2- Breast cancer Flashcards
breast cancer background
most common cancer in the UK
Two main categories
Carcinoma in situ
- Ductal cell carcinoma in situ (DCIS)
- Lobular carcinoma I. situ (LCIS)
Invasive cancer
- Invasive ductal carcinoma
- Invasive lobular carcinoma
Other subtypes
- Medullary carcinoma
- Coilloid carcinoma
- Mucinaous
- Tubular
breast cancer metastasis
Metastasis- anywhere
* L – Lungs
* L – Liver
* B – Bones
* B – Brain
RF
Risk factors
- Female sex
- Older (doubles every 10 years until menopause)
- BRCA1 and BRCA2 mutation
- Family history
- Previous bening disease
- Obesity/smoking
- Alcohol
- Degree of exposure to oestrogen
degree of oestrogen exposure
o Early menarche
o Late menopause
o Nulliparous women
o First pregnancy after 30 years age
o Oral contraceptive or HRT
Red flags
- Swollen lymph nodes under the arm or around the collarbone.
- Swelling of all or part of the breast.
- Skin irritation or dimpling.
- Breast or nipple pain.
- Nipple retraction.
- Redness, scaliness, or thickening of the nipple or breast skin
- Nipple discharge
Breast Screening Programmes
- 50-70yrs to have a mammogram every 3 years; any abnormalities identified will be referred to breast clinic for triple assessment.
- Aim is to detect small impalpable cancers and pre-invasive cancer (incidence of DCIS has increased from 5% of breast cancers to 25% in screened populations)
- Look for asymmetric densities, parenchymal deformities, calcifications
- Assess abnormalities using further imaging, core biopsy and FNAC
negatives of breast screening programme
Negatives
- Anxiety and stress
- Exposure to radiation
- False negatives
- Unnecessary further tests
Genetics
BRCA are tumour suppressor genes – mutations in these increases risk of breast cancer (as well as ovarian and other cancers)
BRCA1 gene on chromosome 17
- 70% will develop breast cancer by 80
BRCA2 on chromosome 13
- 60%
If very high risk e.g. first-degree relative with breast cancer under 40: genetic counselling, annual mammograms. Chemoprevention if very high risk or bilateral mastectomy or oophorectomy.
Pagets disease of the nipple
Background
* Indicates breast cancer involving the nipple
* May represent DCIS or invasive breast cancer
Presentation
* Looks like eczema of the nipple/areolar
* Erythematous, scaly rash
Management
* Requires biopsy, staging and treatment, as with any other invasive breast cancer
investigations for breast cancer
The breast triple assessment is a hospital-based assessment clinic
- Women (and men) can be referred to this ‘one stop’ clinic by their GP if they have signs or symptoms that meet the breast cancer “2 week wait” referral criteria, or if there has been a suspicious finding on their routine breast cancer screening mammography.
What is included in the triple assessment?
1) History
2) Examination (P1-P5)
2) Imaging
- Mammography (M1-M5)
- US (U1-U5)
3) Histology e.g. biopsy
At each stage of the triple assessment, the suspicion for malignancy is graded to create an overall risk index, as discussed below. The key here is to establish whether this is likely a benign lesion or whether the patient should go onto have more definitive biopsy and further intervention.
Referral criteria for triple assessment
Two week wait referral for suspected breast cancer for:
- An unexplained breast lump in patients aged 30 or above
- Unilateral nipple changes in patients aged 50 or above (discharge, retraction or other changes)
- An unexplained lump in the axilla in patients aged 30 or above
- Skin changes suggestive of breast cancer
The NICE guidelines suggest considering non-urgent referral for unexplained breast lumps in patients under 30 years.
History and examination
History
PC
- How long?
- Lump/thiceking?
- Pain
- Nipple discharge
- Nipple retraction
- deformity (size, shape, skin changes)
- any recent traumas
Risk factors
- smoking status
- HRT
- pre/post-menopausal
Past medical history
Family history
- breast, ovarian, prostate
- Dx
Full breast examination
- Inspection (symmetry, scars, nipple retraction/discharge, puckering)
- Breast palpation (light and then deep)
- Assessment of axillary nodes
imaging
mammography or US
Mammography
- More helpful in older women
- Compression views of the breast cross two views
- Oblique and craniocaudal
- Allows for detection of mass lesions or microcalcification
- Pick up calcifications missed in US
Ultrasound scanning
- More useful in women<35 years and in men due to density of the breast tissue
- Due to being more dense
- Also used for core biopsies
histology
- Biopsy required of any suspicious mass or lesion
- Usually core biopsy
o Provides full histology (as opposed to fine needle aspiration (FNA), which only provides cytology)
o Allows differentiation between invasive and in-situ carcinoma - Can be used for grading and staging
Carcinomas in situ
Malignancies that are contained within the basement membrane
- Regarded as pre-malignant conditions
- Rarely symptomatic
- Types: ductal cell or lobular
Ductal cell carcinoma in situ
Background
- Pre-cancerous condition
- Most common non-invasive breast malignancy (20%)
- Malignancy of ductal tissue of the breast- contained within basement membrane
- 20-30% of cases will develop invasive disease
- Subtypes
subtype of ductal cell carcinoma
Comedo (microcalifcations), cribriform (multifocal), micropapillary (multifocal) and solid types, most are mixed
Presentation of DCIS
- Usually asymptomatic
- Microcalcifications on mammography
investigations for DCIS
- Detected during screening
- Confirmed by biopsy
management of DCIS
- Completely wide excision, ensuring surrounding tissue of all margins have no residual disease
- Widespread or multifocal DCIS – complete mastectomy
- Low grade LCIS: Monitoring rather than excision
- If invasive component and BRCA1 or BRCA2 positive -> bilateral prophylactic mastectomy
prognosis of DCIS
Potential to spread locally over years and becomes invasive in around 30%
- Good prognosis if full excision and adjuvant treatment
lobular carcinoma in situ backgroun
- Is a malignancy of the secretory lobules of the breast that is contained within the basement membrane.
- They are much rarer than DCIS however individuals with LCIS are at greater risk of developing an invasive breast malignancy.
RF for LCIS
- Pre-menopausal women
presentation of LCIS
asymptomatic
investigations of LCIS
- Incidental finding during biopsy of breast
management of LCIS
- Depends on extent of disease
- Usually close monitoring
prognosis of LCIS
- Increased risk of invasive cancer (30%)
DCIS vs LCIS
- DCIS much more common and of the ducts
- LCIS much rarer and of the lobules
invasive breast cancer
Carcinoma most common in western world. Classification
- Invasive ductal carcinoma (80%)
- Invasive lobular carcinoma (10%)
- Other subtypes
o Medullary carcinoma
o Colloid carcinoma
presentation of invasive breast cancer
- Can present symptomatically or asymptomatically via screening (particularly for ILC).
- Breast lump
- Asymmetry
- Swelling
- Abnormal nipple discharge
- Nipple retraction
- Skin changes (dimpling/peau d’orange or Pagets-like change)
- Mastalgia
- Palpable lump in axilla
investigations for invasive cancer
Triple assessment:
- Clinical – history, family history, examination
- Radiographic imaging – mammogram (in older) and ultrasound scan (in younger)
- Pathology – core biopsy and fine needle aspiration cytology (FNAC)
Receptor status
Oestrogen, progesterone, human epidermal growth factor
invasive ductal carcinoma (IDC)
- Most common type of breast carcinoma, constituting 80% of all cases.
- Further classified into
o tubular, cribriform, papillary, mucinous (/colloid), or medullary carcinomas, all showing distinct patterns of growth*. - Most commonly incidental finding during screening
- Originates from breast ducts
*Tubular, cribriform and papillary subtypes are well circumscribed and show the most favourable prognoses
presentation of IDC
- Irregular
- Can be seen on mammograms
- Condensed part which tugs other tissue in e.g. inverted nipple or breast dimple
Invasive lobular carcinoma (ILC) Background
- Constituting 10% of all invasive breast cancers.
- It is characterised by a diffuse (stromal) pattern of spread that makes detection more difficult. By the time of diagnosis, tumours are often quite large.
- Originates from breast lobules
- RF more common in older women.
Inflammatory Breast Cancer
- 1-3% of breast cancers
- Presents similarly to a breast abscess or mastitis
- Swollen, warm, tender breast with pitting skin (peau d’orange)
- Does not respond to antibiotics
- Worse prognosis than other breast cancers
further investigations after diangossi with breast cancer
general management of breast cancer
Molecular classification in breast cancer
Guides management
- Oestrogen receptor positive= better prognosis
- Her2 positive and oestrogen positive= better prognosis (can have Herceptin)
- Oestrogen receptor negative and HER2 negative = poor prognosis and usually BRCA1
Sentinel Lymph Node Biopsy
Sentinel node biopsy is performed during breast surgery for cancer. An isotope contrast and a blue dye are injected into the tumour area. The contrast and dye travel through the lymphatics to the first lymph node (the sentinel node). The first node in the drainage of the tumour area shows up blue and on the isotope scanner. A biopsy can be performed on this node, and if cancer cells are found, the lymph nodes can be removed.
Lymphoedema
Chronic condition caused by impaired lymphatic drainage. Can occur in entire arm after breast surgery to remove axially lymph nodes from armpit
- Swelling due to excess fluid
- Infection due to reduced lymphatic action in arm
Management
- Manual lymphatic drainage- massage
- Compression bandages
- Weight loss
- Good skin care
types of surgical approach
1) Breasr conserving
2) Mastectomy
3) Axillary surgery
4) Reconstructive surgery
breast conserving surgery
Indication
- Localised operable disease with no evidence of metastatic disease
- Focal smaller cancers
- Dependent on location and size of breast
Method: Wide local excision (WLE) most common treatment
- Excision of tumour with 1cm margin of macroscopically normal tissue
mastectomy
- Removes all of the tissue of the affected breast along with signif portion of overlying skin (muscles of the chest wall left intact)
Indication
- Multifocal disease
- High tumour: breast tissue ratio
- Disease recurrence
- Patient choice (or in risk-reducing cases)
axillary surgery
Why? Most commonly performed alongside WLE and mastectomies in order to asses nodal status and removal of nodal disease
Sentinel node biopsy (nodal status)
- Removing first lymph node into which the tumour drains
- Method: blue dye (with associated radioisotope) is injected into the peri-areolar skin
-The sentinel node is identified by its radioactivity and visual assessment (as node becomes blue)
- Node removed and sent for histological analysis
Axillary node clearance (removal of nodal disease)
- Removing all nodes in the axilla
- Complications: Paraesthesia, Seroma formation, Lymphedema in upper limb
Chemotherapy in breast cancer
Chemotherapy is used in one of three scenarios:
- Neoadjuvant therapy – intended to shrink the tumour before surgery
- Adjuvant chemotherapy – given after surgery to reduce recurrence
- Treatment of metastatic or recurrent breast cancer
Usually give a combination of 2 or 3 drugs- cytotoxic.
Examples:
* Docetaxel - Cyclophosphamide
* Epiribicin - Cyclophosphamide
hormonal treatment in BC: tamoxifen
Indication
- Pre-menopausal women
MOA
- SERM- selective oestrogen receptor modulator
- converse effects in breast and endometrial tissue
- In endometrium = ER agonist
- In breast = ER antagonist (cell cycle arrest)
- Blockage of oestrogen receptor in breast tissue
ADR
- Risk of thromboembolism during and after surgery or during periods of immobility
- Uterine carcinoma (due to pro-oestrogenic effect on the uterus)
hormonal treatments - aromatase inhibitors
e.g such as Anastrozole, Letrozole, or Exemestane
Indication
- Post-menopausal patients as adjuvant therapy, shown to be superior in this patient subgroup to Tamoxifen, however are more expensive.
MOA
- Act through binding to oestrogen receptors to inhibit further malignant growth and preventing further oestrogen production, as well as blocking the conversion of androgens to oestrogen in peripheral tissues.
immunotherapy in breast cancer
e.g. Herceptin (HER-2)
Indication
- Immunotherapy may be used in patients whose cancers express specific growth factor receptors.
- It can be used either as adjuvant therapy or as a monotherapy in patients who have received at least two chemotherapy regimens for metastatic breast cancer*.
MOA
- One of the most common targets is the human epidermal growth factor receptor(HER-2 positive malignancies) for which Herceptin (Trastuzumab) is a monoclonal antibody that targets its activity.
Side effects
*A common side-effect of treatment is cardiotoxicity, hence cardiac function must be monitored before and during treatment
Oncoplastic management- surgical reconstructive techniques
Several surgical reconstructive techniques in oncoplastic treatment of breast malignancy. Broadly divided into
- Mammoplasty
- Flap formation
–> e.g. Transverse rectus abdominal muscle (TRAM)
–> e.g. Deep inferiror epigastric perforator (DIEP)
- Implants
mammoplasty
flap formation
Transverse Rectus Abdominal Muscle (TRAM) flap
A Deep Inferior Epigastric Perforator (DIEP) flap
