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CANCER OF THE BREAST
Introduction
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Incidence: Low in Africa, Japan; intermediate in India, high in USA, UK and Europe
Commonest cancer in women and second in Africa (after Ca cervix)
Incidence increases with age from 20 years upwards
Peak incidence at 45-55 years; a decade earlier in Africa
Commonest site is the UOQ (50%)
May be multifocal, multicentric or bilateral
Bilateral disease is commoner with infiltrating lobular carcinoma.
Many women have micrometastases at time of diagnosis
Classification: Histological Types
Carcinoma
 Non-invasive
 Ductal carcinoma in situ (DCIS)
2-3%
 Lobular carcinoma in situ (LCIS)
2-3%
 Infiltrative
 Ductal- Not Otherwise Specified (NOS) 70-80%
 Medullary
5-8%
 Mucinous/colloid
2-4%
 Tubular
1-2%
 Papillary
1-2%
 Signet ring, clear cell, squamous cell, juvenile (Rare)
 Lobular
6-8%
Sarcoma
 Cellular intracanilicular fibroadenoma
 Other types of sarcoma
Special Clinical Forms
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Paget’s Disease
Inflammatory Carcinoma
Risk Factors for Ca Breast
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Sex (F:M= 10:1)
Age- Increases with age
Family history- Mother or sister x 2-3 risk
Oncogenes: Familial <5% -BRCA-1 (Ca develops in 50%), BRCA -2
Sporadic- Approximately 25% of Ca. over express erb B (HER-2)
Early menarche (<12 y), late menopause (>55y)
Nulliparity or age >30 years at first delivery
Hormone Replacement Therapy (HRT)
Atypical ductal or lobular hyperplasia on biopsy x 9
Low dose radiation
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Diagnosis
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Commonly presents as a painless palpable lump or mass
Suspicious lesion on screening mammography
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Pain is uncommon but may be present with advanced disease
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Occasionally presents as bleeding per nipple (usually duct papilloma)
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Skin changes ( dimpling, nipple retraction, ‘peau d orange’ eczema of nipple in
Paget’s disease, ulceration, satellite nodules, ‘mastitis carcinomatosis’
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Nodal spread to axillary, internal mammary and supraclavicular nodes
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Hematogenous metastases to lungs, liver or bone
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Transcelomic spread to ovaries (Kruckenberg) and pelvis (Blummer’s shelf)
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Diagnosis is by Triple Assessment
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 Clinical Evaluation – Lump and regional nodes
 Imaging (ultrasound <35 years old or mammography >35 years old)
 Cytology or Biopsy
Cytology is reported as:
 C1 = Inadequate sample
 C2 = Definitely benign
 C3 = Probably benign
 C4 = Suspicious of malignancy
 C5 = Definitely malignant
TNM Staging for Breast Cancer
Tumour Size (T)
Tis
Cancer in situ
T1
Tumour <2 cm (T1a <0.5 cm, T1b >0.5-1 , T1c >1-2 cm)
T2
2 cm-5 cm
T3
Tumour >5 cm
T4a
Involvement of chest wall
T4b
Involvement of skin (includes, direct infiltration, ulceration, peau d'orange
and satellite nodules)
T4c
T4a and T4b together
T4d
Inflammatory cancer
Regional Lymphnodes (N)
N0
No regional node metastases
N1
Palpable mobile involved ipsilateral axillary nodes
N2
Fixed involved ipsilateral axillary nodes
N3
Ipsilateral internal mammary node involvement (rarely clinically detectable)
Distant Metastases (M)
M0
No evidence of metastasis
M1
Distant metastasis (includes ipsilateral supraclavicular or cervical nodes)
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Correlation of Stage (UICC-1987) and TNM Classification
I
T1, N0, M0
II A
II B
III A
III B
IV
T0, N1,
T1, N1;
T2, N0, M0
T2, N1;
T3, N0, M0
T0, N2;
T1, N2;
T2, N2;
T3, N1, N2, M0
T4, Any N;
Any T, N3, M0
Any T; Any N, M1
MODALITIES OF TREATMENT
SURGERY
Historical. Halsted described 50 patients treated by Radical Mastectomy in 1894
Patey described Modified Radical Mastectomy in 1967
Auchincloss (1970) and Scanlon (1975) described modifications
Cope (1976) and Crile (1986) described Local Excision+Radiation
1. Breast Conserving Surgery + Radiotherapy (BCS+R)
 Wide Local Excision (WLE), segmentectomy or quadrantectomy
 Usually combined with axillary node surgery
 Radiation to the breast (40-50 Gy + ‘boost’ to tumour bed 10-20 Gy)
Criteria for BCS
 Small single tumours < 4cm with no fixity to skin, chest wall or muscle
 No fixity of lymph nodes
 No multicentric cancer (mammogram)
For tumours suitable for breast conservation, no difference in local recurrence or overall
survival when BCS + radiotherapy is compared to mastectomy
2. Mastectomy
 Simple Mastectomy/ Total Mastectomy and axillary node excision or radiotherapy
 Modified Radical Mastectomy (Patey, Scanlon, Auchincloss)
 Radical Mastectomy (Described by Halsted; of historical interest)
Breast reconstruction is an option and may be immediate or delayed
Surgery for axillary nodes
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30-40% of patients with early breast cancer have nodal involvement
Clinical evaluation of axilla unreliable (30% false +ve , 30% false-ve)
? Role of sentinel node biopsy : Scintigraphy, (T1, T2)
The aims of axillary surgery is to eradicate local disease and determine prognosis
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Surgical evaluation should be considered for all patients with invasive cancer
Levels of axillary clearance are assessed relative to pectoralis minor
Level 1 - below pectoralis minor
Level 2 - up to upper border of pectoralis minor
Level 3 - to the outer border of the 1st rib
Axillary clearance
 Axillary clearance both stages and treats the axilla
 Sampling potentially misses nodes and understages the axilla
 Surgical clearance possibly gains better local control
 Avoids complications of axillary radiotherapy
 Avoids morbidity of axillary recurrence
Axillary sampling
 Axillary samplings removes > 4 nodes
 Only stages the axilla
 Must be followed by axillary radiotherapy
 The 60% of patients with node negative disease have unnecessary surgery
 Avoids morbidity of axillary surgery
 The combination of axillary clearance and radiotherapy is to be avoided
since it produces unacceptable rate of lymphoedema
Prognostic factors
50% women who receive locoregional treatment alone will die from metastatic disease.
 Prognostic factors have three main uses:
 To select appropriate adjuvant therapy according to prognosis
 To allow comparison of treatment between similar groups of patients
 To improve the understanding of the disease
 Age
 Younger women have poorer prognosis of equivalent stage
 Tumour size
 Diameter of tumour correlates directly with survival
 Lymph node status
 Single best prognostic factor
 Correlation between number and level of nodes involved and survival
 Metastases
 Distant metastases worsen survival
 Histological type
 Some histological types associated with improved prognosis:
Tubular, cribriform, mucinous, papillary, micro-invasive
 Histological grade
 Three characteristics allow scoring of grade into 1.2.3:
Tubule formation, nuclear pleomorphism, mitotic frequency
 Lymphatic / vascular invasion
 25% operable breast cancers have lympho-vascular invasion
 Double risk of local relapse
 Higher risk of short term systemic relapse
 Hormone and growth factor receptors
 ER positivity predicts for response to endocrine manipulation
 EGF receptors are negatively correlated with ER and poorer prognosis
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Oncogenes
Tumours that express C-erb-B2 (HER-2) oncogene likely to be
 resistant to CMF chemotherapy
 resistant to hormonal therapy
 respond to anthracycline and to taxols
Proteases
 Urokinase and cathepsin D presence confers a poorer prognosis
CHEMOTHERAPY
1. Primary (Neoadjuvant) systemic therapy prior to locoregional treatment
2. Adjuvant therapy following locoregional treatment
Decision depends primarily on presence of poor prognostic factors
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Age (young). Menopausal status ( premenopausal))
Size (>2cm). Nodal status, (positive nodes)
Other high risk factors (HR –ve, aneuploid, poor grade, high S-phase fraction)
Combination chemotherapy more effective than single drug
Regimes: CMF, AC/EC, ECF (Cyclophosphamide, Methotrexate, 5 FU,
Adriamycin)
Given as 6 cycles of CMF or 4 cycles of CA, @ monthly intervals
No evidence that more than 6 months treatment is of benefit
Greatest benefit is seen in premenopausal women
Newer options CA x 4  T x 4 (Docitaxel); ECF (Epirubicin, Cisplatin, 5FU)
High -dose therapy + stem cell rescue produces no overall survival benefit
Higher toxicity and may be poorly tolerated in the elderly/debilitated
Primary (Neoadjuvant) chemotherapy
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Chemotherapy prior to surgery for large or locally advanced tumours (Stage III)
Shrinks tumour and may allow breast conserving surgery rather than mastectomy
70% tumours show a clinical response
In 20–30% this response is complete
80% of these patients still have histological evidence of tumour
The addition of preoperative docetaxel (4 cycles) to conventional neoadjuvant AC
therapy improves the pathologic response rate in stage I-IIIA disease,
Surgery required even in those with complete clinical response
Primary systemic therapy has not to date been shown to improve survival
HORMONAL THERAPY
Adjuvant therapy in HR +ve pre and post menopausal women, node positive and high risk
node negative patients
1. (SERM /SERD: Anti-oestrogen) treatment of choice: Tamoxifen
 Effective in both the adjuvant setting and in advanced disease
 Tamoxifen 20 mg per day
 Duration of treatment is 5 years
 Value of treatment beyond 5 years is unknown
 Risk of contralateral breast cancer reduced by 40%
 Greater benefit in ER/PR receptor rich tumours (78%)
 Benefit still seen in ER/PR receptor negative tumours (10%)
 Newer drugs: Terimifene, Fulvestrant
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Progestins (Megestrol acetate- Megace)
GnRH agonist (Goserelin- Zoladex) in advanced cancer in premenopausal
Aromatase Inhibitors (Anastrozole, Letrozole) in postmenopausal
Oophorectomy (surgical/radiation) in premenopausal with advanced disease
IMMUNOTHERAPY
Trastuzumab (Herceptin) Monoclonal antibody binds to HER-2
SUMMARY OF TREATMENT BY STAGE
Stage I and II (Locoregional disease)
 Lumpectomy and Radiotherapy
 Modified Radical Mastectomy/ Total Mastectomy+ Node excision
 Adjuvant systemic therapy for micrometastases (Chemotherapy/Hormonal
therapy)
 5 year survival: I – 95%. II – 60-70%
Stage III (Locally advanced disease)
 Multimodal therapy includes neoadjuvant chemotherapy, radiotherapy and surgery
 5 year survival : 30-55%
Stage IV (Systemic Metastases)
 All treatment is aimed at palliation of symptoms
 Goal is locoregional and systemic control of disease
 5 year survival 5- 10%
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