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The Breast: Sara Sukumar Pathobiology, September 6, 2013
The Breast: Sara Sukumar Pathobiology, September 6, 2013
Sara Sukumar
Pathobiology,
September 6, 2013
1
Breast Cancer
Breast cancer is second only to lung cancer as
a cause of cancer deaths in American women
One out of every eight women
will be diagnosed with breast
cancer in 2011
Fortunately, radical mastectomy
(surgical removal) is rarely
needed today with better
treatment options
2
Trends since 1950 in
age-standardized
death rates
comparing breast and
selected other types
of cancer, among
women in the USA
5
Outline- Part 2
6
Development of the Breast Ductal Tree
Occurs mainly after birth
Female Breast Anatomy
lobes
ducts
lymph nodes
8
Stucture of the Breast
Breast has no
muscle tissue
There are muscles
underneath the
breasts separating
them from the ribs
9
Breast Gland
14
Lymphatic System
Lymph ducts: Drain fluid
that carries white blood
cells (that fight disease)
Lymph node Lymph duct from the breast tissues
into lymph nodes under
the armpit and behind
the breastbone
Lymph nodes: Filter
harmful bacteria and
play a key role in
fighting off infection
A network of vessels
15
Three Types of Vessels
1
Lobules Ducts Nipple Milk
3
Lymph Lymph
Nodes Vessels
Bacteria
2
Blood Cell life
Vessels
16
Signs and Symptoms
Most common:
lump or
thickening in
breast. Often
painless
19
Causes
7/10/2017 20
Normal Breast
Breast profile
A ducts
B lobules
C dilated section of duct to hold milk
D nipple
E fat
F pectoralis major muscle
G chest wall/rib cage
Enlargement
A normal duct cells
B basement membrane (duct wall)
C lumen (center of duct)
Ductal
cancer
cells
Normal
ductal
cell
22
Illustration Mary K. Bryson
Invasive Ductal Carcinoma (IDC
80% of breast cancer)
Ductal cancer
cells breaking
through the
wall
24
Invasive Lobular Carcinoma (ILC)
Lobular cancer
cells breaking
through the
wall
Illustration Mary K. Bryson 25
Cancer Can also Invade Lymph or Blood
Vessels-Metastatic breast cancer
Cancer cells
invade
lymph duct
Cancer cells
invade
blood vessel
27
Breast Cancer Risk Factors
unalterable factors
Age
GENDER - All
Reproductive
women are
History
Family/Personal at risk
History
Menstrual
Race History
Radiation
Treatment with Genetic
DES Factors
Breast Cancer Risk Factors
that can be controlled
Obesity
All Not having
Exercise women are children
at risk
Breastfeeding
Birth Control
Hormone Pills
Alcohol Replacement
Therapy
Potential Applications for
Breast Cancer Biology
15%-20%
5%10% 5%10%
breast cancer
(50%-85%)
male breast cancer
(6%)
ovarian cancer
(10%-20%)
100 44 36 48 Cysteine-rich
domains
Now available--$3400
Should we use it?
For whom?
How?
Candidate Gene Selection
From ~40,000 genes
250
cancer-related
candidate genes
*Sources include:
1) Van 't Veer et al, Nature 415:530, 2002
2) Sorlie et al, Proc. Natl. Acad. Sci. USA 98:10869,
3) Ramaswamy et al, Nature Genetics 33:4, 2003
Paik etet
4) Gruvberger al,al,
SABCS 2003 Res. 61:5979, 2001
Cancer
Three Breast Cancer Studies Used to Select 16
Cancer and 5 Reference Genes
PROLIFERATION ESTROGEN
Ki-67 HER2 ER
STK15 GRB7 PGR
Survivin HER2 Bcl2
Cyclin B1 SCUBE2
MYBL2
GSTM1
REFERENCE
INVASION CD68 Beta-actin
Stromelysin 3 GAPDH
Cathepsin L2 RPLPO
BAG1
GUS
Best RT-PCR performance
and most robust predictors TFRC
Paik et al NEJM 2004
Three Breast Cancer Studies Used to
Develop Recurrence Score (RS) Algorithm
RS = + 0.47 x HER2 Group Score
- 0.34 x ER Group Score
+ 1.04 x Proliferation Group Score
+ 0.10 x Invasion Group Score
+ 0.05 x CD68
- 0.08 x GSTM1
- 0.07 x BAG1
Recurrence
RS (0 100)
Category
Low risk < 18
Intermediate risk 18 30
High risk 31
Paik et al, SABCS 2003
Low recurrence score means:
Clear benefit from tamoxifen
No benefit from chemotherapy
1.0
T CT
P
0.8
0.6
DRFS
0.4
N
0.2 Placebo (B14) 355
Tam (B14) 668
Tam (B20) 227
Tam + Chemo (B20) 424
0.0
0 2 4 6 8 10
Years
1.0
T CT
0.8
0.6
P
DRFS
0.4
N
0.2 Placebo (B14) 355
Tam (B14) 668
Tam (B20) 227
Tam + Chemo (B20) 424
0.0
0 2 4 6 8 10
Years
Paik, SABCS, 2004
High recurrence score means:
No benefit from tamoxifen
Clear benefit from chemotherapy
1.0
CT
0.8
P T
0.6
DRFS
0.4
N
0.2 Placebo (B14) 355
Tam (B14) 668
Tam (B20) 227
Tam + Chemo (B20) 424
0.0
0 2 4 6 8 10
Years
59
Mammography
60
Mammography Equipment
61
Computer-Aided Diagnosis
62
What Mammograms Show
Two of the most important mammographic
indicators of breat cancers
Masses
Microcalcifications: Tiny flecks of calcium like
grains of salt in the soft tissue of the breast that
can sometimes indicate an early cancer.
63
Detection of Malignant Masses
Malignant masses have a more spiculated
appearance
malignant benign 64
Mammogram Difficult Case*
66
Different Views
Side-to-Side
MRI - Cancer can have a unique
appearance many small irregular
white areas that turned out to be
cancer (used for diagnosis)
67
Top-to-Bottom
Calcification Features
69
Outline- Part 2
70
Diagnosis and Treatment
7/10/2017 71
Tumor characteristics
Invasive vs. Non-invasive .
Histologic Type-Ductal (85%) vs. Lobular .
Grade (estimate of the aggressiveness
under microscope) .
Size .
Margins .
Lymph Nodes .
Estrogen/ Progesterone Receptor (2/3
positive) .
Her-2/ neu
7/10/2017 72
. Stage 0 --carcinoma in situ
. Stage I tumor < 2 cm, no
nodes
. Stage II tumor 2 to 5 cm,
Stages +/-nodes
of . Stage III locally advanced
Breast disease, fixed or matted lymph
Cancer nodes and variable tumor size
. Stage IV distant
metastases (bone, liver, lung,
brain)
What now?
Stage 0-III
Risk of recurrence is individual
What can we do to reduce the risk of
recurrence in the breast, and
systemically ?
74
How is breast cancer treated?
Breast cancer
screening programs
5 year gain
16.1%
5 year gain
30.1%
83
Bisphosphonates
Bone strengtheners
Given for therapy-induced osteoporosis or for
cancer that has spread to bone