Breast cancer

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Breast cancer is relatively common and politically visible. For these reasons. a screening programme was established and there have been more problems with objectivity than lower profile malignacies but at the same time a greater understanding by the public and indeed doctors due to relatively plentiful research funding. As a histologically, molecularly, and epidemiologically heterogeneous disease matters are sometimes quite complex however.

Contents

Types

History

  • patients are rarely younger than 35 years
  • 1% occur in males
  • Family history may sometimes indicate a strong trait suggesting one of the small number of recognised mutations.

Risk Factors

  • Family history - 1st degree relatives
    • This risk factor could have either or both genetic and infective (oncovirus) relevance
  • Contralateral breast carcinoma
  • Atypical hyperplasia on previous biopsy
  • Nulliparous
  • Early menarche

Presenting Symptoms

  • Painless lump in the breast
  • Nipple retraction
  • Nipple discharge
  • Skin dimpling
  • Peau d'orange
  • Breast asymmetry
  • Erythema
  • Paget's disease of the nipple
  • Symptoms of metastasis
    • bone pain
    • breathlessness
    • jaundice

Examination

Signs suggestive of carcinoma:

  • Hard irregular mass
  • Fixed to skin or deeply
    • fixed → infiltration of skin, no mobility, skin cannot be moved over lump
    • tethering → infiltration along ligaments of Astley Cooper, some mobility, skin dimples at extremes of movement
  • Paget's disease
  • Peau d'orange
  • Axillary nodes (are they mobile, fixed, matted?)
  • Supraclavicular nodes
  • Signs of metastasis
    • Liver
    • jaundice
    • hepatomegaly
    • ascites
  • Bone
    • bone tenderness
    • pathological fractures
  • Lung
    • Pleural effusion
    • consolidation
  • Brain
    • Headache
    • fits
    • personality change
    • papilloedema

Investigations

'Triple assessment' of the breast lesion

  • clinical examination
  • imaging (mammography/USS/MRI)
  • histology/cytology

Also consider:

  • Hb
  • LFTs
  • Calcium
  • CXR
  • Bone scan
  • USS of liver for secondaries
  • CT scan of brain

Spread

  • direct
    • skin
    • muscle
  • lymphatic
    • giving peau d'orange appearance
    • axillary common (40-50% at presentation)
    • intramammary
    • supraclavicular
    • tracheobronchial
  • blood
    • lung / bone (most frequent)
    • liver
    • adrenals
    • brain
    • pleura leading to effusion
  • infiltrating lobular carcinoma spreads to more unusual sites due to single cell spread

Staging and Grading

TNM System (AJCC 2002)

TNM staging of breast cancer
Tumour Nodes Metastases

Greatest dimension of tumour:

  • TX: Primary tumor cannot be assessed
  • T0: No evidence of primary tumor (this sometimes happens)
  • Tis: Carcinoma in situ; intraductal carcinoma, lobular carcinoma in situ, or Paget disease of the nipple with no associated tumour mass
  • T1: Tumour ≤2cm
  • T2: Tumour >2cm but not >5cm
  • T3: Tumour >5cm
  • T4: Tumour of any size growing into the chest wall or skin
  • NX: Regional lymph nodes cannot be assessed
  • N0: No involved regional lymph nodes.
  • N1: 1 to 3 ipsilateral axillary lymph node(s) and/or in internal mammary nodes with microscopic disease found by sentinel node biopsy but that are not found on imaging studies or by clinical exam.
  • N2: 4 to 9 ipsilateral axillary lymph nodes or in internal mammary nodes found by imaging studies or clinical exam in the absence of axillary lymph node metastasis.
  • N3: 10 or more ipsilateral axillary lymph nodes, or in infraclavicular lymph nodes, or in supraclavicular nodes or in internal mammary lymph nodes found by imaging tests or clinical exam in the presence of 1 or more positive axillary lymph nodes, or in more than 3 axillary lymph nodes and in internal mammary nodes found by sentinel node biopsy but not found by imaging tests or clinical exam.
  • MX: Presence of distant spread (metastasis) cannot be assessed
  • M0: No distant spread
  • M1: Distant spread is present


This breaks down into the following stages:

Staging of Breast Cancer by TNM system
Stage Tumour Nodes Metastases
Stage 0 Tis N0 M0
Stage 1 T1 N0 M0
Stage 2A T0-1 N1 M0
T2 N0 M0
Stage 2B T1 N1 M0
T3 N0 M0
Stage 3A T0-2 N2 M0
T3 N1-2 M0
Stage 3B T4 N0-2 M0
Stage 3C Any T N3 M0
Stage 4 Any T Any N M1

Grading

See also Breast cancer grading

Grading of breast cancer is usually based on the modified Bloom-Richardson grading system, which is used, along with other parameters, to calculate the Nottingham prognostic index.

Molecular Markers

Oestrogen (abbreviated ER) and progesterone receptor (PR or PgR) status is not strictly part of grading. This is commonly assessed using the Quick score (also known eponymously as the Allred score). An alternative method of scoring oestrogen receptor status is the H scoring.

It has implications for treatment in that hormone positive tumours are amenable to oestrogen antagonism, e.g. tamoxifen (see Treatment below) or aromatase inhibitors.

Her2 receptor expression is usually assessed using immunohistochemistry with recourse to in situ hybridisation in equivocal cases (or vice versa). Breast cancers which are Her2 positive can be treated with Trastuzumab (trade name Herceptin®).

When all 3 of the above markers are negative, the tumour is often referred to as a triple negative tumours and it tends to carry a poorer prognosis.

The prognostic relevance of mammary tumor virus sequencies in human breast cancer is presently unknown[1]

Genetic Markers

The 10 IntClust groups appear to offer the most accurate prognostic data[2].

Treatment

Based on modified Manchester (modified) staging (constantly changing based on new advances)
Stage 0 Stage I Stage II Stage III Stage IV
T0N0M0 T1N0M0 T1-2N1 M0 / T3N0M0 T1-4N2-3 M1
  • Cancer-in-situ
  • Lump less than 5cm
  • Not fixed deeply
  • Lump <5cm
  • Not fixed deeply
  • mobile, ipsilateral axillary nodes
  • Lump >5cm
  • fixed to skin
  • fixed ipsilateral axillary nodes
  • supraclavicular nodes
  • peau d'orange
  • arm oedema
  • distant metastases
  • Wide local excision
  • Wide local excision + axillary node sampling +/- radiotherapy
  • Simple mastectomy + axillary node sampling +/- radiotherapy
  • Modified radical mastectomy +/- radiotherapy
  • Modified radical mastectomy/radical mastectomy + radiotherapy
  • Radiotherapy +/- chemotherapy
  • Local palliation
  • Radiotherapy to localised bony mets
  • Aspiration of pleural effusion and instillation of cytotoxic agents
  • Hormonal manipulation
  • Most women, especially those with oestrogen receptor positive tumours (as determined by quick score according to the NHSBSP guidelines), are given tamoxifen for 5 years
  • Trastuzumab has a role in HER2 positive breast cancer and NICE has recently recommended its use in early as well as advanced disease[3].


External Links

References

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