05. BREAST CANCER-DR PHILLIP BMC.ppt

BREAST CANCER
Dr Phillip L.Chalya
M.D. [Dar]; M.MED surg [Mak]
Surgeon Specialist – Bugando
Medical Centre
drphillipoleo@yahoo.com

OUTLINE
• Definition
• Surgical Anatomy of the breast
• Epidemiology
• Aetiological/Risk factors
• Pathophysiology
• Clinical presentation
• Work up
• Triple assessment
• Staging
• Management
• Prognosis
• Prevention

DEFINITION
• Breast cancer is defined as malignant
neoplasm of the breast arising from the
epithelial lining of the lobule, ducts and the
nipple
• Breast cancer is the third most common
cancer worldwide and is the most common
cancer in women

SURGICAL ANATOMY OF THE BREAST

Surgical anatomy of the breast [cont]
• 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 of the ductal
lumen
– A normal duct cells
– B basement membrane
– C lumen (center of duct)

Surgical anatomy of the breast [cont]
• Lymph node areas adjacent
to breast area.
– A pectoralis major muscle
– Axillary LN are divided into 3
levels in relation to PMn
• B axillary lymph nodes:
levels I – lateral to PMn
• C axillary lymph nodes:
levels II – posterior to PMn
• D axillary lymph nodes:
levels III- medial to PMn
– E supraclavicular lymph nodes
– F internal mammary lymph
nodes

EPIDEMIOLOGY
• Incidence
• Mortality/ Morbidity
• Age
• Sex
• Race

Incidence
• There is remarkable variation in the incidence of
breast cancer between different countries
• The rates in the United States and Canada are six
times higher than those in Asia or black Africa
• Japan has a low incidence of breast cancer,
although it is becoming more common

Mortality/ Morbidity
• Overall breast cancer mortality rates have declined
in recent years, attributable to the increased use of
screening mammography and the aggressive use of
adjuvant therapies
• Worldwide, breast cancer is the fifth most common
cause of cancer death
• Mortality rates are highest in the very young (less
than age 35) and the very old (greater than age 75)

Age
• As for other epithelial cancers the incidence of
breast cancer increases with age
• Breast carcinoma is only occasionally seen in the
late teens but thereafter there is a rapid rise in age-
specific rates

Sex
• Being a woman is the main risk factor for
developing breast cancer
• Breast cancer is 100 times more common in
women than in men
• In strict epidemiological terms, therefore, female
sex is a major risk factor for breast cancer,
although it is often forgotten as such.

Race
• White women are slightly more likely to develop
breast cancer than are black women
• Black women are more likely to die of this cancer
• The reasons for this are not known

AETIOLOGICAL/RISK FACTORS
• Socio-demographic risk factors
• Hereditary factors
• Hormonal factors
• Dietary factors
• Factors related to breast conditions
• Environmental factors

Socio-demographic risk factors
• Gender
– Breast cancer occurs one hundred times more
frequently in women than in men
• Age
– Incidence rates rise very sharply with age until about
the age of 45 to 50 when the rise is less steep
– This change in slope probably reflects the impact of
hormonal change (menopause) that occurs about this
time
– At age 75 to 80, the curve flattens and decreases
slightly thereafter

Socio-demographic risk factors [cont]
• Socioeconomic status
– Women of higher SES are at greater risk for breast
cancer [2-fold]
– The influence of socioeconomic status are thought to be
mediated by differing reproductive patterns with respect
to parity, age at first birth, and age at menarche
• Area of residence
– Higher incidence in developed countries than in
developing
– These differences are thought to be accounted for by
differences in parity and age at first live birth, at
menarche, and at menopause

Socio-demographic risk factors [cont]
• Race
– Whites > Blacks
– Most of these racial difference are attributable to
factors associated with lifestyle and socioeconomic
status, which also appear to explain disparities in
treatment and survival that are often attributed solely
to race

Hereditary factors
• Genetic predisposition
– The mutated genes BRCA 1 and BRCA 2 are responsible
for  30-40% of inherited breast cancer
• Family history of beast cancer
– A family history of breast cancer is associated with an
increased risk of the disease
– The risk is greatest in patients with first-degree relatives
(mother or sister) affected, especially if under the age of
50 when the disease developed

Hormonal factors
• Prolonged exposure to and higher concentrations of
endogenous estrogen increase the risk of breast
cancer
– Early age at menarche [≤ 12 years]
– Late age at first pregnancy [>30 years ]
– Late menopause [55years]
– Nulliparity at the age of 40 years
• Exogenous estrogens eg oral contraceptive drugs
have been shown to  risk of developing breast
cancer

Dietary factors
• Weight
– Obesity is associated with a twofold increase in the risk
of breast cancer in postmenopausal women whereas
among premenopausal women it is associated with a
reduced incidence
• Alcohol intake
– Some studies have shown a link between alcohol
consumption and incidence of breast cancer, but the
relation is inconsistent and the association may be with
other dietary factors rather than alcohol
• Smoking
– Smoking is of no importance in the aetiology of breast
cancer. drphillipoleo@yahoo.com

Environmental factors
• Previous exposure to radiations

PATHOPHYSIOLOGY
• Site
• Macroscopic /gross appearance
• Microscopic /histopathological appearance
• Spread

Site
• Upper outer quadrant –
commonest site
• Lower outer quadrant
• Upper inner quadrant
• Lower inner quadrant
• Nipple

Macroscopically
• Ulcerating
• infiltrating
• Satellite nodules
• Retraction
• Dimpling
• Peau d’orange
• Fungating
• Solid mass

Microscopically
• Classified as:-
– Non-invasive
• Lobular carcinoma in situ [LCIS]
• Ductal carcinoma in situ [DCIS]
– Invasive
• Lobular carcinoma
• Ductal carcinoma
• Mucinous / colloid carcinoma
• Medullary carcinoma
• Pagets disease of the nipple
• Mixed connective /epithelial tumors
– Phylloides tumor-benign/malignant, Carcinosarcoma, Angiosarcoma

Spread
• Direct
• Lymphatic
• Blood
• Transcoelomic implantation

Direct
• To the:-
– Skin over the breast
– Pectoral muscles
– Chest wall

Lymphatic spread
• By:-
– Permiation
– Embolization
• 75% to the axillary lymphnodes [pectoral/anterior,
brachial/lateral, subscapular/posterior, central and
apical]- arranged in 3 levels (I, II and III)
• Internal mammary LNodes

Blood spread
• To distant sites via blood vessels eg lungs, liver,
bones, brain etc

Transcoelomic implantation
• Dropping of cancer cells by gravity from
metastases to the liver to the pelvic cavity
causing metastases to the ovary

CLINICAL PRESENTATION
• History /Symptoms
• Physical examination/Signs
– General examination
– Local examination
– Systemic examination

History
• Symptoms referring to the breast:
– Breast lump
– Nipple discharge
– Nipple or skin retraction
– Axillary mass or pain
– Arm swelling
– Loss of hair / development of beards

History [cont]
• Symptoms with reference to possible
metastatic disease
– Cough, chest pain, SOB – lung onvolvement
– Jaundice- liver metastasis
– Bone pain – bone metastasis
– Features of brain metastasis

History [cont]
• Past medical history of breast disease
• Family history of breast cancer
• Reproductive History
– Age at menarche
– Menstrual history
– Age at first pregnancy
– Age of onset of menopause
– Number of pregnancies, and abortions (including
criminal abortions)
– Duration of breast-feeding
– History of hormone use including contraceptive pills

Physical examination
• General examination
– Weight, Height & surface area
– Wasting
– Jaundice
– Dyspnoea
– Anemia

Local examination
• Examination should be carried out in both sitting
and supine position;
• Both breasts and glandular areas should be
examined.
a) Breast mass
– Size
– Shape
– Consistency
– Location (specified by quadrants and the distance from
the edge of the areola)
– Fixation to skin, pectoral muscle or chest wall

Local examination [cont]
b) Skin changes
– Erythema
– Infiltration
– Ulceration
– Satellite nodules
– Dimpling ( peau d'orange) – vidimpo kama ganda la
chungwa
c) Nipple changes
– Retraction – when ligaments of cooper are involved
– Reddening
– Erosion and Ulceration
– Discharge (specify)

d) Nodal status
• Axillary nodes
– Number
– Size
– Location
– Fixation to other nodes or underlying structures
– Clinically suspicious or benign
• Supraclavicular nodes

• e) Arm
– Swelling
– Neurological assessment

Systemic examination
• Respiratory examination R/O lung involvement
• Abdominal examination R/O liver involvement
– Rectal/Vaginal examination R/o Krukenberg’s
tumor of the ovary
• CNS examination R/O brain metastasis
• MSS examination R/O bone metastasis
• etc

WORK UP
• Divided into two main categories:-
– Diagnostic investigations
– Staging investigations
• Aim:-
– To assess the general condition of the patient
– To assess the extend of the disease
– To confirm diagnosis
– To plan for treatment

A. Diagnostic investigations
• Breast imaging
– Mammography – radiography of the breast
– Breast ultrasound
– Galactography – radiagraphy of the breast ducts after
injection of a radio-opaque material into the duct system
– Pneumocystography- cystography (radiography of the
urinary bladder) after injecting air or gas into the
bladder
• Pathological
– Fine Needle Aspiration Cytology [FNAC]
– Core Biopsy
– Open Biopsy drphillipoleo@yahoo.com

Breast imaging
• Mammography
– Imaging technique of first choice in symptomatic patients aged ≥
30 years
• Breast ultrasound
– Is complimentary to mammography
– Provides added information e.g. solid / cystic mass, true size of
lesions
– It may be the technique of first choice in the breast lumps of
young women
• Galactography
– A discharging duct is cannulated and contrast medium injected
– Radiographs are then taken
– It is useful in localization of intraductal growth
• Pneumocystography
– Air is injected into a cyst after aspiration of fluid to detect intra-
cystic growth drphillipoleo@yahoo.com

Pathological investigations
• Fine needle aspiration cytology
– Has high degree of accuracy and when a diagnostic
sample of malignant cells is obtained, definitive surgery
may go ahead without need for open biopsy
– Can be done with or without mammography or US-
guided
• Core Biopsy
– Done when FNAC is inconclusive, can be done under US
guidance

Pathological investigations [cont]
• Open biopsy
– Excisional biopsy
• For small lesions
• Impalpable lesions may require mammographic locarization
– Incisional biopsy
• For big lesions

B. Staging investigations
• Laboratory investigations
• Imaging investigations

Laboratory investigations
• Full blood count
• Serum urea and creatinine [RFT]
• Liver Function Test [LFT]

Imaging
• Chest X-ray R/O lung metastasis
• Abdominal (liver) US R/O liver metastasis
• Skeletal survey R/O bone metastasis
• Bone scan
• CT scan
• MRI

TRIPLE ASSESSMENT
• A pre-operative diagnosis using triple assessment is
essential before treatment is undertaken
• This involves:-
– Clinical evaluation
– Breast imaging
– Pathological examination

a. Clinical evaluation
• This involves:-
– Thorough history
– Local and systemic clinical examination as above

b. Breast imaging
• Patients are divided into three categories;-
– Symptomatic patients, those with breast pain, breast
lump, nipple discharge, skin and areola changes, nipple
retraction etc
– Patients for screening, these include those with family
history of breast cancer, history of benign disease, after
surgery being followed up, and those more than 45
years of age
– Patients for image guided interventional procedures

Breast imaging [cont]
• Imaging procedures offered include:-
– Mammography
– Breast ultrasound
– Galactography
– Pneumocystography

c. Pathological examination
• This include:-
– Fine needle aspiration cytology
– Core biopsy
– Open biopsy
• Incisional biopsy
• Excisional biopsy

STAGING
• Aim
– To assess the extent of the disease
– To assess the prognosis of the disease
– To plan for treatment modality
• Criteria
– TNM classification

TNM classification of breast cancer
• T= Primary TUMOR
• N=Regional lymph NODES
• M=Distant METASTASIS

T-status
• Tx Primary tumor cannot be assessed
• To No evidence of primary tumor
• Tis Carcinoma in situ:
– Ductal carcinoma in situ [DCIS]
– Lobular carcinoma in situ [LCIS]
– Paget’s disease of the nipple
• T1 Tumor ≤ 2cm in greater dimension
• T2 Tumor > 2cm and < 5cm in dimension
• T3 Tumor > 5cm in dimension

T-status [cont]
• T4 Tumor of any size with direct extension to
the chest wall or skin
– T4a Extension to chest wall
– T4b Oedema (including peau d’orange), ulceration of
the skin of the breast, or satellite nodules confined to
the same breast
– T4c Both 4a and 4b, above
– T4d Inflammatory carcinoma

N-status
• Nx Regional lymph nodes cannot be
assessed
• N0 No regional lymph node metastases
• N1 Metastases to movable ipsilateral
axillary nodes
• N2 Metastases to fixed ipsilateral axillary
nodes
• N3 Metastases to ipsilateral internal
mammary nodes drphillipoleo@yahoo.com

M-status
• M0 No distant metastases
• M1 Distant metastases present (including to
supraclavicular lymph nodes

G- Histopathological Grading
• G1 Well differentiated
• G2 Moderately differentiated
• G3 Poorly differentiated

AJCC stage grouping
• Stage 0 Tis,N0,M0
• Stage 1 T1,N0,M0
• Stage IIA T0-1,N1,M0
T2,N0,M0
• Stage IIB T2,N1,M0
T3,N0,M0
• Stage IIIA T0-2,N2,M0
T3,N1-2,M0
• Stage IIIB T4,N0-2,M0
• Stage IIIC any T,N3,M0
• Stage IV any T, any N,M1

AJCC stage grouping [cont]
• Stage I : Early breast cancer
– Tumor confined to the breast
– No nodal involvement
• Stage II: Early breast cancer
– Tumor spread to movable ipsilateral axillary nodes
• Stage III: Locally advanced breast cancer
– Tumor spread to superficial structures of the chest wall
– Involvement of ipsilateral fixed axillary/internal mammary nodes
• Stage IV: Advanced/metastatic breast cancer
– Presence of distant metastases eg lung, liver, bone, brain etc
– Involvement of supraclavicular nodes

MANAGEMENT
• Goals of Treatment
– Cure
– Extend Survival
– Palliation

Treatment options
– Counseling
– Surgery
– Radiotherapy
– Chemotherapy
– Homonal therapy
– Immunotherapy

Counseling
• Like in all cancers the diagnosis of breast cancer is
frightening and exposes the patient and her family
to psychological torture
• Proper counseling should be part and parcel of the
entire management strategy
• Good counseling enables the patient and her family
to cope with the stress that is part and parcel of
cancer and adjust to their life styles
• Counseling should continue during treatment and
during follow up

Surgery
• Breast conserving surgery
– surgical excision of the tumor + with surrounding
margins (lumpectomy)
• Mastectomy (surgical removal of the affected
breast)
– Simple
– Modified
– Toilet
• Surgery of the RLN
– Axillary lymph node dissection[ALND]
– Sentinel lymph node biopsy [SLNB]

Radiotherapy
• Use of high-energy rays to stop breast cancer cells
from growing and dividing
• Can be given as part of the primary treatment or as
palliative
• Can be given after surgery [adjuvant] or before
surgery [neo-adjuvant]
• Given as an external beam radiotherapy to the
breast, axilla and supraclavicular nodes

Chemotherapy
• Use of anticancer drugs to kill breast cancer
cells
• Can be used as an adjuvant or neo-adjuvant
therapy
• Regimes include:-
1. CMF every 3 weeks for 6 cycles
– C= Cyclophosphamide 600mg/m2 i.v.
– M=Methotrexate 40mg/m2 i.v.
– F=5-Fluorouracil 600mg/m2 i.v.

Chemotherapy [cont]
2. CAF every 3 weeks for 6 cycles
– C= Cyclophosphamide 600mg/m2 i.v.
– A=Adriamycin 50mg/m2 i.v.
– F=5-Fluorouracil 600mg/m2 i.v.

Hormonal therapy
• Can be given as an adjuvant therapy after surgery
or as treatment for systemic disease
• First-line therapy
– Antiestrogen eg Tamoxifen 20mg daily for 2-5 years
• Second-line therapy
– Aromatase inhibitor eg Anastrozole 1mg daily
– Medroxyprogesterone acetate 0.4-1.5g daily

Immunotherapy
• Use of monoclonal antibodies directed against
breast cancer cells
• Still under investigation
• Include:
– Trastuzumab

Modes of treatment
• Depends on a variety of factors including:-
– The size of the breast tumor
– Location of the tumor
– The stage of the cancer
– Hormonal receptor status eg ER or PR
• Divided into 4 main categories according to the
stage:-
– Management of early breast cancer
– Management of locally advanced breast cancer
– Management of metastatic and locally recuring breast
cancer
– Management of breast cancer occurring during
pregnancy drphillipoleo@yahoo.com

A. Management of early breast cancer
[Stage I & II ]
• Treatment options
– Counseling
– Surgery
• Breast conserving surgery- only for stage I [T1N0M0,
T2N0M0) tumor size < 3cm
• Mastectomy – for stage II and stage I for multifocal ,central
or tumor > 3cm

• Adjuvant Radiotherapy
– Done after BCS or mastectomy
– To reduce risk of local recurrence
– To plan for ease radiotherapy
• Incision should be short and transverse
• Physiotherapy of the contra-lateral shoulder joint should start
on day 1 Post-operative
• Adjuvant systemic [chemotherapy and hormonal]
therapy
• Neo-adjuvant systemic therapy may be given to
down stage the cancer

Follow up after treatment for early
breast cancer
• Aims:-
– To detect recurrence at an early stage and thus
early treatment
– To detect and manage treatment related toxicity
– To screen for new primary in the contra-lateral
breast
– To provide psychological support

• Follow up involves the following:-
– Palliative care team [Hospice] & Other health workers
• To provide psychological care
• To provide symptomatic care
– Pain management
– Vomiting
– Mammography
• Patients who had mastectomy should have mammography of
the opposite breast every 2 years
• For patients who had BCS both breasts should have
mammography every 2 years
– TCA
• Patients should be seen at 3 and 6 months following
radiotheraphy and then once every year for life

B.Management of locally advanced
breast cancer [stage III]
• Aim of treatment: Palliative
• Counseling
• Multimodalities of treatment
• Surgery:
– Toilet mastectomy should be able to close the surgical
flap, otherwise neo-adjuvant systemic therapy should
be done to down stage the disease
• Radiotherapy
– Can be given as palliative, neo-adjuvant or adjuvant

• Chemotherapy
– Can also be given if the patient can tolerate it
– Can be given as adjuvant, neo-adjuvant or
palliative therapy
• Hormonal therapy

C. Management of metastatic and
locally recurring breast cancer
• The treatment of metastatic and locally recurring
breast cancer are the same
• Aim:
– Palliation depending on individual patient
• Modalities
– Surgery:
• Chest wall involvement →re-excision and flap reconstruction
• Recurrence after BCS→ mastectomy
• Chest wall RT± Surgery

• Chemotherapy who can tolerate it
• For extensive metastases → Chemotherapy ±
hormonal therapy or both
• In elderly or unfit patient, it is better to start with
hormonal therapy
• Bone involvement, spinal cord compression and
superior vena cava obstruction syndrome →RT
• Pathological fractures→ splintage
• Pleural effusion→UWSD + intra-pleural bleomycin
or tetracycline instillation
• Hypercalaemia → i.v. rehydration, if fails→
bisphosphanates

D. Management of Breast cancer
occurring during pregnancy
• Multi-disciplinary approach involving the surgeons,
medical and radiation oncologists, obstetricians is
needed
• Termination of pregnancy is not necessary and does
not improve survival
• 1st / 2nd trimester:
– Radiotherapy and chemotherapy should be delayed until
delivery
– Mastectomy and axillary clearance is the treatment of
choice

• 3rd trimester
– Ideally treatment should be delayed until after delivery
at about 32/40 → treatment as for non-pregnant patient
– Hormonal therapy should be avoided
• Lactation
– Patients receiving chemotherapy should not be allowed
to breastfeed as some of drugs [eg cyclophosphamide
and methotrexate ] are secreted in breast milk and could
be harmful to the child

Palliative care in Breast cancer
• Definition
– Active total care of patients whose disease is not
responsive to curative treatment
– Involves control of pain and other symptoms related to
the disease or treatment modalities
– Also deals with psychological , social and spiritual
problems of the patient

• Palliative care team [Hospice]
– Is multi-disciplinary team of doctors, nurses, social workers,
support staff and volunteers of various categories
• Palliative care options include:-
– Pain control using the WHO criteria for analgesia for somatic
pain
• Step 1: NSAIDs + Paracetamol
• Step 2: NSAIDs + Paracetamol + Weak opioid [Codeine]
• Step 3: NSAIDs + Paracetamol + Strong opioid [Morphine]
– Control of infections→ crushed metranidazole for fungating
lesions
– Control of nausea / vomiting→steroids + anti-emetics
– Appetite stimulants → Corticosteroids
– Counseling / Social support

PROGNOSIS
• With modern treatment, the 5-year survival rate
for:-
– Stage I patients is 94%
– Stage IIa patients, 85%
– Stage IIb patients, 70%
– Stage IIIa patients is 52%
– Stage IIIb patients, 48%
– Stage IV patients, 18%.

Prognostic Indicators
• Age: the younger the pt the poor the prognosis
• Sex: M>F early fixation to the chest wall
• Site: ILQ early metastasis to the mediastinum +abdomen
• Nature of growth; inflammatory ca> medullary
• Axillary nodal status
• Tumor size
• Histological grade
• Tumor stage
• Hormonal receptor status
• Metastasis

PREVENTION
• Primary prevention
– Difficulty
– Modification of risk factors
– Health education → ↑ awareness of the risk
factors
• Secondary prevention
– BSE
– Clinical breast examination
– Mammography screening
• Tertiary prevention
– rehabilitation drphillipoleo@yahoo.com

05. BREAST CANCER-DR PHILLIP BMC.ppt

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