Breast cancer

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.

Types

ductal carcinoma-in-situ
- comedo carcinoma
invasive ductal carcinoma
lobular carcinoma-in-situ
invasive lobular carcinoma

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 Tamoxifen oopherectomy chemotherapy

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

[0] Taneja P, Frazier DP, Kendig RD, Maglic D, Sugiyama T, Kai F, Taneja NK, Inoue K. MMTV mouse models and the diagnostic values of MMTV-like sequences in human breast cancer. Expert review of molecular diagnostics. 2009 Jul; 9(5):423-40.(Link to article – subscription may be required.)

[1] Curtis C, Shah SP, Chin S et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012 doi:10.1038/nature10983

[2] Trastuzumab for the adjuvant treatment of early-stage HER2-positive breast cancer

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Breast cancer

From Ganfyd

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