Breast Flashcards
What are the molecular subtypes of breast cancer
Luminal A - ER+, HER2-
Luminal B - two types
ER+/HER2- and PR- or KI67 high
ER+/HER2+
Non-luminal HER2+ - ER-/HER2+
Triple negative (ER-/PR-/HER2-)
How is DCIS risk assessed
What factors are included
Van Nuys Prognostic index
Size (<15mm, >40mm), margin (>10mm, <1mm), grade/histology (Gr1-2 no necrosis, grade 3), age (<40, >60)
What is the management of DCIS
Based on Van Nuys prognostic index
4-6 -> WLE only
7-9 -> WLE + SLNB if large (5cm) or high risk
+/- Adjuvant whole breast RT (26Gy/5#, or tamoxifen if decline)
> 10 -> Mastectomy & SLNB
When is a mastectomy indicated for DCIS
Disease in ≥2 quadrants, or if clear margins can’t be obtained with WLE (curative if clear margins)
What is the follow up after DCIS
annual mammogram for 5yrs
Who gets adjuvant endocrine therapy
All ER+ pts, regardless of HER2 status and stage, after adj ChT. improves OS
Indications for adjuvant bisphosphonates in breast cancer
Post-MP women receiving neo-adjuvant or adjuvant chemotherapy
Pre-MP pts receiving OFS
For up to 5yrs
Duration of endocrine treatment in post-MP pts
High risk (Gr3, Node positive, T3) - 10yrs
Med/low risk - 5yrs
Duration of endocrine treatment in pre-MP pts
10yrs (5yrs minimum)
Indications for breast conserving surgery (WLE)
And what is the acceptable margin
T2 disease or less (<5cm tumour)
Operable multifocal disease in single quadrant
Acceptable margin - 1mm (2mm for DCIS) -> re-excision or mastectomy (or consider RT + boost)
Indications for mastectomy
Pt related: Patient choice, Pregnancy
RT CI: scleroderma, pre-existing cardiac/lung disease, reduced shoulder movement
Or previous RT to breast
Site: Multifocal, Central tumour
Tumour: > 5cm (T3-4), Inflammatory breast cancer, Extensive DCIS
Prophylactic in BRCA carrier
Indications for post-operative RT
What is the benefit of post-op breast RT?
What is the dose
All breast conserving surgery (unless low risk - T1, node negative, Gr1, ER+, and 5yrs endocrine therapy and 10yrs mammogram)
Benefit
N+ pts: Decrease in local recurrence risk 21%; 15yr risk of death reduced by 8%
N- pts: Decrease in local recurrence risk 15%; 15yr risk of death reduced by 3%
26Gy/5# (can consider 28.5Gy/5# over 5wks if frail / co-morbid)
When can post-op whole breast RT be avoided?
> 70yrs, T1N0 (stage 1A), ER+/PR+, Gr1-2 and pt will take endocrine therapy for 5yrs and have mammograms for 10yrs
Indications for tumour bed boost RT
Dose
Benefit
Positive margins (<1mm) and further resection not possible
All <50yrs
Consider for high risk - G3, DCIS, TNBC
Dose: SIB - 48Gy/15# with 40Gy/15 to whole breast
Or sequential boost of 13.35Gy/5# or 16Gy/8# following 26Gy/5#
Reduction in risk of local recurrence by 4%
No benefit on OS.
Indications for chest wall RT after mastectomy
Dose
Benefit
Absolute indications:
T3-4, ≥4 LNs (N2), positive margin (<1mm) or residual disease after NACT in the axilla or breast
Relative indications:
High risk T2 or N1 (1-3 LNs) - Gr3 or LVSI;
Multifocal with largest tumour >2cm (T2)
26Gy/5#
Reduces local recurrence by 20% in high risk groups
8% survival benefit at 10yrs
No benefit for node negative pts
When is internal mammary nodal RT indicated
T4 disease,
N2 - ≥4 axillary LN
N1 (1-3 axillary nodes) & INNER/CENTRAL quadrant tumour
When is SCF RT indicated in breast cancer
N2 disease (>4 axillary LNs)
N1 (1-3 axillary nodes), and G3 / LVI+ / T3 disease, age <50, TNBC
≥ypN1 following NACT
What is the indication for olaparib in breast cancer adjuvant setting
Adjuvant monotherapy for ER+ HER2- or triple negative breast cancer, treated with NACT or adjuvant chemotherapy, in those with BRCA1/2 mutations and PS 0-1
What is the indication for abemeciclib in breast cancer adjuvant setting
Benefit
Adjuvant treatment of hormone receptor positive, HER-2 negative, node-positive breast cancer at high risk of recurrence, defined as either:
N2 (>4 pALN) , or N1 (1-3 pALN) and either tumour ≥5cm (T3) or Gr3
given for 2yrs with AI
6% increase in invasive disease free survival at 4yrs
When is an oncotype score done in breast cancer
If >T1a and node negative, ER+ HER2- disease
Or Nottingham prognostic index >3.4
Over 50yrs: if oncotype <25 - no chemo; >26 - chemo
<50yrs: 21-25 - consider chemo, >26 - chemo
What are the indications for Neo-adjuvant chemotherapy?
HER2+ and ≥T2 (≥2cm) or node positive
T3-4 disease
Node positive disease
Triple negative breast cancer
Inflammatory breast cancer
What Neo-adjuvant regime is given to HER2+ breast cancer ≥T2 or node positive
Acc EC x3 followed by docetaxel x4
Or carboplatin/docetaxel x6
With Phesgo (trastuzumab/pertuzumab)
When is TDM-1 (Kadcyla) indicated
Based on what trial
For residual disease, up to 14 cycles, after NACT and HER2-directed treatment and surgery/RT, in HER2+ early breast cancer
Based on Katherine trial - decreased risk of death and 10% improvement in invasive disease free survival
When is neratinib indicated
For the extended adjuvant treatment of stage 2-3B (T2 or N+) HR+/HER2+ EBC in those who completed adjuvant trastuzumab monotherapy less than one year previously
AND did not receive NACT
OR still had residual invasive disease in the breast or axilla following NA-treatment
Given orally for one year
What is the benefit of trastuzumab and based on what trial
Hera trial
1yr trastuzumab reduces risk of recurrence by 50% vs observation
8% absolute survival benefit
When can a shorter duration of trastuzumab be considered and based on what trial
HER2+ EBC, post NACT with pCR
6mth can be considered instead of 12mths for T1-2 disease with no aggressive characteristics
Based on Persephone trial
When is Phesgo (trastuzumab/pertuzumab indicated)
With neoadjuvant ChT for HER2+ EBC, continued for 6-12mths adjuvantly if initially node positive disease
6mth can be considered instead of 12mths for T1-2 disease with no aggressive characteristics
Given adjuvantly for those found to be node positive (pN+) but who did not receive NACT
Metastatic setting - given until progression
BRCA1
Chr & Inheritance
What cancers are increased in risk and by how much
Chr 17 - AD inheritance
Lifetime risk of breast cancer 45-60%, typically TNBC
Ovarian cancer 15%
BRCA2
Chr & Inheritance
What cancers are increased in risk and by how much
Chr 13 - AD inheritance
Breast cancer lifetime risk 55-85%, usually ER+
Ovarian cancer risk 60%
What is the risk of contralateral breast cancer with BRCA mut?
What is the monitoring
60% (vs 7% in general population).
Annual MRI from age 30yrs
Breast cancer screening criteria
and what is the outcome
Between 50-70yrs - every 3yrs
Can request if >70yrs, but not routinely invited
10% are recalled, 1% require biopsy and 0.5% have cancer
What is the screening for those with a BRCA mutation
Annual MRI age 30-39
Annual mammogram age 40-69
As per population screening >70yrs
What is the screening for those with a TP53 mutation
Annual MRI age 20-49
Consider MRI age 50-69
When is a staging CT abdo/pelvis indicated for breast cancer
N2 (≥4 LNs)
Tumour >5cm (T3)
Aggressive biology
Suspicion of mets
What are the axillary lymph nodes
Level 1: Lateral to pec minor
Level 2: Deep to pec minor
Level 3: Superior or medial to pec minor
What is the CTV for chest wall RT
CTV - skin flaps and scar, extending to deep fascia posteriorly, and excluding muscle and rib cage
What is the CTV for a tumour bed boost
CTV-PTV margin
CTV - clips and tumour bed
PTV margin = CTV +5-10mm
What is the dose constraint for breast RT - ipsilateral lung
V30Gy <17%
V18Gy <15% for two fields & <30% for 3 fields
What is the dose constraint for breast RT - heart
V13Gy <10%
V25Gy <5%
Mean dose ≤2Gy
What is the dose constraint for breast RT - brachial plexus
Max dose <40Gy (as 2.67Gy/#)
What is the dose constraint for breast RT - spinal cord
Max dose <37Gy (as 2.67Gy/#)
What techniques exist to minimise cardiac dose / toxicity
DIBH
MLC cardiac shielding
Wide tangent technique
What test must be sent in metastatic TNBC, and why
PDL1
If >1% - give abraxane and atezolizumab (de novo metastatic disease only)
or Pembrolizumab-ChT if CPS >10
ChT - nab-paclitaxel, paclitaxel, gemcitabine or carbo/gem, if de-novo mBC or progression after >6mths of adjuvant tx
What is given in metastatic TNBC for gBRCA-mut
PARP inhibitor - tucatinib or olaparib
What would a skin biopsy show for inflammatory breast cancer
Dermal lymphatic invasion
Where do phylloides tumours typically metastasise to
How are they typically treated
Lungs
Referral to sarcoma unit
WLE with wide margins, or mastectomy (preferred)
No need for ALND (don’t spread to LNs)
The rates of what are higher with the addition of pertuzumab to trastuzumab & docetaxel in metastatic HER2+ breast cancer
Febrile neutropaenia
≥Gr 3 Diarrhoea
When is internal mammary node irradiation indicated
T4 disease
≥4 axillary nodes positive
Or 1-3 axillary nodes AND inner quadrant tumour
How should doxorubicin be dosed in liver impairment
Serum Bilirubin 20 – 50 micromol/L use 50% normal dose
Serum Bilirubin 50-85 micromol/L use 25% normal dose
Serum bilirubin >85 micrimol/L avoid use
When should staging be considered
T3 or N2 disease in general
What is needed at diagnosis of lobular breast cancer
Where do they tend to recur
How does the prognosis compare
Bilateral MRI as it can be bilateral involvement in 20-30%
Tend to recur at pleural / pericardial surfaces
Survival curves cross at 10yrs and then lobular does worse
who receives a boost in adjuvant RT
All pts <50
positive margins
high risk (Gr 3 or intraductal components)
DCIS management
If untreated, 30-50% develop invasive breast cancer within 10 years
WLE +/- RT (If Van Nuys prognostic index score 7-9)
Surgery - Aim for margin ≥1mm; NICE guidelines = ≥2mm
Adjuvant whole breast RT - 26Gy/5#
Reduces local recurrence following BCS but no effect on OS (2013 systematic review)
Not for SLNB unless large (>5cm) or high risk DCIS
Consider omitting in low grade DCIS - (<10mm, low / intermediate nuclear grade, adequate surgical margins)
Mastectomy & SLNB
Indication: disease in ≥2 quadrants, or if clear margins can’t be obtained with WLE
Total mastectomy with clear margins in DCIS is curative
Endocrine therapy
Offer Tamoxifen/AI (post-MP) to pts who have WLE and decline adjuvant RT
Consider for patients having WLE alone (i.e. RT not recommended) - small reduction in ipsilateral / contralateral recurrence
Follow-up: Post DCIS tx, annual mammogram for 5yrs
what is the Nottingham prognostic indicator calculation
Prognosis following surgery and RT
0.2 x Size + Grade + Nodes (0 LN = 1, 1-3LN = 2, 4+ LN = 3)
Does doxorubicin need to be dose reduced in renal impairment
no
What are the referral criteria due to breast cancer in relatives
Age at diagnosis <40
Bilateral breast cancer or ipsilateral second primary breast cancer
Personal history of ovarian cancer (any age)
First degree relative with breast or ovarian cancer (any age)
Second degree relative with male breast cancer (any age)
Two or more first or second degree relatives with breast and/or ovarian cancer (any age)
Male sex
What numbers for breast staging
2 & 5
T1 <2cm
T2 2-5cm
T3 >5cm
T4 - local invasion - chest wall or skin
What is the absolute risk reduction for whole breast RT in node positive disease & node negative disease
N+: 10yr recurrence - 20% improvement from 60% to 40%
N-: local recurrence rate halved from 30% to 15%
What is the indication for partial breast RT
> 50yrs, Gr1-2, ER+/HER2-, N0, <3cm, clear margins, LVSI negative and will have endocrine therapy for 5yrs
What is the side effect of Enhertu (trastuzumaab deruxtecan)
ILD
Draw out axillary management diagram
x
Draw out HER2+ early breast cancer management diagram
x
Draw out ER+ HER2- early breast cancer management diagram
x
Draw out triple negative early breast cancer management diagram
x
Draw out HER2+ metastatic breast cancer management diagram
x
what determines 1st line management for metastatic HER2+ breast cancer
suitability for docetaxel
Draw out TN metastatic breast cancer management diagram
x
What are the borders for Chest wall RT
midline to mid axillary line
sternal notch or 2cm above contralateral breast tissue
2cm below inferior mammary fold contra laterally
What are the borders for axillary RT
Ipsilateral vertebral bodies to humeral head (inclusive) laterally
3cm above medial head of clavicle
0.5cm below
What are the borders for SCF RT
Ipsilateral vertebral bodies to medial 2/3 of clavicle
3cm above medial head of clavicle
0.5cm below
What are the borders for internal mammary chain RT
Outline mammary vessels
Grow by 5mm to form CTV
Grow further 5mm for PTV
First 3 intercostal spaces
what is given adjuvantly for a recurrence of breast cancer
Adjuvant taxane following surgery for recurrence
When is neoadjuvant treatment not given in early TNBC
T1a-b (<1cm)
Straight to surgery +/- RT
When is neoadjuvant treatment given in early TNBC, and what is the regimen
≥T1c or N+
If T1c - carbo/taxol & EC, then surgery +/- RT
If T2 or N+ - carbo/taxol & EC, with pembro, then surgery +/- RT
when should a genetic referral be done
<40yrs
male
bilateral breast cancer or sequential contralateral primary
hx of ovarian cancer
First degree relative with breast or ovarian cancer (any age)
Second degree relative with male breast cancer (any age)
two or more first or second degree relatives with breast and/or ovarian cancer (any age)
