Breast Flashcards
How is the Nottingham Prognostic Index Calculated?
(Size (cm) x 0.2) + N + G
Where:
N = 0LN=1, 1-3LN=2, >3LN=3
G1 = 1, G2 = 2, G3 = 3
What are the Nottingham Prognostic Index stage groupings?
2-2.4 - Excellent 93% 5 year survival
2.4-3.4- Good 85%
3.4-5.4 - Moderate 70%
>5.4 - Poor 50%
What are the classical characteristics of a fibroadenoma?
Highly mobile discrete breast lump typically diagnosed in teens/twenties.
Should be excised if >4cm, concerns over histopathology or patient choice
13% of all palpable breast lesions (60% of 18-25)
How are tubular adenomas of breast diagnosed?
On histopathology they are comprised almost entirely of glands with little intervening storm.
Treat similarly to fibroadenomas.
Similar to lactating adenoma in lactating women
What are the characteristic mammography findings of a hamartoma?
1) Circumscribed area of soft and lipomatous tissue
2) Surrounded by thin radiolucent zone
How frequently should patients with the BRCA1/2 gene mutations be imaged?
Annual MRI 30-49, annual mammography 40-69
What is the minimum excision margin recommended for Invasive breast cancer and DCIS?
1mm
What is the management of Paget’s disease of the Nipple?
Excision of nipple areolar complex and radiotherapy
In patients with ER positive breast cancer, which trial was suggestive of clinical benefit to Tamoxifen?
The Early Breast Cancer Trials Collaborative Group (EBCTCG) showed 5 years of tamoxifen reduces recurrence and improves overall survival for the first decade.
What dose of radiotherapy is used for the treatment of bony metastases from breast cancer?
8Gy
What classification system is used for breast capsular contractures?
Baker Classification:
1: Breast soft, impalpable implant
2: Breast solid, implant palpable but not visible
3: Breast hardened, implant is palpable and visible
4: Breast is hard, deformed and painful. Implant is palpable and clearly visible
What condition does a biopsy reported as sclerosing lymphocytic lobulitis suggest?
Diabetic mastopathy
What is the difference between Duct Ectasia and periductal mastitis?
Duct ectasia - older, non smokers creamy yellow
Periductal mastitis - younger, smokers, creamy yellow and green
What is Mondors disease?
Inflammation of breast vein, leading to erythema of overlying skin and underlying hard structure (palpable vein).
Usually treated conservatively with anti-inflammatories and generally never affects upper inside aspect of breast
What are the histological characteristics of fat necrosis?
Anucleate fat cells surrounded by histolytic giant cells
In what circumstances should breast MRI be offered to people with invasive breast cancer? (3)
1) If there is discrepancy regarding extent of disease from examination, mammography and USS
2) If density precludes accurate mammography
3) To assess tumour size if breast conserving surgery is considered in Lobular Cancer.
When should the axilla be staged?
In all patients with early invasive breast cancer, and any abnormal LNs should have USS guided FNAC
When should genetic testing be offered to women diagnosed with breast cancer?
To women <50 with triple -ve breast cancer
Testing for BRCA1 and BRCA2
When and how is SLNB performed?
In all patients with invasive cancer, no obvious nodes on USS.
In patients with DCIS if they are high risk - palpable mass, extensive disease
Dual technique - isotope and blue dye (NSABP-B32 trial showed more accurate)
When should patients be offered further axillary treatment after SLNB?
If there are MACROmetastasis i.e. >2mm present (not micro metastasis <2mm).
If there are 1 or 2 macrometasis and the patient will already be having whole breast radiotherapy and systemic therapy, it may be appropriate to omit clearing the axilla (NICE - could have POSNOC trial)
Can offer clearance or axillary radiotherapy
Isolated tumour cells only should be regarded as node-negative
What are the different patterns of complications after immediate and delayed breast reconstruction?
Immediate - lower tissue breakdown
Delayed - lower mastectomy site complications, flap or implant failure, capsular contracture
What tool is recommended for estimation of prognosis in breast cancer?
Predict 2.0 tool.
In whom is Predict less accurate? (4)
Women <30 ER+
Women ≥70
Women >5cm tumours
Men
What endocrine therapy should be offered for patients with breast cancer?
Premenopausal ER+ –> Tamoxifen
Postmenopausal ER+ low risk –> Tamoxifen
Postmenopausal ER+ medium/high risk –> Aromatase inhibitor
In premenopausal women, also consider ovarian suppression (oophrectomy or radiation menopause)
What are the risks of Tamoxifen treatment?
Thrombosis, endometrial cancer, osteopenia (premenopausal)
In what circumstances is endocrine therapy recommended for DCIS?
BCS without radiotherapy ER+
No effect on OS, but lower rates of DCIS/Invasive cancer at 5-10 years
What adjuvant treatments should be offered to patients with breast cancer?
A regime containing both
1) a taxane (Paclitaxel, Docetaxel)
2) an anthracycline (Epirubicin, Doxorubicin)
Sometimes adding in Cyclophosphamide or 5-FU.
What are the benefits of adding a taxane to an anthracycline containing regimen?
Reduced dose of anthracycline - reduced risk of cardiac toxicity and second malignancies, reduced risk of side effects
Additional side effects of joint and muscle pain, nerve damage, febrile neutropenia
Given as 9-12 week course
When should Trastuzumab be used?
T1c+ HER2+ breast cancer
Given at 3 weekly intervals for 1 year
Consider at T1a/T1b
What are relative contraindications to trastuzumab use?
LVEF≤55%
History of CHF, MI, Angina Pectoris or Cardiomyopathy
Cardiac Arrythmia, valvular heart disease pericardial effusion, poorly controlled hypertension
How should cardiac function be assessed during Trastuzumab treatment?
Baseline cardiac function + repeat every 3 months
If LVEF drops by ≤10% or to below 50%, stop
Repeat every 6 months until 24 months after stopping
When should bisphosphonates be used in patients with breast cancer?
1) N+ invasive cancer
2) N- high risk
Risks - osteonecrosis of jaw and external auditory canal, atypical femoral fractures
What radiotherapy should be offered to patients with breast cancer?
BCS with clear margins - whole breast radiotherapy, 40Gy in 15 fractions
BCS with clear margins and low risk of recurrence and having adjuvant treatment - partial breast radiotherapy (external beam)
Consider omitting if very low risk of local recurrence. Risk of recurrence is still reduced from 0.5% to 0.1% at 5 years, but OS is the same at 10 years
Consider for DCIS with clear margins
When should radiotherapy be given to patients after mastectomy?
1) N+ or R1
2) Consider if T3/T4
Radiotherapy to nodal areas is given when?
1) To SCF with 4+ LNs
2) To SCF if 1-3LNs + other poor prognostic factors
3) Consider including internal mammary chain in radiotherapy field if N+
What are the indications for neoadjuvant chemotherapy in breast cancer?
If HER2+ve Consider neoadjuvant chemotherapy, trastuzumab and pertuzumab combination
IF ER-ve consider chemo to reduce tumour size
If ER+ve consider chemo to reduce tumour size if chemo is indicated, otherwise can consider endocrine therapy (if postmenopausal)
What chemotherapy is typically used in the neoadjuvant setting in Breast cancer
Anthracycline +/- taxane +/- platinum
How should patients treated for breast cancer be followed up?
1) Annual mammography (including for DICS) until screening age or at least 5 years from diagnosis (not ipsilateral after mastectomy)
What is the NHS breast screening programme?
1) Starts at 50-53
2) Every 3 years until 71
3) beyond 71 if choose to
What are the chemotherapy options for advanced breast cancer?
1st line - docetaxel
2nd line - vinorelbine or capecitabine
3rd line - capecitabine or vinorelbine
How can risk of Breast cancer gene mutations be estimated? (e.g BRCA1 BRCA2 etc)
BODICEA tool or Manchester Index
When is Oncotype DX indicated for use?
ER+Her2-ve LN-ve breast cancer of intermediate risk
Why is trastuzumab ineffective for Brain metastases?
It does not cross the BBB
What is lapatinib?
It is a dual TKI - interrupting both the HER2/neu and EGFR pathways. Can be used if relapse on Herceptin
How do bisphosophonates work?
Reduce osteoclast activity and decrease bone resorption.
Side effects - renal impairment, osteonecrosis of jaw
Alendronate/risedronate (PO), Pamidronate (IV)
Nb Raloxifene SERM
What are the USS features of suspicious lymph nodes in the Axilla?
Shape - round (not elliptical)
Increased size
Absence of fatty hilum
Thickened/irregular cortex measuring >3mm
What evidence supports the use of SLNB?
ALMANAC trial
- SLNB vs Axillary clearance
- Improved QoL and arm morbidity with SLNB - no difference in DFS/OS
How are intraoperative SLNB assessed?
Frozen section (half LN snap frozen and analysed)
- Sens/specific
- requires pathologist, only half node
Touch imprint cytology (TIC half LN imprinted on slides and assessed)
-High specificity, low sens, cheap
- cytologist required
One step nucleic acid amplification assay (OSNA -whole node homogenised and PCR)
- Very sensitive and specific
- Expensive, tissue destroyed, some false positives
In what percentage of patients with a +ve SLNB will there be further positive lymph nodes?
47-68%
How should the Axilla be treated where this is indicated?
For T1-T2 cancers the AMAROS study demonstrated equivalent 5-year recurrence between radiotherapy and ANC (1.19% vs 0.43%), with less morbid with radiotherapy
What percentage of breast cancers have a genetic cause?
4-5%
Rises to 25% for under 30s
How would you classify risk of developing breast cancer?
Population risk - 17% lifetime, 10 year risk <3% 40-49
Moderate risk - 17-30% lifetime, 10 year risk 3-8% 40-49
High risk - >30% lifetime, 10 year risk >8% 40-49, >20% chance of faulty BRCA1/2/TP53
What are the cancer risks associated with BRCA 1/2?
Breast 1>2
Ovarian 1>2
Prostate 2>1
Also risk of melanoma, colon, haematological
What are the pathological characteristics of BRCA2 breast cancers?
Similar to non-familial, lower grade, more ER/PR, more DCIS. Mammograms more useful
What are the pathological characteristics of BRCA1 cancers?
High grade, less ER/PR, less DCIS, mammograms less sensitive
More basal cytokeratins - CK5/6, CK14, CK17
How should patients with TP53 mutations be screened for breast cancer?
Annual MRI (high risk of radiotherapy induced cancer) from 20
How should high risk patients be screened for breast cancer?
> 30% lifetime
–<30% BRCA - annual mammography 40-59
–>30% BRCA - annual MRI 30-49 then mammography
What syndromes are associated with increased breast cancer risk?
Li-Fraumeni (TP53) - 18 fold increased risk, annual MRI from 20
Cowden (PTEN/SEC23B) - 85% lifetime
Hereditary diffuse gastric cancer (CDH1 gene) - invasive lobular
Peutz Jaegers (STK11 gene)
Lynch syndrome (MSH6 and PMS2) - x 2 4isk
PALB2 station (similar to BRCA2) - 33-58% risk
CHEK 2 mutation (tumour suppressor) - double in F and x10 in M
What are Wilson and Jungners principles of screening?
1) Condition should be important
2)The natural history of the disease should be understood
3) There should be a recognisable latent stage
4) There should be a suitable, acceptable test
5) There should be a policy and accepted treatment for patients
6) Facilities for diagnosis and treatment should be available
7) The costs should be balanced agains the benefits
What are the features of invasive lobular breast cancer?
Small round tumour cells in single file pattern
More difficult to detect by standard imaging (use MRI)
Frequent late recurrence and poorer OS
Higher immune activity
Increased metastasis to ovary and GI tract, less to other viscera
Lower response to NAC and tamoxifen
Lack of E-cadherin expression (CDH-1)
More likely to be ER+/PR+, less likely HER2 +
Lower Ki67 positivity
When is a popcorn density seen with a breast lump?
An involuting fibroadenoma
What drug causes of gynaecomastia are there?
Spironolactone, cimetidine, digoxin, cannabis, finasteride, oestrogen, anabolic steroids
Rarely - tricyclics, isoniazid, Ca channel blockers, heroin, busulfan, methyldopa
When should patients with DCIS be offered a mastectomy?
Generally >40mm
What is the risk of breast cancer where first degree relatives have already had the disease?
Background risk of 17%
1st degree relative <40 - 1/6
2 1st degree relatives <40 - 1/3
3 1st degree relatives <60 - 1/4
What levels of Axillary lymph node dissection are there?
Level 1 - Inferior to pectoralis minor
Level 2 - Posterior to pectoralis minor
Level 3 - Superior to pectoralis minor
Other LN classification according to anatomy - lateral, pectoral, scapular, central, subclavicular and interpectoral
‘Rotter nodes’ are inter pectoral nodes (Level 2)
What is Polands syndrome?
Congenital absence of breast along with Pectoralis Major. Clasically unilateral.
R>L and M>F.
Caused by vascular anomaly, all muscles and possibly arm
What are the characteristics of a breast angiosarcoma?
<1% of all tumours
Primary 30-50 years very rare
Secondary in older women, median 10.5 years after radiotherapy
Usually treat with mastectomy and adjuvant chemotherapy
What are the types of breast cancer?
Ductal
Lobular
Special - tubular, cribriform, medullary, mucinous, papillary - good prognosis
What is the characteristic histological finding of a medullary breast cancer?
Marked Lymphocytic infiltrates
In what percentage of patients with negative Level 1 axillary lymph nodes will have skip metastases in level 2/3?
about 3%
What are the types of DCIS?
Papillary
Cribiform
Solid (high grade)
Comedo (high grade)
What is the Van Nuys prognostic index?
VNPI - used to determine likelihood of local recurrence.
Comprised of tumour size (15mm, 16-40mm, 41mm+), margin width (≥10mm, 1-9, <1mm) and pathology
What is a Phyllodes tumour?
Similar to FA - arising from periductal stromal cells of the breast.
60% benign, 30% malignant
Usually treated with surgery +/- DXT
What is the risk of developing a breast cancer with atypical ductal hyperplasia?
Difficult to differentiate from DCIS. If >2-3mm - prob DCIS
17% increased risk of breast cancer over 10 years - usually treated with excision biopsy, –> upstaging in 18%
What are the radiological criteria for diagnosis of a radial scar?
1) Central radiolucency
2) Radiating long thin spicules
3) Varying appearance in different projections
4) Radiolucent linear structures parallel to the spicules
5) Absence of palpable mass
What is the most common cause of bloody nipple discharge?
Intraductal papilloma
What were the SOFT and TEXT trials?
SOFT - Tamox vs Tamox + ovarian suppression vs Exemestane + Ovarian suppression
TEXT - Tamox + ovarian suppression vs Exemestane + Ovarian suppression
SOFT - ovarian suppression increases DFS and OS
TEXT - exemstane>tamoxifen in HER2-ve receiving chemo
What are the types of aromatase inhibitor?
Type 1 (irreversible, steroidal) Exemestane
Type2 (reversible, non-steroidal) - Anastrozole/letrozole
What is a mammary duct fistula?
May occur following I&D - persistent defect adjacent to nipple areolar complex
Best treated by excision
When is a Halo sign seen?
With benign breast cysts (compressed fat rings)
How is LCIS managed?
Controversial, but direct malignant potential of this lesion is unclear, and generally can be excised in non-oncological fashion.
Require close observation, as 7 x increased risk of breast cancer
Probably should have hormonal treatment
What nerve injuries can occur with breast surgery?
Long thoracic nerve injury - axillary dissection - winging of scapula
Intercostobrachial neve injury - crosses axilla - paraesthesia of axilla
Thoracodorsal trunk - LD (functionally ok, but cannot use for recon)
What are the indications for chest wall radiotherapy in breast cancer?
+ve LN orT3/T4 or involved margins
Possibly: (but not NICE)
2 or more of:
1-3LN
Grade3
LVI
ER-ve
Age<40
What lymphatic network drains the subareolar region?
The network of Sappey
What lymphatic plexus provides a route for haematogenous spread of metastasis to the spine?
Batson plexus
How is pseudogynaecomastia differentiated from true gynaecomastia
In the pseudo there is accumulation of subareolar fat (rather than glandular tissue)
What is the most common cause of non-lactational breast infection?
Staphylococcus Aureus
What effect does smoking have on the breast?
Change in epithelium of breast duct (keratinising squamous metaplasia)
When should breast cyst aspirate be sent for cytology?
When blood stained.
Complicated cysts should have a core biopsy
What type of breast discharge is most concerning
Bloody or serous types
What treatment do patients with Atypical Ductal Hyperplasia require?
Excisional biopsy (without worrying about margins)
Adjuvant tamoxifen
How do lobular cancers appear histologically?
growing in a linear pattern infiltrating between tissue planes.
Single cells are difficult to distinguish from lymphocytes and SLNB is challenging to interpret
In what proportion of SLNB are lymph nodes not identified?
<5%
10% false negative
When is breast radiotherapy most effective?
When given sequentially after chemotherapy.
High energy has a skin preserving effect as maximal potential deeper
How often is a complete pathological response seen with NAC in triple -ve breast cancer
20-45%
What are contraindications to a nipple sparing mastectomy?
Extensive IDC, Paget’s disease, cancer within 2cm of nipple
How can a Phyllodes tumour be distinguished from a Fibroadenoma?
> 30% proportion of long spindle nuclei amid dispersed stromal cells and stromal hypercellularity
What proportion of patients with bloody nipple discharge have a malignancy?
10%
What is the optimum treatment for inflammatory breast cancer?
Neoadjuvant chemotherapy followed by mastectomy
What is the most common type of breast lymphoma?
40-70% diffuse large B cell lymphoma.
Primary >Secondary
Treat as standard lymphoma, although can be excised if small and low grade
Predisposed for CNS recurrence
Who should be offered annual MRI Surveillance (4)?
• aged 30- 49 years who have not had genetic testing but have a greater than 30% probability of being a BRCA carrier
• aged 30- 49 years with a known BRCA1 or BRCA2 mutation
• aged 20- 49 years who have not had genetic testing but have a greater than 30% probability of being a TP53 carrier
• aged 20- 49 years with a known TP53 mutation.
Who should be offered annual mammogram surveillance (3)?
• aged 40- 49 years at moderate risk of breast cancer
• aged 40-59 years at high risk of breast cancer but with a 30% or lower probability of being a BRCA or TP53 Carrier
• aged 40- 59 years who have not had genetic testing but have a greater than 30% probability of being a BRCA carrier
What is the 5 year survival of breast cancer with bony metastasis?
20% at 5 years
More common in ER+ve and well differentiated
Most common in vertebrae
What scoring system can be used to stratify risk of pathological fracture in bony metastasis from breast cancer?
Mirel scoring system (Site, appearance, width of bone, pain)
If 8+ consider fixation
What is the T staging for breast cancer?
T1 <2cm
T2 2-5cm
T3 >5cm
T4 invading chest wall (not pec major) or skin
What is the N staging for breast cancer?
N1 - 1-3 nodes
N2 - 4-9 axillary or any internal mammary (without axilla)
N3 - 10 or more axillary or supraclavicular
When should patients with breast cancer receive a staging CT scan?
If >3cm in size or LN involved
Generally who should receive chemotherapy in breast cancer?
If LN +ve –> adjuvant
If HER2+ve or Triple -ve –> Neoadjuvant
Which patients who have had a mastectomy require additional radiotherapy?
If >4cm, skin or muscle involvement or +ve LNs
How should small FAs in young patients be managed?
If <25 and <4cm rescan at 3-6 months to exclude Phyllodes
What is the risk of breast cancer with 2 FDR <40?
1 in 3
1 first degree relative affected aged <40= 1 in 6
2 first degree relatives under 40 = 1 in 3
3 first degree relatives under 60= 1 in 4
What is the most common infective organism for breast abscesses (lactational and not)?
Staphylococcus aureus followed by coag negative staph.
Nb periductal mastitis is non infective
What is the pattern of lymphatic drainage of the breast?
70% Axillary
Internal mammary chain
Deep cervical and SCF (late)
What is the blood supply of the breast?
Arterial
-Internal mammary (thoracic)
-External mammary (laterally)
-Anterior intercostal
-Thoraco-acromial
Venous
-superficial venous plexus to subclavian, axillary and intercostal veins
What are the boundaries of the axilla?
Anterior - lat border pec major
Laterally - humeral head
Medially - chest wall and serrates anterior
Floor - subscapularis
Fascia - clavipectoral fascia
What are the contents of the axilla?
Long thoracic nerve of Bell (C5-C7 Serratus anterior)
Thoracodorsal trunk/nerve (LD)
Axillary vein (at apex) –> SCV at outer 1st rib
Intercostobrachial nerves (axillary skin)
Lymph nodes
What treatment is offered for pleomorphic LCIS?
WLE + Radiotherapy (treat like DCIS)
- marked distension of lobules with variation in nuclear size
When should HER2 + ve patients omit neoadjuvant treatment?
If small <15mm
How can ovarian suppression be achieved?
Triptorelin (GnRH blocker) or Goserelin (or radiotherapy or Oophrectomy)
Usually if <35
When is Tamoxifen typically given these days?
ER + Ve Age >40 premenopausal
5 years if low risk otherwise 10 years.
what excision margin is required for a phyllodes tumour?
> 1mm
what is the sensitivity of nipple cytology?
11.1-16.7%
what is he overall impact of adjuvant radiotherapy?
50% reduction in first recurrence
what is the risk of contralateral breast cancer in patients diagnosed in the other breast?
2-3%
what is the rate of node positivity in patients having SLNB for DCIS with mastectomy
1%
How should patients with epithelial cells in a Nipple discharge be treated?
Microdochectomy
What are the types of therapeutic mammoplasty?
Level 1 <20% volume, no skin
Level 2 <50% plus skin
What can be used to reduce breast cancer risk in high risk women?
Tamoxifen or raloxifene (if post menopausal) for 5 years
What are the standard mammographic views?
Craniocaudal
Mediolateral oblique
What is the increased risk of invasive cancer with LCIS
X 10 risk
Which cancers are included in the Manchester scoring system?
Pancreatic
Prostate
Breast
Ovarian
Stratified by age
Which male patients with gynaecomastia should be referred?
Painful, normal blood tests for 6 months
In the absence of a mass what is the most likely underlying diagnosis in Paget’s disease of the nipple?
DCIs 70% IDC 30%
What tumour marker may be useful in metastatic breast cancer?
Ca27.29
What factors are considered in the van nuys prognostic index?
Size
Grade
Margin
Age
What is the mechanism of an Anastrozole?
Blocks conversion of androstenedione to oestrone
How frequently are patients called back after mammographic screening?
1/25
Of whom 25% Ca
Reduction in mortality of 30%
What is the predominant blood supply to the nipple?
Internal mammary artery
What investigations should be arranged for patients with suspected metastatic breast cancer?
CT CAP
Isotope bone scan (because long bones and skull not visualised)
How should patients with metastatic breast cancer be treated?
If ER Positive
- Ovarian suppression + tamoxifen if perimenopausal or aromatase inhibitor if post menopausal
- Add chemotherapy if imminently life threatening (combination e.g. doxorubicin and capcetibaine)
- Men = tamoxifen
- NB HER2
Consider bisphosphonates
if ER-ve –> combination chemotherapy
What USS features are suggestive of lymph node metastasis?
Round rather than elliptical shape
Increased size
Absence of fatty hilum
Thickened/irregular eccentric cortex >3mm
When should adjuvant radiotherapy be given after surgery/chemotherapy?
Within 6 weeks
What are the risks of adjuvant radiotherapy?
Early - fatigue, skin erythema/desquamation
Intermediate - Radiation pneumonitis, breast firmness/shrinkage
Late - lymphedema, cardiac toxicity, angiosarcoma
Where may scars from breast recons be located?
How should an extruded breast implant be managed?
Removal, antibiotics and delayed reconstruction
What is the preferred adjuvant treatment for breast cancer?
Dose dense AC (Doxorubicin + Cyclophosphamide) followed by paclitaxel
