOW RISK LYMPH NODE NEGATIVE PATIENT EVERY THREE WEEKS TIMES FOUR CYCLES. IT'S A VERY POPULAR CHEMOTHERAPY OPTION. IF PATIENTS ARE LYMPH NODE POSITIVE, YOU DEFINITELY WANT TO ADD A TAX -- TO THE THERAPIES SO YOU DO FOUR CYCLES EVERY THREE WEEKS. THAT'S FOLLOWED BY ANOTHER FOUR CYCLES OF ATAXES HERE. IF THE PATIENT IS POSITIVE YOU SAID -- BIOLOGIC AGENTS. THEY ARE MEMBERS OF THE TYPE ONE RECEPTOR KINASE FAMILY. THAT'S THE RELATED FOUR FAMILY MEMBERS UPON LIGAND STIMULATION -- BY SUBSEQUENT PHOSPHORYLATION WHICH IS CATALYZED BY THE RECEPTOR KAY NICE ACTIVITY. THIS WILL RESULT IN AN ARRAY OF SIGNALING AS WE ALL KNOW. AND THE IMPORTANT THING IS THAT THE INCIDENCE OF ERBB2 APPLICATION IS THE BREAST CANCER AND THAT IDENTIFIES IT AS A THERAPEUTIC TARGET. THIS IS THE-- FAMILY. THE HER2 DOES NOT HAVE A LIGAND BINDING DOMAIN. IT'S ACTIVE UPON THE DIMERIZATION. THE OTHER MEMBERS OF THE FAMILY THAT HAD MULTIPLE LIGANDS THAT WILL BIND. THIS IS AN ANTIBODY THAT TARGETS THE HER2 PROTEIN. IT'S 95% HUMAN, 5% MURINE. THIS COMBINATION DECREASES ITS POTENTIAL FOR AMINO -- IT IS APPROVED FOR EARLY STAGE BREAST CANCER IN 2005. CHEMOTHERAPY INCREASES OVERALL SURVIVAL AND DISEASE-FREE SURVIVAL AND PATIENTS WITH -- POSITIVE. IT'S THE B31 STUDY THAT SHOWED WHEN YOU ADD IT TO THE CHEMOTHERAPY, IT WILL IMPROVE THE DISEASE FREE SUR1R50EU68. SO FOR EXAMPLE AT FOUR YEARS, 85% ARE DISEASE FREE. WHEN YOU ADD 67% WITHOUT -- TRIPLE NEGATIVE BREAST CANCER. IT REFERS TO A SPECIFIC SUBTYPE OF BREAST CANCER THAT DOES NOT EXPRESS THE GENE, PROGESTERONE RECEPTOR. IT IS DIAGNOSED IN AFRICAN AMERICANS, HISPANICS AND THOSE WITH BRCA1 MUTATIONS. IT'S ASSOCIATED WITH POOR OVERALL PROGNOSIS. SO I HAVE TO MENTION THIS. SINCE MOST OF YOU ARE RESEARCHERS, I THINK YOU KNOW ABOUT POWER INHIBITORS. THIS WAS POWERFUL 23450DZ IN 20 09. SO PARP INHIBITORS JUST TO REITERATE, THEY'RE AN EXPERIMENTAL CLASS OF DRUG THAT WE THOUGHT MAY HAVE POTENTIAL FOR THE TREATMENT OF TRIPLE NEGATIVE BREAST CANCER. THE ENSIGN USED BY CANCER CELLS TO REPAIR DNA DAMAGE. SO PARP INHIBITORS ARE BEING USED TO TARGET INHIBITORS WHERE ONE PATHWAY IS SHUT DOWN. FOR EXAMPLE IN BRCA 1 AND BRCA 2 FORMATIONS THEY RELY HEAVILY ON THE PART PATHWAY OR TUMORS THAT ARE BEING TREATED WITH CHEMOTHERAPY THEY LOSE THEIR DNA REPAIR MECHANISM. SO THIS WOULD BE A GOOD CLASS OF TUMORS. SO ALL THE EXCITEMENT BACK IN 2009 CAME FROM THIS TRIAL BY -- IN, IT WAS USING THE BSI-201 WHICH 116 WOMEN WITH TRIPLE NEGATIVE MET STERILIZATIONIC -- METASTATIC BREAST CANCER RANDOMIZED TO STANDARD CHEMOTHERAPY. IT SHOWS THAT THE MEDIAN SURVIVAL AND THE OVERALL SURVIVAL INCREASED WHEN YOU ADDED THE PARP INHIBITOR TO THE STANDARD CHEMOTHERAPY. BUT I HAVE TO SAY THAT THIS STUDY WAS NOT TARGETING SIMPLY TRIPLE NEGATIVE BREAST CANCER. THIS WAS A PHASE TWO STUDY LOOKING AT ALL SORTS OF BREAST CANCER PATIENTS AND THE TRIPLE NEGATIVE WAS A SUBANALYSIS OF THAT STUDY. IN EARLY 2011, THIS EXCITING CLASS OF COMPOUNDS RECEIVED A DOUBLE BLOW. UNFORTUNATELY IN JANUARY -- ANNOUNCESSED THAT THE SI-201 WHICH WAS THE MOST ADVANCED PARP INHIBITOR IN TRIAL FAILED ITS SURVIVAL IN IT'S FIRST PHASE TRIAL IN TYPICAL NEGATIVE BREAST CANCER DESPITE THE PROMISING RESULTS. I TOLD YOU THE PHASE TWO WAS NOT NECESSARILY A PERFECT PHASE TWO. WHEN THEY LOOKED BACK IT SEEMED LIKE THE PATIENTS WITH TUMORS THAT HAD BETTER PRAGUE NOAPSZ JUST BY CHANCE HAPPENED TO BE ON THE ARM THAT WAS RECEIVING THE PARP INHIBITORS. SO THEN IN FEBRUARY 2011, A MONTH LATER, AS TRA SENECA ANNOUNCED IT WOULD BE PURSUE PHASE THREE IN BRCA 1 AND BRCA 2 INHIBITORS THAT WAS IN THE USE OF PARP. FOR BREAST CANCER PARP INHIBITORS ARE ON THE BACK BURNER RIGHT NOW. THAT'S NOT TO SAY WE'RE NOT LOOKING AT IT IN OTHER CANCERS. I THINK THERE ARE A LOT OF CLINICAL TRIALS UNDER WAY, OVARIAN CANCER WHICH MAY BE STILL SHOWING SOME PROMISING RESULTS IN PHASE TWOTRIALS BUT THE STANDARD IS DEFINITELY SURVIVAL. THAT'S A PHASE THREE TRIAL. SO IT REMAINS TO BE DETERMINED. THERE IS SOME QUESTION OF WHETHER, THIS IS ALL BASED ON BSI, THE BSI RESULTS. MAYBE THERE'S A DIFFERENCE BETWEEN THE VARIOUS PARP INHIBITORS. I THINK FOR BREAST CANCER THIS IS KIND OF ON THE BACK BURNER FOR RIGHT NOW. SO HOW CAN WE DO BETTER IN TREATING PATIENTS? SO BETTER SELECTION OF CHEMOTHERAPY REGIMENS IS ONE THING. WE CAN USE GENE EXPRESSION PROFAILING TO PREDICT RESPONSE TO A PARTICULAR AGENT OR YOU CAN ALSO HAVE BETTER SELECTION OF PATIENTS WITH TREATMENT FOR CHEMOTHERAPY. AND YOU WILL WANTED TO TREAT ONLY THOSE PATIENTS WHO ARE MOST LIKELY TO RECUR AND WHO WILL THEREFORE BENEFIT FROM CHEMOTHERAPY. SO THIS IS OUR GOAL FROM THE FUTURE. WE DON'T WANT TO TREAT PATIENTS WHO DON'T NEED THE THERAPY. AT THE CURRENT JUNCTURE, WE DON'T HAVE THE INFORMATION ABOUT WHICH PATIENT NECESSARILY IS MOST LIKELY TO REOCCUR OTHER THAN THE STAGING AND THE NORMAL THINGS THAT WE USE. BUT THERE'S A LOT OF THINGS IN CLINICAL TRIAL RIGHT NOW UNDER RESEARCH THAT ARE POINTING US IN THAT DIRECTION, TOWARDS MORE PERSONALIZED MEDICINE. SO PREDICTING RESPONSE TO CHEMOTHERAPY -- IS ONE WAY, IT'S A PRESURGICAL CHEMOTHERAPY. IT'S USED IN RESEARCH CLINICAL TRIALS BECAUSE THE LESION ITSELF HAS NOT BEEN REMOVED SURGICALLY. AND WHEN YOU GIVE THE CHEMOTHERAPY, YOU CAN ACTUALLY WATCH WHETHER THE LESION IS RESPONDING OR NOT RESPONDING. THOUGH A LOT OF CLINICAL TRIALS ARE BASED LIKE THAT BUT WE USE IT IN THE CLINIC AS WELL. GENE EXPRESSION PROFILING TO PREDICT CHEMOTHERAPY RESPONSE. THIS WAS ACTUALLY, IT'S BEEN A WHILE NOW. IT'S FROM CHANG ET AL. IT WAS PUBLISHED IN 2003. HE LOOKED AT 24 PATIENTS WHO WERE TREATED WITH KNEE HOE -- THERAPY SO BASICALLY USING THE NEO ADJUVANT HE WAS ABLE TO SEE WHICH PATIENTS WERE THE RESPONDERS AND NON-RESPONDERS AND DIVIDED THE PATIENTS INTO TWO GROUPS THAT CORRELATED. THIS IS A CLASSIC. IT WAS REPORTED -- IN 2001, A PORTRAIT OF -- GENE PROFILING ABLE TO DESCRIBE FIVE DIFFERENT TYPES OF BREAST CANCER. LUMINAL A AND B ARE LIKE LUMINAL ENDOTHELIAL CELLS. IT'S LIKE NORMAL BREAST TISSUES. HER2 WAS IDENTIFIED PREVIOUSLY AND THE -- IS ALMOST COMMON. SO AN IMPORTANT QUESTION IN BREAST CANCER TREATMENT IS WHAT IS THE LIKELIHOOD OF DISTANT RECURRENCE IN PATIENTS WITH BREAST CANCER WHO HAVE NO INVOLVED LYMPH NODES AND ESTROGEN RECEPTOR POSITIVE TUMORS. SO THESE ARE THE PATIENTS THAT KIND OF LIE ON THE FENCE. SO WHAT DO WE DO WITH THESE PATIENTS. DO WE GIVE CHEMOTHERAPY, DO WE TREAT THEM WITH HORMONE TREATMENT ALONE? WE DON'T WANT TO OVERTREAT PATIENTS. THAT'S DEFINITELY HAS ITS OWN DOWN SIDE. WHAT DO WE DO? SO THE LAST TIME I GAVE THIS LECTURE I TALKED ABOUT THIS BUT I THINK I WANTED TO TALK ABOUT IT AGAIN BECAUSE IT'S AT THE CENTER OF ONGOING RESEARCH RIGHT NOW. IT'S THE UP COTYPE DX. IT WAS A MULTISTEP APPROACH THAT WAS USED TO DEVELOP THIS ASSAY. THEY DEVELOPED AN ASSAY FOR THE EXPRESSION OF TUMOR-RELATED GENES FOR USE WITH PARAFFIN IMBEDDED ARE TISSUE. AND THEN THEY USED THE MULTISTEP APPROACH TO ASSAY IT CLINICALLY AS WELL. SO -- THE METHOD WAS TO QUUNT FI THE GENE EXPRESSION WITH THE IMBED BOARD OF DIRECTOR TUMOR TISSUE. THEY LOOKED AT 250 CANDIDATE GENES FROM THE PUBLISHED LITERATURE FROM THE GENOMIC DATA BASIS AND IT WAS DONE ON FRESH FROZEN TISSUED. THEY LOOKED AT THREE INDEPENDENT STUDIES OF BREAST CANCER THAT INVOLVED 447 PATIENTS TO TEST THE RELATIONSHIP BETWEEN THE EXPRESSION OF THESE 250 GENES THAT THEY HAD IDENTIFIED AND THE RECURRENCE OF BREAST CANCER. SO BASICALLY THEY'RE GOING BACK TO THE REPOSITORY TRIAL AND THEY ARE USING THE IMBEDDED TISSUES IS WHAT THEY'RE DOING TO GO BACK AND LOOK AT THE DIFFERENT CANDIDATE GENES FROM THOSE PARAFFIN IMBEDDED TISSUES WITH RECURRENCE. THEY USED THE RESULT OF THREE STUDIES TO SELECT A PANEL OF 16 CANCER-RELATED GENES AND YOU SEE THOSE HERE. THIS IS THE REFERENCE GENES AND THE REST OF THEM, THEY IDENTIFIED THESE GENES. THEY BASE THAT ON THE BEST RTPCR PERFORMANCE AND THE MOST ROBUST PREDICTIONS. FROM THAT THEY DESIGNED AN ALGORITHM BASED ON THE LEVEL OF THE EXPRESSION OF THESE GENES FOR A RECURRENT SCORE FOR EACH TUMOR SAMPLE BEING TESTED. SO BASICALLY LOOKING AT THOSE PARAFFIN IMBEDDED TISSUES FOR THOSE THREE CLINICAL TRIALS, THEY, DEPENDING ON THE EXPRESSION OF THESE GENES, THEY GAVE EACH TUMOR A RECURRENT SCORE. SO NOW THEY HAVE THIS ASSAY. IT HAS TO BE VALIDATED. SO THE PARAFFIN IMBEDDED TISSUE SAMPLES FROM PATIENTS WHO WERE ACTUALLY ENROLLED IN THE B14 TRIAL WERE USED TO VALIDATE THE ABILITY OF THESE 21 GENES. THE 21 GENES RTCPR ASSAY AND THE RECURRENT SCORE ALGORITHM TO QUANTIFY THE LIKELIHOOD OF WE CURRENCE IN PATIENTS. THEY ARE -- ER POSITIVE EARLY STAGE BREAST CANCER AND WHO HAD BEEN PREVIOUSLY TREATED WITH TAMOXIFEN ON THE B14 TRIAL. SO IT BASICALLY SHOWED THAT IF YOU WERE A, IF YOU HAD A HIGH SCORE, HIGH RECURRENCE SCORE, YOUR RATE OF DISTANT RECURRENCE WAS HIGH AT 30.5%. IF YOU HAD A LOW RECURRENCE SCORE THAT THEY CALCULATED, THEN YOUR RATE OF DISTANT RECURRENCE WAS, IT CORRELATED VERY LOW. AND THE INTERMEDIATE WERE RIGHT IN THE MIDDLE. SO THIS IS BASICALLY A CONTINUUM OF WHAT I JUST SAID, THAT THE PATIENTS WHO HAD A LOW SCORE, AS THE SCORE INCREASES, YOUR RISK INCREASES. AS THE RECURRENT SCORE INCREASES, YOUR RISK INCREASES. SO BASICALLY THE CRISES OF CHEMOTHERAPY COMES UP. THAT'S THE WHOLE QUESTION ABOUT ALL OF THIS. SO PATIENTS WITH TUMOR THAT HAVE A HIGH RECURRENCE SCORE HAVE A LARGE -- SORRY. THEY HAVE A LARGE ABSOLUTE BENEFIT OF CHEMOTHERAPY. SO YOU KNOW THESE PATIENTS HAVE A LARGE RECURRENT SCORE. SO YOU CAN SEE THAT THIS IS THE CHEMOTHERAPY IS ON TOP. YOU SEE THAT THEY'RE GOING TO HAVE A GOOD BENEFIT FROM THAT. THE PATIENTS WHO HAVE A LOW RECURRENCE SCORE THEY'RE NOT GOING TO GET ANY BENEFIT THERE CHEMOTHERAPY. WHAT ARE YOU GOING TO DO WITH THE PATIENTS IN THE MIDDLE? DO YOU GIVE THEM CHEMOTHERAPY OR DO YOU NOT GIVE THEM CHEMOTHERAPY. THAT'S THE QUESTION. SO THE TAILOR RX IS AN ONGOING TRIAL. IT'S A LANDMARK TRIAL AND REPRESENTS THE CULMINATION OF A MAJOR INITIATIVE TO INTEGRATE MOLECULAR DIAGNOSTIC TESTING INTO CLINICAL DECISION-MAKING. THEY ARE USING ONCOTYPE GX TO ASSIGN TREATMENTS TO MORE THAN 10,000 BREAST CANCER PATIENTS FROM 1500 SITES. AND THEY COMPLETED ACCRUAL LAST YEAR. RESULTS ARE GOING TO COME OUT INTO 2015. THE PRIMARY OBJECTIVE IS TO DETERMINE WHETHER YOU WANT TO GIVE CHEMOTHERAPY OR NOT TO THAT GROUP OF PATIENTS THAT'S IN THE MID RANGE. AND THEY WANT TO CREATE A TISSUE BANK OF PATIENTS ENINVOLVED IN THIS TRIAL. BASICALLY THE PATIENTS WHO HAVE A MID RANGE SCORE, THEY'RE GOING TO BE ACTUALLY RANDOMIZED TO TWO ARMS, EITHER GETTING HORMONE THERAPY ALONE WHICH IS -- THIS IS AN ONGOING STUDY LIKE I SAID. KEY PAYMENTS GENES THAT ARE FREQUENTLY ASSOCIATED WITH RECURRENCE FOR WOMEN IN EARLY STAGE BREAST CANCER WITH BE USED TO ASSIGN PATIENTS TO THE MOST APPROPRIATE AND EFFECTIVE TREATMENT. MOVE ON. I'M GOING TO GIVE THIS. METASTATIC BREAST CANCERS. JUST WANT TO PROLONG SURVIVAL, IMPROVE THEIR QUALITY OF LIFE. THAT'S THE MOST IMPORTANT THING. I JUST WANT TO MENTION THIS LAST THING BECAUSE I HAVE A MINUTE. THIS IS THE FDA -- WE ALL KNOW IS ANTIBODIES DIRECTED AGAINST -- AND LABORATORY EVIDENCE WE KNOW SUPPORTS THE RULE OF ANGIOGENESIS AND BREAST CANCER. BUT IN A CONTROVERSIAL 2008 DECISION, THE FDA GAVE A FAST TRACK APPROVAL FOR THIS EXPENSIVE 88,000 PER YEAR DRUG FOR THE TREATMENT OF ADVANCED BREAST CANCER AND IT WAS BASED ON A SINGLE STUDY. THEY WERE TOLD AND THEY'RE THE MAKERS THAT THEY WERE REQUIRED TO CONTINUE RESEARCH ON THE DRUG. IT WAS APPROVED BASED ON THIS ECON 2100 TRIAL THAT BASICALLY SHOWS -- THAT WAS THE DESIGN AND IT SHOWED THE OBJECTIVE RESPONSE WAS BETTER WHEN YOU ADD BEVACIZUMAB. THE KEY IS IT DID NOT INCREASE OVERALL SURVIVAL. IT JUST INCREASED, THIS IS PROGRESSION-FREE SURVIVAL. IT DID NOT INCREASE OVERALL SURVIVAL. IT WAS APPROVED IN 2008 WITHOUT THE FACT THAT WE KNEW IT INCREASED OVERALL SURVIVAL. UNFORTUNATELY SUBSEQUENT RESULTS WERE DISAPPOINTING AND THE FDA HAS REVOKED THEIR APPROVAL FOR BREAST CANCER. THEY APPEALED THE DECISION AND A PUBLIC HEARING TOOK PLACE IN JUNE. PATIENTS ACTUALLY TESTIFIED FOR THE DRUG. FDA HELD FIRM ITS CONCLUSION AND IT'S NOT INDICATED FOR BREAST CANCER ANY LOWRNG. I THINK I'M DONE. I HAD A FEW MORE SLIDES BUT IT'S BASICALLY ABOUT BREAST CANCER WHAT MY PREDICTIONS FOR THE FUTURE ARE. IT'S IN THE HANDOUT. YOU CAN TAKE A LOOK. THANK YOU. [APPLAUSE] >> QUESTIONS? WHEN YOU TALK ABOUT RECURRENCE, OFTEN TIMES THE BREAST CANCER CHANGES FROM THE ONE THAT HAS OCCURRED. ISN'T THAT THE CASE? >> ABSOLUTELY TERRY, THAT'S RIGHT. FOR THE FIRST REOCCURRENCE, THE RULE IS WE BIOPSY AGAIN. WE BIOPSY AND WE RETEST FOR THE DIFFERENT RECEPTORS AND WE RETEST FOR -- STATUS AND OFTEN TIMES THESE THINGS DO CHANGE. THAT WILL CHANGE THE TREATMENT STRATEGY. >> [INDISCERNIBLE] >> IT'S A TRIPLE NEGATIVE -- THAT'S THE QUESTION FOR DCIS, DO YOU TREAT, DO YOU NOT TREAT. WE ARE CHECKING HORMONE RECEPTORS, THESE DAYS. ACTUALLY THIS HAS BEEN GOING ON FOR SOME YEARS NOW. EVEN WITH THE DCIS, THAT IS POSITIVE FOR HORMONE RECEPTORS. WE OFTEN WILL TREAT THE PATIENT WITH HORMONAL THERAPY. SO WE DO TAKE, NO MATTER WHAT STAGE THE CANCER IS AT WE DO LOOK AT OTHER FEATURES TO SHOW WHETHER THAT IS AN AGGRESSIVE TUMOR OR NOT A AGGRESSIVE TUMOR. THAT DOES CHANGE OUR STRATEGY THROUGHOUT TIME, YES. >> OUR NEXT SPEAKER IS STEFAN AMBS AND HE WAS EDUCATED IN GERMANY BUT AT NCI WE TRY TO GET THE BEST RESEARCHERS FROM ALL OVER THE WORLD. WE CERTAINLY GOT ONE IN STEFAN. AND THE TITLE OF HIS TALK IS MAGNITUDE AND CAUSES OF CANCER HEALTH DISPARITIES. STEFAN. >> THANK YOU. ALL RIGHT. SO IN MY PRESENTATION I -- CANCER HEALTH DISPARITY. I WILL TALK ABOUT THE CAUSES OF CANCER HEALTH DISPARITY. IN THE SECOND HALF OF MY PRESENTATION, I WILL SHOW DATA FROM OUR RESEARCH THAT IS EXAMINING TUMOR BIOLOGY. AND HOW TUMOR BIOLOGY CONTRIBUTE TO SURVIVAL HEALTH DISPARITIES BETWEEN TWO PATIENTS, AFRICAN AMERICANS AND EUROPEAN AMERICANS IN PROSTATE CANCER. WHY ARE WE STUDYING CANCER HEALTH DISPARITIES WITH AFRICAN AMERICANS AND EUROPEAN AMERICANS. IT'S GENERALLY BELIEVED THAT THE REDUCTION OR HOPEFULLY ELIMINATION OF CANCER HEALTH DISPARITIES TO REDUCE CANCER OVERALL IN THE UNITED STATES. SECONDLY WE ARE CONDUCTING RESEARCH STUDIES -- LARGE AFRICAN AMERICAN POPULATION. AND THEN MOST IMPORTANTLY, IT HAS BEEN SHOWN THAT AFRICAN AMERICANS HAVE THE HIGHEST DEATH RATES FROM ALL CANCERS COMBINED AND THE MALIGNANCY OF LUNG -- AND THE CERVIX OF ALL RACIAL GROUPS IN THE UNITED STATES. NOW IT'S CLEARLY OTHER POPULATION GROUPS IN THE UNITED STATES AND GLOBALLY HAVE AN EXCESSIVE CANCER BURDEN WHEN YOU COMPARE THEM TO AN AFFLUENT WHITE POPULATION. I WELL TOUCH ON THAT, I DON'T HAVE THE POPULATION GROUPS DOING MY PRESENTATION. THIS SLIDE HERE SHOWS THE LIFE EXPECTANCY GAP EXPERT COMPARING AFRICAN AMERICANS WITH EUROPEAN AMERICANS AND WHAT YOU SEE IS HERE THERE'S A BIG GAP BETWEEN WHITE FEMALES AND AFRICAN AMERICAN FEMALES AND THEN EUROPEAN MALES AND EUROPEAN AND AFRICAN AMERICAN MALES. SO IN 2003, THE LIFE EXPECTANCY GAP BETWEEN AN AFRICAN AMERICAN FEMALE AND EUROPEAN FEMALE WAS 4.5 AND FOR THE MALE IT WAS 6.3 YEARS. AND THEN YOU ALSO SEE THE LIFE EXPECTANCY GAP BETWEEN ACTUALLY BETWEEN FEMALES AND MALES. THIS GRAPH SHOWS YOU HOW THIS GAP DEVELOPED OVER TIME AND YOU SEE THERE WAS ACTUALLY A PEAK IN THE 90'S FOR MALES AND FEMALES AND THEN A REDUCTION. THIS PEAK IS EXPLAINED ACTUALLY BY THE HIV EPIDEMIC AND ALSO BY HOMICIDE-RELATED DEATHS THAT PEAKED IN THE 90'S AMONG AFRICAN AMERICANS. THEN WE HAVE A DECLINE OF THE GAP. AND YOU SEE IT CONTINUES THE TREND OVER THE LAST 30 YEARS FOR FEMALES. BUT THEY ARE ACTUALLY REALLY FOR MALES -- WE HOPE WHAT WE SEE HERE IS WHAT WE WILL CONTINUE IN THE FUTURE. NOW WHEN YOU HAVE SUCH A LIFE EXPECTANCY GAP, YOU ASK THE QUESTION, WE ACTUALLY MADE IMPROVEMENTS AND WHERE WE HAVE ACTUALLY FAILED TO MAKE IMPROVEMENTS. AND THIS IS ACTUALLY SHOWING HERE, THIS SHOWS A LITTLE BIT THAT WE HAVE FAILED, WE HAVE MADE IMPROVEMENTS. USING THE LUNG CANCER HEALTH DISPARITY WHERE THEY DO HIV AND HOMICIDES FOR MALES. AND THEN HARD DISEASE, FOR HIV AND HOMICIDES AMONG THE FEMALES. BUT THEN THERE ARE MANY OTHER DISEASES WHERE WE ACTUALLY DIDN'T DO WELL. FOR THE PURPOSE OF THIS TALK ON CANCER WE ACTUALLY DIDN'T DO WELL AND CLOSE THE GAP FOR COLORECTAL CANCER AND -- CANCER. SO IN MANY WAYS, IN RELATION TO CANCER HEALTH DISPARITIES, AFRICAN AMERICANS AND OTHER MINORITY GROUPS IN THE U.S. HAVE NOT BENEFITED AS MUCH AS THE WHITE EUROPEAN AMERICAN POPULATION FROM OUR KNOWLEDGE, FROM OUR NEW KNOWLEDGE THERE CANCER IN GENERAL AND INTERVENTION AND TREATMENT OF CANCER. HERE I GIVE YOU JUST AN EXAMPLE THAT ACTUALLY SHOWS YOU A LITTLE BIT WHAT THAT REALLY MEANS IN RELATIONSHIP TO BREAST CANCER. THE AFRICAN AMERICANS AND THE EUROPEAN AMERICANS, UP TO 1980, ON HERE, WHAT YOU HAVE HERE IS THE BREAST CANCER MORTALITY RATE UP TO 90, UP TO 1990, THERE WAS ACTUALLY NO DISPARITY IN BREAST CANCER SURVIVAL BETWEEN THE TWO PATIENT GROUPS. BUT THEN STARTING IN 1980, A GAP OPENED UP AND THE SURVIVAL RATES IN DIFFERENT WAYS ARE LEADING TO A CANCER -- IS NOW ABOUT 30% EXCESS OF AFRICAN AMERICAN PATIENTS VERSUS EUROPEAN AMERICAN PATIENTS. WE HAVE A DEVELOPMENT NOT AS STRONG OF HISPANIC LATINO WOMEN. SO HOW DO WE IDENTIFY CANCER HEALTH DISPARITIES. WE CAN IDENTIFY HEALTH DISPARITIES ACTUALLY BY STARTING DATA COLLECTED THROUGH -- PROGRAM THAT COLLECTS AND ARCHIVES DATA ON CANCER INCIDENCE, CANCER MORTALITY, TREATMENT DATA, DATA BY ETHNICITY AND ALSO GENERAL CLINICAL PATHOLOGY DATA FROM CANCER PATIENT ABOUT 26% OF THE U.S. POPULATION. AND THE ETHNICITY DATA, THEY WERE COLLECTED AND CATEGORIZED INTO FIVE POPULATION GROUPS. IT'S NOT PERFECT BUT AT LEAST WE HAVE SOME OF THIS DATA ALLOWING YOU TO CATEGORIZE PATIENTS INTO EUROPEAN AMERICAN, AFRICAN AMERICAN, ASIAN AMERICAN, AMERICAN NATIVES, HISPANIC LATINOS. AND WHAT YOU SEE HERE IS ACTUALLY INCIDENCE RATE AMONG THESE TWO POPULATION GROUPS BUT ALL SITES COMBINED AND THEN SEPARATED BY SEX. AND THEN THE MAJOR CANCER SITES. WHAT YOU FIND IS THAT AFRICAN AMERICAN MALES HAVE THE HIGHEST CANCER INCIDENT RATE IN THE UNITED STATES FOLLOWED BY EUROPEAN AMERICANS AND THEN BY THE OTHER THREE POPULATION GROUPS. YOU LOOK AT THE EUROPEAN FEMALES WHICH HAVE THE HIGHEST CANCER RATE AND THEN THE OTHER THREE POPULATION GROUPS. SO WE HAVE TWO POPULATION GROUPS CATEGORY WITH A HIGHER INCREASED INCIDENT RATE OUT OF THE POPULATION GROUPS THAT HAVE ACTUALLY -- WE'RE NOT SURE IF THESE RATES ARE REALLY CORRECT. IT COULD BE UNDER REPORTING OR YOU'RE BORN -- WHICH MEANS THE DEATH IS ACTUALLY TO SOMEBODY WHO IS NOW CATEGORIZED EUROPEAN AMERICAN THAT WE PERHAPS UNDER ESTIMATE THE TRUE INCIDENCE MORTALITY, INCIDENCE OF MORTALITY. WE UNDER ESTIMATED AND CATEGORIZED THE EUROPEAN AMERICANS POPULATION. SO THEN WE CAN GO BY THE FOUR DIFFERENT SITES AND YOU SEE HERE AN EXCESS RISK FOR AFRICAN AMERICAN MEN DEVELOP PROSTATE CANCER COMPARED TO EUROPEAN AMERICAN -- AND THEN YOU HAVE THE OTHER FOUR POPULATION GROUPS. THAT'S REALLY REALLY -- AMONG EUROPEAN WOMEN FOR LUNG CANCER, IT'S IN EXCESS RISK FOR AFRICAN AMERICAN MALE TO DEVELOP LUNG CANCER AND THEN THE HIGHEST RISK IS ACROSS THE AFRICAN AMERICAN COMPARED TO THE EUROPE MEAN AND OTHER POPULATION GROUPS. THERE ARE OTHER CANCERS NOT SHOWN HERE THAT ARE ACTUALLY, THAT YOU HAVE EXCESSIVE BURDEN -- SO THE QUESTION IS ARE THE CAUSES OF THESE DIFFERENCES IN THESE INCIDENCE RATES. LUNG CANCER IS MAINLY CAUSED BECAUSE OF EXPOSURE TRUE TOBACCO SMOKE. MOST CANCERS DEVELOP SMOKERS AND YOU SAY THESE RATES REFLECT JUST TENDENCY AMONG THE POPULATION GROUPS WHICH IS ACTUALLY TRUE. HOWEVER, WHEN YOU LOOK AT AFRICAN AMERICANS VERSUS EUROPEAN AMERICAN MALES SMOKING IS NOT VERY DIFFERENT. IT'S 40% RISK. WHAT I CAN EXPLAIN IS -- IT TURNS OUT THAT AFRICAN AMERICAN MEN TEND TO SMOKE MENTHOLLATED CIGARETTES. AND THEN SUBJECTS FROM LOW INCOME GROUPS SMOKE DIFFERENTLY, INHALED STRONGER, THE TOBACCO SMOKE PENETRATES DEEPER INTO THE LUNG. THIS HAS SOMETHING TO DO. IT'S AT EXCESS RISK. THIS IS ONE EXPLANATION BUT IT COULD ALSO BE DIFFERENCES TO THE ABILITY TO LUNG CANCER. WE ALL KNOW OUT OF 10 SMOKERS TWO DEVELOP LUNG CANCER. TWO ARE MORE SUSCEPTIBLE THAN THE OTHER EIGHT. IT MAKES YOU MORE LIKELY TO DEVELOP LUNG CANCER. IT'S PERHAPS INTERESTING WHEN YOU COMPARE GROUPS -- LOOKED AT LUNG CANCER RATES AMONG SMOKERS THAT GOT CATEGORIZED INTO EQUAL EXPOSURE SEPARATED BY SEX, DOMAIN. AND FOR SMOKERS THAT SMOKED 30 CIGARETTES PER DAY -- YOU WOULD CONSIDER A HEAVY SMOKER. THE RESEARCHERS LOOKED AT THE LUNG CANCER. THEY INDEED FOUND DIFFERENCES AND THEY FOUND THAT AFRICAN AMERICANS AND HAWAIIANS ARE MORE LIKELY TO DEVELOP LUNG CANCER THAN WHITES AND OTHER POPULATION GROOCHTION. MALES AND FEMALES HAVE THE SAME EXPOSURE -- THAN YOU HAVE -- WHEN YOU HAVE EXPOSURE AND DIFFERENT CANCERS -- SO THIS COULD ACTUALLY BE A SIGN INDICATIONS THAT THERE MAY BE DIFFERENT SUSCEPTIBILITY TO LUNG CANCER IN POPULATION GROUPS. NOW THIS STUDY WAS ALSO PUT ASIDE AND PEOPLE SAID WELL -- IT'S NOT GOOD ENOUGH. IT'S STILL DIFFERENT BEHAVIOR AMONG THESE PEOPLE AND THAT COULD EXPLAIN IT. THERE IS A POSSIBILITY THAT THERE IS SUSCEPTIBILITY THAT CONTRIBUTE TO LUNG CANCER HEALTH DISPARITY. OKAY. SO WE HAVE RECEIVED THE MORTALITY RATES AND NOW WE ARE LOOKING AT PEOPLE DYING FROM CANCERS. HERE AGAIN THE FIVE POPULATION GROUPS AND THEN THE FOUR MAJOR CANCER. THEN WE SEE AFRICAN AMERICAN MALES ARE THE GROUP THAT HAS THE HIGHEST BURDEN DOING FROM CANCER OVERALL. NOW WE SEE FEMALES, AFRICAN AMERICAN FEMALES HAVE THE HIGHEST RATE FOR CANCER MORTALITY. THIS CHANGED BEFORE YOU SAW IT, THE HIGHEST RATE OF FEMALES. THIS ALREADY INDICATES THAT THERE IS A SURVIVAL HEALTH DISPARITY. THAT'S NOW AN EXCESS MORTALITY AND YOU LOOK AT PROSTATE CANCER, THE DIFFERENCE BETWEEN EUROPEAN AMERICAN AND AFRICAN AMERICAN -- THIS TELLS YOU THERE ARE TWO TYPES OF HEALTH DISPARITIES. THERE'S AN INCIDENCE AND SURVIVAL TYPE DISPARITY. THEY ARE MOST LIKELY VERY DIFFERENT. FOR BREAST CANCER YOU SAW EUROPEAN AMERICAN WOMEN WERE MORE LIKELY TO DEVELOP BREAST CANCER THAN AFRICAN AMERICAN WOMEN AND NOW YOU SEE THAT'S A 40% EXCESS MORTALITY. THAT TELLS YOU THERE'S SURVIVAL HEALTH DISPARITY IN BREAST CANCER 30 TO 40% THIS IS DENT RISK FOR AFRICAN AMERICANS TO DIE OF THE DISEASE COMPARED TO EUROPEAN AMERICANS. FOR LUNG CANCER HERE WE SEE AN EXCESS OF 30% FOR MORTALITY LUNG CANCER -- APPROXIMATELY THE SAME SO HERE THEY WOULD SAY INCIDENT EXPLAINS THE EXCESS MORTALITY. WE HAVE TO KNOW JUST POINTING OUT ESSENTIALLY CANCER HEALTH DISPARITY COMBINED INCIDENCE AND MORTALITY HEALTH DISPARITY WITH DIFFERENT CAUSES, SURVIVAL HEALTH DISPARITY AND HERE IS PROBABLY MAINLY AN INCIDENT HEALTH DISPARITY. FOR CANCER AGAIN WE HAVE A 40% INCIDENCE RISK FOR THE AFRICAN AMERICANS TO DIE FROM -- COMPARED TO EUROPEAN AMERICANS. YOU SEE MORTALITY IS THE LOWEST AMONG THE OTHER THREE GROUPS. THIS IS MAINLY DRIVEN BY THE INCIDENCE RATE. WHEN YOU REALLY LOOK AT HISPANIC LATINO WOMEN OR MEN AND THEY DEVELOP THE DISEASE, THEY ARE INDEED LESS LIKELY TO SURVIVE THIS DISEASE WHEN COMPARED TO EUROPEAN AMERICANS. SO YOU HAVE TO BE CAREFUL JUST BY LOOKING AT THESE RATES HERE. THERE IS MORE MINORITY GROUPS AN EXCESSIVE BURDEN OF DYING FROM CANCER AFTER DEVELOPING THE DISEASE WHEN COMPARED TO THE OTHER WHITE POPULATION OF THE UNITED STATES. SO WHAT ARE THE CAUSES FOR CANCER HEALTH DISPARITIES. IT'S THOUGHT TO BE MOSTLY SOCIO-ECONOMIC AND CULTURAL FACTOR. CANCER HEALTH DISPARITY EQUALS IS ALWAYS DEFINED COMMONLY AS A HEALTHCARE DISPARITY MEANING IF YOU DO NOT HAVE A HEALTHCARE DISPARITY THERE WILL NOT BE A CANCER HEALTH DISPARITY. THERE'S PLENTY OF EVIDENCE. THREE -- THERE'S NO QUESTION THAT THEY SAY IT'S AN APPROPRIATE EQUATION WE HAVE HERE ON TOP. TOO WHAT EXTENT DO THEY CONTRIBUTE THE CANCER HEALTH DISPARITIES. SO POOR TREATMENT AND POOR POST TREATMENT QUALITY OF LIFE, ABILITY TO -- THE LIKELIHOOD OF DYING FROM THE DISEASE CANCER AND CAN LEAD TO HEALTH DISPARITIES. I HAVE EXAMPLES HERE THAT THIS IS THE CASE FROM THE STUDY OF BREAST CANCER PUBLISHED IN 2005 SAYING THAT BREAST CANCER -- CAN MEANING THEY DIE FROM BREAST CANCER BECAUSE THEY HAVE DIABETES AND HYPERTENSION THAT'S NOT TAKEN CARE OF. AND THEN WE WOULD REALLY TREAT THE DISEASE COURT MORBIDITIES THAT WOULD BE LESS MORTALITY FROM BREAST CANCER. HERE'S ANOTHER STUDY FROM THE CANCER PATIENTS SHOWING THAT THEY ARE LESS LIKELY TO RECEIVE SURGICAL TREATMENT AND THEY ARE MORE OFTEN DYING FROM COMPETING CAUSESES CO-MORBIDITY. THEY MADE ACTUALLY A CALCULATION. IF THEY WOULD GET SUCH A GOOD TREATMENT AS FREQUENTLY AS THE EUROPEAN AMERICANS WE WOULD TAKE CARE OF THE COMPETING CAUSES. THE SURVIVAL HEALTH DISPARITY WAS 20% HERE AND -- THIS IS ACTUALLY VERY IMPORTANT RESEARCH BECAUSE IT CAN REALLY -- IN TERMS OF WHERE YOU SHOULD INTERFERE AND HOW YOU CAN IMPROVE SURVIVAL BREAST CANCER -- CANCER SURVIVAL INDEPENDENT REALLY FROM TREATING THE CANCER. SO THE QUESTION REMAINS IS OUR SOCIOECONOMY FACTOR TO HEALTHCARE IS THE ONLY FACTOR THAT CONSTITUTES THE CANCER HEALTH DISPARITIES. AND THEY ARE ACTUALLY A GOOD NUMBER THAT WOULD INDICATE THAT THE ADDITIONAL EFFECT. THERE ARE MAINLY STUDIES THAT TRY TO ACCOUNT FOR SOCIO-ECONOMIC FACTORS AND ACCESS TO HEALTHCARE IN THE ANALYSIS OF CANCER HEALTH DISPARITIES AND FIND THAT THESE FACTORS CANNOT COMPLETELY ACCOUNT FOR THE CANCERS HEALTH DISPARITIES. AND MOST OF THESE STUDIES WHERE YOU HAVE TO REMAIN AN UNEXPLAINED EXCESS OF CANCER BURDEN AMONG SPECIALLY MINORITY GROUPS DEALING WITH BREAST AND PROSTATE CANCER. EMERGING FROM THE CANCER HEALTH DISPARITY IS THE -- NEIGHBORHOOD ON HEALTH. SO RECOGNIZE THAT NEIGHBORHOOD CONFERS ADDITIONAL MORTALITY RISK BEYOND INDIVIDUAL SOCIO-ECONOMIC CHARACTERISTICS OF INDIVIDUALS AND FAMILIES. IT HAS AN ADDITIONAL EFFECT. THE HYPOTHESES HAS BEEN GENERATED THAT PERHAPS THE NEIGHBORHOOD EFFECTS HAS OUTCOME THROUGH PHYSIOLOGICAL -- SO THAT WOULD BE A LONG-LASTING ADAPTATION. THIS IS ACTUALLY SIMILAR TO WHAT HAS BEEN PROPOSED BY THE HYPOTHESES. YOU CAN GOOGLE THAT WORD -- IT HAS BEEN DEVELOPED BY -- AND IT DEALS WITH THE DEVELOPMENT OF AUTO DISEASE. HE ACTUALLY PROPOSES THAT DEVELOPMENTAL EXPOSURE ALREADY SETS YOU UP FOR AN INCREASE DISEASE RISK LATER IN LIFE. NOW HOW COULD THAT HAPPEN? IT COULD BE IN THE BEGINNING THERE WAS NO REAL MECHANISM TO PLAY -- MODIFICATION OF GENE EXPRESSION, A LASTING DEFECT. VERY INTERESTINGLY, THIS PAPER CAME RECENTLY OUT. THIS MAY DESCRIBED POPULATION DIFFERENCES IN -- LOOKING AT BLACK -- AND THEY COMPARED THAT FROM 103 AFRICAN AMERICAN NEWBORNS. THERE ARE DIFFERENCES IN THE PATTERN. VERY INTERESTING THAT THEY REGULATE -- THESE ARE ALL VERY PRELIMINARY BUT I KNOW PEOPLE ARE VERY INTERESTED IF IT ACTUALLY EXISTS. AND THERE ARE PROBABLY FUTURE STUDIES WITH THE KIND OF MECHANISM WHEN YOU LOOK AT THE POOR DEVELOPED NEIGHBORHOODS THOSE DIFFERENCES MAY MANIFEST. NOW, IT'S UNCERTAIN THAT A RACE ISN'T FOR A POPULATION DIFFERENCES IN TUMOR BIOLOGY COMPUTE TO THE CANCER HEALTH DISPARITY INTO THE UNITED STATES OR GLOBALLY. BUT THEY BELIEVE THAT TUMOR BIOLOGY AND GENETICS PLAYS A MAJOR ROLE IN SOME CANCER HEALTH DISPARITIES. THERE ARE EXAMPLES I JUST PUT OUT, THIS EXAMPLE HERE THAT DISPARITIES AND BREAST CANCER SURVIVAL BETWEEN AFRICAN AMERICAN AND EUROPEAN AND PERSISTENT RANDOMIZED -- IT WAS AN ANALYSIS OF SEVERAL TRIALS -- AND THEY SAW THAT THERE ARE ACTUALLY DIFFERENCES IN OUTCOME. THIS WOULD ACTUALLY SUPPORT THE HYPOTHESES OF PERHAPS DIFFERENCES IN TUMOR BIOLOGIES EXIST BETWEEN THESE PATIENTS. THIS IS CONTROVERSIAL BECAUSE THERE ARE MANY OTHER TRIALS THAT FOUND DIFFERENCES AND OTHERS HAVE NOT FOUND IT. THAT'S THE POSSIBILITY OF CON FOUNDING SO YOU CANNOT BE SURE. THEN I TOLD YOU EVIDENCE FROM CANCERS EPIDEMIOLOGY, GENETICS AND GENOMICS RESEARCH THAT EXPOSURE TO ENDOGENOUS INSPECTORS CAN BE DIFFERENT BETWEEN A POPULATION COPSE. THIS IS SOMETHING WE'VE KNOWN FROM OUR SPEAKER ACTUALLY POPULATION DIFFERENCES IN TUMOR -- FOR BREAST CANCER PATIENTS. IT'S LONG KNOWN. AFRICAN AMERICAN BREAST CANCER PATIENTS TEND TO EXPRESS THE RECEPTOR NEGATIVE DISEASE -- MORE FREQUENTLY THAN BREAST CANCER PATIENT AND OTHER POPULATION. IT CAME OUT IN 2006 THIS POPULATION WHERE IT WAS CONSIDERED A LANDMARK PAPER REPORTING THE ETHNIC DIFFERENCES IN THE PREVALENCE OF -- YOU HEARD A LOT ABOUT -- NEGATIVE BREAST CANCER IN THE PREVIOUS PRESENTATION. IT'S A BAD OUTCOME, POOR OUTCOME PHENOTYPE. WHAT THEY OBSERVED IS THAT PREMENOPAUSAL AFRICAN WOMEN TEND TO HAVE THIS KIND OF -- THAN THE ONE AFRICAN AMERICAN BREAST CANCER PATIENT. AND IT HAS BEEN CALCULATED THAT -- AND THIS IS ACTUALLY PREMENOPAUSAL AFRICAN AMERICAN. THIS IS FOR BREAST CANCER AND IT'S BEEN CALCULATED THAT ACTUALLY THE PREVALENCE OF THE BASAL -- DISEASE IN THIS PATIENT CALLED REALLY ACCOUNTS FOR THE HIGH MORTALITY AMONG THEM. THERE ARE FOLLOW UP STUDIES -- THEY STARTED BREAST CANCER IN WEST AFRICA. WHAT THEY FOUND IS THE HIGH PROPORTION OF BREAST CANCER PATIENT IN WEST OF AFRICA -- 55%. THERE'S MUCH, A MUCH HIGHER FREQUENCY THAN YOU WOULD FIND HERE IN THE U.S., PROBABLY 35, 40 AFRICAN AMERICAN AND OTHER POPULATION GROUPS INDICATING THAT THERE IS PERHAPS A SUSCEPTIBILITY IN WOMEN THAT THE AFRICAN ANCESTRY TO DEVELOP THIS TYPE OF DISEASE OR THERE'S AN EXPOSURE OR THERE'S A COMBINATION OF THOSE. THERE HAS BEEN ASSOCIATED WITH THE DEVELOPMENT -- THAT RELATES TO THE PRODUCTIVE FACTOR AND RELATES TO OBESITY. FOR ME IT'S NOT CLEAR TO SEE HOW WE DID EXPLAIN THIS BIG DIFFERENCES BETWEEN WHAT WE SEE IN WEST AFRICA AND WHAT WE SEE IN AFRICAN AMERICAN POPULATION. THEN BETWEEN THE EUROPEAN POPULATION. SO WE STILL DON'T KNOW BUT IT COULD BE THROUGH SUSCEPTIBILITY. NOW I WANTED TO TELL YOU, LOTS OF PEOPLE ARGUE THAT EXCESS BURDEN OF CUMULATIVE BASAL LIKE BREAST CANCER -- EXPLAINS THE EXCESS MORTALITY AMONG THEM. AND THAT'S REALLY WHAT IT IS, IT'S JUST A DIFFERENT DISEASE, IT'S MORE COMMON IN ONE VERSUS THE OTHER POPULATION GROUP. THEY ARE TELLING YOU THAT CANCER SURVIVAL IN THE U.S. IRRESPECTIVE OF -- SO THE NEGATIVE BASAL LIKE DISEASE IS MORE COMMON IN AFRICAN AMERICANS CANNOT EXPLAIN. WE HAVE DISPARITY OVERALL BETWEEN AFRICAN AMERICANS AND EUROPEAN. THERE ARE OTHER FACTORS INVOLVED. AND THEN HERE WHAT I ALSO WANT TO POINT OUT, THERE ARE DIFFERENCES IN GENOMIC METHYL LATION. THEY FOUND HYPER METHYLATION, THEY SAW TUMORS IN AFRICAN AMERICAN MEASURES AND PERHAPS BECAUSE OF THE DIFFERENCE IN TUMOR BIOLOGY. I PUT THAT UP HERE BECAUSE THEY ARE SIMILAR DATA FOR PROSTATE CANCER. THERE ARE SEVERAL STUDIES. THEY PULL THIS EXACTLY THE SAME DIRECTION. THERE ARE SEVERAL STUDIES GOING IN THE SAME DIRECTION SO THERE MIGHT BE SOMETHING BEHIND IT. SO THAT'S SOMETHING WE HAD TO STUDY. IF THIS IS REALLY TRUE. THEN OF COURSE WE HAVE TO FIGURE OUT WHY WOULD THERE BE A DIFFERENT METHYLATION PATTERN AND WHAT IT MEANS IN TUMOR BIOLOGY. THEN OKAY SO WHAT ELSE IN TUMOR BIOLOGY CAN BE CAUSED BY EXPOSURE, BY EXPOSURE DIFFERENCES AMONG POPULATION GROUPS LEADING PERHAPS TO HEALTH DISPARITIES. IT COULD BE THAT EXPOSURE LEADS TO DIFFERENT MUTATION PATTERN AMONG POPULATION GROUPS. THAT ACTUALLY CAN REALLY AFFECT RESPONSE TO THERAPY. NOW AN EXAMPLE, PERHAPS I'LL COME TO IT, IT'S MUTATIONS IN THE TUMOR SUPPRESSOR GENES. WE HEARD BEFORE ABOUT THE -- SUPPRESSOR GENE IS THE MOST COMMON MUTATOR IN CANCER -- FOR BREAST CANCER WE KNOW THAT -- THAT PC3 MUTATION FREQUENCY IN BREAST TUMOR IS HIGHER IN PATIENTS -- SO THEY SAID WELL IT HAD SOMETHING TO DO WITH THE COMMUNITY EXPOSURE. THEY SAY INTO COMMUNITIES YOU LOOK AT BREAST CANCER PATIENTS, THEY HAVE ACTUALLY MORE -- TUMORS WHICH IS SOMEWHAT CONSISTENT -- THAT SUPPORTED THE MUTATIONS OF TUMORS IS TO BE RELATED TO THE SPECIFIC EXOGENOUS AND ENDOGENOUS CUSTOMER. THEY REPORTED, IT HAPPENS TO BE MY BOSS, THEY REPORTED WHEN YOU GO FROM TUMOR TYPE TO TUMOR TYPIST DIFFERENT BUT ALSO WHEN YOU GO FROM REGION TO REGION IT'S DIFFERENT. WE THOUGHT WELL THERE MUST BE DIFFERENT EXPOSURES CAUSED FROM DIFFERENT MUTATIONS. MUTATIONS AFFECTS TUMOR BIOLOGY AND ALSO THE TYPE OF SPECTRUM EFFECTS TUMOR BIOLOGY. AND THEN THEY ARE ALSO OBSERVATIONS THE DIFFERENCES -- BETWEEN AFRICAN AND EUROPEAN AMERICAN PATIENTS. THERE WAS A PUBLICATION IN 2004 -- ACTUALLY OBSERVES THE -- I'M PRETTY SURE, I THINK ONE OR TWO OTHER STUDIES OUT THAT MAKES THE SAME OBSERVATION THAT ACTUALLY -- ARE MORE COMMON THIS BREAST TUMORS IN THE AFRICAN AMERICAN PATIENT -- OR IF THERE'S A HIGHER LIKELIHOOD TO ACQUIRE THIS MUTATION. BUT THEN IF YOU HAVE A RESPONSE TO THERAPY. OKAY. THEN WE HAVE SIMILAR DATA FOR TRAWS TATE CANCER AND I JUST PUT SOME UP HERE. WE KNOW OBVIOUS EVIDENCE THAT ACTUALLY A TUMOR, PROSTATE TUMORS IN AFRICAN AMERICAN PATIENTS WAS FASTER THAN EUROPEAN MALES -- COMING OUT IN 2010 LOOKING AT THIS PROBLEM -- 1998 FOUND THAT INFLATION IN ONE'S PROSTATE IS MORE PREVALENT AMONG AFRICAN AMERICAN AND EUROPEAN MEN. THIS IS NOT FOLLOWED UP, I HAVE BEEN TOLD THAT NOW PEOPLE -- VERY LARGE STUDY -- WHEN YOU HAVE A LOW INFLATION IN YOUR PROSTATE -- IT'S A PREDISPOSING FACTOR TO DEVELOP THE DISEASE. THEN THE RESPONSE THAT CAME OUT FROM GREAT BRITAIN REPORTING DISTINCT GENETIC ALGORITHMS -- COMPARED TO MEN FROM EUROPE OR THE UNITED STATES OR WHAT THEY FOUND THAT ACTUALLY TWO VERY COMMON TUMORS IN EUROPE AND IN THE UNITED STATES ARE QUITE A WAY UP IN THE, IN ASIAN MEN. THAT IS THE LOSS OF THE TUMOR SUPPRESSOR GENE AND THEN THE DEVELOPMENT OF AN ONCOGENE AND -- WHEN YOU HAVE A LITTLE BIT ALSO -- THEN YOU HAVE SUCH A DIFFERENCE BETWEEN POPULATION THAT INDICATES THAT THERE ARE EXPOSURES THAT EXPOSE THE DIFFERENCES THAT LEAD TO PROSTATE CANCER THAT LEAD TO CANCER IN THIS POPULATION. AND IT'S ALSO AT THE END NEARLY AFFECTS TUMOR BIOLOGY. THESE ARE MAJOR PATHWAYS. THEY ARE REALLY DIFFERENT TUMOR BIOLOGY AND HOW WE TARGET THESE TUMORS COULD BE DIFFERENT. SO THEN OKAY, HEALTH DISPARITY AND GENETICS. I DON'T WANT TO GO INTO IT TOO MUCH BUT THERE'S AT LEAST FOR ONE LOCAL, IT'S GOOD EVIDENCE THAT THERE MAY BE A CONTRIBUTION TO EXISTING CANCER HEALTH DISPARITIES. THIS IS THE LOCAL 8Q24. THEN YOU HAVE GENETIC VARIATIONS AND SOME OF THESE COMMON GENETIC VARIATIONS INCREASE YOUR REACH TO DEVELOP PROSTATE CANCER -- SO THIS IS PROBABLY SOME MAJOR SUSCEPTIBILITY FOR CANCER. NOW, THIS WAS ACTUALLY FIRST TIME DESCRIBED FROM A STUDY IN 2006. MANY PEOPLE THINK IT'S A LANDMARK PAPER. THAT STARTED NEARLY DESCRIBED AN INCREASED RISK FOR AFRICAN AMERICAN MALE WHEN COMPARED TO EUROPEAN AMERICAN CONFERRED BY THE LOCALS -- NOW THIS WAS OUT THERE AND THEN FOR GENOMIC STUDIES ACTUALLY CONFIRMED THE FINDING. THEY ACTUALLY FOUND, AND I HAVE JUST TWO OF THEM, THAT THESE ALLELES ARE MORE COMMON AMONG AFRICAN AMERICAN MEN LEADING TO THE HIGHEST POPULATION OF THE RISK CONFERRED BY THE LOCALS IN THIS POPULATION. AND THEY CAME OUT AND SAID AT LEAST ONE POPULATION THAT MUCH OF THE EXCESS RISK TO DEVELOP PROSTATE CANCER FOR AFRICAN ANCESTRY CAN BE EXPLAINED BY GENETIC -- FIRST OF ALL, THIS IS LOW SUSCEPTIBILITY DOES NOT CAUSE CANCER, IT JUST DOESN'T. IT'S MORE THAT IT PREDISPOSES YOU AND YOU NEED THE RIGHT ENVIRONMENT. AND THEN YOU LIVE IN THAT ENVIRONMENT AND IT COMES UP. SO MY ENVIRONMENTAL CHANGE, YOU COULD NEARLY MAKE GENETIC PREDISPOSITION OBSOLETE. IS IT POSSIBLE THAT SUSCEPTIBILITY -- IS REALLY QUESTIONABLE. I CAN SAY, WE DON'T KNOW WHAT THE METHOD IS AND HOW ACTUALLY THE GENETIC -- INCLUDES THIS. WE HAVE NO IDEA. AND WE CERTAINLY HAVE NO IDEA HOW THE ENVIRONMENT INFLUENCES IT. THERE WAS ONE STUDY THAT SAID THAT EXPOSURE TO CANDIDATES IN AMONG -- MODULATES THE RISK OF A24 AND PROSTATE CANCER. SO THAT COULD BE ENVIRONMENTAL EXPOSURE. NOW, WHAT ARE YOU DOING IN LOOKING AT CANCER HEALTH DISPARITIES. HOW DO WE TRY TO FIGURE OUT CAUSES OF CANCER HEALTH DISPARITIES. SO WE HAD ACTUALLY A CASE STUDIES, WE CONDUCTED CASE STUDIES IN THE -- AREA. INCLUDING AFRICAN AMERICAN AND EUROPEAN AMERICANS TO EXAMINE THE CONTRIBUTION OF THE ENVIRONMENTALLY HEALTH -- AMONG AFRICAN AMERICANS. WE HAVE TWO PEOPLE, KIRK AND MYSELF -- AND KIRK WAS IN LONG AND COLON CANCER. SO IN THE RESEARCH OF MICROBE FOCUSING ON PROSTATE AND BREAST CANCER WE ARE CURRENTLY AT TUMOR BIOLOGY AND WHAT CAN WE LEARN. IN TERMS OF INFLUENCE THE PRESENTATION OF THE DISEASE OR CAUSING MORE DISEASE OR INFLUENCE OF RESPONSE TO THERAPY INFERIOR RESPONSE AMONG AFRICAN AMERICAN PATIENTS. BECAUSE THEY HAD, LIKE I POINTED OUT, THEY HAD SURVIVAL HEALTH DISPARITY IN BOTH OF THESE DISEASES. SO WITH THIS HYPOTHESES IN GENE EXPRESSION -- BECAUSE THAT'S REALLY NOT. KNOWN. FOR BREAST CANCER YOU HAD THE SUBTYPES BUT THEN YOU LOOK AT BIOLOGY THAT GOES DEEPER. WE HAVE NO IDEA WHAT COULD BE DIFFERENT. SO YOU HAVE THIS APPROACH AND THEN TRY TO PINPOINT WHAT COULD BE DIFFERENCE BEYOND WHAT IS CURRENT KNOWLEDGE. AND THE GENE EXPRESSION PROFILE IN 33 AFRICAN AMERICANS WITH COP AMERICAN PATIENTS -- THEN WE ANALYZE THE DIFFERENCES OF THE -- AND WHAT WE FOUND IS THE 162 GENES THAT EXPRESS -- THIS IS REALLY DIFFERENT BETWEEN THESE TWO PATIENT GROUPS AND THE PROSTATE TUMORS. AND THEN YOU ENDED UP -- RELATED TO HOW IT'S EXPRESSED IN THE TUMORS OF THE AFRICAN AMERICAN PATIENTS. THEN WE TOOK OUR GENES AND ASKED THE QUESTION HOW DO THESE GENES COMPARE TO MARKET GENES FOR PROSTATE CANCER IDENTIFIED IN PREVIOUS STUDIES. WE HAD -- 2002 AND THEY DESCRIBED 80 MARKER GENES THAT ARE REALLY DIFFERENT -- VERY IMPORTANT GENES FOR PROSTATE CANCER. ACROSS STUDIES OF THE RELATED GENES. WHAT WE FOUND WAS -- BETWEEN OUR LIST AND THEIR LITTLE. THE PREVIOUSLY IDENTIFIED MARKER GENE FOR PROSTATE CANCER BETWEEN AFRICAN AMERICAN AND EUROPEAN AMERICAN -- THE SAME. HOWEVER, WE DID A PARTIAL ANALYSIS, WE FOUND THAT THE DIFFERENTLY EXPRESSED GENES BETWEEN AFRICAN AMERICAN AND EUROPEAN AMERICAN PATIENTS ARE ACTUALLY CONTROLLED -- AND INFLAMMATION. AS I SAID IT WAS DISCOVERED BY PATHWAY ANALYSIS. IT TOOK DIFFERENTIALLY EXPRESSED GENE AND ASKED THE QUESTION BETWEEN TUMORS FROM AFRICAN AMERICAN AND EUROPEAN AMERICAN PATIENT ASKED THE QUESTION HOW DOES THAT RELATE TO PASS RATE. WE FOUND THAT THESE GENES -- PRESENTATION, INFLAMMATION, CYTOKINE AND SO FORTH. AND THE RED ACTUALLY SHOWS SIGNIFICANCE OF THE ENRICHMENT OF GENES IN THE PATHWAYS THAT REACHED SIGNIFICANT LEVELS UP TO MINUS 30. THAT WAS DIFFERENT. IT WAS IMMUNE GENES -- SAME ANALYSIS LOOKING AT THE NORMAL SURROUNDING TISSUE COMPARED TO -- DID NOT FIND IT IN THIS PATHWAY. SO THIS IS A -- RESTRICTED TO THE TUMOR ENVIRONMENT. WE WOULD HAVE SEEN IN THE ENVIRONMENTAL -- HAS SOMETHING TO DO WITH THE TUMOR -- ACTIONS BUT IT COULD ALSO BE ACQUIRED THAT YOU HAVE ACQUIRED MUTATIONS WITH THOSE CHANGES IN THE TUMOR. AND THERE WOULD BE AGAIN A DIFFER MUTATIONS BETWEEN THE AFRICAN AMERICAN AND THE EUROPEAN AMERICAN PATIENTS. THIS IS NOT DOING THE ANALYSIS BUT IT WAS RECENTLY PUBLISHED IN THE JOURNAL OF MEDICINE LOOKING AT DNA COPIES IN TUMORS OF AFRICAN AMERICANS AND EUROPEAN AMERICANS IN ONE STUDY AND THEN THEY HAVE THE VALIDATION STUDY. AND THEY FOUND DIFFERENCES BETWEEN THE TWO PATIENT GROUPS AND THEY FOCUSED AT THE END ONLY THAT THEY ARE REALLY DIFFERENTLY AFFECTED IN BOTH STUDIES. AND THEN THEY ASKED THE QUESTION, WHAT KIND OF GENES ARE EXPRESSED -- AND THEY FOUND THAT -- THEY USED THE GENE EXPRESSION PROFILING THAT HAD ACQUIRED MUTATIONS, HAVE ALSO SOMETHING TO DO WITH IT. THAT MEANS THE MUTATIONS -- THIS WOULD BE LARGE GENOMIC ALTER RATIONS WHICH COULD LEAD TO TUMORS IN THE AFRICAN AMERICAN PATIENT. WE ALSO NOTICED AT THAT TIME THE TUMORS IN THE OF AFRICAN AMERICAN PATIENTS. WE SAW MANY OF THE GENES WERE -- IN THEIR TUMORS. WE WERE WONDERING WHAT THAT MEANS A TUMOR BIOLOGY ASK -- AND WHERE IT WAS COMING FROM. WE KNOW WHAT IT MEANS TUMOR BIOLOGY FROM OTHER APPLICATIONS. AFTER WE MAKE THESE FINDINGS, PUBLICATION CAME OUT REPORTED THE RELATED GENES FOR DNA DAMAGE RESISTENT. AND THEN ANOTHER PUBLICATION PUBLISHED IN THE EMT -- COVERED IT COMPLETELY AND INDEPENDENTLY. WE SEE IT IS IDENTICAL TO THE SIGNATURE WE ARE FINDING IN THE TUMORS OF THE AFRICAN AMERICAN. SO IN THESE PEOPLE -- IS THIS COMMON IN BREAST CANCER, YES -- THE FIRST GROUP ALSO VALIDATED ACTUALLY THE GENES AND THEN IT COULD SHOW EXPERIMENTALLY THAT GENES IN THAT SIGNATURE CONFER THE SYSTEM. ALL RIGHT. LET'S GO ON, ARE LET'S GO ON. LET'S GO ON. NOW IN -- PROSTATE CANCER -- AND WE DID A PILOT STUDY AND LOOKED AT TUMORS OF AFRICAN AMERICAN -- BREAST CANCER PATIENTS AND WE USED -- IS GOOD BECAUSE WE COULD ACTUALLY REALLY MICRO DISSECT THE STROMA -- WE USE VALIDATION TO ACTUALLY VALIDATE SOME OF OUR FINDINGS. AGAIN, WHAT WE FOUND IS THAT THERE ARE GENE EXPRESSION DIFFERENCES AND WE FOUND THOSE DIFFERENCES ARE RELATED TO -- WHEN WE LOOKED -- RELATED TO THE TUMOR STROMA THAT'S WHAT WE SAW ARE THE DIFFERENCES. IN THE CHEMISTRY WE FOUND THE TUMORS FROM THE AFRICAN AMERICAN PATIENTS TEND TO DO HAVE AN INCREASED -- MICRO PHAGE INFILTRATION -- THIS WAS AGAIN MORE PREVALENT IN THE AFRICAN AMERICAN PATIENT. SO LET ME GO ON. OKAY, GOOD. HERE, CONCLUSIONS. WE HAD INDICATION OF THE DISTINCT TUMOR MICRO ENVIRONMENT BY ETHNICITY, DIFFERENCES IN HUMOR BIOLOGY AND -- IN THE PRESENCE OF -- WHICH ARE CURRENTLY ACTIVELY PURSUE. WE WANT TO KNOW WHERE IT'S COMING FROM AND WHAT AGAIN DOES IT DO TO TUMOR BIOLOGY. THE RELATED DIFFERENCES COULD BE IMPORTANT FOR TUMOR PROGRESSION AND ALSO MAY AFFECT THE OUTCOME. AS I ALREADY POINTED OUT OTHER PEOPLE HAVE SHOWN IT. POTENTIAL IMPLICATION, OKAY. WELL, ALL RIGHT. HOW DID THAT HAPPEN? OKAY, GOOD. SO WE THINK THAT THE NEW SIGNATURE IS ACTUALLY MANY MORE SLIDES RELATED INTO STRESS. I WANTED TO GO INTO STRESS TODAY. WE THINK THAT SIGNATURE MAY ALSO JUST BE REFLECTIVE OF INFLAMMATION THAT'S MORE PREVALENT IN TUMOR IN THE AFRICAN AMERICAN PATIENT LEADING TO THE TUMORS OF T CELLS, INCREASED ANGIOGENESIS AND TISSUE REMODELING. AND THEN INCREASES ACTUALLY METASTASES. >> [INDISCERNIBLE] >> NO, THE FIRST ONE WAS. >> [INDISCERNIBLE] >> NO. THE FIRST SLIDE IS THE NEW SLIDE. >> [INDISCERNIBLE] >> I HAVE IT ON MY OWN. OKAY, GOOD. SO THEN SO WHERE DID 9 SIGNATURE COME FROM. I POINTED OUT IT MAY COME FROM TUMORS -- IT MAY ACTUALLY COME FROM UNRELATED FACTORS THAT WOULD BE -- AFFECTING THE IMMUNE SYSTEM OR IT COULD COME FROM STRESS OR FROM MILD INFECTIONS. WE LIKE TO UNDERSTAND THESE EXPOSURES -- INTO A STUDY WHERE THE RECORD BREAST CANCER PATIENTS AND GIVE THEM A QUESTIONNAIRE AND ASK THEM ABOUT STRESS IN DIFFERENT WAYS. AND THEN COLLECT TUMORS FROM PARTICIPATION. LOOK AT -- PATHWAY HAS RECENTLY BEEN LINKED TO TUMOR -- AND ALSO BEEN SHOWN IN THE MODEL WHICH PATHWAY'S ACTIVATED IN CANCER MODELS THAT LEADS TO PROGRESSION. WE WANTED TO KNOW, CAN WE FIND GOOD PATIENTS AND THEY WOULD PAUSE TO BE STRESS STRESS RELATED TO DISCRIMINATION AND LIFE EVENTS AND IT WILL BE EVALUATED. DOES IT RELATE TO -- CAN WE FLY A TUMOR SIGNIFY WHICH ARE THAT IT'S RELATED TO STRESS. TAKE THE SIGNATURE OUT OF CONTEXT AND GO TO THE DATA BASES AND ASK HOW DOES THE SIGNATURE RELATE TO A PATIENT OUTCOME AND RESPONSE TO THERAPY IN A BIG PICTURE. AND THEN WE HAVE THAT SIGNATURE. IF IT EXISTS AND IF THE POOR OUTCOMES, WE CAN VALIDATE IT IN THE DATA BASE AND THE EXPRESSION WOULD BE DOES THE SIGNATURE TELL US HOW WE IN THE FIELD YAW THIS SIGNATURE OR CAN WE DEVELOP THE SIGNATURE -- INTERFERE WITH THOSE PEOPLE WHO HAD POOR OUTCOME, IT COULD BE BETTER THERAPY, IT COULD BE BEHAVIORAL THERAPY. IN ORDER TO REALLY ADDRESS KIND OF HOW STRESS MAY ACTUALLY REALLY AFFECT TUMOR BIOLOGY AND COME UP WITH SOME OTHER WAY -- OF BREAST CANCER PATIENTS THAT WILL ACTUALLY BENEFIT FROM THE THERAPY AND WE DON'T HAVE NO WAY TO DO IT AT THIS POINT IN TIME. AND THEN OF COURSE AS I RELATED TO YOU, TOLD YOU ABOUT THE SIGNATURE IDENTIFIED BEFORE EVERYTHING WE WOULD LIKE TO KNOW ACTUALLY WHEN THOSE EXPOSURES ARE RELATED -- TUMORS. IN MY LAST PRESENTATION WHAT I RELATED TO LAST YEAR IS ALSO THAT PERHAPS GENETIC VARIATIONS HAVE SOMETHING TO DO WITH -- GENE EXPRESSION. AS WAS PERHAPS PICKED UP IN OUR STUDY, CAN I GO BRIEFLY INTO THAT FOR YOU IN THE LAST FIVE MINUTES. THERE WAS IN 2007, THERE WAS A KIND OF CONTROVERSIAL STUDY, IT WAS A FIRST STUDY THAT OTHER PEOPLE DIDN'T LIKE SO MUCH, WHAT THEY WERE DOING AT THAT TIME. THEY LINKED SNIPS TO DIFFERENCES IN GENE EXPRESSION AMONG DIFFERENT GROUPS. THIS WAS NOT REALLY RELATED TO DISEASE, IT'S JUST A PROOF THAT THEY EXIST. THEN THERE WAS TWO STUDIES FROM THE RESEARCHERS AT THE UNIVERSITY OF CHICAGO, THEY LOOKED AT GENE EXPRESSION MODIFICATION DERIVED FROM HEALTHY INDIVIDUALS WITH EUROPEAN ANCESTRY. AND THE LAST PAYROLL -- YOU CAN ACTUALLY BUY THOSE. YOU CAN GET IT FROM -- AND THEY SAID WE HAVE A LARGE PANEL. THERE ARE CONSISTENT DIFFERENCES BETWEEN THESE LINES. THIS SHOULD REFLECT EXPRESSION DIFFERENCES IN THE POPULATION. AND THEY NEED IT AND THEY FOUND INDEED A CONSISTENT EXPRESSION. THOSE DIFFERENCE ACTUALLY SHOULD AFFECT RESPONSE IN HEMATOMA TYPES. PRETTY MUCH ALSO FOLLOWING THE TUMORS. SO THIS WAS THE TWO STUDIES. OVERALL, IT TELLS US YES IT COULD BE ACTUALLY A COMMON GENETIC VARIATION THAT REALLY HAS AN EFFECT ON GENE EXPRESSION OVERALL AND AFFECTING CERTAIN PATHWAYS. ONE FAMOUS POLYMER -- ANTIGEN THIS WAS DISCOVERED IN 1995 IS A GENE EXPRESSION OF THIS STUDY -- PHENOTYPE IS COMMON IN AFRICAN POPULATION. WHY IS IT COMMON, IT IS ELECTED TO BE RESISTENT TO MALARIA, THE E WRISTED PHENOTYPE HAS A REASON WHY YOU HAVE IT. NOW WHAT ELSE MIGHT THESE POLYMER -- YOU DO NOT EXPRESS THE ANTIGEN ANYMORE. BUT IT'S ALSO BEEN SHOWN THAT STRONGLY INFLUENCE AVAILABILITY OF CHEMO KINDS -- MANY ARE CANCER RELATED. YOU HAVE THE DISEASE SUSCEPTIBILITY -- THAT POPULATION WILL BENEFIT BECAUSE OF THE MALARIA BUT IT MAY COME AT A COST. AND THAT'S AN INTERESTING PART. ALSO WAS A TUMOR SUPPRESSANT AND YOU PUT IT ALL TOGETHER THAT THE PHENOTYPE MAY ACTUALLY INCREASE METASTASIS. THEN YOU HAVE THE POPULATION -- THAT IS NEGATIVE AND THEN THERE ARE OTHER EXAMPLES OF SUCH KIND OF FUNCTIONAL POLYMER MORPHISM THAT IS SELECTED TO THE PATIENT FOR THE ENVIRONMENT. REALLY YOU ADAPT TO THE ENVIRONMENT IN ORDER TO SURVIVE AT A YOUNG AGE. SO REALLY THE DISEASES ARE NOT PART OF THE SELECTION PROCESS BUT WHAT YOU CAN HAVE WITH ANOTHER PATIENT TO YOUR ENVIRONMENT, THE SAME ADAPTATION YOU HAVE CAN PREDISPOSE YOU LATER TO A DISEASE. AND THIS IS ALSO CAME OUT OF THESE VERY RECENTLY WITH THE PAPER THAT LOOKED AT -- NO, IT'S NOT HERE. I THINK I HAVE IT ON ANOTHER ONE. NO, I DON'T HAVE IT. OKAY. FROM THOSE POLYMER -- THEN THERE'S ALSO AN EXAMPLE FOR THE IO28B GENE THAT HAS SOMETHING THAT MODULATES THE RESPONSE TO INTERFERON THERAPY. IT WAS ALWAYS KNOWN THAT AFRICAN AMERICANS HAVE A POOR RESPONSE AND NOW PEOPLE SAY IT MAY HAVE SOMETHING TO DO WITH THIS TYPE OF POLYMER THAT'S MORE COMMON IN THAT POPULATION. THIS IS AN EXAMPLE OF HOW PERHAPS ACTUALLY COMMON VARIATION IN POPULATIONS MAY HAVE TO DO SOMETHING WITH DIFFUSED SUSCEPTIBILITY AND DIFFERENCES WITH DIFFUSED SUSCEPTIBILITY BY POPULATION HAS TO DO WITH CANCER. I WANTED TO ACKNOWLEDGE THE POST DOCS -- TO OF THE SUPPORT OF MANY OTHER RESEARCHERS, INCLUDING THE ADVANCE BIO MEDICAL COMPUTING CENTER -- EXTRA RESEARCHERS AND I WANT TO ACKNOWLEDGE THE NIH -- SUPPLIED US WITH TISSUES TO DO SOME OF THESE STUDIES. THANK YOU SO MUCH. [APPLAUSE] >> QUESTIONS. I'M SORRY. >> [INDISCERNIBLE] >> ACTUALLY DIFFERENCES IN COMMON GENETIC POLYMORPHISMS BETWEEN POPULATIONS MY INTERACT WITH SOCIO-ECONOMIC FACTOR IN TERMS OF -- AMONG POPULATIONS. >> [INDISCERNIBLE] >> THIS WOULD DECIDE THOSE PEOPLE WHO DO THE LABS IS GENOME ASSOCIATION STUDIES. WE ARE PART OF ONE STUDY IN BREAST CANCER BUT THIS IS REALLY MORE COMBINED EFFORT. WE ARE TOO SMALL. SO BUT THERE IS OF COURSE AN EFFORT IN DOING EXACTLY THESE KIND OF STUDIES LOOKING AT EXPOSURES, LOOKING AT THESE QUESTIONS. IN THE BEGINNING PEOPLE JUST GOT THE PATIENTS TOGETHER AND THE CONTROL ROOM WITH GENOMIC STUDIES AND IDENTIFIED THE ASSOCIATES WITH DIFFERENT DISEASES. I THINK NOW PEOPLE GET MUCH MORE SOPHISTICATED AND GET PATIENT CONTROLLED THAT HAVE THAT INFORMATION, QUESTION THEIR INFORMATION THAT YOU REALLY CAN DEFINE EXPOSURES. AND THEN EVEN LOOKING AT LAB STUDIES AND HOW ACTUALLY A FEW SNIPS MAY INTERACT WITH THOSE KIND OF EXPOSURES AND THEN HOW THAT MODIFIES RISK. I WOULD SAY THAT SUMS IT UP -- THEY HAVE REALLY LARGE EFFORT. HERE IN THE U.S. CURRENTLY THERE ARE ASSOCIATION STUDIES THAT HAVE LOOKED JUST AMONG -- FOR SUSCEPTIBILITY IN MINORITY POPULATION THAT JUST STARTED, JUST AMONG AFRICAN AMERICANS, JUST AMONG HISPANIC LATINOS. I THINK THOSE STUDIES -- WILL THEN GO THE NEXT STEP AND ALSO INCORPORATE THE EXPOSURE. THAT'S ALWAYS, YOU KNOW, IT'S A LARGE EXPERIMENT OF STUDIES. WHEN YOU COME UP WITH SOME HUGE STUDIES, IT'S SO MUCH, SO UNCERTAIN AND PEOPLE SAY YOU SPEND ALL THAT MONEY IN THE BEGINNING. SO WHY -- SHOW YOU ME THE -- SUSCEPTIBILITY REALLY EXIST. AND THEN THAT'S WHAT YOU DO FIRST. THEN IT HAS TO BE VALIDATED IF THE ASSOCIATION -- MANY TIMES BUT NOT FOR ALL THOSE SITES. THEN YOU HAVE PEOPLE STUDYING AND YOU HAVE MORE ANGLES AND THEY DESIGN THE NEXT STEP -- UNCERTAINTY. WE CAN STUDY EXPOSURE. MY GROUP IS REALLY, WE ARE REALLY LOOKING AT TUMOR BIOLOGY PAUSE -- BECAUSE WE CAN DO IT. WE'RE IN A UNIQUE SITUATION WHERE WE VERY EARLY ON COLLECTED TUMORS FROM CANCER PATIENT. WE HAVE ALSO AN EVEN DEEM -- EPIDEMIOLOGICAL PROFILE FOR THESE PEOPLE -- WE HAVE STRONG EVIDENCE THAT TUMOR BIOLOGY IS -- POPULATION OF AFRICAN AMERICAN AND EUROPEANS -- IT MAY ACTUALLY BE -- RELATED TO TUMOR BIOLOGY NOW COMES THE NEXT QUESTION FOR US, WHAT'S THE EXPOSURE AND HOW CAN WE -- WHAT DEVELOPS. DO YOU HAVE IDEAS AND AS YOU DEVELOP IDEAS YOU HAVE TO DEFINE NEW STUDIES AND THAT'S WHAT I ACTUALLY WANTED. WE STARTED DEVELOPING A NEW STUDY THAT CAN ACTUALLY ANSWER THAT QUESTION. AND THEN THE NEXT THING WOULD BE THAT IT'S WHAT YOU PUBLISH AND THEN YOU COME TO THE RESEARCH COMMUNITY. THERE ARE OTHER PEOPLE THAT READ AND MAKE IT INTERESTING. THEY MAY HAVE THE RESOURCES. THEY ALSO ARE CHOMPING AND SAY OKAY, THAT'S REALLY AN INTERESTING POINT. WE CAN DO IT AND WE CAN ANSWER THE QUESTION TOO AND I JUST HOPE THAT SUCH THINGS HAPPEN. THAT'S REALLY HOW RESEARCH WORKS. IT DOESN'T HAVE TO BE DONE BY YOU. IT'S MORE THAT YOU ADD SOMETHING AND SOMEBODY ELSE ADD SOMETHING AND OVERALL SLOWLY THE WHOLE PICTURE DEVELOPS. AND HOPEFULLY IT CAN BE REPEATED -- AND THEN IT CAN BE REPEATED AND SET IN STONE THAT THIS IS TRULY HAPPENING. THEN I'M GOING TO DEFINE THE EXPOSURE. THEN WHAT YOU DO, CAN YOU INTERFERE. WHAT SHOULD WE DO. IS IT VERSELESS OR IS IT REALLY HELPFUL TO COME UP WITH THE THERAPY. >> THANK YOU SO MUCH. >> OKAY, THANK YOU.