Breast Flashcards
1
Q
Most common breast cancer genetic syndrome
A
BRCA1/BRCA2
2
Q
Syndromes associated with Breast Cancer
A
BRCA1/2
TP53 (Li-Fraumeni)
STK11 / Peutz-Jeghers Syndrome
NF1
3
Q
Other cancers associated with BRCA2
A
prostate (most common gene alteration in early onset PCA)
4
Q
Is BRCA mutation associated with higher RT toxicity?
A
no
5
Q
Risk factors for breast cancer
A
- Personal history of BCA
- Genetic syndromes
- Endogenous hormone production (increases ovulatory cycle)
- Exogenous hormone usage
- Lifestyle (alc, obesity, physical activity)
6
Q
What percentage of IHC required for ER/PR status
A
1%
7
Q
Strategy to confirm Her2 status
A
IHC –> FISH if equivocal
If 0 or 3 no FISH
If 1 on IHC –> negative
If 2 on IHC –> FISH
8
Q
Screening guidelines
A
For women 45-54 with average risk of BC, annual mammogram +/- clinical breast exam recommended
9
Q
Confirming adequate mammo
A
MLO/CC views, confirm strip of pec major and inframammary fold
10
Q
If architectural distortion –> next step
A
diagnostic mammo
11
Q
BIRADS 0
A
need additional imaging info
12
Q
BIRADS 1
A
Negative –> annual mammo
13
Q
BIRADS 2
A
Benign –> annual mammo
14
Q
BIRADS 3
A
Probably benign –> 6 month FU mammo
15
Q
BIRADS 4
A
Suspicious –> biopsy considered
16
Q
BIRADS 5
A
Highly suggestive of cancer –> bx required
17
Q
BIRADS 6
A
Cancer confirmed
18
Q
Options to reduce contralateral risk
A
- Antiestrogens
Tamoxifen if premenopausal (20 mg/day) x 5 years
Raloxifene 60 mg/day x 5 years
19
Q
Risks of tamoxifen
A
VTE, endometrial ca
20
Q
Risks of AI
A
bone issues
21
Q
BRCA1
A
Risk depends on penetrance, ~65% with contralateral risk of 60%
22
Q
BC type associated with BRCA1
A
TNBC
23
Q
BRCA2
A
Lifetime risk 45-84%, ovarian risk if 15-20%
More prevalent in men, associated with prostate and panc as well
24
Q
BC type associated with BRCA2
A
ER+
25
Lateral extent of breast
mid axillary line (lat dorsi)
26
Rotter's nodes
Intrapectoral (Level 2)
27
Level 3
infraclav/subclav nodes (medial or superior to pec minor)
28
Internal mammary nodes most often involved with which tumors
LIQ
29
Why use breast MRI
multicentric disease --> ineligible for breast conservation
30
Path features associated with risk of local recurrence
1. Size
2. ER status
3. Ki67
31
Path features associated with risk of DM
1. LVSI
| 2. Nodal mets
32
% of clinically node negative pts who have nodal mets
20-30%
33
Luminal A
ER+
PR+
Her2-
34
Luminal B
Triple positive
35
Basal
Aka Her2+
| ER/PR negative
36
Oncotype Dx
21 gene panel to prognosticate and predict response to chemo [16 cancer-related genes, 5 comparator]
37
Margins for IDC
no tumor on ink
38
Margins for DCIS
>2 mm
39
T1
<2 cm
40
T2
2-5cm
41
T3
>5cm
42
T4a
extension to chest wall
43
T4b
ulceration or ipsi satellite nodules / edema of skin (including peau d'orange) which do not meet inflammatory criteria
44
T4c
both T4a and T4b
45
T4d
Inflammatory (changes involving one-third or greater of the skin of the breast)
46
LCIS
benign entity
47
Mgmt of LCIS
- -Observe classical LCIS
- -Resect nonclassical LCIS
- -Consider chemoreduction with Tamoxifen 20 mg/day
48
In breast tumor recurrence risk for DCIS
1% per year (30% at 30 years)
49
IBTR for low grade DCIS
1% per year
50
IBTR for high grade DCIS
2% per year
51
Mix of invasive/DCIS recurrence
50/50
52
Local risk reduction from RT for DCIS
50%
53
How is DCIS diagnosed
90% by routine mammo --> calcs --> spot compression --> mag views
54
Path feature of DCIS
E-cadherin+
| 70% are ER+
55
Pagets of breast association with malignancy
Underlying breast malignancy is present in 85 to 88 percent of cases, and a palpable mass is present in approximately one-half.
56
Treatment of low risk Paget
BCT followed by whole breast RT (local control >85%)
57
Treatment of high risk Paget
Mastectomy (diffuse with positive margins)
58
General treatment of DCIS
excision with negative margins followed by whole breast RT
59
NSABP B-17
RCT of local excision +/- RT
60
B-17 findings
Reduce local failure from 35% to 20%
61
Reduction of DCIS with tamoxifen
3% if ER+
62
Role of RT for DCIS
reduced local recurrence by 50%, no diff in OS
63
RTOG 9804
Low risk DCIS (grade 1-2, wide margins >3mm) randomized to BCS vs. BCS+RT
64
When is APBI ok for DCIS
1. Age >50
2. screening detected
3. grade 1-2
4. size <2.5 cm
5. margins >3mm
65
grade 1 dermatitis
faint erythema or dry desquamation
66
grade 2 dermatitis
moderate/brisk erythema, patchy moist d in skin folds
67
grade 3 dermatitis
moist d in areas other than skin folds, bleeding with minor abrasions
68
grade 4 dermatitis
life threatening consequences, skin necrosis/ulceration, skin graft indicated
69
NSABP B-04
clinically node negative randomized to
1. radical mastectomy
2. simple mastectomy and nodal irradiation
3. simple mastectomy, no nodal treatment with salvage ALND
NO differences between the arms
70
Rate of axillary relapse in B-04 for no axillary mgmt
23%
71
Who can receive hypofractionated WBRT
Anyone over 50 (266 x 15) if sep <25
72
Trials showing equivalence of hypofrac to standard frac
1. Canadian
| 2. UK START B
73
Dose from Canadian hypofrac trial
50/25 vs. 42.5 in 16
| No significant differences in 10 year local, distant, OS or cosmesis
74
Dose from UK START B
50/25 vs. 40/15
Demonstrated improved cosmesis with hypofrac
No diff in locoregional outcomes
75
Candidates for boost
Age <50
LN+
LVSI+
Margin+
76
Boost doses
Younger patients: 250 x 4
| Older (50-60): 250 x 2
77
Study showing benefit to boost
EORTC
Pts <70 with T1-T2N0 with complete resection and ALND decrease in IBRT with boost
Biggest benefit in YOUNGER patients
78
Candidates for APBI
1. Age 60+
2. No BRCA mutation
3. T1 IDC or other favorable histology
4. Negative margins >2mm
5. No LVSI
6. ER+, unifocal, no EIC, node negative
7. no neoadjuvant chemo
79
What dose for APBI for prior RT
45 in 1.5 Gy BID
| Last BCT >1 year prior with negative margins
80
Techniques for APBI
1. Brachytherapy (LDR, HDR)
2. Intracavitary
3. EBRT
81
GEC-ESTRO brachy study findings
Better cosmesis with APBI
| More fat necrosis
82
Mammosite - how much space between balloon surface and skin
1 cm
83
Trial for intracavitary APBI
TARGIT Trial
84
Findings of TARGIT
Similar LF between IORT and EBRT but IORT LF increased on 5 year FU
85
Margins for EBRT APBI
```
CTV= seroma + 1cm
PTV = CTV + 0.8 cm trim from chest wall
```
86
Goal for ratio of PTV to breast volume
<20%
| Non target breast getting 50% of dose <50%
87
APBI doses
1. Formenti: 6x5 QOD
2. Vicini 3.85 x 10 BID
3. MGH 3.4-4 BID (34-40)
88
ASTRO suitable criteria for PBI [IDC]
1. Age >50
2. 2mm margins
3. Tis or T1
89
ASTRO suitable criteria for PBI [DCIS]
1. screen detected
2. low-int grade
3. <2.5 cm
4. 3mm margins
90
ASTRO unsuitable criteria for PBI
Age <40
+margin
DCIS >3cm
91
TAILORx trial
RCT of ER/PR+Her2- women who had midrange Oncotype score (11-25) and randomized to receive either:
a) chemo-endocrine therapy
b) endocrine therapy
92
Findings of TAILORx
Overall, endocrine therapy alone non-inferior to chemo-endocrine therapy in terms of BC recurrence and OS
93
Which TAILORx group possibly benefits from chemo
Young women (<50) with score 16-25
94
Low Oncotype score
<11
95
Mid range Oncotype score
11-25
96
PERSPEHONE Trial
RCT of 6 vs. 12 months of trastuzumab for women with early stage Her2+ BC with primary outcome of DFS
97
Findings of PERSEPHONE
6 mos was non-inferior to 12 mos of herceptin, better toxicity profile
98
N1
1-3 nodes (axillary or IMN only on SLNB)
99
N2
4-9 axillary nodes or IMN
100
N3
>10 axillary nodes OR
infraclav node
axillary and IMN
supraclav
101
Does chest wall invasion count pec invasion
no
102
what causes peau d'orange
dermal lymphatic disruptions
103
Difference between radical mastectomy and modified radical mastectomy
modified does not remove the pecs or chest wall muscles
104
Extended radical mastectomy
breast, axilla, chest wall muscles, IMNs
105
Absolute contraindications to BCT
Prior breast/thoracic RT
Persistently positive margin after re-excisions
Diffuse disease/multicentric
Pregnancy prior to 3rd trimester
106
Relative contraindications to BCT
1. BRCA+
2. Large tumor relative to breast size
3. Anticipated poor cosmesis
4. Connective tissue disease
107
What is benefit of PMRT
10% OS benefit
108
EBCTCG Meta analysis
22 randomized studies of women who received mastectomy and ALND found benefit for
1-3 nodes
4+ nodes
109
PMRT benefit for 1-3 nodes
Lower RR of any recurrence (LRFS and DFS for TNBC)
110
SUPREMO trial
Stage II breast cancer with 1-3 N+ following MRM + ALND with adjuvant or neoadjuvant chemo: PMRT or no PMRT
111
NCIC TailorRT
RCT of PMRT vs,. none in biomarker low risk node positive (1-3+) BC
112
Z0011 trial design
RCT of cT1-2N0 with 1-2 sentinel nodes randomized to whole breast RT and adjuvant chemo or ALND + chemo
113
Findings of Z0011
No difference in 10 year DFS between arms, no need for ALND
114
MA-20 study design
Node positive or high risk node negative women who got BCT to receive WBRT alone or WBRT + RNI with adjuvant chemo
115
MA-20 findings
WBRT+RNI had improved DFS (82% at 10 years vs. 77%); no diff in OS
116
B-51 design
cT1-3N1 BC who get 8-12 weeks of neoadjuvant chemo with negative nodes by SLNB/ALND randomized to
1. mastectomy: PMRT vs. systemic therapy
2. bCT: whole breast RT plus RNI vs. whole breast alone
117
B-51 allowed surgeries
mastectomy or BCT
118
Most powerful predictor of DFS and OS
LN involvement
119
Indications for chemo
1. axillary disease
2. multicentric
3. inflammatory
4. T3/T4
120
Standard regimen
Adriamycin+Cytoxan --> Taxol
121
B18 design
neoadjuvant chemo vs. adjuvant
122
Benefits of neoadjuvant chemo
downstaging to permit BCT
123
How did MA-20 handle the axilla
completion ALND if SLNB+ (levels 1 and 2)
124
AMAROS design
RCT of unifocal invasive cancer cN0 with SLNB+ randomized to
1. ALND
2. axillary RT
125
AMAROS findings
similar axillary recurrence and overall outcomes but > risk of lymphedema in the ALND arm
126
Role of RT for phylloides tumor
1. >2cm tumor size post lumpectomy
| 2. >10 cm tumor size post mastectomy
127
MONALEESA-3
Trial for MBC ER+ who received endocrine therapy: Ribociclib + fulvestrant vs. fulvestrant --> improved PFS and OS
128
Side effect of CDK 4/6 inhibitors
leukopenia
129
Most common site of metastatic spread
Bone > brain, liver, lungs, nodes
130
What are the UK START studies testing
Hypofractionation
131
UK START A
50/25 vs. 41.6/13 or 39/13 over 5 weeks. Boost allowed not required
132
UK START B
50/25 vs. 40/15 over 3 weeks. Boost allowed not required
133
UK FAST Study
Ultra hypofractionation: cT1-2N0 >50 with 50/25 vs. 30/5 or 28.5/5 (once weekly).
134
FAST findings
No IBTR differences, worse cosmesis with 30/5
135
UK FAST Forward trial
pT1-3N0-1 s/p mastectomy or BCS getting 40/15 or 27/5 or 26/5 [over 1 week]
136
Findings off FAST foward
5 fractions non-inferior to 40/15 but possible higher late toxicity with 27/5
137
Dose in Chinese PMRT study
43.5/15
138
What percentage of male breast cancers ER+
80%
139
Mechanism of exemestane
irreversible steroidal AI
140
Mechanism of anastrozole/letrozole
reversible competitors for aromatase [non-steroidal]
141
Objective of B17 trial
RCT of BCS followed by RT for DCIS. Dose of RT was 50/25
142
Risks of breast and ovarian Ca with BRCA1
60% each, endometrial as well
143
Risks of breast and ovarian Ca with BRCA2
55% breast, 17% ovarian
144
Type of BC associated with Li-Fraumeni
ER+/HER2+
145
How many TNBC patients have BRCA mutation
20%
146
Systemic therapy for HER2+
Neoadjuvant AC T + trastuzumab --> adjuvant T-DM1 (per KATHERINE trial)
147
Inflammatory paradigm
Neoadjuvant chemo (+herceptin) --> mastectomy/ALND -->
148
Lymphedema rates after ALND
23% per AMAROS
149
Lymphedema rates after SLNB+RNI
11% per AMAROS
150
SUPREMO trial for PMRT (which groups included)
Intermediate risk post mastectomy
1. T3N0
2. pT1-2N1
3. N0 but grade 3 or LVSI
151
Impact of breast size on cosmesis after hypofrac WBRT
Potentially better in large breasts and should not dissuade from using shorter course
152
Mechanism of tamoxifen
selective estrogen receptor modulator (antagonist in breast, agonist in bone)
153
Cautionary age for PBI
40-49
154
Unsuitable tumor size for PBI
>3
155
Suitable tumor size for PBI
<2
156
Suitable margin status for PBI
>2mm
157
Cautionary LVSI for PBI
limited/focal
158
What is negative ER status considered for PBI
cautionary
159
What is ILC considered for PBI
cautionary
160
How much DCIS is unsuitable for PBI
>3 cm
161
What is required axillary testing prior to PBI
SLNB or ALND
162
What is neoadjuvant therapy considered for PBI
unsuitable
163
Chinese PMRT study design
RCT of PMRT to CW/RNI randomizing 50/25 or 43.5/15, primary endpoint of 5y LRR, noninferiority
164
Finding of Chinese PMRT study
Hypofractionation non-inferior, ~8% risk of 5 year LRR
165
Design of B-21 study
cN0, tumors < 1 cm underwent lumpectomy and randomized to either:
1. Tamoxifen
2. WBRT alone
3. WBRT + Tamoxifen
166
Finding of B21
RT improved IBTR and possibly better even with RT+Tamoxifen but this is less clear
167
Differences between preop/postop chemo
No difference in outcomes
| Decreases size of primary tumor leading to smaller surgical resections and better cosmesis
168
Role of HER2 testing for DCIS
No role and high false + rate. Patients should not get adjuvant herceptin
169
Risks of tamoxifen
Increased risk of endometrial ca, PE/VTE, cataracts
170
Role of SLNB for DCIS
Not routinely performed, can be considered as second procedure if invasive cancer found
171
Situations where SLNB NOT recommended
1. Large and/or locally advanced disease
2. IBC
3. DCIS when BCS is performed
4. Pregnancy
172
Benefit of addition of docetaxel to AC chemo
Significantly improved cCR and pCR rates, but no difference in outcomes or BCS rates
173
PRIME II study
RCT of lumpectomy randomized to receive either WBRT or observation [older women, 65+]
174
Surgery required by PRIME II study
lumpectomy plus path axillary staging (SLNB or ALND)
175
Current guidelines of which lumpectomy patients can avoid RT
Per Hughes trial
1. Age >70
2. pT1
3. ER+
4. Receiving hormonal therapy
176
B-39 trial
APBI trial - randomizes patients to receive either 50 Gy to whole breast with boost to 60-66.6 Gy vs PBI
177
Options for APBI on B-39 trial
1. Interstitial brachy (3.4 x 10 BID)
2. Intracavitary brachy (3.4 x 10 BID)
3. 3DCRT (3.85 x 10 BID)
178
Dose prescription for interstitial APBI
1.5 cm from lumpectomy cavity, PTV >5mm from skin surface
179
Dose prescription for intracavitary APBI
1.0 cm from lumpectomy cavity, PTV >5mm from skin surface
180
Dose prescription for EBRT APBI
1.5 cm from lumpectomy cavity, PTV 1.0 cm expansion and PTV >5 mm from skin surface
181
B-17 IBTR rates
31% with lumpectomy vs. 15.7% with RT
182
Bottom line of Z11
Patients with 1-2 positive nodes on SLNB do not need completion ALND
183
How many risk factors justifies PMRT for T1-2 tumors
```
3
Age <50
Tumor size >2
LVSI
Close or positive margins
No systemic therapy
```
184
What histologic subtype of DCIS has worst prognosis
comedo
185
Danish 82b study design
T3-4 disease or N+
| RCT of mastectomy + chemo or mastectomy +PMRT + chemo
186
Difference between 82b and 82c
82b: premenopausal, got chemo
82c: postmenopausal, got tamoxifen
187
Criticisms of Danish studies
insufficient ax dissection
188
Findings of Danish studies
Benefit in locoregional failure and OS if >8 or >4 nodes removed
189
When should PMRT be offered if neoadjuvant therapy given
If residual axillary disease
190
What features of DCIS on mammo
microcalcs, linear branching are high grade
191
What feature of LCIS on mammo
cannot see it
192
UK IMPORT LOW trial design
3 arm non-inferiority - randomized to
1. WBRT to 40/15
2. WBRT to 36 Gy with boost to 40 Gy
3. PBI to 40/15
193
Findings of IMPORT LOW
5 year local relapse rate same
| Possible advantage in terms of breast appearance for PBI
194
What axillary staging should occur for Phylloides tumor
none
195
10 year BC mortality risk for woman treated with DCIS
1-5%
196
5 year locoregional control for IBC
~85%
197
Dose used in repeat BCT
3DCRT to PBI to 45 Gy in 30 fx BID
198
Inferior border for tangent
1 cm below inframammary fold
199
Superior border for tangent
1 cm above palpable breast tissue (inferior edge of sternoclavicular junction)
200
Lateral border for tangent
1 cm margin on breast tissue (mid-axillary line)
201
Medial border for tangent
mid sternal line
202
Anterior border for tangent
2cm flash on breast tissue
203
Usage of boost in B-17
Very low <10%, most got 50/25
204
From Z11, how many women had additional positive nodes in ALND arm after SLNB
27%
205
Rate of locoregional recurrence in Z11
5-6% at 10 years [1.5% in ipsi axilla]
206
Role of preop RT for IBC
if no response to chemo
207
What does T2 reflect for PBI
cautionary
208
RAPID trial design
RCT for whole breast (50/25 or 42.5/16) vs. APBI (38.5/10), endpoint was cosmesis at 3 and 5 years assessed by trained nurses
209
RAPID results
At 3 years APBI had significantly more adverse cosmesis, more telangiectasia and fat necrosis with APBI
210
DCIS criteria to allow PBI off protocol
1. low intermediate grade (1-2)
2. screen detected
3. size <2.5 cm
4. >3mm margins
211
Mechanism of lapatinib
TKI which interrupts HER2 and EGFR pathway
212
Bevacizumab works against
VEGF-A
213
T1mi definition
<1 mm
214
T1a definition
1-5 mm
215
T1b definition
5-10
216
T1c
1-2 cm
217
pN1mic
0.2mm to 2 mm
218
Multifocal definition
multiple lesions same quadrant
219
Multicentric definition
multiple lesions different quadrant
220
Goal of MA-20 study
Determine if RNI improves survival for N+ or high risk node negative breast cancer
221
Which subgroup had improved OS in MA-20
ER- patients
222
Two arms in MA-20
1. WBRT
| 2. Comprehensive
223
What axillary treatment did patients get in MA-20
All got SLNB or ALND
| Mandated ALND if SLNB+
224
Which outcomes were improved in MA-20 with RNI
1. DFS
2. locoregional DFS
3. Distant DFS
225
What outcome improved with IMN radiation in Danish study
OS (3% improvement)
226
How much of breast affected to be considered IBC
>1/3
227
Anatomic borders for IMN coverage
First 3 intercostal spaces
| Superior to first rib to superior to 4th rib
228
Side effects of taxanes
Peripheral neuropathy, allergic reactions, myalgias/arthralgias
229
Side effects of 5-FU
Mucositis/stomatitis
230
Cancers elevated risk in BRCA2 vs BRCA1
Prostate, pancreas, uveal melanoma, male breast cancer
231
Most common out of field nodal failure location for high risk patients getting RNI
SCV -- consider posterior and lateral SCV nodes
232
EORTC 22922 trial
RNI improved DFS, distant met free survival and BC-specific mortality but not OS
233
Expected false negative rate of SLNB
~10%, can be improved in era of neoadjuvant chemo by clipping involved nodes and ensuring removed
234
4:1 rule
Comes from EBCTG meta-analysis demostrating 20% reduction in IBTR (26-->7%) at 5 years corresponds to 5% absolute reduction in breast cancer survival at 15 years (35.9% --> 30%)
235
Purpose of wedge
decrease hot spot
236
Rates of capsular contraction for irradiating tissue expander
20% grade III/IV but not higher rates of implant revision
237
Difference between APBI and WBRT in B-39
10 year IBTR risk favored WBRT and APBI did not meet equivalence threshold, but difference is small (<1%)
238
In Chinese hypofractionated PMRT trial, what was better for hypofrac arm
Less acute skin toxicity
239
Dose used in Chinese hypofrac trial
43.5/15
240
Rate of lymphedema after SLNB and RNI
5-15%
241
How do outcomes compare for same stage given neoadjuvant vs. adjuvant chemo
LRR is worse in patients given neoadjuvant chemo likely due to downstaging from higher stages
242
Risk reduction of LR for RT after BCS
70% (26% --> 7%)
243
Difference between RAPID and B-39
RAPID did not allow N+, B-39 did
244
Dose used in RAPID trial
38.5 ./ 10 fx
245
Conclusions of RAPID study: IBTR
APBI is non inferior
246
Conclusions of RAPID study: acute tox
APBI is better (less dermatitis/edema)
247
Conclusions of RAPID study: late tox
APBI is worse (telangietasia)
248
OS benefit for PMRT from meta analysis
5% (lower than studies) mainly in N+ patients
249
Characteristics of supraclav field
1. Single anterior oblique beam
2. Angled 5-10 degrees from cervical spine
3. Prescribed to depth 3 cm
250
SCV field for L
Right Anterior oblique
251
What bony landmark can be used to define axillary stations
coracoid process (origin of pec minor)
