Downloaded 238 times
More Related Content
Similar to Breast carcinoma march 15. 2015
![Polymer [ बहुलक ] Chemistry Notes PDF - Irfanullah Mehar - JJ Sir Chemistry.pdf](https://cdn.slidesharecdn.com/ss_thumbnails/polymerchemistrynotespdf-irfanullahmehar-jjsirchemistry-260210172118-3f9b37f7-thumbnail.jpg?width=640&height=640&fit=bounds)
Breast carcinoma march 15. 2015
- 1.
- 4.
- 5. Breast Carcinoma Statistics •THE most common cancer in women in the United States (excluding skin cancer) • The second most common cause of cancer mortality in women (lung cancer is first) • One in eight women will get breast cancer, and one third of women with breast cancer will die of the disease.
- 7. Breast Lung & bronchus Leukemia Bladder Brain&CNS NHL Colorectal Larynx Skin excluding Melanoma Stomach Uterus including Cervix and corpus) Hodgkin disease Thyroid Kidney, pelvis& ureter Ovary Prostate Pancreas Bone & cartilage Liver &bile ducts Esophagus Type of cancer, in Iraq, by primary tumor site (2004) 6
- 10. Risk Factors forBreast Cancer • Geography • Age • Menstrual history • Pregnancy • Benign breast disease (Hx of previous breast pathology) • Other: • Estrogen • Oral contraceptive • Lack of breast feeding is a risk. • Obesity • High fat diet • Alcohol • Smoking • Radiation Exposure • Carcinoma of the contralateral breast or endometrium • Environmental Toxins • ABORTIONS?
- 11. Causes of BreastCancer • Genetic • Environmental • Hormonal
- 12. Genetic changes Proto-oncogen • HER2/NEU •30% • Poor prognosis • RAS & MYC Tumor suppressor gene • Rb, • p53, • ER gene inactivation
- 13. Gene profilingof breast cancerGene profiling of breast cancer • 1. ER +ve, HER2 –ne • 2. ER +ve, HER2 +ve • 3. ER -ne, HER2 +ve • 4. ER -ne, HER2 –ne • Different Outcome & Therapy.
- 14. Genetic Factors Inhereted Mutations(10%) • 10% breast cancers are familial (90% sporadic) • Positive Family History, especially in 1st degree relatives (mother, daughter, sister) confers increased risk for breast cancer • Tumor suppressor genes (BRCA1, BRCA2) • Risk is greatest with: • Relative with BILATERAL disease • Relative affected at a YOUNG AGE
- 15. BRCA1 Gene (17q21) •Responsible for up to 1/2 of “inherited” breast cancers (5% of cancers) • Increased risk of ovarian and colon cancers (“Breast-Ovarian” cancer gene) • Breast cancer develops in >50% of these women by age 50 (“Early onset” breast cancer gene) • Carried by 1 in 200-400 people
- 16. BRCA2 Gene (13q) •Responsible for up to 70% of inherited breast cancer NOT due to BRCA1 (3.5% of cancers) • Characterized by increased risk of breast cancer in women and MALE breast cancer (“Male Breast Cancer” gene)
- 17. Li-Fraumeni Syndrome (p53) •Due to Inherited p53 Tumor Suppressor Gene Mutation (cell cycle checkpoint) • Family cancer syndrome characterized by increased risk of breast cancer, osteosarcoma, soft tissue sarcomas, brain tumors, leukemia, other • Accounts for approximately 1% of breast cancers detected before age 40
- 18. OTHER Recognized Susceptibility Loci •ESR 6q24-27 (Estrogen receptor) • AR X11.2-q12 (Androgen receptor) • PTEN 10q22-23 (Cowden’s syndrome)
- 19. Hormonal Factors • “Incessantovulation”: Early menarche, late menopause, nulliparity, late age at first term pregnancy all INCREASE the risk of breast cancer. • Oophorectomy before age 35 DECREASES the risk of breast cancer. • Oral contraceptive use and hormone replacement therapy may be associated with a ????? SMALL increased risk • Etiology: ? hormonal stimulation of proliferation and differentiation of cycling breast epithelium.
- 20. Environmental Factors • 4-5fold greater incidence of breast cancer in industrialized countries than in less developed countries. • Increased risk may be related to: – Higher fat diet – Earlier menarche – Less physical activity – Decreased parity – Later age at parity
- 21. Radiation Exposure • Increasedrisk of breast cancer after: – Radiation therapy for Hodgkin’s Disease in young women, postpartum mastitis in mothers – Survivors of atomic bomb blasts • Increased risk when exposure is at a young age, little increase in risk after age 40 – Indicates that the risk is GREATEST to the developing and hormonally cycling breast
- 22. Histopathologic Risk Factors ForBreast Cancer • Presence of a history of breast pathology increases risk of breast cancer
- 23. Relative Risk forInvasive Carcinoma Based on Histologic Evaluation of Breast Tissue Without Invasive Carcinoma • NON-Proliferative Fibrocystic Changes (1X, No increased risk) – Small simple cysts, apocrine metaplasia, mild epithelial hyperplasia • Proliferative Fibrocystic Changes (1.5-2X, Slight increased risk) – Moderate to florid hyperplasia – Sclerosing adenosis – Intraductal papilloma – Fibroadenoma • Proliferative Fibrocystic Changes WITH ATYPIA (3-5X, Moderate increased risk) – Atypical ductal hyperplasia – Atypical lobular hyperplasia • Carcinoma IN SITU (8-10X, HIGH RISK) – Ductal carcinoma in situ (DCIS)
- 24. Atypical hyperplasia with familyhistory or in a premenopausal woman has a risk of invasive carcinoma similar to DCIS Relative Risk of Invasive Breast Carcinoma
- 25.
- 26.
- 27. 6. Breast CancerPathology In Situ Carcinomas Invasive Carcinomas Special Subtypes
- 28. Ductal Carcinoma InSitu (DCIS) • Arises in the terminal duct lobular unit (TDLU) and DOES NOT demonstrate invasion through the myoepithelial layer and BM • DCIS is a surgically treatable entity • The likelihood of developing an invasive carcinoma, or recurrent DCIS varies with a) Histologic subtype of the in situ carcinoma b) Size/ extent of DCIS c) Distance to the margins of excision.
- 29. Ductal Carcinoma inSitu • Clinical: – DCIS usually does not present as a palpable mass, if it does it is usually high grade and a large lesion • Mammogram: – The most common method of detection is by identifying mammographic calcifications – The calcifications may be linear and branching...following the lumens of the involved ducts
- 30. DCIS is confined to withinthe ductal system
- 31. Mammography showing anormal breast (left) and a cancerous breast (right).
- 33.
- 34.
- 35. Architectural Patterns of DCIS •Comedo – Grade 3 nuclei and necrosis – Often has associated microcalcifications • Solid – Carcinoma fills and distends the ducts • Micropapillary – Papillary structures that extend into the lumen of the duct • Cribriform – Forms a rigid “cartwheel” pattern
- 36.
- 37.
- 39.
- 40.
- 41.
- 42.
- 45. Ductal Carcinoma inSitu, Axillary Metastases? • In theory the risk of metastasis is 0% • In reality, the risk is <3% – Invasive carcinoma outside the biopsy specimen or not in the plane of sections examined – Invasive carcinoma in a mastectomy specimen not sampled (mastectomy specimens are too large to entirely sample) – Invasive carcinoma not distinguishable at the light microscopic level (present at EM level) – Focus of invasive carcinoma overlooked
- 46. Lobular Carcinoma inSitu (LCIS) • LCIS considered a “marker of risk for invasive cancer in EITHER breast”. • Proliferation of neoplastic population of cells within the TDLU which usually fill and distend lobules, and may extend into adjacent ducts. • Low nuclear grade monotonous cells
- 47.
- 49. Invasive Carcinoma ofthe Breast Infiltrating ductal carcinoma is • the most common form of breast cancer. – It is characterized by invasion of the breast stroma by a malignant epithelial cell population derived from the terminal ducts. • Clinical: – Often forms a firm palpable mass – May cause skin dimpling (from traction on Cooper’s ligaments) or nipple retraction • Mammogram: – Often shows a stellate distortion, may have associated calcifications
- 50.
- 51. Infiltrating Ductal Carcinoma •Gross: – Firm, pale gray/white, gritty, often stellate • Micro: – Grading (Differentiation) depends on: • 1) degree of tubule formation • 2) nuclear grade • 3) mitotic rate – Desmoplastic stromal response: pronounced fibrosis – May have associated calcifications
- 52.
- 53.
- 54. Poorly differentiated infiltrating ductal carcinoma Highgrade nuclei High mitotic rate
- 55.
- 56. Infiltrating ductal carcinoma, invadingand replacing breast stroma
- 57. Invasion of adiposetissue of breast
- 58. Infiltrating Lobular Carcinoma •2nd most common form of invasive breast cancer. • Gross: – May or may not form a mass • Micro: – Single cells and linear profiles of malignant cells with low nuclear grade, may form a targetoid pattern, may show intracytoplasmic vacuoles, characteristically show minimal mitotic activity – LACKS a desmoplastic stromal response – Show LOSS of E-cadherin membrane staining, (a cytoplasmic membrane adhesion molecule)
- 59. Infiltrating Lobular Carcinoma •Often clinically and mammographically occult, and therefore microscopically more extensive than expected • Propensity to be multifocal and bilateral • Propensity to metastasize to unusual sites: – Gyn tract, GI tract • Same prognosis as infiltrating ductal carcinoma, when matched for stage • Usually ER/PR positive, C-erbB-2 negative • Pleomorphic lobular variant: high nuclear grade, more aggressive course
- 60.
- 61. INFILTRATING LOBULAR CA.,INFILTRATINGLOBULAR CA., ““INDIAN” FILE PATTERNINDIAN” FILE PATTERN
- 63. Positive cytokeratin stain confirmingthe epithelial nature of lobular carcinoma
- 64. Infiltrating ductal carcinoma, in contrast,with architectural distortion
- 65. Uncommon types ofInvasive Carcinoma of the Breast • Mucinous (Colloid) Carcinoma – Older women – Malignant cells floating in pools of mucin – Better prognosis than invasive ductal or lobular • Tubular Carcinoma – Younger women – Well differentiated, characterized by haphazardly arranged tubules – Excellent prognosis
- 66. INFILTRATING DUCTAL CA.,INFILTRATINGDUCTAL CA., ““TUBULAR” PATTERN or TYPETUBULAR” PATTERN or TYPE
- 67. INFILTRATING DUCTAL CA.,INFILTRATINGDUCTAL CA., MUCINOUS (COLLOID) PATTERN or TYPEMUCINOUS (COLLOID) PATTERN or TYPE
- 68.
- 69. INFILTRATING DUCTAL CA.,INFILTRATINGDUCTAL CA.,
- 71. Inflammatory Carcinoma • Definedas invasive carcinoma involving superficial dermal lymphatic spaces • Poor prognosis (T3 disease) • Erythema and induration of the skin, so called “inflammatory changes” – Peau d’orange-dimpling of involved skin due to retraction caused by lymphatic involvement and obstruction
- 72.
- 73.
- 76. Paget’s Disease • Invasionof the SKIN of the nipple or areola by malignant cells, singly or in small nests • Associated with an underlying cancer: either IN SITU OR INVASIVE carcinoma • Clinically-erythema, scaling, ulceration
- 77.
- 78. Paget’s Disease ofthe Nipple Intra-epidermal adenocarcinoma cells
- 79. Breast cancer showingan inverted nipple, lump and skin dimpling.
- 80. BREAST CANCER TNM stagegroupingTNM stage grouping Stage 0Stage 0 Tis N0 M0 Stage IStage I T1* N0 M0 Stage IIAStage IIA T0 N1 M0 T1* N1** M0 T2 N0 M0 Stage IIBStage IIB T2 N1 M0 T3 N0 M0 Stage IIIAStage IIIA T0, T1,* T2 N2 M0 T3 N1, N2 M0 Stage IIIBStage IIIB T4 Any N M0 Any T N3 M0 Stage IVStage IV Any T Any N M1 * Note: T1 includes T1 mic. ** Note: The prognosis of patients with N1a is similar to that of patients with pN0. AJCC® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.
- 81. BREAST CANCER Tumor definitionsTumordefinitions • TX Primary tumor cannot be assessed • T0 No evidence of primary tumor • Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple with no tumor • T1 Tumor 2 cm or less in its greatest diameter T1mic Microinvasion more than 0.1 cm or less in its greatest diameter T1a Tumor more than 0.1 cm but not more than 0.5 cm in its greatest diameter T1b Tumor more than 0.5 cm but not more than 1 cm in its greatest diameter T1c Tumor more than 1 cm but not more than 2 cm in its greatest diameter • T2 Tumor more than 2 cm but not more than 5 cm in its greatest diameter • T3 Tumor more than 5 cm in its greatest diameter • T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below T4a Extension to chest wall T4b Edema (including peau d’orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast T4c Both (T4a and T4b) T4d Inflammatory carcinoma AJCC® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.
- 82. BREAST CANCER Commonly assessedprognosticCommonly assessed prognostic factorsfactors Slamon DJ. Chemotherapy Foundation. 1999;46. Winer E, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1651-1717. Nuclear grade Estrogen/progesterone receptors HER2/neu overexpression Number of positive axillary nodes Tumor size Lymphatic and vascular invasion Histologic tumor type Histologic grade
- 83. BREAST CANCER 5-year survivalas function of the number5-year survival as function of the number of positive axillary lymph nodesof positive axillary lymph nodes 0% 20% 40% 60% 80% 5-YearSurvival5-YearSurvival 0 1 2 3 4 5 6-10 11-15 16-20 >20 Number of Positive NodesNumber of Positive Nodes Harris J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1557-1616.
- 84. Other Prognostic Markers •DNA content (DNA ploidy) • Tumor suppressor genes (p53, others) • Angiogenesis (Microvessel density) • Proteases • Gene profiling by microarrays***
- 85. c-erbB-2 (HER-2/neu) • Oncogenewhich shares extensive sequence homology with epidermal growth factor receptor (EGFR)
- 86. Strong overexpression of HER-2/neu(c-erbB-2) at cell surfaces
- 87. HER-2 Gene Amplificationby FISH
- 88. BREAST CANCER HER-2/neuHER-2/neu overexpressionoverexpression •There is a significant decrease of 5-year survival in patients whose tumors overexpress HER-2/neu • This decrease in survival for both node-positive and node-negative patients • In vitro studies show that HER-2/neu overexpression increases the following cell activities in malignant breast epithelial cells: DNA synthesis Cell growth Anchorage-dependent growth Tumorgencity Metastatic potential Slamon DJ. Chemotherapy Foundation Symposium. 1999;46. Abstract 39. Goldenberg MM. Clinical Therapeutics. 1999;21(2):309- 318.
- 89.
- 91. Total Cancers PerCent In Situ Carcinoma 15–30 Ductal carcinoma in situ, DCIS 80 Lobular carcinoma in situ, LCIS 20 Invasive Carcinoma 70–85 No special type carcinoma ("ductal") 79 Lobular carcinoma 10 Tubular/cribriform carcinoma (Better prognosis than average) 6 Mucinous (colloid) carcinoma (Better prognosis than average) 2 Medullary carcinoma (Better prognosis than average) 2 Papillary carcinoma 1 Metaplastic carcinoma, (Squamous)
- 92. MALE BREAST • GYNECOMASTIA(related to hyperestrogenism) • CARCINOMA (1% of ♀ )
- 93. Gynecomastia • Reversible enlargementof the male breast • Unilateral or bilateral subareolar mass +/-pain • Ductal and stromal proliferation • Etiology- Systemic disease-hyperthyroidism, cirrhosis, chronic renal failure – Drugs-cimetidine, digitalis, tricyclic antidepressants, marijuana – Neoplasms-pulmonary, testicular germ cell tumors – Hypogonadism: testicular atrophy, exogenous estrogen, Klinefelter’s syndrome
- 94.
- 95.
- 96.
- 97. Carcinoma of theMale Breast • < 1% of breast cancer • Infiltrating ductal carcinoma is by far the most common type • Tends to present at a more advanced stage – Less fat and breast tissue, therefore involvement of chest wall occurs earlier • Similar prognosis when matched, stage for stage, with female breast cancer • Associated with inherited BRCA2 mutation
- 98. Breast Anatomy andLocation of Disease Processes
- 100. Multistage Model of Carcinogenesis Normal Atypical Hyperplasia Carcinoma InSitu Invasive Carcinoma Metastasis
- 101. “Skip Stage” Modelof Carcinogenesis Normal Atypical Hyperplasia Carcinoma In Situ Invasive Carcinoma Metastasis
- 102. “Skip Stage” Modelof Carcinogenesis Normal Atypical Hyperplasia Carcinoma In Situ Invasive Carcinoma Metastasis
- 103.
- 104. Microdissection of a singleduct of DCIS Microdissection of single cells Microdissection Methodologies
Editor's Notes
- #2 Note the tiny little “pits” in the orange peel.
- #4 Know the 2 major arteries (lateral and internal thoracic) and three lymph node groups which supply the breast.
- #5 Know the 2 major arteries (lateral and internal thoracic) and three lymph node groups (axillary, internal thoracic (mammary) and supraclavicular) which supply the breast.
- #56 90% of infiltrating breast carcinomas are simply called “Infiltrating Ductal Carcinoma” on the pathology report.
- #63 Indian file, British or American origin?
- #67 The “tubular” pattern is somewhat better in behavior.
- #68 The mucinous variant is also somewhat better in behavior.
- #70 The medullary variant (i.e., lots of immune calls or lymphocytes) is also somewhat better in behavior. If you want to think that the reason for this is because there are a lot of immune cells “fighting” the tumor cells, you might be right.
- #73 Inflammatory carcinoma with its classic peau d’orange appearance.
- #75 Note the tiny little “pits” in the orange peel.
- #81 Breast Cancer: TNM Stage Grouping The current breast cancer staging system is the 5th edition of the American Joint Committee on Cancer (AJCC) system, sponsored jointly by the American Cancer Society, the National Cancer Institute, the College of American Pathologists, and the American Colleges of Physicians, Radiology, and Surgeons. The AJCC system is a clinical and pathologic staging system based on the TNM system. T refers to tumor, N to nodes, and M to metastasis.
- #82 Tumor definitions This slide further delineates the breakdown in staging of the primary tumor.
- #83 Breast Cancer: Commonly Assessed Prognostic Factors A prognostic factor is defined as a biologic or clinical measurement associated with disease-free or overall survival in the absence of adjuvant systemic therapy. The most useful prognostic factor is the number of positive axillary lymph nodes based on a level I/II (or higher) axillary dissection and detailed histologic evaluation. Tumor size correlates with the number of involved nodes, but has independent prognostic significance.
- #84 Breast Cancer: 5-year Survival as Function of the Number of Positive Axillary Lymph Nodes As the number of involved lymph nodes increases, 5-year survival rates decrease.
- #89 HER-2/neu Overexpression The HER-2/neu proto-oncogene is now known to have prognostic value. Approximately 25% to 30% of all breast cancer patients overexpress HER-2/neu. These patients, whether node-negative or node-positive, have been found to have a significant decrease in 5-year survival rates. In vitro studies have shown that HER-2/neu overexpression increases DNA synthesis, cell growth, anchorage-dependent growth, tumorigencity, and metastatic potential in human breast epithelial cells.
- #96 Note that no matter how big a male’s breasts may get, they should never for m lobules, but just end as blunt ducts.