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

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

Breast – typical exocrine gland

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

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 22.000+ per year in Canada Deaths 5.000+ per year in Canada NL dx 350+ per year NL deaths ?

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

Breast cancer: Incidence vs Mortality

Breast ca vs major cancers: Survival

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

Breast cancers: clinical trends

Chances of Developing Breast Cancer (F) By 25 years >1 in 1,000 By 50 years 1 in 63 By 75 years 1 in 15 By 90 years 1 in 9 risk increases with age

Breast diseases: common symptoms

Breast diseases: symptoms vs screening: what to expect

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

Invasive Breast Cancer

Most common histotype: Invasive Ductal Cancer –biopsy

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

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

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

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

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

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.

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

Estrogene/ Progesterone Receptors Negative? Positive Weak Positive Positive

Her2 Positive Equivocal- needs FISH Negative

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.

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

Phyllodes tumor: from benign to malignant

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

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

DCIS- mammography Microcalcifications: Helpful sign

DCIS on biopsy- mcalcs

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

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

Breast ca Natural History

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: 4-5 risk of invasive cancer Atypical Ductal Hyperplasia =Treat Atypical Lobular Hyperplasia =follow-up Flat apithelial atypia =?follow-up

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

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

Inflammation- Breast Abscess

Fibrocystic change Very common Totally benign No risk of cancer

Benign Breast Diseases Fibroadenoma

Fibroadenoma

Fibroadenoma on biopsy Common, Benign, Negligible risk of cancer

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

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

CANCER RESEARCH

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 !?

Thank you Give me you feedback: The clearest point of this lecture was: The muddiest point of this lecture was:

Sources used: Robbin’s Pathologic Basis of Diseases, 7th Ed Author’s practice cases/photos