Transcript breast cancers

BREAST
TUMORS
Ch. 18
p (704 – 713)
LYMPHATIC
DRAINAGE
AXILLARY (MOSTLY)
INTERNAL MAMMARY
SUPRACLAVICULAR
Fibroadenoma
Fibroadenoma
Cleft
Intraductal papilloma
Phyllodes tumor
Cystosarcoma phyllodes
• arises from the interlobular stroma,
• In contrast to fibroadenomas, it is
uncommon & is often larger in size
and more cellular.
Projections of stroma
between the ducts
create the leaflike pattern
for which these tumors
are named (from the
Greek word phyllodes,
meaning “leaflike”).
One in eight women will get breast cancer, and one third of
women with breast cancer will die of the disease
Causes of Breast Cancer
• Hormonal
• Genetic
• Environmental
Risk Factors for Breast Cancer
 Estrogen, (F / M = 100 / 1)
• Menstrual history & Reproductive history.
- Long & Strong exposure; (Early menarch & late Menopause)
- Pregnancy; (Nilliparous, Late 1st pregnancy)
- Lactation, decrease risk
- Oophorectomy (decrease the risk to 1/3)
 Age (Peak; 60 – 70y)
 Family historty; (1st degree, early age, bilat)/ 2 folds
• Benign breast disease (Hx of previous breast pathology)
- Fibrocystic disease +/- epith hyperplasia +/- atypia.
- CIS
- 0X, 2X, 5X, 10X
• Geography
 In 2002 Estrogen declared as carcinogen by National
Toxicology Program
The two most common risk factors for breast cancer are:
Being female
Getting older
Breast Cancer (C50): 2011-2013
Other Risk Factors for Breast Cancer
• Oral contraceptive
• Radiation Exposure
• Carcinoma of the contralateral breast or
endometrium
• Obesity
• High fat diet
• Alcohol
• Smoking
• Environmental Toxins
• Breast augmentation.
• ABORTIONS?
Genetic changes
Proto-oncogen
• HER2/NEU
- 30%
- Poor prognosis
• RAS & MYC
Tumor suppressor gene
• Rb,
• p53,
• ER gene inactivation
 Gene 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.
Genetic Factors
Inherited Mutations (10%)
• 10% breast cancers are familial
- 90% are 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:
• First degree relative
• relatives with BILATERAL disease
• relatives affected at a YOUNG AGE
 BRCA1 Gene (17q21)
• “Breast-Ovarian” cancer gene
• “Early onset” breast cancer gene
•
High grade breast Ca.
•
Responsible for up to 50% of “inherited”
breast cancers, (5% of all breast cancers)
 BRCA2 Gene (13q); “Male Breast Cancer”
gene
Breast Cancer Pathology
Ductal Ca. (85 – 93%)
Lobular Ca. (7 – 15%)
In Situ Carcinomas (CIS) (15 )
Invasive Carcinomas (85%)
Special Subtypes (> 5%)
Ductal Carcinoma in Situ
• Clinical:
– DCIS usually does not present as a palpable
mass.
• Mammogram:
– The most common method of detection is by
identifying mammographic calcifications
• MRI
• FNA
• Biopsy
-Calcification,
-50 - 60% in ca.
-20% in benign
Mammography showing a normal breast (left) and a cancerous breast
(right).
Mammography is the standard for detection of DCIS.
MRI could help especially in high-grade DCIS
Cribriforming DCIS
Micropapillary
DCIS
Solid DCIS,
Comedoca
Lobular carcinoma in situ
Multicentric , Bilateral
Invasive Duct Ca
90% of infiltrating breast carcinomas
Infiltrating Ductal Carcinoma
• Gross: Firm & gritty, pale - white
• Micro:
Grading;
1) tubule formation
2) nuclear grade
3) mitotic rate
- Desmoplastic stromal
response (fibrosis).
Infiltrating Lobular Carcinoma
• 2nd most common
invasive breast ca.
• Multifocal & bilateral
• Same prognosis as
infiltrating ductal ca, when
matched for stage
• - Single cells & linear
profiles of malignant cells
with “Indian file pattern”
- Dense fibrous tissue.
Invasive ductal carcinoma
Invasive lobular carcinoma
Infiltrating ductal ca. Tubular type
V. Good prognosis
Infiltrating ductal ca. Mucinous type
Good prognosis
Mucin
Infiltrating ductal ca. Medullary type
(lots of lymphocytes)
better prognosis
Infiltrating ductal ca. Mucinous type
Good prognosis
Inflammatory Carcinoma
invasive carcinoma involving
superficial dermal lymphatic.
Erythema & induration
Peau d’orange of involved skin
caused by lymphatic involvement
and obstruction.
Inflammatory carcinoma: dermal lymphatic
spaces containing tumor cells
Paget’s Disease
• Invasion of the SKIN of nipple
or areola by malignant cells.
• Associated with in situ or
invasive ca
• erythema, scaling, ulceration
Intra-epidermal
malignant cells
Extramammary Paget disease
Tumor grade
 HISTOLOGY
• WHO grading
Well differentiated
Mod. differentiated
Poor differentiated
•
B-R grading
Glands
Nuclei
Mitosis
 CYTOLOGY
– Nuclei
•
•
•
•
Size
Membrane
Chromatin
Nucleoli
Nuclear grade 1-3
Good correlation with histologic
grade
BREAST CANCER
TNM stage grouping
Stage 0
Tis
N0
M0
Stage I
T1*
N0
M0
Stage IIA
T0
T1*
T2
N1
N1**
N0
M0
M0
M0
Stage IIB
T2
T3
N1
N0
M0
M0
Stage IIIA
T0, T1,* T2
T3
N2
N1, N2
M0
M0
Stage IIIB
T4
Any T
Any N
N3
M0
M0
Stage 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.
BREAST CANCER
TNM stage grouping
• 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.
BREAST CANCER
Commonly assessed prognostic
factors
Number of positive axillary nodes
Nuclear grade
Tumor size
Estrogen/progesterone
receptors
Lymphatic and vascular invasion
HER2/neu overexpression
Histologic tumor type
Histologic grade
Molecular changes
Slamon DJ. Chemotherapy Foundation. 1999;46.
Winer E, et al. Cancer: Principles & Practice of Oncology. 6th
ed. 2001;1651-1717.
BREAST CANCER
5-year survival as function of the number
of positive axillary lymph nodes
5-Year Survival
80%
60%
40%
20%
0%
0
1
2
3
4
5
6-10 11-15 16-20 >20
Number of Positive Nodes
Harris J, et al. Cancer: Principles & Practice of
Oncology. 5th ed. 1997;1557-1616.
Histopathologic Grade
If B-R score is 3, 4, 5 = low grade
If B-R score is 6, 7 = Intermediate grade
If B-R score is 8, 9 = High grade
BREAST CANCER
5-year survival as function of tumor grade
Histologic grade
c-erbB-2 (HER-2/neu)
• Oncogene which shares extensive sequence
homology with epidermal growth factor receptor
(EGFR)
Total Cancers
Per Cent
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)
The “Triple Test”:
–
–
–
Clinical picture
Mammographic findings
Cytologic findings
MALE BREAST
• GYNECOMASTIA (related to
hyperestrogenism)
Gynecomastia
• Reversible enlargement of male
breast
• Unilateral or bilateral subareolar
mass +/-pain
• Ductal and stromal proliferation,
NO lobules
• Etiology
Periductal
edema
- Systemic disease –
hyperthyroidism, cirrhosis, CRF
– Drugs; cimetidine, digitalis,
tricyclic antidepressants,
marijuana
– Neoplasms -pulmonary, testicular
germ cell tumors
– Hypogonadism: testicular atrophy,
exogenous estrogen, Klinefelter’s
syndrome
Epithelial hyperplasia
THE MALE BREAST
Carcinoma
 Very rare occurrence; female cancer
to male cancer ratio approx 100:1
 Pathology and behavior is similar to
cancers seen in women although with
less breast tissue, skin involvement is
more frequent
 Associated with inherited BRCA2 mutation
Lecture Objectives
Can you?
1. Discuss the etiology/pathologic features of
different forms of benign non-neoplastic and
neoplastic breast disease.
2. List the benign breast diseases that increase a
patient’s risk of developing breast cancer and
classify these conditions by the degree of risk.
Lecture Objectives
Can you?
3. Outline other risk factors predisposing to breast
cancer & incidence/prevalence of breast cancer.
4. Classify breast cancer into histologic subtypes
and describe the pathologic features of each.
5. List the prognostic factors for breast cancer.