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  • 1. Management ofManagement of Breast DiseaseBreast Disease Joseph A. Lucci III, M.D.Joseph A. Lucci III, M.D. Department of Obstetrics and GynecologyDepartment of Obstetrics and Gynecology Division of GynecologicDivision of Gynecologic OncologyOncology
  • 2. Breast Disease • Reproductive HealthReproductive Health • DiagnosisDiagnosis • TreatmentTreatment • Cancer ScreeningCancer Screening Role of Primary Care Physician
  • 3. Breast Anatomy • SkinSkin • FatFat • GlandGland • Connective TissueConnective Tissue • VesselsVessels COMPONENTS
  • 4. Breast Anatomy • BodyBody • TailTail • Nipple ComplexNipple Complex TOPOGRAPHY
  • 5. Breast Anatomy • 10 – 20 Ducts10 – 20 Ducts • Duct Drains LobeDuct Drains Lobe • Lobe Contains 20 – 40 LobulesLobe Contains 20 – 40 Lobules • Lobule Contains 10 – 100 AlveoliLobule Contains 10 – 100 Alveoli GLAND
  • 6. Breast Anatomy • Camper’s FasciaCamper’s Fascia • Pectoral FasciaPectoral Fascia • Cooper’s LigamentsCooper’s Ligaments FASCIAL SUPPORT
  • 7. Breast Anatomy • ARTERIALARTERIAL – Internal MammaryInternal Mammary – Lateral ThoracicLateral Thoracic • LYMPHATICSLYMPHATICS – DrainageDrainage – Nodal LevelsNodal Levels VASCULATURE
  • 8. Breast Anatomy • Level I – Lateral Pectoralis MinorLevel I – Lateral Pectoralis Minor • Level II – Deep Pectoralis MinorLevel II – Deep Pectoralis Minor • Level III – Medial Pectoralis MinorLevel III – Medial Pectoralis Minor NODAL LEVELS
  • 9. Breast Cancer Location
  • 10. Components of Appropriate Screening Program • Professional Physical ExaminationProfessional Physical Examination • Breast Self Examination (BSE)Breast Self Examination (BSE) • MammographyMammography
  • 11. Breast Exam • OBSERVEOBSERVE – Mass EffectMass Effect – Arm PositionArm Position • PALPATEPALPATE – BreastBreast – NodesNodes SITTING POSITION
  • 12. Breast Exam • PositioningPositioning • PalpationPalpation • DischargeDischarge LYING POSITION
  • 13. Breast Disease • BenignBenign 88%88% • MalignantMalignant 12%12% Nipple Discharge – 432 Patients
  • 14. Nipple Discharge 1.1. GalactorrheaGalactorrhea 2.2. Intraductal papillomaIntraductal papilloma 3.3. Duct ectasiaDuct ectasia 4.4. CarcinomaCarcinoma
  • 15. Screening Recommendations Professional Breast Exam AgeAge Physical ExamPhysical Exam 20 – 40 yrs20 – 40 yrs Every 3 yearsEvery 3 years > 40 yrs> 40 yrs AnnuallyAnnually
  • 16. Screening Recommendations Breast Self Exam (BSE) Recommended monthly for allRecommended monthly for all women over the age of 20women over the age of 20
  • 17. Breast Disease • MAMMOGRAPHYMAMMOGRAPHY – 2 Views2 Views – MagnificationMagnification • ULTRASOUNDULTRASOUND IMAGING
  • 18. Carcinoma Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc; 1985:91.
  • 19. Comedo Carcinoma Dean P. Teaching atlas of mammography. New York, New York: Thieme Inc; 1985:168
  • 20. Ductal Carcinoma Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:169
  • 21. Breast Cancer Mammographic Screening AgeAge ACSACS NCINCI MortalityMortality ReductionReduction 40 – 4940 – 49 Q 1 yrQ 1 yr Q 1-2 yrsQ 1-2 yrs 17%17% 50 – 6950 – 69 Q 1 yrQ 1 yr Q 1 yrQ 1 yr 25 – 30%25 – 30% 70+70+ Q 1 yrQ 1 yr Q 1 yrQ 1 yr ??
  • 22. Absolute Indications for Breast Biopsy • Biopsy any suspicious palpableBiopsy any suspicious palpable lesions.lesions. • Biopsy any suspicious area seen onBiopsy any suspicious area seen on mammogram, but not palpablemammogram, but not palpable
  • 23. Breast Mass Presumed Benign B i o p s y M a s s r e c u r r e n c e F o l l o w N o r e c u r r e n c e O b s e r v e X 1 m o N o n b l o o d y f l u id , m a s s d is a p p e a r s T r e a t m e n t C a n c e r F o l l o w B e n ig n E x c i s i o n a l b i o p s y B lo o d y f l u i d , n o f lu id o r i n c o m p l e t e d i s a p p e a r a n c e o f m a s s N e e d l e A s p ir a t i o n s PP OO EE PP
  • 24. • 50 – 80% of all women50 – 80% of all women • EtiologyEtiology • DiagnosisDiagnosis • TreatmentTreatment FIBROCYSTIC CHANGES
  • 25. FIBROCYSTIC CHANGES Diagnosis • PalpationPalpation • MammographyMammography • UltrasoundUltrasound • AspirationAspiration • BiopsyBiopsy
  • 26. Fibrosystic Changes • OCP’SOCP’S • MethylxanthinesMethylxanthines • NicotineNicotine • Vitamin EVitamin E • HormonesHormones • BromocriptineBromocriptine TREATMENT
  • 27. Fibrosystic Changes • Extent of Proliferative ChangesExtent of Proliferative Changes • VariableVariable CANCER RISK
  • 28. Proliferative Breast Disease CANCER RISK HyperplasiaHyperplasia 1.91.9 Atypical HyperplasiaAtypical Hyperplasia 4.54.5 AH + FM HXAH + FM HX 1111 CystsCysts 1.51.5 Cysts + FM HXCysts + FM HX 3.03.0
  • 29. Sclerosing Lesions • Fibrocystic ChangesFibrocystic Changes • Small, IrregularSmall, Irregular • Resembles CAResembles CA • DX: FNADX: FNA • TX: ExcisionTX: Excision
  • 30. Sclerosing Duct Hyperplasia Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:106
  • 31. Adenoma • Age: 20 – 30 yrsAge: 20 – 30 yrs • GroupsGroups – TubularTubular – LactatingLactating • DX: FNADX: FNA • TX: Observe, ExcisionTX: Observe, Excision
  • 32. Fibro-adeno-lipoma Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:25
  • 33. Lipoma Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:21
  • 34. Fibroadenoma • Age 20 – 49 yrsAge 20 – 49 yrs • Firm, PainlessFirm, Painless • Bilateral 15 – 25%Bilateral 15 – 25% • DX: FNADX: FNA • TX: Observe, ExciseTX: Observe, Excise
  • 35. Fibroadenoma Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:200
  • 36. Phylloides Tumor • Age: 30 – 55 yrsAge: 30 – 55 yrs • Slow GrowingSlow Growing • Epithelial and StromalEpithelial and Stromal • 10% Sarcoma10% Sarcoma • DX: FNADX: FNA • TX: ExcisionTX: Excision
  • 37. Cystosarcoma Phylloides Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:63
  • 38. Intraductal Papilloma • Age: 45 – 50 yrsAge: 45 – 50 yrs • Bloody DischargeBloody Discharge • Unilateral, smallUnilateral, small • TX: ExcisionTX: Excision • CA Risk: Rare, Multiple LesionsCA Risk: Rare, Multiple Lesions
  • 39. Intraductal Papilomatosis Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:192
  • 40. Intraductal Papillomatosis Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:48
  • 41. Ductal Ectasia • Age: PerimenopausalAge: Perimenopausal • BilateralBilateral • Sticky, Thick, Green DischargeSticky, Thick, Green Discharge • DX: ExamDX: Exam • TX: ABX, ExcisionTX: ABX, Excision • CA Risk: RareCA Risk: Rare
  • 42. Breast Cancer US Statistics, 2000 • 182,800 new cases in women182,800 new cases in women • 40,800 deaths in women40,800 deaths in women • 1:8 women will develop breast1:8 women will develop breast cancer in lifetimecancer in lifetime Greenlee et al, CA Cancer J Clin 2000, 50:7-33
  • 43. Cancer Incidence 1998 NewNew DeathDeath BreastBreast 180,300180,300 43,50043,500 LungLung 83,30083,300 68,40068,400 ColonColon 68,90068,900 28,90028,900 EndometriumEndometrium 36,10036,100 6,3006,300 OvaryOvary 25,40025,400 14,50014,500 CervixCervix 13,70013,700 4,9004,900 Cancer Facts and Figures – ACS, 1998
  • 44. Breast Cancer Five Year Survival (1989- 95) LocalizedLocalized 97%97% RegionalRegional 78%78% DistantDistant 22%22% OverallOverall 86%86% Greenlee et al, CA Cancer J Clin 2000, 50:7-33
  • 45. Breast Cancer • Incidence has plateaued since 1987Incidence has plateaued since 1987 • Mortality rates have been stable or decliningMortality rates have been stable or declining • 5 year survival for localized disease has improved5 year survival for localized disease has improved 19401940 78%78% 19931993 93%93% 19971997 97%97%
  • 46. Presentation of Breast Cancer (744 Patients)
  • 47. Breast Cancer • SexSex • ParityParity • MensesMenses • SocioeconomicSocioeconomic • RaceRace • DietDiet • WeightWeight RISK FACTORS
  • 48. Breast Cancer Risk Assessment Modified Gail Model • AgeAge • Family history of breast cancerFamily history of breast cancer • Age at first live birth, if anyAge at first live birth, if any • Number of breast biopsiesNumber of breast biopsies • History of atypical hyperplasiaHistory of atypical hyperplasia • Age at menarcheAge at menarche • RaceRace
  • 49. Breast Cancer Family History Family HistoryFamily History Relative RiskRelative Risk of Breastof Breast CancerCancer CalculatedCalculated Lifetime RiskLifetime Risk UnilateralUnilateral PremenopausalPremenopausal 3.13.1 21.7%21.7% PostmenopausalPostmenopausal 1.51.5 10.5%10.5% BilateralBilateral 5.45.4 37.8%37.8% PremenopausalPremenopausal 8.88.8 61.6%61.6% PostmenopausalPostmenopausal 4.04.0 28.0%28.0%
  • 50. Breast Cancer Risk Factors RRRR First Pregnancy (>30 yrs)First Pregnancy (>30 yrs) 1.481.48 Body mass index (>29.68 kg/mBody mass index (>29.68 kg/m22 )) 1.481.48 College graduateCollege graduate 1.361.36 Alcohol use (>5 g/d)Alcohol use (>5 g/d) 1.161.16 Delayed menopauseDelayed menopause 1.14 (5 yrs)1.14 (5 yrs) HRT (current)HRT (current) 1.12 (5 yrs)*1.12 (5 yrs)* *based on data from Collaborative Group on Hormonal Factors in Breast Cancer. Lancer. 1997; 350-1047.
  • 51. Breast Cancer • Early PregnancyEarly Pregnancy • CastrationCastration • ExerciseExercise • Avoid ETOHAvoid ETOH DECREASED RISK
  • 52. Chemical Structure of Estradiol and Selected SERMs
  • 53. BCPT Design: SchemaBCPT Design: Schema Randomization n = 13,388 Eligible Women at High Risk (5-yr risk ≥ 1.66% or age over 60) Tamoxifen 5 years n = 6681 Placebo 5 Years n = 6707 Fisher et al. J Natl Cancer Inst 1998; 90:1371-1388.
  • 54. BCPT Objectives • Primary End PointPrimary End Point • Incidence of invasive breast cancerIncidence of invasive breast cancer • Secondary End PointsSecondary End Points • Breast cancer mortalityBreast cancer mortality • Incidence of cardiovascular eventsIncidence of cardiovascular events • Incidence of bone fracturesIncidence of bone fractures Fisher et al. J Natl Cancer Inst 1998. 90:1371-1388
  • 55. BCPT Results: Invasive Breast Cancer Fisher et al. J Natl Cancer Inst 1998; 90:1371-1388
  • 56. BCPT Results: Invasive Breast Cancer Cases by Previous Pathology *Not statistically significant Fisher et al. J Natl Cancer Inst 1998;90:1371-1388
  • 57. Tamoxifen Chronic Effects: NSABP P-1 Hip FractureHip Fracture .84.84 .46.46 Total FractureTotal Fracture 5.285.28 4.294.29 Cardiac IschemiaCardiac Ischemia 2.372.37 2.732.73 DVTDVT .84.84 1.341.34 PEPE .23.23 .69.69 CVACVA .92.92 1.451.45 TIATIA .96.96 .73.73 CateractsCateracts 21.7221.72 24.8224.82 Cateract SurgeryCateract Surgery 3.003.00 4.724.72 Fisher et al. J Natl Cancer Inst 1998; 90:1371-1388. Per 1000 Women/Yr Placebo Tamoxifen
  • 58. Endometrial Cnacer: NSABP P-1 Invasive CaInvasive Ca 1515 3636 .91.91 2.302.30 << 49 yrs49 yrs 88 99 1.091.09 1.321.32 > 49 yrs> 49 yrs 77 2727 .76.76 3.053.05 Stage IStage I 1414 3636 Stage IVStage IV 11 00 DeathsDeaths 11 00 Ca in situCa in situ 33 11 .06.06 .35.35 Fisher et al. J Natl Cancer Inst 1998; 90:1371-1388. Rate Per 1000/Yr Placebo Tamoxifen Number Placebo TamoxifenEvent
  • 59. BCPT QOL: Symptoms Reported at Least Once Over 36 Months All age GroupsAll age Groups %% RiskRisk RatioRatioSymptomSymptom TamoxifenTamoxifen PlaceboPlacebo Vaginal dischargeVaginal discharge 5555 3434 1.601.60 Cold sweatsCold sweats 2121 1515 1.451.45 Genital itchingGenital itching 4747 3838 1.231.23 Night sweatsNight sweats 6767 5555 1.221.22 Hot flashesHot flashes 7878 6565 1.191.19 Day et al. J Clin Oncol 1999. 17(9):2659-2669
  • 60. More studyMore study Postmenopausal women With osteoporosis (n = 7704) Raloxifene 60 mg/d Raloxifene 120 mg/d Cummings SR et al. Proc Am Soc Clin Oncol. 1998;17-2a Palcebo
  • 61. Raloxifene and Breast Cancer Prevention Trials • MORE TrialMORE Trial – Breast Cancer risk not specificallyBreast Cancer risk not specifically addressed at entryaddressed at entry – 70% reduction at 33 months70% reduction at 33 months • 9 trials – 10,575 patients9 trials – 10,575 patients – Mean follow-up = 40 monthsMean follow-up = 40 months – 67 breast cancer events67 breast cancer events – 55% reduction in relative risk55% reduction in relative risk
  • 62. Carcinom a Tabar L, Dean P. Teaching atlas of mammography. 2nd ed. New York, New York: Thieme Inc. 1985:95
  • 63. Breast Cancer • EvaluationEvaluation – H&PH&P – CXRCXR – Bone ScanBone Scan – LabsLabs • TNMTNM STAGING
  • 64. Breast Cancer • SurgerySurgery • RadiationRadiation • ChemotherapyChemotherapy • HormonesHormones TREATMENT
  • 65. Breast Cancer • In SITUIn SITU • LocationLocation • Tumor SizeTumor Size • Breast SizeBreast Size • Patient AgePatient Age • Patient PreferencePatient Preference • Mammographic AppearanceMammographic Appearance SURGICAL THERAPY
  • 66. Breast Cancer • Breast ConservationBreast Conservation – LumpectomyLumpectomy – Sentinal Node(s)Sentinal Node(s) • Modified Radical MastectomyModified Radical Mastectomy and Papillary Node Disectionand Papillary Node Disection SURGICAL THERAPY
  • 67. Breast Cancer • SizeSize • NodesNodes • StageStage • GradeGrade • PloidyPloidy • S – PhaseS – Phase • NecrosisNecrosis • HER-2/neuHER-2/neu PROGNOSTIC FACTORS
  • 68. Breast Cancer • Premenopausal – ChemoPremenopausal – Chemo • Postmenopausal – HormonesPostmenopausal – Hormones ADJUVANT THERAPY
  • 69. Breast Cancer • RegimensRegimens – CMFCMF – CAFCAF – ACAC • 6 – 12 Cycles6 – 12 Cycles CHEMOTHERAPY
  • 70. Breast Cancer • All Breast Concerving Surgical TherapiesAll Breast Concerving Surgical Therapies • High Risk PatientsHigh Risk Patients • WhenWhen – After ChemoAfter Chemo – Middle of ChemoMiddle of Chemo RADIOTHERAPY
  • 71. Breast Cancer • Tamoxifen x 5 yearsTamoxifen x 5 years • All PatientsAll Patients • Ovarian AblationOvarian Ablation HORMONE THERAPY
  • 72. Breast Cancer Survival Rate According to AJCC Stage