Breast carcinoma etiology and classification.pptx

lecture notes for medical students

1. Tips on using my ppt. You can freely download, edit, modify and put your name etc. Don’t be concerned about number of slides. Half the slides are blanks except for the title. First show the blank slides (eg. Aetiology ) > Ask students what they already know about ethology of today's topic. > Then show next slide which enumerates aetiologies. At the end rerun the show – show blank> ask questions > show next slide. This will be an ACTIVE LEARNING SESSION x three revisions. Good for self study also. See notes for bibliography.

2. Learning Objectives

3. Learning Objectives Introduction & History Relevant Anatomy, Physiology Aetiology Pathophysiology Pathology Classification Clinical Features Investigations Management Prevention Guidelines Take home messages

4. Introduction & History.

5. Introduction & History. Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the 2nd leading cause of cancer death among women. 1 in 8 urban women will catch Ca. Breast.

6. Aetiology

7. Aetiology Idiopathic Congenital/ Genetic Nutritional Deficiency/excess Traumatic Infections /Infestation Autoimmune Neoplastic (Benign/Malignant) Degenerative / lifestyle Iatrogenic Psychosomatic Poisoning/ Toxins/ Drug induced

8. Etiology Idiopathic Congenital/ Genetic Traumatic Infections /Infestation Autoimmune Neoplastic (Benign/ Malignant ) Degenerative Iatrogenic

9. Etiology Risk factors -seven broad categories— Age Family history of breast cancer Hormonal factors Proliferative breast disease Irradiation of the breast or chest wall at an early age Personal history of malignancy Lifestyle factors.

10. Etiology Risk Factors That Cannot be Modified Increasing age Female gender Reproductive Risk Factors Family history of breast cancer Genetic predisposition ( BRCA1  and  BRCA2  mutation carriers) Personal history of breast cancer Race, ethnicity (white women have increased risk compared with others) History of radiation exposure

11. Etiology Risk Factors That Could be Modified Reproductive factors Age at first live birth (full-term pregnancy after age 30 yr) Parity Lack of breast-feeding Obesity Alcohol consumption Tobacco smoking Use of hormone replacement therapy Decreased physical activity Shift work (night shifts)

12. Etiology Histologic Risk Factors Proliferative breast disease ADH- atypical ductal hyperplasia ALH-atypical lobular hyperplasia LCIS

13. Increasing Age

14. Increasing Age Rare in persons younger than 20 years Gradually increases to 1 in 8 by age 80 years

15. Personal History of Breast Cancer

16. Personal History of Breast Cancer Second primary cancer in the contralateral breast. 0.5% to 1%/year in younger patients to 0.2% in older patients

17. Family history of breast cancer First-degree relatives (mothers, sisters, and daughters) of patients with breast cancer have a twofold to threefold excess risk. In families with multiple affected members, particularly with bilateral and early-onset cancer, the absolute risk in first-degree relatives approaches 50%, consistent with an autosomal dominant mode of inheritance in these families.

18. Genetic Risk Factors

19. Genetic Risk Factors Responsible for 5% to 10% of all breast cancer cases, but they may account for 25% of cases in women younger than 30 years.

20. Genetic Risk Factors BRCA1 & BRCA2 Genes These are tumor suppressor genes and their mutations cause cancers. BRCA1- chromosome 17 mutations 40% of familial breast cancers -Also increased risk for ovarian cancer BRCA2- mutations 30% of familial breast cancers. Also increased breast cancer risk in males.   Mutations of the E-cadherin gene ( CDH1 )

21. Breast Cancer Prevention for  BRCA1 and  BRCA2  Mutation Carriers For women who carry a mutation in the  BRCA1  or  BRCA2  genes, the risk of breast cancer by age 70 years is approximately 65% and 45%, respectively.  Breast cancer prevention bilateral mastectomy and premenopausal bilateral salpingo-oophorectomy (BSO). 

22. Breast Cancer Prevention for  BRCA1 and  BRCA2  Mutation Carriers Who decline bilateral mastectomy, or choose to delay it until they are older, tamoxifen should be considered, 

23. Genetic testing Incidence of clinically significant  BRCA1  or  BRCA2 mutations in the general population is approximately 1 in 300 to 500.

24. Indications for genetic testing Personal history of young age at diagnosis (<50 years) Bilateral breast cancer Breast and ovarian cancer in the same individual Male breast cancer.

25. Indications for genetic testing Family history (maternal or paternal) of two or more individuals with breast and ovarian cancer Close male relative with breast cancer Close relative with early-onset breast or ovarian cancer (<50 years) Known  BRCA1  or  BRCA2  mutation.

26. Reproductive Risk Factors

27. Reproductive Risk Factors Early age at menarche (onset of menses prior to age 12 yr ) F irst live childbirth after age 30 Older age at menopause (onset beyond age 55 yr ) Nulliparity

28. Management of High-Risk Patients Prophylactic contralateral mastectomy. ? Close surveillance with clinical breast examination Mammography Breast MRI Interventions to reduce risk, Chemoprevention with tamoxifen or raloxifene Bilateral prophylactic mastectomy and/or oophorectomy .

29. Exogenous Hormone Use

30. Exogenous Hormone Use OCs and HRT HRT- women receiving combination HRT with estrogen and progesterone for 5 years have approximately a 20% increased risk for the development of breast cancer. Women who take estrogen -only formulations (because of previous hysterectomy) do not appear to suffer an increased incidence of breast cancer.

31. Exogenous Hormone Use OCs Aggregate data suggest the possibility of a 1.5 fold increased risk of breast cancer in young women who have used OCs for 3 years before an FTP with possibly slightly higher risks with longer durations of use

32. Lifestyle-related

33. Lifestyle-related Drinking alcohol Being overweight or obese after menopause  Not being physically active Not breastfeeding Not having children F irst child after age 30 Night shift  

34. Aetiology of Aetiology

35. Aetiology of Aetiology Idiopathic Congenital/ Genetic Nutritional Deficiency/excess Traumatic Infections /Infestation Autoimmune Neoplastic (Benign/Malignant) Degenerative / lifestyle Iatrogenic Psychosomatic Poisoning/ Toxins/ Drug induced

36. Pathophysiology

37. Pathophysiology Etiopathogenesis is that invasive cancers arise through a series of molecular alterations at the cell level. These alterations result in cells with immortal features and uncontrolled growth. About 100 genet etic changes need to occur to transform cell into malignant. Which 100 differs from patients to patients means not two patients have same carcinoma breast.

38. Classification

39. Classification Classification Vs. Grade Vs. Staging. Classification is histological types of cancer. Grading is measurement of aggressiveness of malignancy. Staging is measurement of how much spread has occurred.

40. Pathological Classification Noninvasive Epithelial Cancers Invasive Epithelial Cancers Mixed Connective and Epithelial Tumors

41. Classification Noninvasive Epithelial Cancers LCIS- Lobular Carcinoma In situ DCIS –Ductal Carcinoma In Situ or intraductal carcinoma Papillary Cribriform, Solid Comedo types

42. Classification Invasive Epithelial Cancers Invasive lobular carcinoma (10%) Invasive ductal carcinoma Invasive ductal carcinoma, infiltrating ductal carcinoma NOS (not otherwise specified) (50-70%) Tubular carcinoma (2%-3%) Mucinous or colloid carcinoma (2%-3%) Medullary carcinoma (5%) Invasive cribriform carcinoma (1%-3%) Invasive papillary carcinoma (1%-2%) Adenoid cystic carcinoma (1%) Metaplastic carcinoma (1%) Inflammatory breast cancer

43. Classification Modern classification schemes are replacing these older morphologic descriptions with the determination of molecular markers and breast cancer subtype by microarray analysis. Categorizing breast cancer according to the expression of molecular targets of treatments is practical. 21-gene test MammaPrint assay. analyzes data from 70 genes to develop a risk profile. The test provides a simple readout of low-risk or high-risk disease

44. Classification Molecular Markers and Breast Cancer Subtypes I mmunohistochemical detection- triple-negative breast cancers- high grade, ER- and progesterone receptor (PR)–negative, and negative for the human epidermal growth factor receptor 2 (HER-2/neu; HER-2, erb-B2/neu protein) cell surface receptor basal-like breast cancer  describes a specific subtype of breast cancer as defined by microarray analysis

45. Classification Mixed Connective and Epithelial Tumors Phyllodes tumors, benign and malignant Carcinosarcoma Angiosarcoma Adenocarcinoma

46. Classification Grade- low grade cancers tend to be less aggressive than high grade cancers.  Nottingham Histologic Score system (also termed “the Elston-Ellis modification of Scarff-Bloom-Richardson grading system.

47. Grade Three histologic features are used The amount of gland formation (the cell “differentiation,” or how well the tumor cells are trying to recreate normal glands) The nuclear features (the degree of "pleomorphism" or how "ugly" the tumor cells look) The mitotic activity (how much the tumor cells are dividing, or proliferating)

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49. Get this ppt in mobile

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