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
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