Early Stage Breast Cancer Flashcards
(95 cards)
1
Q
What is the T staging for breast cancer?
A
- Tis (DCIS): Ductal carcinoma in situ
- Tis (Paget): Paget disease of the nipple NOT associated with invasive carcinoma and/or DCIS in the underlying breast parenchyma.
- T1mi: ≤ 0.1cm (microinvasive)
- T1a: >0.1 to ≤0.5 cm
- T1b: >0.5 to ≤1 cm
- T1c: >1 to ≤2 cm
- T2: >2 to ≤5 cm
- T3: >5 cm
- T4a: Extension to the CW (not including pectoralis muscle)
- T4b: Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema (including peau d’orange) that does not meet the criteria for inflammatory carcinoma
- T4c: Both T4a and T4b
- T4d: Inflammatory carcinoma
- NB: LCIS is a benign entity and removed from the staging system!
2
Q
What is the MOA of palbociclib?
A
Selective inhibitors of CDK4 and 6
3
Q
What are letrozole and anastrozole?
A
Reversible non-steroidal aromatase inhibitors
4
Q
What is the usual dose of anastrozole?
A
1 mg QD
5
Q
What is tamoxifen?
A
- Selective Estrogen Receptor Modulator (SERM)
– Antagonist in breast
– Agonist in bone, uterus, etc
6
Q
What is the usual dose of tamoxifen
A
20 mg QD
7
Q
What is exemestane?
A
- ExemeSTane:
– Irreversible STeroidal aromatase inhibitor
8
Q
What were the findings of the Paloma-2 study (NEJM 2016) for metastatic breast cancer (MBC)?
A
- Post-menopausal W with (ER+/HER-2/Neu negative) MBC
– ~50% had prior chemotherapy
– ~56% had prior ET - Randomization
– Palbociclib and letrozole vs.
– Placebo and letrozole - Results: Palb + let vs. let
- median PFS: 24.8 mos vs. 14.5 mos
- Conclusion: The degree of benefit and very manageable adverse events profile should make the combination of palbociclib and letrozole a first-choice option for most women with ER+ breast cancer
9
Q
Do you use a bolus w/ PMRT? Why? What kind?
A
- Traditionally, yes, but it is becoming more controversial now
– Skin is at high risk for recurrence
– Bra-mesh bolus or tissue eq bolus may be used
– Bolus is a/w higher skin tox - ESTRO does NOT recommend bolus unless inflammatory, T4, or skin involvement
ASTRO makes no recs either way
10
Q
What is unique to a bolus being used for PMRT?
A
- It can be removed after erythema development
- No need to replan as dosimetric studies show little change in PDD w/ bolus vs. w/o bolus
11
Q
What is the suggested workup for a new dx of DCIS?
A
- H&P
- Diagnostic b/l mammogram
- Pathology review
- Determination of estrogen receptor (ER) status of the tumor
- Genetic counseling (if high risk for hereditary breast cancer)
- Breast MRI as indicated
12
Q
What is gestational breast cancer?
A
- Gestation breast cancer is a cancer that develops:
– Throughout pregnancy
– During lactation
– The first post-partum year
13
Q
What is the approach to the evaluation/management of axilla for a newly dx gestational breast cancer undergoing BCS?
A
- Ambiguous
– ALND: Preferred
– SLNBx: Safety is under question. Iso-sulfan blue dye should NOT be given to pregnant pts 2/2 risk of RT exposure to the fetus, even though the dose is very low
14
Q
What is the brand name for pembrolizumab?
A
- Keytruda
- Hence many studies with pembro are name KEYnote
15
Q
Per Keynote-522, how should IO (Keytruda) be sequenced w/ RT for breast cancer pts undergoing BCS?
A
- Keytruda per Keynote-522:
– ASCO recs IO for TNBC
– Give during neoadj. CHT (200 mg q3wks or 400 mg q4wks)
– Continue after surgery
– 9C or 1-yr total of Keytruda
– Improves pCR rates and EFS
16
Q
What are the NCCN definitions of menopause?
A
- Hx of bilateral oophorectomy
- Age >60 years
- Age <60 and amenorrheic for ≥12 mos in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression
– women < 60 who are on tamoxifen or toremifene must have FSH and estradiol in the post-menopausal range
17
Q
What are the 10-yr LR and DM rates for a Phyllodes tumor?
A
- 10-yr LR: 8%
- 10-yr DM: 13%
18
Q
What factors for Phyllodes tumor make it more likely to metastasize?
A
- Size ≥ 7 cm
- Stromal overgrowth
- Increased stromal cellularity
- Infiltrative borders
- High mitotic count
- Necrosis
19
Q
What is the preferred management of recurrent Phyllodes tumors?
A
- Excision w/ wide-margins
- w/o LN staging
- can consider PORT (Category 2B)
20
Q
Are tangents considered 3d-CRT?
A
Yes
21
Q
What were the randomization and tx arms of the Wang et al., JCO 2020 trial for breast cancer?
A
- Evaluating hypofractionated breast RT (HFRT) w/ boost vs. CFRT w/ boost in the Asian population.
- Randomization:
– CRT: 50 Gy in 25 fx w/ 10 Gy in 5 fx boost
– HFRT: 43.5 Gy in 15 fx w/ 8.7 Gy in 3 fx boost - Results: HFRT vs. CFRT
– Median FU 73.5 mos - 5-yr LR = 1.2% vs. 2% CFRT (p=0.017)
- HFRT had less acute grade 2-3 skin tox. (p=0.019)
22
Q
If a young woman is dx w/ TNBC, what mutation does she likely carry?
A
BRCA1
23
Q
What were the pt populations, tx arms, results and conclusions of the Florence trial (Liv et al. 2015)?
A
- APBI of W ≥ 40 yrs old w/ unifocal, early-stage breast cancer, tumor size ≤ 2.5 cm, w/o EIC, lumpectomy w/ margins ≥ 5 mm
- Randomization:
– 50 Gy/25 fx w/ boost
– ABPI. 30 Gy in 5 fx QOD - Targets: Used IMRT
– CTV = Surg Clips + 1 cm expansion
– PTV = CTV + 1 cm - Results: APBI vs. CFRT at 10-yrs
– IBTR: 3.7% vs. 2.5% (NS).
– OS ~92%
– Breast cancer mortality ~3%
– Less acute and late tox w/ APBI
24
Q
What were the tx arms of the FAST trial for breast cancer?
A
- 50Gy in 25 fx QD
- 30Gy in 5 fx once-weekly
- 28.5Gy in 5 fx once-weekly
25
What were the tx arms of the FAST-FORWARD trial for breast cancer?
- 26 Gy in 5 fx QD
- 27 Gy in 5 fx QD
- 40 Gy in 15 fx QD
26
Which gene is generally lost in LCIS?
- CDH-1 → loss of E-cadherin
- Benign but predisposes pts to breast cancer
27
What is Paget's disease?
- Paget's dz: Crusting, bleeding, pruritus, and ulceration of the nipple
- ~50% will have a palpable mass
- If a mass is detected, then ~90% will have invasive carcinomas
28
Which trial of HFRT for breast cancer included pts w/ *pure* DCIS (no inv. component)?
- DBCG HYPO trial
- Supports the use of HFRT for pure DCIS
29
What were the arms of the NSABP B-39 trial for breast cancer?
B-39 Arms:
1. CFRT: 50-50.4 Gy (Opt boost to 60-66.6 Gy)
2. PBI:
-- Interstitial brach (Rx to 1.5 cm from the cavity): 3.4 Gy x 10 fx BID, 34 Gy total
-- Intracavitary/balloon brach (PTV 1 cm from the balloon): 3.4 Gy x 10 fx BID, 34 Gy total
-- 3D-CRT (15 mm expansion for CTV): 3.85 x 10 fx BID, 38.5 Gy total
30
What were the results of the NSABP B-39 trial for breast cancer?
- Results: WBI vs. APBI
-- 10-yr IBTR: 3.9% vs. 4.6%
*--- Absolute difference of 0.7%
--- APBI did NOT meet the criteria for equivalence and instead favored WBI*
-- There were no significant differences between APBI and WBI for distant DFS, OS, tox or second primary cancers
31
Why is a dynamic wedge preferred over a physical wedge to reduce hotspots w/ tangents used for whole-breast RT?
Physical wedge increases scatter dose to contralateral breast
32
Can prophylactic contralateral breast irradiation be considered for BRCA carriers?
- Yes, per phase II data
- May reduce development of breast cancer by ~10%
33
Is LCIS a unilateral or b/l process?
B/l in 35-60% of the cases
34
Which ET is preferred in high-risk women w/ breast cancer?
Exemestane + ovarian suppression
35
What are the risk factors for the development of DCIS (non-invasive breast cancers)?
- Previous breast biopsy: OR=3.56
- Menopause (≥55, compared with < 45 years old): OR=1.71
- Older age at pregnancy (compared with < 20): OR= 1.68 (20-29 years) OR=1.77 (>30 years)
- Fewer full-term pregnancies: OR=0.86 (for each additional pregnancy)
36
What are the borders of IM nodes?
- Borders:
-- Sup: *Cranial* aspect of the 1st rib
-- Inf: *Cranial* aspect of the 4th rib
37
Which SLNBx trials are BCS only?
- MA.20 and Z-11
- Aside from the Italian IBCSG 23-01 study, if the study has a dash or a dot in the title, it does not include MRM (i.e., MA.20 and Z-11 are BCS only, EORTC 22922 and AMAROS included a subset of MRM, like IBSG 23-01).
38
What was the pt population, randomization, results, and conclusion of the Z-11 trial for DCIS?
- Pts: T1-2, cN0, s/p BCS and SLNBx w/ -margins, and 1-2 sLN+ w/o ECE
-- Excluded: ≥ 3 LNs+, matted LNs, or neoadj. CHT
- Randomization:
1. ALND (I + II)
2. No further surgery
-- All pts received RT and, at the discretion of the tx physician, systemic therapy
- Results: no ALND vs. ALND
-- ALND Group: 27% had additional LN+
-- 10-yr DFS: 80.2% vs. 78.2% (NS)
-- 10-yr OS: 86.3% vs. 83.6% (NS)
-- Regional recurrence: 1 vs. none
39
What RT was recommended in the Z-11 group and what did the pts actually receive?
- Rec RT: WBRT only
- Delivered RT had some modifications
-- 15% received SCV radiation
-- 50% received high-tangents
- This is why some ROs will use high tangents in pts meeting Z-11 criteria
40
How much anterior breast flash is used for tangents?
2 cm
41
When using 30 Gy in 5 QD fx APBI, what are your usual dosimetric parameters?
- PTV
-- V95% = 100%
-- Dmax< 105%
-- Dmin = 28 Gy
- Contralateral breast
-- V15 Gy <50%
-- Dmax < 1 Gy
- Ipsilateral lung V10 Gy < 20 %,
- Contralateral lung V5 Gy < 10%
- Heart V3 Gy < 10%
42
What prophylactic intervention has a demonstrated benefit for decreasing the risk of lymphedema in breast cancer pts s/p ALND?
Compression Sleeves
43
For pts w LCIS s/p lumpectomy, what are the recurrence rates?
Recurrence rates after lumpectomy for LCIS
- 12-yr IBTR: 14%
-- ~1/3 rd are inv.
- 12-yr CBTR: 8%
44
Who can benefit from chemoprevention for breast cancer?
- Women ≥35 yrs, and >10 yr life expectancy, and one of the following:
-- Atypical hyperplasia
-- LCIS
-- Consider with Flat epithelial atypia
-- ≥1.7% 5-yr risk for breast cancer (p`er Gail model)
45
What can be used for chemoprevention for breast cancer?
- Premenopausal - tamoxifen
- Postmenopausal: Raloxifene/tamoxifen/aromatase inhibitor
46
How do outcomes compare between male and female breast cancer pts?
Males have worse outcomes across all stages
47
What are the minimum established criteria for inflammatory breast cancer?
1. Rapid onset of breast erythema, edema, peau d'orange, or warm breast with or without an underlying palpable mass.
2. Flattening, crusting, or retraction of the nipple (not always present).
3. Diagnosis of mastitis not responding to antibiotics for > 1 week.
4. Symptom ≤ 6 months.
5. Erythema ≥ 1/3 of the breast.
6. Pathologic confirmation of invasive breast cancer from a biopsy of the breast.
48
What was the pt population, randomization, results, and conclusion of the NCIC MA.20 trial for breast cancer?
- Pts s/p BCS and SLNBx/ALND:
-- LN+ (cT1-3, cN+). 85% had N1 disease, 5% had N2
-- High-risk LN-. Only 1% of this population had T3 disease
--- cT3 N0
--- cT2+ with < 10 LNs removed on ALND + Gr 3 disease, ER-, or LVSI+) post-lumpectomy breast
- Randomization:
-- WBI (50 Gy in 25 fx)
-- WBI (50 Gy in 25 fx) + RNI (45 Gy in 25 fx)
- Results: no RNI vs. 45 Gy RNI
-- 10-yr DFS: 77% vs. 82% (p=0.01)
-- 10-year breast cancer mortality: 10% vs. 12% (p=0.11)
-- 10-year OS: 81.8% vs 82.8% (p=0.38)
-- Prelim DM: ↓ by 5% w/ RNI
-- Increased lymphedema and radiation pneumonitis w/ RNI
49
What is the ASTRO treatment algorithm for the tx of early-stage breast cancers?
50
Which pts are appropriate for APBI?
51
What is the % risk reduction in LR for pt's w/ DCIS undergoing BCS f/b WBRT with vs. without boost?
- ~ 5%
- 97.1% - 92.7%
52
What were the arms of the START A trial?
1. 50 Gy in 25 fx
2. 41.6 Gy in 13 fx or 39 Gy in 13 fx
* 10 Gy boost was allowed
53
What were the arms of the START B trial?
1. 50 Gy in 25 fx
2. 40 Gy in 15 fx
* 10 Gy boost was allowed
54
Between all the arms of START A and B, which arm had the best cosmetic outcome
40 Gy in 15 fx
55
What % of pts in START A or B received a boost?
~50% balanced across all the arms
56
What were the arms of the NSABP B-06 trial?
1. Total mastectomy
2. Lumpectomy
3. Lumpectomy plus adjuvant RT
57
What were the 20 yr results of the NSABP B-06 trial?
- Lumpectomy + RT vs. Lumpectomy vs. Mastectomy
-- 20 yr IBRT: 14% vs. 39% vs. NA
-- 20-yr DFS: 35% vs. 35% vs. 36%
-- 20-yWr OS: 47% vs. 46% vs. 46%
58
What was the patient population, randomization, results, and conclusion of the FAST-FORWARD trial for breast cancer?
- Pts: pT1-3, pN0-1, M0 s/p BCS (93%) or mastectomy (7%).
- Randomization:
-- 40 Gy in 15 fx
-- 27 Gy in 5 fx
-- 26 Gy in 5 fx
* ~25% of patients received a 10 Gy or 16 Gy boost
- Results:
-- 26 Gy in 5 fx non-inferior to 30 Gy in 15 fx
-- Comparable 5-yr normal tissue effects
59
For APBI, what are the CTV expansions per the NSABP B-39 and the Florence trials?
APBI Expansions:
- Florence: 1 cm → CTV, 1 cm → PTV
- B-39: 1.5 cm → CTV, 1 cm → PTV
60
What were the 15-yr results of the EORTC 22922 trial investigating RNI in LN+ or high-risk LN- breast cancer pts s/p BCS + ALND (76%) or mastectomy + ALND (24%)?
- WBRT/CWRT vs. WBRT/CWRT + RNI
-- 15-yr OS: 70.9% vs. 73.1% (P=0.36)
-- 15-yr DFS: 59.9% vs. 60.8% (P=0.18)
-- 15-yr distant DFS: 68.2% vs. 70.0% (P=0.18)
-- 15-yr rate of any breast cancer recurrence: 27.1% vs. 24.5% (P=0.024)
-- 15-yr rate of death from breast cancer: 19.8% vs. 16.0% (P=0.0055)
61
What outcomes were improved w/ the addition of RT in the UK PRIME II trial?
IBRT: RT vs. no RT
- 10-yr IBTR: 9.5% vs. 0.9%
62
What is the general tx paradigm for inflammatory breast cancer?
- Neoadj. CHT
- Mastectomy + ALND (Lvl I, II)
- RT to CW + SCL LNs
63
What is the % increase in major coronary events w/ each additional Gy of mean heart dose?
- 7.4%
- No threshold
64
What target and dose can be considered for a breast-conserving approach to a second cancer in a breast previously treated w/ BCS + RT?
- Dose: 45 Gy BID
- Target:
-- Lumpectomy cavity + 1.5 cm → CTV
-- CTV + 1 cm → PTV
65
What systemic therapy options exist for pts who do not have a pCR after neoadj. CHT for breast cancer?
Consider further systemic therapy based on molecular features of the breast cancer:
- BRCA1/2+ → PARP inhibitor (olaparib).
- Her2+ → T-DM1 (ado-trastuzumab emtansine) based on the KATHERINE trial
- ER+/PR+/Her2- → ET ± capecitabine or pembrolizumab
66
How does the benefit of an RT boost for breast cancer depend on a pts age?
67
What kind of side effects are a/w an RT boost for breast cancer?
Increased rates of moderate and severe fibrosis
68
What is a common side effect of anastrozole frequently requiring a switch to tamoxifen?
- Myalgias
- Arthralgias
- Vaginal sx
69
What factors are prognostic for a pt w/ DCIS?
70
What are the results of the NSABP B-17 trial for DCIS?
- DCIS, -margins pts only: Excision alone vs. Excision + RT (optional boost)
-- 12-yr EFS = 50.4% vs. 63.6%, p=0.00004.
-- 12-yr IBTR = 31.7% vs. 15.7%, p=0.0005.
-- 12-yr OS = 86% vs. 87% (NS)
71
Should HER2/neu IHC 2+ be initiated on her2-directed therapy?
- No, only those with 3+ IHC are currently initiated on her2-directed therapy
- 2+ IHC should reflex to FISH
72
How much does each mo of adjuvant RT delay increase the risk of recurrence of breast cancer s/p BCS?
- Absolute increased risk: 0.5%
- Relative increased risk: 8%
73
Beyond what cut-off post-BCS does survival start to decrease w/ delays in starting RT?
20 weeks
74
What was the pt population, arms, main findings, and conclusions of the UK IMPORT LOW study for breast cancer?
- Phase 3 non-inferiority trial
-- Women age ≥ 50, unifocal disease, gr 1-3, size ≤3 cm, 0-3 LN+, no neoadj. CHT, and margins ≥ 2 mm
- Randomization:
-- 40 Gy WBI in 15 fx
-- 36 Gy WBI + PB boost to 40 Gy in 15 fx
-- 40 Gy PBI in 15 fx
- Results: Median follow-up of 72.2 months
-- 5-yr LRR: 1.1% vs. 0.2% vs. 0.5% (PBI) (NS)
-- Based on photographs, there was no difference in the mild/marked changes in the breast at 5 years: 23% vs. 22% vs. 18% (PBI) (NS)
-- Patients reported less overall breast appearance change in the partial breast arm compared to whole breast (p<0.0001)
75
What are the NRG guidelines for contouring the CW CTV for PMRT?
- Sup: Caudal border of the clavicular head
- Inf: Clinical reference + apparent loss of contralateral breast
- Ant: Skin (typically includes mastectomy scar)
- Post: Rib-pleural interface (includes pec muscles, chest wall muscles, and ribs)
-- Per ESTRO: pec muscle or ribs are not included
-- Per RADCOMP: ribs are not included
- Lat: Clinical reference + mid axillary line (typically excludes latissimus dorsi muscle)
- Med: sternal-rib junction
76
What is an acceptable systemic option for pre-menopausal women w/ high-risk early-stage breast cancer requiring CHT?
- Exemestane + Ovarian suppression
-- Ovarian suppression is achieved through GnRH agonists
-- Reduces distant recurrence compared to tamoxifen + ovarian suppression
(Results from the TEXT and SOFT trials)
77
What is the risk of breast cancer in women w/ LCIS compared to the gen pop?
- Presence of LCIS → 7-10 x higher risk of developing breast cancer
- LCIS itself is a benign entity that does not impact staging
78
What are some relative contraindications to BCS?
- Known genetic predisposition to breast cancer
- Pathologic p53 mutation (Li-Fraumeni syndrome)
- Active connective tissue disease involving the skin (eg, scleroderma or lupus)
- Hx of prior RT to the area; knowledge of doses and volumes prescribed is important
79
Which malignancies besides breast and ovarian cancers are more common in BRCA2 vs. BRCA1 carriers?
- Prostate
- Pancreas
- Uveal melanoma
- Male breast cancer
80
What implications does HER2 testing have in the tx of DCIS?
- None!
- HER2 testing and targeted therapies are not recommended for DCIS
- B-43: The addition of Trastuzumab to adjuvant RT did not achieve the objective 36% reduction in IBTR rates
81
What were the findings of the EORTC 22922 trial for breast cancer?
- Pts s/p mastectomy (24%) or BCS (76%) and ALND randomized to WBRT/CWRT vs. WBRT/CWRT + RNI
-- RNI improved 10 yr DFS, distant DFS, BCSMS, but NOT OS
-- RNI increased pulmonary fibrosis
82
Which systemic CHT has demonstrated efficacy for brain mets from breast cancer?
trastuzumab deruxtecan
83
What is the false negative rate for a -SLNBx in a pt with cT1-2 cN0 breast cancer?
- ~5-10%
- Can be decreased even more by using 2 dyes (isosulfan blue and radioactive colloid), taking ≥ 1 SLN, and avoiding excisional bx
84
What is the false negative rate for a -SLNBx in a pt with cT1-2 cN+ breast cancer s/p neoadj. CHT?
- FNR > 10%
- Can be reduced by clipping the LNs at dx (before CHT) and removing them at the time of SLNBx
85
What are the rates of lymphedema a/w SLNBx vs. ALND?
- SLNBx: 5-10%
- ALND: 15-20%
86
How does APBI compare to CFRT in terms of acute and late tox?
APBI:
- ↓ acute tox
- ↑ late tox (induration and telangiectasia)
- ↓ cosmesis at 3 yr (by nursing. eq cosmesis by pt self-assessment)
87
What % of cases of LCIS have multicentric disease? What % are b/l?
- Multicentric: 90%
- Bilateral: 35-59%
88
When is pre-op RT indicated in the tx of inflammatory breast cancer?
- In those pt w a poor response to CHT
89
What is the BID fractionation scheme for post-op RT for inflammatory breast cancer?
- 45 Gy in 30 fx BID w/ a 15 Gy boost
- Total: 66 Gy
90
What is the BID fractionation scheme for pre-op RT for inflammatory breast cancer?
- 51 Gy in 34 fx (BID)
91
Which inflammatory breast cancer should be considered for dose escalation?
- Patients < 45 years
- Less than a partial response to chemotherapy
- Positive, close, or unknown margins
92
What are the complications w/ dose escalation (66 Gy vs. 50 Gy) for inflammatory breast cancer?
- 60 Gy vs. 66 Gy for inflammatory breast cancer:
-- Grade 3-4 late complication was 29% (66 Gy) vs. 15% (60 Gy), p=0.08
-- Lymphedema 9% vs. 2.5%
-- Fibrosis 6% vs. 4%
-- Brachial plexopathy 2% vs. 0%
93
What were the outcomes for pts w/ inflammatory breast cancer at MDACC tx w/ post-op RT to 60 Gy or 66 Gy?
- 5-yr LRC: 76%
- 5-year distant metastasis-free survival: 40%
- 5-yr OS: 44%
94
What was the main outcome in the keynote 522 trial for breast cancer tx w/ or w/o noadj. and adj. pembrolizumab?
- W/ pembrolizumab
-- pCR: 51% → 65%
-- 1.5 yr EFS: 85% → 91%
95
Is there a benefit to routine resection of additional margins from the lumpectomy cavity?
- Yes
- decreases +margin rates: 34% → 19%
- Chagpar, NEJM 2015
