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Breast cancer

  • 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

Clinical picture of breast carcinoma

  • 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

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

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

Blue sentinel node

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 2030% 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

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

Locally advanced breast carcinoma

  • 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

locally recurrent breast carcinoma

  • 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

Bibliography

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Carty N J.  Management of ductal carcinoma in situ of the breast.  Ann R Coll Surg 1995; 77: 163 - 167.

Coleman R.  The management of advanced breast cancer.  Curr Pract Surg 1996; 8: 7 - 12.

Eltahir A,  Heys S, Hutcheon A W et al.  Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy.  Am J Surg 1998;  175:  127-132

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