Epidemiology

• Breast cancer affects 1:12 women
• In United Kingdom there are 24,000 new cases and 15,000 deaths annually
• It is the commonest cause of cancer death in women
• It accounts for 6% of all female deaths
• Britain has highest breast cancer mortality in the world

WHO Classification

• Epithelial
• Non-invasive
  • Ductal carcinoma in situ (DCIS)
  • Lobular carcinoma in situ (LCIS)

• Invasive
  • Ductal (85%)
  • Lobular (1%)
  • Mucinous (5%)
  • Papillary (<5%)
  • Medullary (<5%)
• Mixed Connective tissue and Epithelial
• Miscellaneous

Diagnosis and assessment

• Most symptomatic cancers present as a painless lump

• Breast pain is an uncommon presentation of breast cancer
• Diagnosis is by Triple Assessment
  • Clinical Evaluation – Lump and regional nodes
  • Imaging (ultrasound <35 years old or mammography >35 years old)
  • Cytology or Histology
• Cytology is reported as:
  • C1 = Inadequate sample
  • C2 = Definitely benign
  • C3 = Probably benign
  • C4 = Suspicious of malignancy
  • C5 = Definitely malignant
  
  

Aims of breast cancer surgery

• To achieve cure if excised before metastatic spread has occurred
• To prevent unpleasant sequelae of local recurrence

Surgical options for the breast

• Breast Conserving Surgery (BCS) + radiotherapy
  • BCS is regarded as either wide local excision, quadrantectomy or segmentectomy
• Simple mastectomy
• Radical mastectomy - obsolete
• Mastectomy + reconstruction (immediate or delayed)

Tumours suitable for breast conservation

• Small single tumours in a large breast
• Peripheral location
• No local advancement or extensive nodal involvement
• For tumours that are suitable for breast conservation there is no difference in local recurrence or overall survival when BCS + radiotherapy is compared to mastectomy

Aims of axillary surgery

• 30-40% of patients with early breast cancer have nodal involvement
• The aims of axillary surgery is to:
  • To eradicate local disease
  • To determine prognosis to guide adjuvant therapy
• Clinical evaluation of the axilla is unreliable (30% false positive, 30% false negative)
• No reliable imaging techniques available
• Surgical evaluation important and 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 samplings removes more than 4 nodes
• Pre-operative axillary ultrasound and biopsy may allow a tailored approach to the axilla

Arguments for 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

Arguments for axillary sampling

• Only stages the axilla
• Must be followed by axillary radiotherapy
• The 60% of patients with node negative disease have unnecessary surgery
• Radical lymphadenectomy in other cancers (e.g. melanoma) produces disappointing results
• Avoids morbidity of axillary surgery
• The combination of axillary clearance and radiotherapy is to be avoided
• Produces unacceptable rate of lymphoedema

Picture provided by Eldeeb Mabrouk, University Hospital, Alexandria, Egypt

Sentinel node biopsy

• Currently under investigation and should still be regarded as experimental
• Aims to accurately stage the axilla without the morbidity of axillary clearance
• Technique used to identify the first nodes that tumour drains to
• Can be located following the injection of either
  • Radioisotope
  • Blue dye
  • Combination of isotope and blue dye
• Can be injected in peritumoural, subdermal or subareolar site
• Allows more detailed examination of nodes removed
• Significance of micrometastatic deposits identified in sentinel nodes is unclear

Picture provided by O Olsha, Shaore Zedek Medical Centre, Jerusalem, Israel

Prognostic factors

• 50% women with operable breast cancer 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 patient at risk of recurrence or death
  • To improve the understanding of the disease
• Prognostic factors can be:
• Chronological
  • Indication of how long disease has been present
  • Relate to stage of the disease at presentation
• Biological
  • Relate to intrinsic behaviour of tumour

Chronological prognostic factors

• 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
  • Direct correlation between number and level of nodes involved and survival
• Metastases
  • Distant metastases worsen survival

Biological prognostic factors

• Histological type
  • Some histological types associated with improved prognosis:
    • Tubular
    • Cribriform
    • Mucinous
    • Papillary
    • Micro-invasive
• Histological grade
  • Three characteristics allow scoring of grade into grades one, two or three depending on:
    • 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

Biochemical measurements

• Hormone and growth factor receptors
  • ER positivity predicts for response to endocrine manipulation
  • EGF receptors are negatively correlated with ER and poorer prognosis
• Oncogenes
  • Tumours that express C-erb-B2 oncogene likely to be
  • resistant to CMF chemotherapy
  • resistant to hormonal therapy
  • respond to anthracycline
  • respond to taxols
• Proteases
  • Urokinase and cathepsin D found in breast cancer
  • Presence confers a poorer prognosis

Chemotherapy in breast cancer

• Can be given as:
  • Primary systemic therapy prior to locoregional treatment
  • Adjuvant therapy following locoregional treatment
• Post-operative adjuvant chemotherapy
• Depends primarily on:
  • Age / menopausal status
  • Nodal status
  • Tumour grade
• Combination chemotherapy more effective than single drug
• Most commonly used regimen = CMF (Cyclophosphamide, Methotrexate, 5-Flurouracil)
• Given as six cycles at monthly intervals
• No evidence that more than 6 months treatment is of benefit
• Greatest benefit is seen in premenopausal women
• High -dose chemotherapy with stem cell rescue produces no overall survival benefit

Primary (neoadjuvant) chemotherapy

• Chemotherapy prior to surgery for large or locally advanced tumours
• Shrinks tumour often allowing breast conserving surgery rather than mastectomy
• 70% tumours show a clinical response
• In 20–30% this is response is complete
• Surgery required even in those with complete clinical response
• 80% of these patients still have histological evidence of tumour
• Primary systemic therapy has not to date been shown to improve survival

Endocrine therapy in breast cancer

• It is just over 100 years since Beatson described response to oophorectomy in women with advanced breast cancer

Tamoxifen

• Tamoxifen is an oral anti-oestrogen
• Effective in both the adjuvant setting and in advanced disease
• 20 mg per day is as effective as higher doses
• 5 years treatment is better than 2 years
• Value of treatment beyond 5 years is unknown
• Risk of contralateral breast cancer reduced by 40%
• Greater benefit seen in oestrogen receptor rich tumours
• Benefit still seen in oestrogen receptor negative tumours
• Benefit observed in both pre and post menopausal women

Aromatase inhibitors

• Several new endocrine therapies are available
• Reduced the peripheral conversion of androgens to oestrogens
• Only effective in post menopausal women
• May be superior to tamoxifen
• To date have not been shown to have survival benefit compared with tamoxifen

Locally advanced breast cancer

• Regarded as a tumour that is not surgically resectable
• Clinical features include
  • Skin ulceration
  • Dermal infiltration
  • Erythema over the tumour
  • Satellite nodules
  • Peau d'orange
  • Fixation to chest wall, serratus anterior or intercostal muscles
  • Fixed axillary nodes

• If oestrogen receptor-positive usually treated with primary hormonal
• If oestrogen receptor-negative chemotherapy may be useful
• Radiotherapy may be useful in local control of disease
• If adequate response a salvage mastectomy can be consider

Recurrent breast cancer

• Most local recurrences are symptomatic

• Often associated with the development of metastatic disease
• Restaging is therefore essential
• Commonest sites for ductal carcinoma are liver, bone and lung
• Lobular carcinoma less predictable often spreading to bowel, retroperitoneum etc
• Recurrence whilst on adjuvant tamoxifen consider:
  • Further surgery for
  • Isolated 'spot' recurrence after mastectomy
  • Local recurrence in the conserved breast
  • Radiotherapy if not previously given
  • Change of hormonal agent to anastozole or megestrol acetate

Male breast cancer

• 1% of all breast cancers occur in men
• Pathologically, the disease is similar to that which occurs in women
• The principles of treatment are the same
• The proportion of men undergoing mastectomy is higher
• Adjuvant therapy is the same as for women

Picture provided by Faisal Ashfaq, Civil Hospital, Quetta, Pakistan

Picture provided by Namada Deivasigamani, Stanley Hospital, Chennai, India

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