1. Dr.Nik Makretsov, MD, PhD, FRCPC
BREAST DISEASES
Dr.Nik Makretsov, MD, PhD, FRCPC
Clinical Assistant professor, UBC
St.Paul’s Hospital –Path lab
For Medical Technologists Feb 2013

2. Breast pathology in a nutshell
1 hour for:
Breast cancer - invasive
Breast cancer non-invasive (in situ)
Benign conditions

3. Breast – typical exocrine gland

5. Breast pathology in a nutshell
1 hour for:
Breast cancer- invasive
Breast cancer non-invasive
Benign conditions

7. Invasive Breast Cancer
You must know this:
1st most commonly diagnosed cancer in women
2 nd major killer-cancer of women:
Fairly common disease:
New diagnoses per year in Canada
Deaths per year in Canada
NL dx per year
NL deaths ?

8. Invasive Breast ca vs other cancers: Incidence Trends
Prostate
Lung
Breast
Colon Lung

9. Breast cancer: Incidence vs Mortality

11. Breast ca vs major cancers: Survival

12. Breast ca vs Major Cancers: Survival vs Age
Prostate
Breast cancer
Colorectal cancer
Lung cancer

13. Breast cancers: clinical trends

14. Chances of Developing Breast Cancer (F)
By 25 years >1 in 1,000
By 50 years in
By 75 years in
By 90 years in
risk increases with age

15. Breast diseases: common symptoms

16. Breast diseases: symptoms vs screening: what to expect

17. Breast Cancer: Team Management
European Model: Breast Units
Radiologist
Pathologist
Surgeon
Medical oncologist
Radiation oncologist
Psycho-social support/Primary Care

18. Invasive Breast
Cancer

19. Most common histotype: Invasive Ductal Cancer –biopsy

20. Second common histotype: Invasive lobular cancer - biopsy
Other: Rare types- several dozens. Clinical significance ???

21. Prognostic vs Predictive Factors in Cancer
Prognostic - predict outcome, i.e. survival
Predictive - predict response to cancer
therapy

22. Major Prognostic Factors for Breast Cancer
Invasive carcinoma or in situ disease.
Distant metastases.
Lymph node metastases.
Tumor size.
Locally advanced disease.
Inflammatory carcinoma.

23. Minor (but nasty) Prognostic Factors.
Histologic subtypes.
Tumor grade (tubules/nuclei/mitosis).
Estrogen and progesterone receptors.
Lymphovascular invasion (LVI).
Proliferative rate.
DNA content.

24. Predictive Factors in Breast Cancer
1.Steroid Hormone Receptors in Tumor
(Estrogene and Progesterone)
=predict response to antiestrogene threrapy
2.Her2 (or Her2neu)
(tyrosine kinase receptor, epidermal growth factor familiy)
=predict response to Herceptin

25. Issues with Predictive Factors= Immunohistochemistry
Not black and white tests:
-ER/PR/HEr2 always show a dynamic range in different patients (I.e no “normal” values), cut points instead
-Tests require standardization
-Test require constant quality control
Canadian guidelines are still under development.
Immunohistochemistry is an emerging art vs science.
Evidence supports it is superior to older technics.

26. Major Predictive Factors
Protein overexpressed when Gene amplified
Her 2
ER or PR

27. Estrogene/ Progesterone Receptors
Negative?
Positive
Weak Positive
Positive

28. Her2
Positive
Equivocal- needs FISH
Negative

29. FAMILIAL BREAST CANCER
Only 5-10% of all breast cancers due to germline mutation
BRCA1/2 gene (tumor suppressor, DNA repair)
Other syndromes(genes) loosely associated to familial breast cancer:
Li-Fraumani (P53), AT, Cowdens (PTEN), Familial stomach cancer (E-Cadherin)
Many familial breast ca have no known genetic abnormality - area of active research.

31. OTHER BREAST MALIGNANCIES (>1%)
Phyllodes Tumour-primary breast lesion
Angisarcoma- post radiation
Lymphangiosarcoma- post axillary dissection (due to lymphostasis)
Lymphoma
Other sarcomas
Metastasis from other sites

32. Phyllodes tumor: from benign to malignant

34. Breast pathology in a nutshell
1 hour for:
Breast cancer invasive
Breast cancer
non-invasive (in situ)
Benign conditions

35. Carcinoma In Situ : Ductal- DCIS and Lobular- LCIS do not invade basement membrane of ducts/lobules- spreads along the ducts/lobules

36. DCIS- mammography
Microcalcifications:
Helpful sign

37. DCIS on biopsy- mcalcs

38. DCIS on biopsy
=major feature: does not extend beyond basement membrane

39. DCIS on biopsy
=major feature: does not extend beyond basement membrane

40. Breast ca Natural History

41. Carcinoma in situ and atypias
CIS: 8-10 risk of invasive cancer
DCIS-ductal carcinoma in situ
=always treat!
LCIS=lobular carcinoma in situ
= Treat vs follow-up?
Atypias: risk of invasive cancer
Atypical Ductal Hyperplasia =Treat
Atypical Lobular Hyperplasia =follow-up
Flat apithelial atypia =?follow-up

43. Breast pathology in a nutshell
1 hour for:
Breast cancer invasive
Breast cancer non-invasive
Benign Breast Diseases
-Inflammation
-Fibrocystic change
-Fibroadenoma
-Developmental

44. Breast pathology in a nutshell
1 hour for:
Breast cancer invasive
Breast cancer non-invasive
Benign Breast Diseases
-Inflammation
-Fibrocystic change
-Fibroadenoma
-Developmental

45. Inflammation- Breast Abscess

46. Fibrocystic change
Very common
Totally benign
No risk of cancer

47. Benign Breast Diseases
Fibroadenoma

48. Fibroadenoma

49. Fibroadenoma on biopsy
Common, Benign, Negligible risk of cancer

50. Developmental problems
Milkline Remnants
Accessory Axillary Breast Tissue
Congenital Nipple Inversion.
Macromastia.
=Relatively rare. Benign.
Solution: plastic surgery
Reconstruction or Augmentation.

51. MALE BREAST 1.GYNECOMASTIA- ESTROGENIC DISBALANCE, BENIGN
2.CANCER: rare, <1% of all breast ca
SIMILAR TO FEMALE,
BUT RARE and UNEXPECTED
= LATE DIAGNOSIS

53. CANCER RESEARCH

54. News Last Decade: Molecular signatures of breast diseases: future of
breast pathology
-cDNA array technology,
-microRNA signatures:
tell us more
then routine histology
-once prices drop !?

55. Thank you Give me you feedback:
The clearest point of this lecture was:
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56. Sources used:
Robbin’s Pathologic Basis of Diseases, 7th Ed
Author’s practice cases/photos