Search This Blog

Monday, November 08, 2010

Breast Cancer Causes, Examination and Treatment

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
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

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

  • 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

Bibliography

Baum M, Houghton J. Contribution of randomised controlled trials to understanding and management of early breast cancer. Br Med J 1999; 319: 568-571.
Bundred N J Downey S E. The management of early breast cancer. Curr Pract Surg 1996; 8: 1 - 6.
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
Falk S J. Radiotherapy and the management of the axilla in early breast cancer. Br J Surg 1994; 81: 1277 - 81.
Fentiman I S, Mansel R E. The axilla: not a no-go zone. Lancet 1991; 337: 221-223.
Fentiman I S, Fourquet A, Hortobagyi G N. Male breast cancer. Lancet 2006; 365: 595-604
Forrest A P M et al. The Edinburgh randomised trail of axillary sampling or clearance after mastectomy. Br J Surg 1995; 82: 1504-8
Galea M H, Blamey R W, Elston C E, Ellis I O. The Nottingham prognostic index in primary breast cancer. Breast Cancer Research and Treatment 1992; 22: 207-219
Greenall M J. Why I favour axillary node sampling in the management of breast cancer. Eur J Surg Oncol 1995; 21: 2-7
Holcombe C Mansel R E. Axillary surgery in the management of breast cancer. Curr Pract Surg 1996; 8: 17 - 21.
Holland P A Bundred N J. The management of ductal carcinoma in situ. The Breast 1994; 3: 1 - 2.
Hortobagyi G N. Treatment of breast cancer. N Eng J Med 1998; 339: 974-984.
Johnston S R D. Systemic treatment of metastatic breast cancer. Hosp Med 2001; 62: 289-295.
MacMillan R D, Purushotham A D, George W D. Local recurrence after breast conserving surgery for breast cancer. Br J Surg 1996; 83: 149 - 155.
McIntosh S A, Purushotham A D. Lymphatic mapping and sentinel node biopsy in breast cancer. Br J Surg 1998; 85: 1347-1356.
Noguchi M. Sentinel lymph node biopsy and breast cancer. Br J Surg 2002; 89: 21-34.
Purushotham A D, MacMillan R D, Wishart G C. Advances in axillary surgery for breast cancer - time for a tailored approach. EJSO 2005; 31: 929-931
Sainsbury J R C. Breast cancer. Postgrad Med J 1996; 72: 663 - 666.
Saunders C M. The current management of breast cancer. Br J Hosp Med 1993; 50: 588 - 593.
Taylor I. How should the axilla be treated in breast cancer ? Eur J Surg Oncol 1995; 21: 2 - 7

0 comments:

Post a Comment