CARCINOMA OF BREAST pdf - علي خير الله

CARCINOMA OF BREAST

ALI K. SHAAELI

MB,CH FACS, FRCSI

Nov. 2018

CARCINOMA OF BREAST

• 1 in every 12 women will develop the disease

during their lifetime.

• The incidence is expected to continue rising

as the population ages

Etiological factors

1- Geographical

• Carcinoma of the breast occurs commonly in the Western world,

accounting for 3–5% of all deaths in women. In developing countries it

accounts for 1–3% of deaths.

2- Age

• Carcinoma of the breast is extremely rare below the age of 20 years but,

thereafter, the incidence steadily rises so that by the age of 90 years

nearly 20% of women are affected.

3- Gender

• Less than 0.5% of patients with breast cancer are male.

4- Genetic

• It occurs more commonly in women with a family history of breast cancer

than in the general population.

• Breast cancer related to a specific mutation accounts for about 5% of

breast cancers

Etiological factors

5- Diet

• Because breast cancer so commonly affects women in the ‘developed’ world,

dietary factors may play a part in its causation.

• A high intake of alcohol is associated with an increased risk .

6- Endocrine

• Breast cancer is more common in nulliparous women and breast feeding is

protective.

• Having a first child at an early age, late menarche and early menopause are

protective

• It is known that in postmenopausal women, breast cancer is more common

in the obese. This is thought to be because of an increased conversion of

steroid hormones to oestradiol in the body fat.

• oral contraceptive pill and HRT, have a role in the development of breast

cancer.

7- Previous radiation

• It is higher risk in women who have been treated with mantle radiotherapy

as part of the management of Hodgkin’s disease.

Pathology

• Breast cancer may arise from the epithelium of the duct

system any where from the nipple end of the major

lactiferous ducts to the terminal duct unit. The disease may

be 1- entirely

in situ

2-or invasive cancer.
• The degree of differentiation of the tumor is usually

described using three grades

: well differentiated,

moderately differentiated or poorly differentiated

• Previously, descriptive terms were used to classify breast

cancer (‘scirrhous’, meaning woody, or ‘medullary’,

meaning brain-like). More recently, histological descriptions

have been used. These have been shown to have clinical

correlations.

Current nomenclature

• Ductal carcinoma is the most common variant
• lobular carcinoma occurring in up to 15% . Invasive

lobular carcinoma is commonly multifocal and/or

bilateral

• Inflammatory carcinoma is a fortunately rare, highly

aggressive cancer that presents as a painful, swollen

breast, which is warm with cutaneous edema. This is

the result of blockage of the subdermal lymphatics

with carcinoma cells. Inflammatory cancer usually

involves at least one-third of the breast and may mimic

a breast abscess.

Current nomenclature

• Carcinoma

in situ

is pre-invasive cancer that has

not breached the epithelial basement membrane.
is becoming increasingly common because of the
advent of mammographic screening.

• Ductal Carcinoma

in situ

(DCIS) or

• Lobular carcinoma in Situ (LCIS), the latter often

being multifocal and bilateral. Both are markers
for the later development of invasive cancer.

The spread of breast cancer

1- Local spread

• The tumor increases in size and invades other

portions of the breast. It tends to involve the skin

and to penetrate the pectoral muscles and even

the chest wall if diagnosed late.

2- Lymphatic metastasis

• Lymphatic metastasis occurs primarily to the

axillary and the internal mammary lymph nodes.

• Tumors in the posterior one-third of the breast

are more likely to drain to the internal mammary

nodes.

The spread of breast cancer

• The involvement of lymph nodes represents a marker

for the metastatic potential.

• Involvement of supraclavicular nodes and of any

contralateral lymph nodes represents advanced

disease.

3- Spread by the bloodstream

•

It is by this route that skeletal metastases occur, In

order of frequency, the lumbar vertebrae, femur,

thoracic vertebrae, rib and skull are affected and these

deposits are generally osteolytic.

• Metastases may occur in the liver, lungs and brain and,

occasionally, the adrenal glands and ovaries;

Clinical presentation

• breast cancer is found most frequently in the upper

outer quadrant .

• Most breast cancers will present as a hard lump, which

may be associated with the nipple retraction.

• As the disease advances locally there may be skin

involvement with peau d’orange

• frank ulceration and fixation to the chest wall.
• About 5% of breast cancers in the UK will present with

either locally advanced disease or symptoms of
metastatic disease. This figure is much higher in the
developing world.

peau d’orange

Malignant ulcer

Nipple retraction

Staging

• Tis Carcinoma in situ
• T1   Tumor less than 20 mm in greatest dimension
• T2   Tumor >20 mm but ≤50mm in greatest dimension
• T3   Tumor >50 mm in greatest dimension
• T4   Tumor of any size with direct extension to the

chest wall and/or to the skin (ulceration or skin
nodules)

• N0 No regional lymph node metastases

Staging

• N1 Metastases to movable ipsilateral level I, II axillary

lymph node(s)

• N2 Metastases in ipsilateral level I, II axillary lymph nodes

that are clinically fixed or matted;

• N3 Metastasis in ipsilateral infra-clavicular (level III axillary)

lymph node(s) with or without level I, II axillary lymph node

involvement.

• M 0 No clinical or radiographic evidence of distant

metastases

• M1 Distant detectable metastases as determined by classic

clinical and radiographic means and/or histological

TNM stage grouping

early carcinoma are limited to breast and axilla which are

I,IIA&B and IIIA

Stage

STAGE I

Early

STAGE IIA

early

STAGE IIB

Early

STAGE IIIA

Early

N1,
N2

STAGE IIIB

Late

N1,
N2

STAGE IIIC

Late

any T

STAGE IV

late

any T

any N

Axillary lymph nodes

Treatment of cancer of the breast

• The two basic principles of treatment are to reduce the

chance of local recurrence and the risk of metastatic

spread.

• Treatment of early breast cancer will usually involve

surgery with or without radiotherapy.

• Systemic therapy such as chemotherapy or hormone

therapy is added if there are adverse prognostic factors

such as lymph node involvement, indicating a high

likelihood of metastatic relapse.

• Locally advanced or metastatic disease is usually

treated by systemic therapy to palliate symptoms, with

surgery playing a much smaller role.

The multidisciplinary team approach

• good doctor–patient communication plays a

vital role in helping to alleviate patient
anxiety.

• Participation of the patient in treatment

decisions is of particular importance in breast
cancer when there may be uncertainty as to
the best therapeutic option.

The multidisciplinary team approach

• As part of the preoperative and postoperative

management of the patient it is often useful to

employ the skills of a trained breast counselor

and also to have available advice on breast

prostheses, psychological support and

physiotherapy.

• In many specialist centers the care of breast

cancer patients is undertaken as a joint venture

between the surgeon, medical oncologist,

radiotherapist and allied health professionals

such as the clinical nurse specialist.

Local treatment of early breast cancer

• Local control is achieved through surgery and/or

radiotherapy

• Surgery still has a central role to play in the management of

breast cancer but there has been a gradual shift towards

more conservative techniques

• It was initially hoped that avoiding mastectomy would help

to alleviate the considerable psychological morbidity

associated with breast cancer, but , about 30% of women

develop anxiety and depression following both radical and

conservative surgery. After mastectomy women tend to

worry about the effect of the operation on their

appearance and relationships, whereas after conservative

surgery they may remain fearful of a recurrence.

Local treatment of early breast cancer

Mastectomy is indicated for large tumors , central tumors

beneath or involving the nipple, multifocal disease, local

recurrence or patient preference.
• The modified radical (Patey) mastectomy is more

commonly performed, The breast and associated structures

are dissected

en bloc

and the excised mass is composed of:

1-the whole breast;
2- a large portion of skin, the center of which overlies the

tumor but which always includes the nipple; all of the fat,

fascia and lymph nodes of the axilla.
• Simple mastectomy; involves removal of only the breast

with no dissection of the axilla.

Patey mastectomy

Patey mastecomy

Conservative breast cancer surgery

• This is aimed at removing the tumor plus a rim of at 1mm- 1 cm of

normal breast tissue. This is commonly referred to as a wide local

excision.. A quadrantectomy involves removing the entire segment

of the breast that contains the tumor. Both of these operations are

usually combined with axillary surgery, usually via a separate

incision in the axilla. There is a somewhat higher rate of local

recurrence following conservative surgery, even if combined with

radiotherapy, but the long-term outlook in terms of survival is

unchanged.

• Patients whose margins are involved should have a further local

excision (or a mastectomy) before going on to radiotherapy.

• Conservative Excision of a breast cancer without radiotherapy leads

to an unacceptable local recurrence rate

Sentinel node biopsy

• This technique has become the standard of care in the

management of the axilla in patients with clinically
node-negative disease. The sentinel node is localized
peroperatively by the injection of patent blue dye and
radioisotope labelled albumin in the breast.

• The recommended site of injection is in the subdermal

plexus around the nipple although some still inject on
the axillary side of the cancer. The marker passes to the
primary node draining the area and is detected visually
and with a hand-held gamma camera.

Radiotherapy

• Radiotherapy to the chest wall after mastectomy is

indicated in selected patients in whom the risks of local
recurrence are high.

• This includes patients with large tumors and those with

large numbers of positive nodes or extensive
lymphovascular invasion.

• There is some evidence that postoperative chest wall

radiotherapy improves survival in women with node-
positive breast cancer.

• It is conventional to combine conservative surgery with

radiotherapy to the remaining breast tissue.

Adjuvant systemic therapy

• It is now widely accepted that the outcomes of

treatment are predetermined by the extent of
micro-metastatic disease at the time of diagnosis.

• Variations in the radical extent of local therapy

might influence local relapse but probably do not
alter long-term mortality from the disease.

• However, systemic therapy targeted at these

putative micro-metastases might be expected to
delay relapse and prolong survival.

Adjuvant systemic therapy

• the appropriate use of adjuvant chemotherapy or hormone therapy

will improve relapse-free survival by about30% , which ultimately

translates into an absolute improvement in survival 10% at 15

years.

• lymph node-positive and many higher risk node-negative women

should be recommended adjuvant combined chemotherapy.

• Women with hormone receptor positive tumors will obtain a

worthwhile benefit from about five years of endocrine therapy,

either tamoxifen if premenopausal or the newer aromatase

inhibitors (anastrozole, letrozole) if postmenopausal.

• It is no longer appropriate to give hormone therapy to women with

oestrogen or progesterone receptor- negative disease.

Hormone therapy

• Tamoxifen has been the most widely used

‘hormonal’ treatment in breast cancer. it has now

been shown to reduce the annual rate of

recurrence by 25%, with a 17% reduction in the

annual rate of death.

• The beneficial effects of tamoxifen in reducing

the risk of tumors in the contralateral breast have

also been observed, as has its role as a

preventative agent.

• the optimal duration of treatment five years is

preferable.

Hormone therapy

• Other hormonal agents These include the LHRH

agonists, which induce a reversible ovarian
suppression.

• the oral aromatase inhibitors (AIs) for

postmenopausal women.

• There is an increase in bone density loss with

patients on an AI and a bone density scan is
advised prior to commencement with treatment
of underlying osteopenia or osteporosis.

Chemotherapy

• Chemotherapy using a first-generation regimen such as a

six monthly cycle of cyclophosphamide, methotrexate and

5-fluorouracil (CMF) will achieve a 25% reduction in the risk

of relapse over a 10- to 15-year period.

• modern regimens include an anthracycline (doxorubicin or

epirubicin) and the newer agents such as the taxanes.

• Chemotherapy was once confined to premenopausal

women with a poor prognosis but is being increasingly

offered to postmenopausal women with poor prognosis

disease as well.

• Chemotherapy may be considered in node negative

patients if other prognostic factors, such as tumor grade,

imply a high risk of recurrence.

Chemotherapy

• The effect of combining hormone and chemotherapy is additive

although hormone therapy is started after completion of

chemotherapy to reduce side effects..

• neoadjuvant is being used in many centers for large but operable

tumors that would traditionally require a mastectomy .The aim of

this treatment is to shrink the tumor to enable breast-conserving

surgery to be performed.

• Newer ‘biological’ agents will be used more frequently as molecular

targets are identified – the first of these, trastuzamab (Herceptin),

is active against tumors containing the growth factor receptor c-

erbB2. Other agents currently available include bevacizumab, a

vascular growth factor receptor inhibitor, and lapitinab, an oral

combined growth factor receptor inhibitor.

Thank you