BREAST CA

DONE BY
DUAA SUMAAN
6th y medical student
Supervised by DR Rami Yagan
Surgery rotation /KAUH
29/9/2015

Objects
Histological classification of malignant
breast ca
Phyllodes tumor
Significance of estrogen receptor
positivity
Significance of HER2 mutation positivity

Anatomy
Lobule ( 10-100) ductule
Lactiferous duct ( 15-20) ampulla
nipple

Histology
The breast
composed mainly
of :
ducts and lobules ;
lined by epithelium ,
imbedded in
fibrous stroma ;
connective tissue ,
mesenchymal origin
with fat cells .

Histological classification of breast

cancer
1. Epithelial tumors
Ductal
Ductal carcinoma in situ
(DCIS)
Invasive ductal
carcinoma (IDC)
Inflammatory breast
carcinoma
Pagets disease
Lobular
Lobular carcinoma in situ
(LCIS)
Invasive lobular
carcinoma (ILC)

2. Stromal or
mesenchymal
tumors
Sarcoma
3. Biphasic tumors
Phylloides
Fibroadenoam
4. Others
Lymphoma
Secondary
metastasis

Epithelial tumors
95% are ductal ( arise from the ducts )
5% are lobular ( arise from lobules).
If the tumor cells invade the basement membrane
it is called invasive or infiltrative , we have
Invasive ductal carcinoma (IDC)
Invasive lobular carcinoma (ILC )
If the tumor cells dont show invasion
beyond the basement membrane ,
its called In situ , we have
Ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ (LCIS)

 Breast cancer can produce what is

called dysmoplastic reaction , which
is the formation of fibrosis around the
tumor as if the body is trying to
confine the tumor , so most of the
bulk of breast tumor will actually be
a fibrous tissue

DCIS
usually occurs in localized areas of breast ,
but may be extensive , if untreated will
become invasive .
Generally asymptomatic , appear as
mammogram finding , sometimes with
microcalcification .
Because of its malignant potential ,
treatment is complex excision of the
disease , and extensive disease ( >or = 4 )
may necessitate mastectomy

LCIS
It is a marker of increased risk of
breast cancer (approximately 20%
over 20 year period)
An incidental finding of LCIS on
diagnostic biopsy requires no surgery
.
However when LCIS is found on core
biopsy of an area of mammographic
calcification , it may be associated
with invasive lobular carcinoma and
therefore formal diagnostic excision

Invasive lobular carcinoma

Around 10%
The most common between the age
45-55
It does not always form a firm lump
but rather an area of thickening , so
tend to present late .

IDC is the most common type 85%

IDC

Invasive
ductal
carcinoma
IDC not
otherwise
specified
(NOS )
Is the commonest
type
Is called scirrhous
carcinoma of the
breast because it
contains fibrous
tissue due to

Less
common
forms of IDC
:
tubular
medullary
cribriform
mucinous

Inflammatory breast cancer

Most malignant form of breast ca , Poor
prognosis .
Constitute < 3% of all cases .
One variant of ductal carcinoma
The clinical findings consist of rapidly
growing , Present as a picture of
inflammation (mastitis or cellulitis ) with
erythema , pain , hotness & edema .
Usually theres no palpable mass because
the skin is thick & edematous .

Orange peel appearance or peau

dorange appearance; are caused
by carcinomatous invasion of
subdermal lymphatics , with
resulting edema and hyperemia .
Appear as pitted skin at the site of
hair follicles.

 If the practitioner suspect infection but the

lesion not respond rapidly (1-2 weeks) to
antibiotics , biopsy should performed .
The diagnosis should be made when the
redness involves more than 1/3 of the skin over
the breast and biopsy shows infiltrating
carcinoma with invasion of subdermal
lymphatics .
Metastases tend to occur early and widely , and
for this reason , inflammatory carcinoma is
rarely curable .
Radiation, hormone therapy, and chemotherapy
are measure most of value rather than
operation .
Mastectomy is indicated when chemotherapy

Pagets disease of the nipple

Rare malignant condition - 1%
It affects the nipple and may
or may not be associated with
breast mass .
The 1st symptom is often
itching or burning of the
nipple, with superficial erosion
or ulceration .
Chronic skin changes involving
the nipple of the breast such
as dry scaling or red weeping.
The basic lesion is usually a
well differentiated infiltrating
ductal carcinoma or a DICS .

Should be
differentiated from
eczema , which
involves the areola
with little
involvement of the
nipple.
The diagnosis is
established by
biopsy of the area
of erosion.

Mesenchymal breast
cancers
sarcomas big in size .
V. rare 0.5 %
Any mesenchymal cell in the breast
can retain its progenesety and
produce any type of mesenchymal
cancers .
E.g; osteosarcoma in the breast or
vascular sarcomas ..

Biphasic breast tumors

Involving more than one type of
tissue in these tumors .
Include :
Fibroadenoma : ( commonest benign
tumor)
Involve both epithelial and stromal
cells
Phyllodes :
fibroepithelial tumors
composed of an epithelial and a cellular
stromal component .

phyllodes
FIBROADENOMA LIKE TUMOR with cellular stroma that
grows rapidly . cystosarcoma phyllodes
The name "phyllodes," which is taken from the Greek
language and means "leaflike," refers to that fact that the
tumor cells grow in a leaflike pattern
Around 40s
The lesion can be benign or malignant , usually benign
( 10% frank benign , 10% frank malignant & 80%
intermediate )
It may reach a large size , and if inadequately excised , will
recur locally .

 It has a smooth, sharply demarcated

texture and typically is freely
movable.
It is a relatively large tumor, with an
average size of 5cm. However,
lesions of more than 30cm have
been reported.
The etiology of phyllodes tumors is
unknown

 If benign , phyllodes tumor is treated by

local excision with a margin of
surrounding breast tissue .
The treatment of malignant phyllodes
tumor is more controversial , but
complete removal of the tumor with a
rim of normal tissue avoids recurrence .
Because these can be large , simple
mastectomy is sometimes necessary
L.N dissection is not performed , since
sarcomatous portion of the tumor
metastasizes to the lung .

Micrograph of
a phyllodes
tumor (right of
image) with
the
characteristic
long clefts and
myxoid cellular
stroma.
Normal breast
and fibrocystic
change are
also seen (left
of image). H&E
stain

Phyllodes tumor in
mammography

Biomarker
The ER &PG status and HER-2/neu status of
the tumor should be determined at the time
of initial biopsy .
These markers may be obtained on core
biopsy specimens, which will be necessary to
institute neo-adjovant therapy .
The presence or absence of ER and PR is a
critical element of breast cancer
management.
Pt whose primary tumors are receptor +
have more favorable coarse than those
receptor - .

 Estrogen receptors (ERs) , Progesterone

receptors (PgRs) are exepressed on the
surface of tumor cells in breast ca .
Up to 60% of patients with metastatic
breast ca will respond to hormonal
manipulation if ER receptor + . Fewer than
5% of pt with metastatic , ER tumors can
be treated .
Hormone receptors have no relationship to
response to chemotherapy .

Hormons & growth factors receptors

Cancers are divided into:
1.hormone sensitive (ERS+ , PgRs +)
Which benefit from anti estrogen therapy
such as tamoxifen , raloxifen or aromatase
inhibitor
2.Hormone resistant (ERs - , PgRs -) :
no benefit from hormone therapy , so poor
prognosis

Estrogen receptors:
The female hormone estrogen can play a part in stimulating
some breast cancers to grow.
If your breast cancer has receptors within the cell that bind
to estrogen it is known as estrogen receptor positive or ER+
breast cancer.
All breast cancers are tested for estrogen receptors using
tissue from a biopsy or after surgery, and your pathology
report will state if there are any ER+ cells. Some reports will
also comment on whether there are progesterone receptor
positive (PR+) cells.
If you have invasive breast cancer which is estrogen receptor
positive you will usually be advised to have hormone
(endocrine) therapy.
Hormone therapy is much less commonly used with ductal
carcinoma in situ (DCIS) because the benefits are less certain.
If your breast cancer is hormone receptor negative, hormone
therapy drugs will not be of any benefit to you.

 Tumors that are ER/PR-positive are much more likely to respond to

hormone therapy than tumors that are ER/PR-negative.
You may have hormone therapy after surgery, chemotherapy, and
radiation are finished. These treatments can help prevent a return of
the disease by blocking the effects of estrogen. They do this in one of
several ways.
The medication tamoxifen (Nolvadex) helps stop cancer from coming
back by blocking hormone receptors, preventing hormones from binding
to them. Its sometimes taken for up to 5 years after initial treatment
for breast cancer.
A class of medicines called aromatase inhibitors actually stops estrogen
production. These include anastrozole (Arimidex), exemestane
(Aromasin), and letrozole (Femara). Theyre only used in women whove
already gone through menopause

HER2 testing:

Human epidermal growth factor receptor

All invasive breast cancers are tested for HER2 levels.
25% of breast ca are HER 2 + ( overexpressed)
Its done in a hospital laboratory on a sample of breast cancer tissue
removed during a biopsy or surgery. The results are usually available one
to three weeks later.
Outside of a clinical trial , HER2 testing is normally only done on invasive
breast cancer, so this is unlikely to be mentioned if you have ductal
carcinoma in situ (DCIS).
The following are the three most commonly used ways to measure HER2
levels.
IHC (immunohistochemistry) is usually done first. Its reported as
a score ranging from 03.
A score of 0 or 1+ is means the breast cancer is HER2 negative.
A score of 2+ is borderline,
a score of 3+ means the breast cancer is HER2 positive.
The other ways of measuring HER2 are called FISH (fluorescent in
situ hybridisation) and CISH (chromogenic in situ hybridisation).

 People with HER2 positive invasive breast

cancer are likely to be advised to have
chemotherapy and also drug treatments
called targeted therapies.
These drugs work by blocking specific ways that
breast cancer cells divide and grow.
The most well-known targeted therapy
istrastuzumab (Herceptin). Trastuzumab works
by attaching itself to the HER2 proteins (also
known as receptors) so that the cancer cells are
no longer stimulated to grow.
It also helps the bodys immune system destroy
breast cancer cells.
Only people whose cancer is HER2+ will benefit
from having trastuzumab.

 Another drug, lapatinib (Tykerb), is often given if

trastuzumab doesnt help. Ado-trastuzumab
emtansine (Kadcyla) can be given after
trastuzumab and a class of chemotherapy drugs
called taxanes, which are commonly used to treat
breast cancer.
Pertuzumab (Perjeta) can be used with
trastuzumab and other chemotherapy medicines
to treat advanced breast cancer. This combination
can also be given before surgery to treat early
breast cancer. In one study, the combination of the
two drugs it was shown to extend life

The most important growth factor group is

human epidermal growth factor receptors
known as HER.
We have 4 subtypes , most important is
HER 2 which is +ve in 20% of cases of
breast ca
Cancer cells express more number of HER 2
receptors on their surface , so more
uncontrolled growth.
Monoclonal AB block HER2 receptors called
herceptin or trastuzumab cause growth
reduction & shrinkage of tumor cells.
All breast cancers should be checked for Ers
and HER2.

Triple-Negative Breast Cancer

Some breast cancers -- between 10% and 20% -- are
known as triple negative because they dont have
estrogen and progesterone receptors and dont
overexpress the HER2 protein. Most breast cancers
associated with the gene BRCA1 are triple negative.
These cancers generally respond well to chemotherapy
given after surgery. But the cancer tends to come back.
So far, no targeted therapies have been developed to
help prevent cancer returning in women with triplenegative breast cancer. Cancer experts are studying
several promising strategies aimed at triple-negative
breast cancer

Thank
yu