Cancer: bladder and breast Flashcards
Muscle Invasive Bladder Cancer (MIBC) treatment
- Neoadjuvant chemotherapy: Cisplatin-based combination chemotherapy
- Radical cystectomy: Complete surgical removal of the bladder, prostate or uterus, and regional lymph nodes. Will have to implement one of the urinary diversion options.
- Bladder-sparing approaches: For select patients, a multimodal approach combining maximal TURBT, radiotherapy, and chemotherapy may be considered.
- Adjuvant chemotherapy: May be considered for patients with high-risk features following cystectomy or bladder-sparing treatment. Done intravesical (into the bladder through a catheter)
Surgery for invasive bladder cancer
cystoprostatectomy or cystectomy plus hysterectomy and pelvic lymphadenectomy with creation of urostomy with ileal conduit
Metastatic bladder cancer treatment
- First-line therapy: Platinum-based combination chemotherapy, such as gemcitabine-cisplatin or MVAC.
- Immune checkpoint inhibitors: For patients ineligible for cisplatin or after progression: pembrolizumab, atezolizumab, or nivolumab are options.
- Targeted therapy: For patients with specific molecular alterations (e.g., FGFR3), targeted therapies like erdafitinib may be considered.
Bladder cancer: urinary diversion options
- Urostomy with an ileal conduit (most common): Urine drains the ileum to the skin and into a urostomy bag
- Continent urinary diversion: creating a pouch in the abdomen patient needs to intermittently insert a catheter and drain it
- Neobladder reconstruction: creating a new bladder from a section of the ileum
- Ureterosigmoidostomy: urine drains through the colon. Rarely used now due to infection risk
Follow up badder cancer
regular cystoscopy within 3 months then every year or two
Breast cancer predisposing factors: genetic
- BRCA1, BRCA2 genes - 40% lifetime risk of breast/ovariancancer
- Li-Fraumeni syndrome, Cowden syndrome (breast & GI cancer, thyroid disease), ataxia telengietasia and Peutz Jeghers
- 1st degree relative premenopausal relative with breast cancer (e.g. mother)
- P53 gene mutations
- 10% of breast cancers are hereditary
Other risk factors for breast cancer (not genetic)
- Nulliparity, 1st pregnancy > 30 yrs (twice risk of women having 1st child < 25 yrs)
- Early menarche, late menopause
- COCP, HRT
- Past breast cancer
- Not breastfeeding
- Ionising radiation
- Obesity, alcohol
- Previous surgery for benign disease
How does hereditary breast cancer differ from normal
- younger age of onset
- frequent bilateral occurence
- higher proportion are hormone receptor negative
Common breast cancer types
- Invasive ductal carcinoma. This is the most common type of breast cancer.
- Invasive lobular carcinoma: most of the remaining cases
- Ductal carcinoma-in-situ (DCIS): more likely to become invasive than LCIS, wont cause lymph node metastasis
- Lobular carcinoma-in-situ (LCIS)
Paget’s disease of the nipple
is an eczematoid change of the nipple associated with an underlying breast malignancy and it is present in 1-2% of patients with breast cancer. In half of these patients, it is associated with an underlying mass lesion which is an invasive carcinoma.
Inflammatory breast cancer
where cancerous cells block the lymph drainage resulting in an inflamed appearance of the breast. 1 in 10,000 cases of breast cancer. Red, hot, swollen breast. Causes peau d’orange
Clinical features if breast cancer
- Breast lump: typically painless. Classically described as fixed, hard. Persists throughout menstrual cycle
- Breast pain, change in breast size or shape. Lump in breast or armpit
- Breast skin changes
- Bloodynipple discharge
- Inverted nipple
- Neck or axillary mass
- Pagets disease: eczema skin appearance, breast mass and bloody nipple discharge
- Left breast most commonly affected: upper outer quadrant or retro areolar region
- Most common site of metastasis: bone
What to look for on examination of breast cancer
- Neck and axilla: lymphadenopathy
- Nipple: is there discharge or retraction?
- Breast tissue: is there discolouration, oedema, peau d’orange, erythema, nodules, ulceration, lack of symmetry, skin thickening?
- Chest: signs of consolidation, nodules in skin
Most common metastatic sites of breast cancer and how they present
- Bone: bone pain, fractures, spinal cord compress (most common)
- Lung: plural effusion
- Liver: hepatomegaly
- MSK: focal tenderness in axial and peripheral skeleton due to bone involvement
Breast self examination
Recommended to perform monthly from 20. associated with better prognosis as diagnosed quicker.
Breast cancer epidemiology
most common cause of cancer for women in the UK and is the most common cause of death for 35-55. Increased risk if caucasian. Left breast more common then right
2WW for breast cancer
- Aged 30 and over and have an unexplained breast lump with or without pain. OR
- Aged 50 and over with any of the following symptoms in one nipple only: discharge, retraction, other changes of concern
- Consider: with skin changes that suggest breast cancer or aged 30 and over with an unexplained lump in the axilla
Triple assessment breast cancer
- Clinical examination
- Breast examination: Mammography, US, MRI
- Fine needle aspiration or core biopsy: Needle core biopsy, Mammotome (vaccum assisted biopsy)
- Mammography: features of malignancy include asymmetry, a mass and architectural distorsion
- Cytological: C1-5
Breast cancer: staging
- All staged with CXR, US of liver, bone scan
- All suspicious lesions are explored with CT, MRI or PET-CT
- Stage patients with tumour >5cm and >3 affected nodes (clinically palpable)
Imaging for boney metastasis
- MRI: assess for lesion in medullary cavity of bone
- Bone scan: initial test for boney metastasis
Breast cancer evaluation of masses
- Cystic mass: fine needle aspiration (FNA)- if just a cyst can be aspirated to resolution, US determines if lesion is solid or cystic and if a cyst is simple or complex, Biopsy if the cysts fluid is bloody
- Solid mass: Mammography, Fine needle aspiration, Core biopsy
- Non palpable mass (found on mammography): Wire excision biopsy, Stereotactic guided core biopsy, US guided core biopsy, Breast MR imaging
Breast cancer management
- Surgery: either wide local excision or a mastectomy with axillary clearance. Will be offered breast reconstruction
- Radiotherapy: in wide local excision you get whole breast radiotherapy. In mastectomy its offered for T3-T4 tumours and with 4 or more positive axillary nodes
- Hormone therapy: If positive for hormone receptors. Tamoxifen is used for 5 years after diagnosis in pre-menopausal women. In post-menopausal women offer an aromatase inhibitor i.e. anastrozole
- Biological therapy: trastuzumab which is sued in tumours that are HER2 positive
- Chemotherapy: downsize primary lesions or post surgery
Mastectomy versus wide local excision criteria
- Mastectomy: multifocal tumour, central tumour, large lesion in small breast DCIS >4CM
- Wide local excision: solitary lesion, peripheral tumour, small lesion in large breast, DCIS <4cm
Side effects of tamoxifen, triple assessment and breast screening
Side effects of tamoxifen: endometrial cancer, venous thromboembolism and menopausal symptoms
Breast screening: 50-70: mammogram offered every 3 years. Afterwards can make their own appointments
Triple assessment: clinical assessment, imaging and biopsy
How might breast cancer present
- Breast lump – either painful / painless
- Nipple changes / eczema / blood stained discharge
- Nipple or skin tethering and indrawn
- Axillary lymphadenopathy
- How would you describe lump: Site, size, shape, surface, colour, consistency, contour, temperature, tethering, tenderness
Fibroadenoma
Most are smooth or slightly lobulated and are usually 2-3 cm in diameter. They occur most commonly in women aged 16 to 30 years. They are very mobile – “breast mouse” and approximately 10% of fibroadenomas are multiple. Most can be observed, and excision is indicated if it is a large lump, if the patient chooses, or if the diagnosis is uncertain
Breast cancer investigations
- Mammogram: dual plane x-ray of the breast. Bilateral mammogram is offered to all patients over 40. Rarely performed under 40 due to dense breast
- Ultrasound: any patient with breast abnormality will undergo an ultrasound regardless of age, ultrasound of abnormality and not whole breast
- Lymph node spread: US of axilla, US guided biopsy of any abnormal nodes
- Immunohistochemical markers: ER, PR, HER2
- Bloods: FBC, LFT, calcium, CA 15.3
Inflammatory breast cancer
- Widespread tenderness with oedema and erythema
- Rapid increase in breast size
- Sensation of heaviness or burning in breast
- Inverted nipple
- Swollen lymph nodes
- Skin is pitted or ridged (peau d’orange)
- Due to build of lymph in the breast as cancer cells have blocked lymph vessels
Duct ectasia
due to contraction, thickening and widening of milk ducts which become obstructed with debris and become infected. Common sign is a slit like nipple retraction, can be exaggerated in smokers. Frequently bilateral and presents with green-brown discharge, nipple inversion and pain.
Family history BRCA
- Women who have BRCA and TP53 and women with a significant family history are classified as high risk
- Women with BRCA mutation (1 and 2) start screening at the age of 30 with yearly MRI and possibly a mammogram
- TP53 mutation: screening at the age of 20 with yearly MRI
Grade and size of tumour and axilla lymph node status
- Grade: measure of cellular differentiation from grade 1 (well differentiated) to grade 3 (poorly differentiated)
- Lymph nodes: 1-3 with 1 being 0 nodes affected and 3 being >3 nodes affected
- Can be combined to give a 5 year survival probability in the Nottingham Prognostic Index (NPI): (0.2 x size) + grade + lymph node score
- A score below 2.5 has a 93% 5-year survival, and a score of 5.5+ has a 50% 5-year survival.
- Other prognostic factors includehistologyandstage.
Breast cancer histology
- Ductal carcinoma in situ (DCIS): is pre-cancerous and can progress to invasive cancer if left untreated
- Lobular carcinoma in situ (LCIS): doesn’t become invasive but is a marker for developing breast cancer (lobular or ductal and in either breast). Risk isnt reduced by removing the LCIS. Require no active treatment but need annual mamographic surveillance
Staging of breast cancer
- Tumour (“T”): 0 (no evidence of cancer) to 4 (grown into chest wall/skin, or inflammatory breast cancer)
- Node (“N”): from 0 (no evidence of spread) to 3 (4+ axillary lymph nodes)
- Metastasis (“M”): 0 is no evidence and 1 is evidence of distant mets.
- Can be staged from 0-4. Stage 0 refers to non-invasive breast cancers. Stages I through III describe varying tumour sizes and degrees of lymph node infiltration. Stage IV is metastatic breast cancer.
Breast cancer Molecular subtyping
- The gene expression of tumour cells: can show subtype
- Subtype: oestrogen receptor (ER), progesterone receptor (PR) and HER2 receptor expression. Is either positive or negative
- ER: Gene expression of theoestrogen and progesterone receptorspredicts response tohormone therapy.. It isnot prognostic. Translated into Allred’s score (0-8), a negative result is 0 or 2
- HER2: Gene expression of HER2 predicts response to a monoclonal antibody treatment calledtrastuzumab and indicates apoorer prognosis so normally receive chemotherapy. Either positive or negative
- A cancer that is ER-, PR- and HER2- is termed triple negative. Often PR status is omitted because its the same as ER. Usually given chemotherapy
Treatment for different types of breast cancer
- LCIS: range from observation with annual screening to bilateral prophylactic mastectomy
- DCIS or LCIS: no role for chemo
- Early breast cancer: wide local excision and axillary node surgery (dissection, sampling or sentinel lymph node biopsy) followed by adjuvent breast radiotherapy
breast cancer Deciding on chemotherapy
- In ER+HER- will have discussion about whether to give chemotherapy. If lots of lymph nodes involved give otherwise no
- Oncotype Dxis a predictive test that gives the likeliness of a patientbenefitting from chemotherapy(and hormone therapy),and the likelihood ofcancer recurrence. It is carried out in some ER+ HER2- LN- patients.
Breast cancer: key points on subtype
- Molecular subtyping involves testing ER status, HER2 status, and in some patients oncotype DX
- ER status predicts response to hormone therapy
- HER2 predicts response to trastuzumab and has a poor prognosis
- HER2+ and triple negative cancers are given chemotherapy
- TNM stage and sometimes oncotype DX determine whether chemotherapy is necessary in ER+ HER2- cases
Breast cancer: summary of treatment options
- Local: surgery, radiotherapy
- Systemic treatments: chemotherapy, Hormone therapy
Breast cancer: surgery
- Usually the first treatment patients receive, therapy received after surgery is adjuvant and before is neo-adjuvant
- Breast surgery is either breast conserving or a mastectomy with axillary clearance.
- Side effects of axillary clearance: chronic lymphodema due to impaired lymphatic drainage
- Breast conserving is almost always offered with radiotherapy
- Mastectomies can be followed with reconstructive surgery, either in the same surgery (“immediate reconstruction”) or at a later time (“delayed reconstruction”)
Breast cancer: axillary surgery
- Axillary clearance, sentinel node biopsy or omitted. Axilla surgery gives information about local recurrence, does not affect survival
- Axillary clearance: ≥4 lymph nodes affected
- 1-3 lymph nodes: axillary clearance or targeted axillary dissection
- If ultrasound clear use sentinal node biopsy
- In DCIS axillary surgery is omitted
- Don’t take blood from the same arm axillary clearance surgery has been performed on can cause Lymphoedema
Breast cancer: radiotherapy
- Reduces risk of recurrence less impact on survival
- Given to breast, chest wall and/or lymph nodes
- Can be used to treat distant symptomatic metastases in a palliative setting, e.g. symptomatic bone metastases.
- Carries out 6 weeks after chemotherapy or surgery.
- Risks: rib fracture, sunburn, blistering, lung fibrosis, osteonecrosis
- Contraindications: connective tissue disorder with significant vasculitis, prior radiotherapy, TP53 mutation
When to give radiotherapy in breast cancer
- Mandatory in breast conservation surgery, can be an alternative to axilla surgery
- Should be offered post mastectomy if: tumours >5cm, tumours deep in the breast where surgical clearance is <3mm, 4 or more lymph node metastasis
Breast cancer systemic treatment: Hormone therapy
- Anyone ER+ gets it
- Hormone therapy prevents the binding of oestrogen to oestrogen receptors, inhibiting ER+ tumour cell proliferation
- In premenopausal women use Tamoxifen. Its a SERM that blocks oestrogen receptors in the breast tissue. May be offered a LHRH analogue. Protects against osteoporosis, increases endometrial cancer risk
- In postmenopausal women use aromatase inhibitors. They block non-ovarian sources of oestrogen like fat cells. Reduces recurrence
- Usually started after all other treatment: normally a tablet taken OD for 5 years, can be used neo-adjuvant or in very elderly instead of surgery ‘primary hormone therapy’
Breast cancer systemic treatment chemotherapy
- Usually given as adjuvant therapy to reduce recurrence and improve survival. Can be neo-adjuvant
- Normally have 8 cycles
- Regime options: FEC(fluorouracil, epirubicin, and cyclophosphamide) andEC(epirubicin and cyclophosphamide).
- Taxanes (i.e. docetaxel) can be added in patients with poorer prognosis i.e. node positive patients. Can cause neuropathy but reduce recurrence
Complications of chemotherapy
- Side effects: nausea, weight loss, fatigue, change to skin and nails, immunosuppression, easy bleeding and bruising
- Side effects: deterioration in kidney function, thrombosis
- Severe complications: cardiotoxicity, neutropenic sepsis, death, infertility, secondary malignancy
When to offer adjuvent chemo
- If higher risk of recurrence
- Tumour >1cm
- ER-
- Involved axillary lymph nodes
What targeted treatment is used for HER2+ breast cancer
- monoclonal antibodies that target HER2, such as: trastuzumab (Herceptin), pertuzumab (Perjeta)
- tyrosine kinase inhibitors such as:- neratinib (Nerlynx)
Treatment for metastatic breast cancer
- Radiotherapy for painful bone metastasis
- Aromatase inhibitors
- ER- disease: combination chemo
- Trastuzumab: for relapsed HER2+ disease
- Bisphosphonates in bone metastasis
Preventing breast cancer
- Prophylactic mastectomy
- Ovarian ablation: makes patient post-menopausal reducing breast cancer risk
- Tamoxifen: pre-menopausal
- Aromatase inhibitors: post menopausal
- Increased surveillance: annual mammogram for 5 years
Breast cancer complications
- Local invasion: lymphoedema, pleural effusion, ascites
- Bone metastasis: bone, liver, lung, brain. Spinal cord compression
- Non-metastatic: Hypercalcaemia
