4 Breast Cancer Epidemiology EtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentIncidence:Invasive breast cancer 11.4 million new cases in 2008Incidence rates for 2002 varied internationally3.9 cases per 100,000 in Mozambique101.1 cases per 100,000 in the United StatesPast 25 yearsBreast cancer incidence rates have risen globallyHighest rates occurring in the westernized countriesChange in reproductive patternsIncreased screeningDietary changesDecreased activityMortalityMortality has been decreasingEspecially in industrialized countries.1 American Cancer Society
5 Breast Cancer Epidemiology EtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentProjection (2009)United StatesEstimated 192,370 new cases in women1,910 cases in menIncidence rates70’s to 90’s had increasing incidenceDecreased by 2.2% per yearWhy?Reduced use of hormone replacement therapy (HRT)Women’s Health Initiative in 2002Swart, R; Downey, L, Breast Cancer
6 Breast Cancer Epidemiology EtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentLifetime Risk of Breast CancerAll Women12.7%Non-Hispanic Whites13.3%African American Women9.98%More likely to be diagnosed with larger, advanced stage tumors (>5 cm)Swart, R; Downey, L, Breast Cancer
7 Breast Cancer Epidemiology EtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentDeath ratesSteadily decreased since 1990Estimated 40,610 breast cancer deaths for 2009Women < 50 yearsLargest decrease in mortality3.3% per yearThought to representEarlier detectionImproved treatment modalitiesSwart, R; Downey, L, Breast Cancer
8 Breast Cancer Etiology EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMechanism-Current understanding of breast tumorigenesisMolecular alterations at the cellular levelOutgrowth and spread of breast epithelial cellsImmortal featuresUncontrolled growthGenomic profilingDemonstrated the presence of discrete breast tumor subtypesLuminal ALuminal BBasalHER2+The exact number of disease subtypes and molecular alterations from which these subtypes derive remains to be fully elucidatedGenerally align closely with the presence or absence of hormone receptor and mammary epithelial cell type (luminal or basal).Swart, R; Downey, L, Breast Cancer
9 Breast Cancer Etiology EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentThe figure below summarizes the current general understanding of breast tumor subtypes, prevalence, and the major associated molecular alterations. This view of breast cancer, not as a set of stochastic molecular events, but as a limited set of separable diseases of distinct molecular and cellular origins, has altered thinking about breast cancer etiology, type-specific risk factors, prevention, and treatment strategies.
10 Breast Cancer Risk Factors EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentRisk factors found by studiesMany of these factors form the basis for breast cancer risk assessment tools.Common denominatorLevel and duration of exposure to endogenous estrogenIncrease lifetime exposure to estrogenPremenopausal womenEarly menarcheNulliparityLate menopausePostmenopausal womenObesity and hormone replacement therapy
11 Breast Cancer Risk Factors EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentFamily History of breast cancer1st degree relativeRisk 5 times greater in women with 2 or more first-degree relativesA family history of ovarian cancer in a first-degree relativeEspecially if the disease occurred at an early age (< 50 years old)Associated with a doubling of risk of breast cancer
12 Breast Cancer Risk Factors EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentExogenous hormonesOral contraceptives (OCs)Hormone replacement therapy (HRT)1.25 increased risk among current users of oral contraceptivesRisk appears to decreaseAs age and time from oral contraceptive discontinuation increasesBreast cancer risk returns to that of the average population after approximately 10 years following cessation of oral contraceptives
13 Breast Cancer Risk Factors EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentHRTConsistent epidemiologic data support an increased risk of breast cancer incidence and mortality (2003) with the use of postmenopausal HRTDirectly associated with length of exposureLobular (relative risk [RR]=2.25, 95% confidence interval [CI]= )Mixed ductal–lobular (RR=2.13, 95% CI= )Tubular cancers (RR=2.66, 95% CI= ).
14 Breast Cancer Risk Factors EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentCombo estrogen plus progestinIncreased risk as compared to estrogen onlyNot statistical significance (p=0.06)Women’s Health Initiative (WHI)Indicate that the adverse outcomes associated with long-term use outweigh the potential disease prevention benefits particularly for women older than 65 yearsProtective factorsLate menarcheAnovulationEarly menopause (spontaneous or induced)Lowering endogenous estrogen levelsShortening the duration of estrogenic exposure.
15 Breast Cancer Risk Factors Advanced ageFamily history Two or more relatives (mother, sister)One first-degree relativFamily history of ovarian cancer in women <50yPersonal history Personal history Positive BRCA1/BRCA2 mutation Breast biopsy with atypical hyperplasia Breast biopsy with LCIS or DCISReproductive historyEarly age at menarche (<12 y)Late age of menopauseLate age of first term pregnancy (>30 y)/nulliparityUse of combined estrogen/progesteroneCurrent or recent use of oral contraceptivesLifestyle factors Adult weight gain Sedentary lifestyle Alcohol consumption>4>5>23-44-58-1021.5-21.251.5EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatment
17 Breast Cancer Risk Assessment Tools EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMultivariate Methods for estimating breast cancer2 typesEstimate absolute risk of developing cancerEstimate likelihood that an individual is a carrier of a gene mutationBRCA1BRCA2
18 Breast Cancer Risk Assessment Tools EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentBRCA screensBRCAPROIdentifies 50% of mutation negative familiesFails to screen 10% of mutation carriersMyriad I, IIManchesterOntario Family HistoryU.S. Preventive Services Task Force (USPSTF)Does not specifically endorse any of these genetic risk assessment models because of insufficient data to evaluate their applicability to asymptomatic, cancer-free women.USPSTF does support the use of a greater than 10% risk probability for recommending further evaluation with an experienced genetic counselor for decisions regarding genetic testing.
19 Breast Cancer Risk Assessment Tools EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentRisk Prediction ModelsGail Model (1989)Made from data from Breast Cancer Detection and Demonstration studyProbability of developing breast cancer over a defined age intervalIntended to improve screening guidelinesGail Model 2Includes history of first-degree affected family membersUsed extensively in clinical practiceMost accurate for non-Hispanic White women who receive annual mammogramsTends to overestimate risk in younger women who do not receive annual mammogramsReduced accuracy in populations with demographics (age, race, screening habits) that differ from the population on which it was built
20 Breast Cancer Risk Assessment Tools EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentCareAddress concerns regarding applicability of the Gail Model to African American womenData from a large case control study of African AmericanCARE Model demonstrated high concordance between the numbers of breast cancer predicted and the number of breast cancers observed among African American women when validated in the WHI cohort.Improvements in risk prediction and clinical tools are likely to emerge in the next few years with the addition of such factors as breast density, mammographic density change across exams, use of HRT, and a variety of other factors such as weight, age at birth of first live child, and number of first-degree relatives with breast cancer. Going forward, it is likely that there will be models specifically for risks of premenopausal versus postmenopausal cancers and for specific breast cancer subtypes (luminal versus basal).
21 Breast Cancer Genetic Factors EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentHeredity5-10% of women have an identifiable familial predisposition20-30% of women with breast cancer have a relative with historyBRCA1 and BRCA2 mutationsResponsible for 3-8% of all cases of breast cancer15-20% of familial casesGene mutation on Chromosome 17 and 18Account for majority of inherited diseaseBelieved to be tumor suppressor genesRare mutations are seen in the PTEN, TP53, MLH1, MLH2, and STK11 genes.
22 Breast Cancer Genetic Factors EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMutation rates may vary by ethnic and racial groups.BRCA1 mutationsHighest rates occur among Ashkenazi Jewish women (8.3%)Hispanic women (3.5%)Non-Hispanic white women (2.2%)African American women (1.3%)Asian American women (0.5%)Women with BRCA1 or BRCA2 geneEstimated 50-80% lifetime risk of developing breast cancer.Specifically, BRCA1 mutations are seen in 7% of families with multiple breast cancers and 40% of families with breast and ovarian cancer. People with a BRCA1 mutation have a lifetime risk of 40% for developing ovarian cancer and are also at a higher risk of colon cancer and prostate cancer. Breast cancer that develops in BRCA1 mutation carriers are more likely to be high-grade, and ER, PR, and HER-2/neu negative (triple negative) or basal-like subtype.BRCA2 mutations are identified in 10-20% of families at high risk for breast and ovarian cancers and in only 2.7% of women with early-onset breast cancer. Women with a BRCA2 mutation have approximately 10% lifetime risk of ovarian cancer. BRCA2 mutation carriers who develop breast cancer are more likely to have a high grade, ER+/PR+, and HER-2/neu negative cancer (luminal type). BRCA2 is also a risk factor for male breast cancer.Other cancers associated with BRCA2 mutations include prostate, pancreatic, fallopian tube, bladder, non-Hodgkin lymphoma, and basal cell carcinoma.Li-Fraumeni syndrome, caused by TP53 mutations , is associated with multiple cancers, including the SBLLA syndrome (sarcoma, breast and brain tumors, leukemia, and laryngeal and lung cancer). Cancer susceptibility is transmitted in an autosomal dominant pattern, with a lifetime risk of breast cancer of 90%. Li-Fraumeni syndrome is responsible for approximately 1% of cases of familial breast cancer. Bilateral breast cancer is noted in up to 25% of patients.Cowden disease is a rare genetic syndrome caused by PTEN mutations. It is associated with intestinal hamartoma, cutaneous lesions, and thyroid cancer. The prevalence rate of breast cancer in women with this disease is approximately 30%. Benign mammary abnormalities (eg, fibroadenomas, fibrocystic lesions, ductal epithelial hyperplasia, and nipple malformations) are also common. Other rare genetic disorders, such as Peutz-Jeghers and hereditary nonpolyposis colorectal carcinoma (HNPCC), are associated with an increased risk of breast cancer.
23 Breast Cancer Breast Cancer Screening EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentEarly detectionPrimary defense available to patientsPreventing the development of life-threatening breast cancerBreast tumors that are smaller or nonpalpableTreatable and have a more favorable prognosisSurvival benefit of early detectionEarly detection is widely endorsedWomen younger than 40 yearsMonthly breast self-examination practicesClinical breast exams every 3 years are recommended, beginning at age 20 years.In addition, rather than annual screening, the USPSTF guidelines recommend that screening mammography be performed biennially (Grade B recommendation). The USPSTF concludes that there is currently insufficient evidence to assess the additional benefits and harms of screening mammography in women 75 years or older and thus recommends stopping screening at age 74 years.4
24 Breast Cancer Breast Cancer Screening EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMammographyAnnual screening mammography beginning at age 40 yearsWidely recommended approach in the United StatesU.S. Preventive Services Task Force (USPSTF) Nov 2009Updated breast cancer screening guidelinesRecommend against routine mammography before age 50 years40 to 49 years of ageUSPSTF suggests that the decision to start regular screening mammography be individualized and should include the patient's values regarding specific benefits and harmsAmerican College of Obstetricians and Gynecologists (ACOG)Continues to recommend adherence to current ACOG guidelinesScreening mammography every 1-2 years for women aged 40-49Screening mammography every year for women age 50 or olderACOG notes, however, that because of the USPSTF downgrading, some insurers may no longer cover some of these studies.In addition, rather than annual screening, the USPSTF guidelines recommend that screening mammography be performed biennially (Grade B recommendation). The USPSTF concludes that there is currently insufficient evidence to assess the additional benefits and harms of screening mammography in women 75 years or older and thus recommends stopping screening at age 74 years.4
25 Breast Cancer Breast Self Examination EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentBreast self-examinationInexpensive and noninvasive procedureEvidence supporting effectivenessControversial and largely inferredNot been found to reduce mortalityImprovements in treatment for early, localized diseaseBreast self-examination and clinical breast exam, continues to be recommendedClinical trials support combining clinical breast exam with mammography
26 Breast Cancer Breast Self Examination EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentRecommendationsUSPSTFInadequate evidence to make a recommendation for teaching or performing BSE2009 USPSTF guidelines recommend against teaching women how to perform BSEResulted in additional imaging procedures and biopsiesACOGContinues to recommend counselingBSE has potential to detect palpable breast cancer
27 Breast Cancer Mammography EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMammographyDemonstrated to be an effective toolPrevention of advanced breast cancer in women at average riskBest available population-based method to detect breast cancer at an early stageOften reveals a lesion before it is palpable by clinical breast examinationOn average 1-2 years before noted by breast self-examination20-30% of women still do not undergo screening as indicatedPhysician recommendationAccess to health insuranceDigital MammograpyAllows the image to be recorded and storedComputer-aided diagnosis (CAD) systemsUsing an image modified to improve evaluation of specific areas in question.
28 Breast Cancer Mammography EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentRecommendations:USPSTFEstimates benefit of mammography in women50-74 years to be a 30% reduction risk of death40-49 years, the risk of death is decreased by 17%Non-white women and those of lower socioeconomic status remain less likely to obtain mammography services and more likely to present with life-threatening, advanced-stage disease
29 Breast Cancer Mammography EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentUltrasoundWidely available and useful adjunct to mammographyMRICombination of T-1, T-2, and 3-D contrast-enhanced MRI techniques has been found to be highly sensitiveApproximating 99%Limitations10-fold higher cost than mammographyPoor specificity (26%)Significantly more false-positive readsSignificant additional diagnostic costs and procedures.While mammography remains the most cost-effective approach for breast cancer screening, the sensitivity (67.8%) and specificity (75%) are not ideal. As reported, mammography combined with clinical breast examination slightly improves sensitivity (77.4%) with a modest reduction in specificity (72%). Comparisons between recently introduced digital mammography and screen-film mammography suggest that the sensitivity of full-field digital mammography is superior to screen film mammography in certain subsets of women. For example, digital mammography demonstrates improved detection rates for younger women and for women with more dense breasts. Improved imaging modalities with greater sensitivity are of particular benefit for women at the highest risk and for women whose breast images are difficult to interpret.Generally used to assist the clinical examination of a suspicious lesion detected via mammogram or physical examination. As a screening device, the ultrasound is limited by a number of factors, but most notably by the failure to detect microcalcifications and poor specificity (34%).
30 Breast Cancer Mammography EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentBelow are the criteria for using breast MRI screening per the American Cancer Society (ACS).6Annual breast MRIEvidence basedBRCA mutationFirst-degree relative of BRCA carrier, but untestedLifetime risk approximately 20-25% or greater as defined by BRCAPRO or other risk modelsLifetime risk of breast cancerRadiation to chest when aged yearsLi-Fraumeni syndrome and first-degree relativesCowden and Bannayan-Riley-Ruvalcaba syndromes and first-degree relatives
31 Breast Cancer Mammography EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentInsufficient evidence to recommend for or against MRI screeningLifetime risk 15-20%, as defined by BRCAPRO or other risk modelsLobular carcinoma in situ or atypical lobular hyperplasia (ALH)Atypical ductal hyperplasia (ADH)Heterogeneously or extremely dense breast on mammographyWomen with a personal history of breast cancer, including ductal carcinoma in situAmerican Cancer Society does not recommend the use of breast MRI in women who have less than 15% lifetime risk
32 Breast Cancer Presentation EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMammogram-Often irst detected as an abnormality on a mammogramMammographic featuresAsymmetryMicrocalcificationsA massArchitectural distortionLarger tumorsMay present as a painless massPain5% of patients with a malignant mass present with breast painOther symptomsImmobilitySkin changes (ie, thickening, swelling, redness)Nipple abnormalities (ie, ulceration, retraction, spontaneous bloody discharge)
33 Breast Cancer Workup Core biopsy Percutaneous vacuum-assisted EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentCore biopsyPercutaneous vacuum-assistedImage guided breast biopsyRecommended diagnostic approachPerformed withUltrasoundStereotactic, or MRI guidanceCore biopsies spare the need for operative interventionProvides pathological results quicker than surgical excisionsExcisional biopsyAs the initial operative approachShown to increase the rate of positive marginsTypically, patients who undergo a core needle biopsy, whether directed by imaging studies or palpation, have a titanium marker clip placed at the biopsy site. These clips are particularly helpful when planning a lumpectomy for non-palpable breast lesions that require preoperative image-guided wire-localization or for patients who undergo neoadjuvant chemotherapy, resulting in a pathological complete response.
34 Breast Cancer Workup Palpation directed core biopsy EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentPalpation directed core biopsyIf a breast mass may be palpable but not correlate with imagingComplications of a diagnostic core or excisional biopsyHematomaInfectionScarringRe-operationSampling error resulting in inaccurate diagnosis.Typically, patients who undergo a core needle biopsy, whether directed by imaging studies or palpation, have a titanium marker clip placed at the biopsy site. These clips are particularly helpful when planning a lumpectomy for non-palpable breast lesions that require preoperative image-guided wire-localization or for patients who undergo neoadjuvant chemotherapy, resulting in a pathological complete response.
35 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentDuctal Carcinoma in situ (DCIS)Lobular Carcinoma in situ (LCIS)Medullary CarcinomaMucinous CarcinomaTubular CarcinomaPapillary CarcinomaMetaplastic CarcinomaMammary Paget’s DiseaseIncreased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are
36 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentDuctal Carcinoma in situ (DCIS)Identified in ducts (non-invasive)Identified on mammographySuspicious calcifications,DistributionLinearClusteredSegmentalFocalMixedDCIS is divided into comedo (ie, cribriform, micropapillary, solid) and noncomedo subtypes, which provides additional prognostic information regarding likelihood of progression or local recurrenceIncreased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are
37 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentDuctal Carcinoma in situ (DCIS)Standard treatment of DCIS is surgical resection with or without radiationAdjuvant radiation and hormonal therapiesReserved forYounger womenPatients undergoing lumpectomyComedo subtypeMastectomy30% of women with DCIS in the United StatesConservative Surgery30% with conservative surgery aloneConservative surgery with whole breast radiation40% with conservative surgery followed by whole-breast radiation therapyIncreased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are
38 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentDuctal Carcinoma in situ (DCIS)Axillary or sentinel lymph node dissection is not routinely recommended for patients with DCISMetastatic diseaseDisease to the axillary node in 10% of patientsWhole-breast radiotherapyDelivered 5-6 weeks followingTamoxifenAdjuvant therapy for breast conserving surgeryOnly hormonal therapy currently approvedAromatase inhibitor (anastrozole)Currently in clinical trialsIncreased use of screening mammography has resulted in a dramatic increase in the detection of DCIS. Approximately 64,000 cases of DCIS are diagnosed annually in the United States. Today, 90% of DCIS cases are
39 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentLobular Carcinoma in situ (LCIS)Found in the lobules (or glands)Non-palpable massDiffuse distribution throughout the breastIncidenceDoubled over last 25 years2.8% per 100,000 womenPeak incidence is in women aged yearsNo consistent features on breast imagingOften an incidental finding10-20% of women with LCIS develop invasive breast cancerWithin 15 years from diagnosis.LCIS is considered a biomarker of increased breast cancer riskTreatment optionsChemoprevention with a SERMBilateral mastectomyClose observation.
40 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMedullary CarcinomaRelatively uncommon (5%)InvasiveOccurs in younger womenPresentationBulky palpable mass with axillary lymphadenopathyDiagnosisSheets of anaplastic tumor cells with scant stromaModerate or marked stromal lymphoid infiltrateHistologic circumscription or a pushing borderOther findingsDCIS may be observed in the surrounding normal tissuesER, PR, and HER2/neu are typically negative, and TP53 is commonly mutated.Roughly 30% of patients have lymph node metastasis.PrognosisGoodRecent analysis of 609 medullary breast cancer specimens from various stage I and II NSABP protocols indicate that overall survival and prognosis are not as good as previously reported.
41 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMucinous CarcinomaRare histologic typeFewer than 5% of invasive breast cancerProduces MucinUsually presents during the seventh decadeExcellent prognosis (>80% 10-year survival).Mucin production is the histologic hallmark with 2 main forms, type A and B, with AB lesions possessing features of both. Type A mucinous carcinoma represented the classic variety with larger quantities of extracellular mucin, whereas type B is a distinct variant with endocrine differentiation. DCIS is not a frequent occurrence, though it may be found. Most cases are ER and PR positive, but HER2/neu overexpression is rare. Additionally, these carcinomas predominantly express glycoproteins MUC2 and MUC6
42 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentTubular CarcinomaUncommon histologic type1-2% of all breast cancersSingle layer of epithelial cellsLow incidence of lymph node involvementVery high overall survival rate
43 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentPapillary Carcinoma1-2% of all carcinomasUsually seen in women older than 60TypesCystic (non-invasive)Good prognosisMicropapillary ductal carcinoma (invasive)Poor prognosisLymph node metastasis
44 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMetaplastic Carcinoma1% of breast cancersCombination of adenocarcinoma plus mesenchymal and epithelial componentsWide variety of histological patternsSpindle-cell carcinomaCarcinosarcomaSquamous cell carcinoma of ductal originAdenosquamous carcinomaCarcinoma with pseudosarcomatous metaplasiaMatrix-producing carcinomaMetaplastic breast cancer tumorsLargerMore rapidly growingCommonly node negativeTypically ER, PR, and HER-2 negativeAverage age of onset in the sixth decadeHigher incidence in African Americans.
45 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMetaplastic CarcinomaDemonstrated a worse prognosis for metaplastic breast cancer as compared to infiltrating ductal carcinoma3-year overall survival rate of 48-71%3-year disease-free survival rate of 15-60%Prognosis / predictors of poor overall survivalLarge tumor sizeAdvanced stageNodal status does not appear to impact survival in metaplastic breast cancerSurgery is used to treat up to 95% of women with metaplastic breast cancer. Few data support the effectiveness of systemic chemotherapy in patients with metaplastic breast cancer and its use has been extrapolated from the treatment of more common types of breast cancer. A review of chemotherapy and response in a series of 27 patients with metaplastic breast cancer found only one partial response with a doxorubicin-containing regimen in the setting of metastatic disease. As in soft-tissue sarcomas, metaplastic breast cancer shows a tendency for local recurrence and for hematogenous spread to lung, liver, and bone.
46 Breast Cancer Histological Findings EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMammary Paget’s Disease1-4% of all breast cancersPeak incidence is seen in the sixth decade of life (mean age 57 y)AdenocarcinomaLocalized within the epidermis of the nipple-areola complexPaget cellsLargePale epithelial cellsPresentationLesionsUnilateral developing insidiouslyScalyFissuredOozingErythematous nipple-areola complexRetraction or ulceration of the nipple is often notedItching, tingling, burning, or pain.Mammary Paget disease is associated with an underlying breast cancer in 75% of cases.Overall 5-year and 10-year survival rates are 59% and 44%, respectively.Standard treatment of mammary Paget disease is surgical excision (modified radical mastectomy with lymph node excision). Breast conserving surgery can achieve satisfactory results, but at the risk of local recurrence. Adjuvant chemotherapy with tamoxifen may increase survival in premenopausal patients with lymph node metastasis. Poor prognostic factors include a palpable breast tumor, lymph node involvement, histological type, and patient younger than 60 years
47 Breast Cancer Prognosis EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentPredictors / prognostic factors of BCAxillary lymph node statusTumor sizeLymphatic/vascular invasionPatient ageHistologic gradeHistologic subtypes (eg, tubular, colloid [mucinous], papillary)Response to neoadjuvant therapyEstrogen receptor/progesterone receptor statusHer2/neu gene amplification and/or overexpressionBreast cancer predictive factors include the following:Lymph node statusStandard treatment of mammary Paget disease is surgical excision (modified radical mastectomy with lymph node excision). Breast conserving surgery can achieve satisfactory results, but at the risk of local recurrence. Adjuvant chemotherapy with tamoxifen may increase survival in premenopausal patients with lymph node metastasis. Poor prognostic factors include a palpable breast tumor, lymph node involvement, histological type, and patient younger than 60 years
48 Breast Cancer Staging T- tumor size N- Lymph node status M- Metastasis EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentT- tumor sizeN- Lymph node statusM- MetastasisSeparated into stages 0- IVSurvival Rates 5 yearStages99-100%I95-100%II86%III57%IV20%
49 Breast Cancer Staging National Cancer Center Network (NCCN) guideline EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentNational Cancer Center Network (NCCN) guidelineStage I or IIRecommends a history and physical examinationLaboratory studies (CBC with differential, liver and renal function tests, and calcium levels)Stage IIIChest x-ray or CT scan of the chestCT scan of the abdomen and pelvisBone scan for evaluation of distant metastasisTumor markers (CEA and CA15.3 or CA27.29) may also be obtained in these patients
50 Breast Cancer Treatment EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentLumpectomyMastectomyBreast ReconstructionManagement of Contralateral breastSentinel Node DissectionAxillary Lymph node dissectionBreast Conserving radiation therapyAdjuvant ChemotherapyAdjuvant Hormonal TherapyBehavioral therapy--- Very Important
51 Breast Cancer Treatment EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentLumpectomyDefined as complete surgical resection of a primary tumorGoal of achieving widely negative margins (ideally a 1 cm margin around the lesion)Synonyms for lumpectomyPartial mastectomySegmental mastectomyTylectomyA quadrantectomy is a type of lumpectomyComplete removal of the entire affected breast quadrantPerformed with palpation guidance or with image guidanceNSABP-B6 did find a significant difference in the rate of local recurrence between the 3 treatment arms. Patients in the lumpectomy alone without radiation therapy group had a significantly higher local recurrence rate than patients undergoing lumpectomy plus radiation therapy (39.2% vs 14.3%, respectively). Patients who underwent modified radical mastectomy had a 10.2% risk of chest wall recurrence. This landmark study established breast-conserving surgery with radiation therapy to be equivalent to modified radical mastectomy.
52 Breast Cancer Treatment EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentMastectomyTotal mastectomyComplete removal of all breast tissueClavicle superiorlySternum mediallyInframammary crease inferiorlyAnterior axillary line laterally with en bloc resection of the fascia of the pectoralis majorThe nipple-areolar complex (NAC) is resected along with a skin paddle to achieve a flat chest wall closure when performing a total mastectomy.No removal of any axillary nodesModified radical mastectomyTotal mastectomy with axillary lymph node dissection
53 Breast Cancer Treatment EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentPostmastectomy Radiation TherapyPositive postmastectomy marginsPrimary tumors larger than 5 cmInvolvement of 4 or more lymph nodesBreast ReconstructionSSMNSM
54 Breast Cancer Treatment EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentManagement of Contralateral breastSentinel Node DissectionTechnetium 99Methylene blue dyeFirst set of nodes that drain from the breast to the axillaLymph nodes checked for metastasisIf positive usually recommend axillary dissectionAxillary Lymph node dissection
55 Breast Cancer Treatment EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentBreast Conserving radiation therapyUsed to eliminate residual subclinical diseaseSide effectsFatigueBreast painSwellingSkin desquamationLate toxicity (lasting 6 mo or longer following treatment)Persistent breast edemaPainFibrosisSkin hyperpigmentation
56 Breast Cancer Treatment EpidemiologyEtiologyRisk FactorsScreeningPresentationWorkupStagingTreatmentAdjuvant ChemotherapyAdjuvant Hormonal TherapyEstrogen-receptor positive early stage breast cancerHormonal therapy plays a main roleMay be used with chemotherapyFunction to decrease estrogen's ability to stimulate existing micro-metastases or dormant cancer cellsCan reduce the relative risk of distant, ipsilateral, and contralateral breast cancer recurrence by up to 50%
57 Breast Cancer Any questions? Powerpoint can be found at