Breast Flashcards
1
Q
What was study population for EBCTCG DCIS meta-analysis?
A
N = 3729 pts, DCIS s/p lumpectomy, WBrT vs observation, combined data from SweDCIS, EORTC, UK/ANZ and NSABP B17 trials
2
Q
What were results of EBCTCG DCIS metanalysis in terms of IBTR? BCM?
A
~50% reduction in IBTR (28% vs 13%), no reduction in BCM (or OS benefit)
3
Q
What was study populton for NSABP B-17?
A
N=818 pts, DCIS s/p negative margin resection, 50 Gy WBRT vs observation
4
Q
What were results of NSABP B-17 in terms of IBTR?
A
50% reduction in IBTR (32% vs 16%), benefit observed for both DCIS and invasive recurrences, no survival benefit
5
Q
What was study population for SweDCIS trial?
A
N = 1067 pts, DCIS <1/4 of breast s/p WLE sector resection, 50 Gy WBRT vs observation
6
Q
What were outcomes of SweDCIS on IBTR?
A
~50% reduction in IBTR (27% vs 12%), less effect observed with younger age
7
Q
What was study population for EORTC 10853?
A
N = 1002, DCIS s/p WLE, 50 Gy WBRT vs observation (5% received boost)
8
Q
What were outcomes of EORTC 10853 in terms of IBRT?
A
~50% reduction in IBTR; 10 yr (26% vs 15%), 15 yr (31% vs 18%), benefit also observed in positive margin and high risk pts in this trial
9
Q
Are there data supporting BCM benefit for addition of RT for DCIS post-lumpectomy?
A
Yes, Giannakeas SEER analysis (JAMA, 2018) demonstrated 15-yr BCM benefit with lumpectomy + RT with clear benefit for grade 3 and tumors 1-1.9 cm and >5 cm. *Interpret large database studies with caution as have been shown to correlate with Ph3s at essentially chance
10
Q
Does risk impact benefit of RT s/p lumpectomy for DCIS patients?
A
Yes, Sagara SEER (2016), propensity score matching. High nuclear grade, young age, large tumor associated with greater survival benefit. BCM improved across all subcategories. *Interpret database analyses with caution, has not been replicated in RCTs
11
Q
What is the approximate recurrence rate of low risk DCIS post-lumpectomy per year on RTOG 9804 (adjuvant RT vs observation)?
A
1% per year (11.4% at 12 years)
12
Q
What was the benefit of adjuvant RT compared to observation after lumpectomy on RTOG 9804 (low risk DCIS)?
A
Reduced LRR and mastectomy rates, no benefit on OS
13
Q
What were the rates of IBTR at 5 and 12 yrs from the ECOG ACRIN E5194 study (WBRT vs observation) for low/intermediate and high grade?
A
5 yrs: 6.1% low/int, 15.3% high<br></br>12 yrs: 14.4% low/int, 24.6% high
14
Q
How does age impact IBTR lifetime risk on ECOG ACRIN E5194 (WBRT vs observation for DCIS post-lumpectomy)?
A
Age <45 yrs 54% recurrence, age >45 10%
15
Q
What the principal geographic pattern of recurrence of DCIS post lumpectomy without RT or tamoxifen?
A
In same quadrant (74% per Harvard series)
16
Q
What were the arms of the UK/ANZ DCIS trial?
A
1) observation, 2) TAM x 5 years, 3) WBRT 50 Gy, 4) RT + TAM
17
Q
What benefit was observed with tamoxifen in patients that received RT on the UK/ANZ DCIS trial?
A
No benefit in ipsilateral invasive or DCIS recurrence for tamoxifen when RT was given (RT reduced 10 yr IBTR from ~15% to ~2%, no additional benefit of TAM)<div><br></br></div><div>*Notable limitation: receptor analysis not performed in this study</div>
18
Q
What were the study arms on NSABP B-24 s/p lumpectomy for DCIS?
A
1) 50 Gy + TAM x 5 yrs, 2) 50 Gy alone (38.5% did receive boost across trial)
19
Q
Was a benefit of tamoxifen observed in combination with whole breast RT in women with DCIS s/p lumpectomy on NSABP B-24?
A
Slight reduction in invasive recurrence (all comers), reduced total invasive breast cancer events with tamoxifen (ER+ subset analysis)<div><br></br></div><div>Local control benefit of RT is why it remains category 1 on NCCN compared to TAM (probably just tumoristatic)</div>
20
Q
Is there a benefit of anastrazole vs tamoxifen x 5 yrs for post-menopausal women with ER+ DCIS s/p lumpectomy and RT? (IBIS-II DCIS trial)
A
No, no difference observed in overll recurrences or death with anastrazole vs tamoxifen x 5 yrs
21
Q
How do the side effect profiles differ for anastrazole vs tamoxifen?
A
Tamoxifen: more muscle spasms, gyn cancers, gyn symptoms, vasomotor symptoms, DVTs<div><br></br></div><div>Anastrazole: more fractures, MSK events, hypercholesteremia, strokes</div>
22
Q
Is there a benefit of anastrazole compared to tamoxifen for women under 60 with ER+ DCIS s/p lumpectomy and RT (NSABP B-35)?
A
Yes, anastrazole improved breast cancer free interval compared to tamoxifen for women under 60
23
Q
What effects were observed with hypofractionation and/or boost for non-low risk DCIS from the BIG 3-07/TROG 07.01 trial?
A
Compared conventional vs hypofrac, and boost (16 Gy) vs no boost.<div><br></br></div><div>No diff with fractionation (5-yr LC 94%)</div><div><br></br></div><div>Boost improved 5-yr LC(97% vs 93%)</div>
24
Q
Is hypofractionation acceptable for patients with DCIS s/p lumpectomy?
A
Yes, DBCG HYPO study compared 40 Gy/15 fx to 50 Gy/25 fx with allowed boost. No difference in LRR or OS with fractionation. No increased induration with hypofx, and better cosmetic outcomes
25
What are rates of discontinuation of adjuvant endocrine therapy in IBC/DCIS patients?
20-60%
26
How can Oncotype be used in DCIS patients?
327 pts from ECOG trial with DCIS s/p surgery without RT were examined. 10-yr invasive breast cancer risk incresed linearly with Oncotype score (low 4%, int 12%, high 19%).
Could be used to determine if TAM is needed in a patient that is considering no therapy, or does not wish to pursue RT
27
What did the EBCTCG meta-analyses demonstrate in terms of benefit of RT vs observation following breast conservation surgery?
78 trials included with 42k patients (major trials included NSABP B-06, Milan I, EORTC, Danish, NCI, Gustave-Roussy)
RT after BCS improved LRR and BCM, halves LRR and DM and reduces mortality by about 1/6th in all populations
1 breast cancer death avoided for every 4 LRRs avoided
28
What were the design and arms on NSABP B-06?
Stage I/II, <4 cm, 1851 pts, 1) total mastectomy, 2) lumpectomy, 3) lumpectomy + RT. Negative margins required, ALND required in all arms
29
What were the results of mastectomy vs BCS from NSABP B-06?
No diff in OS (46%), CSS (60%) or distant DFS at 20 years, IBTR 14% with RT vs 39% w/o, local control reduced with BCS
30
What were the results of the Milan I study (mastectomy vs BCS)?
cT1N0, <70 (N=701 pts), no difference in OS (58%) or CSS (75%) at 20 years
LR 8.8% with BCS+RT, vs 2.3% with mastectomy
31
What benefit was observed with tamoxifen in addition to RT in early stage IBC on NSABP B-21?
Design: <=1 cm s/p WLE, 1) TAM x 5 yrs, 2) TAM + 50 Gy, 3) 50 Gy alone
RT reduces 8-yr IBTR (17% TAM, 3% TAM+RT, 9% RT alone), some possible synergy with TAM
32
Was benefit of RT added to TAM preserved in elderly in CALGB C9343?
Yes, trial included age >=70 cT1N0, ER+ s/p lumpetctomy. 1) TAM + RT 45 Gy + 14 Gy boost, vs 2) TAM alone. RT improves 10-yr LRR (10% vs 2%), no diff in OS or DM
-
33
What is benefit of RT vs observation after lumpectomy from PRIME II?
Improved 10-yr IBRT (9.8% vs 0.9%), no diff in OS or DM
Age >65, T1-2, <3 cm, ER/PR+, >=1 mm margins, 1) RT 40-50 Gy/15-25 fx vs 2) observation
34
What are risk factors for recurrence that may benefit from boost (per EORTC 22881)?
Young age, adjacent DCIS (at 20-yr MVA), grade 3 was shown initially but fell out at later time points
Pts randomized to 50 Gy and 1) no boost, or 2) 16 Gy boost
35
"What was benefit of boost in ""Lyon study"" at 5 yrs?"
N = 1024 pts, <=3 cm tumor s/p WLE and ALND, 1) 50 Gy vs 2) 50 Gy + 10 G boost
Improved 5-yr LC (4.5% vs 3.6%), more telangectasias but no difference in self-assessed cosmesis
36
What is the data for breast SIB following BCS from the UK IMPORT HIGH study?
pT1-3, N0-3a, M0 randomized to 1) 40 Gy/15 fx + sequential 16 Gy boost, 2) SIB IMRT 36 Gy WBRT + 40 Gy PBI (1.5 cm CTV from tumor bed) + 48 Gy boost in 15 fractions, 3) SIB IMRT 36 Gy WBRT + 40 PBI + 53 Boost in 15 f
-No difference in cosmesis at 3 yrs, borderline worse induration with 53 Gy boost
IBTR results are pending
37
What is the deigns of the ongoing RTOG 1005 trial for SIB boost + hypofrac?
Early stage, high risk: age <50, +axillary N, LVI, >=2 close margins, 1 close and EIC, + margin, ER/PR-, grade 3, oncotype >25, ypstage 0-II, grade 3 DCIS, <50 yrs
1) WBRT 50 Gy or 42.7 Gy + sequential 12-14 Gy boost, or 2) hypofrac SIB 40 Gy/15 fx + 48 Gy/3.2 Gy daily boost
38
What does IMRT-MC2 trial show comparing sequential vs SIB breast boost?
1) WBRT 50.4 Gy with SIB to 64.4 vs 2) WBRT 50.4 Gy then sequential 16 Gy boost
2-yr LC 100% in both, no difference in breast retraction or cosmesis
39
What were design and primary results from OCOG (Canadian) trial comparing hypofractionation and conventional?
BCS, T1 or T2, N0, neg margins, all had ax dissection, 1) 42.5 Gy/16 fx vs 2) 50 Gy/25 fx, no boost
5 and 10-yr LC equivalent, no difference in cosmetic outcomes
Grade 3 favored conventional RT (not replicated in START A/B trials)
40
What was and design and arms for START A/B breast hypofrac trials?
pT1-3a, N0-1, some BCS, some mastectomy
START A: 50 Gy/25 fx vs 39 Gy/13 fx vs 41.6 Gy/13 fx
START B: 50 Gy/25 fx vs 40 Gy/15 fx
10 Gy boost allowed (61%), nodal and chest wall RT allowed
41
What were important primary and subset analyses from START A/B?
No diff in 10-yr LRR (4-6%) with hypofrac vs conventional
Improved cosmesis with 39 Gy and 40 Gy
No worsened outcomes in grade 3 (contrast with Canadian trial)
42
What were outcomes with ultra hypofractionation in breast from UK FAST FORWARD trial?
pT1-3, N0-1 M0, BCS or mastectomy (93% BCS), noninferiority
1) 40 Gy/15 fx vs, 2) 27 Gy/5 fx, vs 3) 26 Gy/5 fx
Recurrence and survival at 5-yr noninferior, cosmetic outcomes worse with 27 Gy, increased induration, skin changes
Why were 26 and 27 Gy both evaluated? BED calculations predicted falloff at this point
43
What were results of UK meta-analysis of PBI vs WBRT?
IBC, suitable for BCT, 9 randomized trial of PBI vs WBRT
-No difference in BCM,non-BCM and OS improved by ~1% with PBI (cardiac toxicity?)
44
In Princess Margaret PBI Meta-analysis (9 trials), what were the outcomes in terms of local recurrence and survival?
Increased LR (OR = 1.69) with PBI, less death w/o recurrence (OR = 0.55) with PBI, trend toward improved OS with PBI
45
What was the best modality for PBI according to the Princess Margaret meta-analysis?
External beam
46
What were negative predictors of benefit for PBI in Princess Margaret meta-analysis?
Larger tumors, node positivity
47
What were the 3 arms in the UK IMPORT LOW trial?
40 Gy/15 fx WBRT, 36 Gy WBRT + SIB PBI to 40 Gy/15 fx, 40 Gy/15 fx PBI
48
What were the local recurrence, distant recurrence and survival outcomes of partial breast or reduced dose whole breast + PBI boost in UK IMPORT LOW compared to hypo-fractionated WBRT?
Non-inferior 5-yr LR, DR, BC mortality and overall mortality at 5 year
Lower rates of adverse outcomes with partial breast and reduced dose compared to WBRT
49
What was study design of RAPID trial for EBRT PBI?
Age >40, size <3 cm, IDC or DCIS, Arm 1: 38.5 Gy/10 fx EBRT PBI vs WBRT hypofrac or conventional (boost optional)
50
What were recurrence and cosmetic outcomes of accelerated partial breast arm in RAPID compared to standard WBRT arm?
Non-inferior 8 yr IBRT (3% vs 2.8%), worse cosmetic outcomes with accelerated PBI (grade 2 or greater induration: 32% vs 13%, grade 3 4.5% vs 1.0%, 7-yr subjective cosmesis 18% worse)
51
What are the outcomes data for IMRT PBI in early stage IDC/DCIS?
Florence, Italy: 30 Gy/5 fx IMRT PBI vs WBRT 50 Gy/25 fx + 10 Gy boost, 5-yr IBRT 1.5% in both arms, improved acute and late toxicity and physician reported cosmesis with IMRT
52
What are outcomes data for PBI with electrons/HDR compared to WBRT?
Budapest (Polgar, 2020): APBI (either HDR 36.4 Gy/7 fx, or electrons 50 Gy/25 fx) vs WBRT 50 Gy/25 fx
No difference in LC, CSS, DF or OS, better cosmesis with HDR APBI
53
What were arms on RTOG 0413/NSABP B39 examining multiple modalities of APBI compared to standard whole breast?
50 Gy/25 fx with optional boost, APBI 34 Gy in 3.4 Gy fractions BID with multicatheter interstitial or Mammosite, OR 38.5 Gy in 3.85 Gy BID fractions with EBRT
54
What were recurrence and cosmetic outcomes with APBI (either interstitial or EBRT) on RTOG 0413?
IBRT equivalent at 10 years, slightly worse grade 3 toxicity with PBI, cosmetic outcomes by physician and patient not different
55
What were results of GEC-ESTRO APBI brachy trial compared to WBRT?
32 Gy/8 fx or 30.3 Gy/7 fx BID compared to WBRT 50 Gy/25 fx + 10 Gy boost, no difference in 5-yr LR or DFS, toxicity and cosmetic outcomes no different between arms
56
What was design and arms of TARGIT-A trial for partial breast treatment?
Early stage breast, age >45, unifocal, TARGIT IORT 20 Gy/1 fx vs WBRT 45-56 Gy, if adverse features seen on path in TARGIT group they received supplemental RT boost
57
What were primary outcomes of TARGIT-A in terms of recurrence, survival and toxicity?
15% of TARGIT patients required supplemental EBRT due to high risk features
Non-inferior 5-yr LR (2.11% vs 0.95%), decreased non-cancer deaths (1.4% vs 3.5%) with TARGIT vs EBRT, mortality increased when EBRT added to TARGIT
58
What was design of ELIOT trial for IORT?
IORT 21 Gy/1 fx with electrons vs WBRT 50 Gy + 10 Gy boost, equivalency trial, early stage breast, suitable for lumpectomy with tumor size < 2.5 cm
59
What were outcomes of ELIOT trial in terms of IBTR and what is the contention?
IORT is equivalent to WBRT as defined by trial design although is generally statistically worse (4.4% vs 0.4%)
60
How does anastrazole compare to tamoxifen in postmenopausal women with early stage breast cancer?
ATAC Group: 1) TAM x 5 yrs, 2) anastrazole, 3) TAM + anastrazole; 10-yr recurrence risk decreased with anastrazole, no difference in OS. Fractures increased with anastrazole, while more serious adverse events with tamoxifen
61
How does short term tamoxifen (2 yrs) impact long term survival in the SBII:2pre trial?
15-yr cumulative mortality decreased (HR = 0.84), 15-yr BCM reduced (HR = 0.72)
62
What effect does anastrazole have on recurrence risk compared to placebo in early stage breast cancer?
IBIS-II: anastrazole vs placebo, post-menopausal, any ER; 40% reduction in breast cancer recurrence, 54% in ER+, 59% in DCIS (mostly ER+), no benefit in OS or BCM
63
What impact does addition ovarian suppression to tamoxifen have on in pre-menopausal women distant metastases from the SOFT/TEXT trial?
TAM vs TAM + ovarian suppression vs exemestane + ovarian suppression
Improved 8-yr OS with addition of OS to TAM (91.5% vs 93.3%), improved DM survival by about 5%, even further benefit observed with exemestane (10-15% in highest risk patients), lots of toxicity with ovarian suppression (1/4th withdrew), ovarian suppression = triptorelin, oophorectomy or RT
64
Is there benefit of 10-yrs of tamoxifen vs 5 years?
Yes, ATLAS trial showed reduction in BCM between 5-14 years (12.2% vs 15%), and decreased risk of recurrence (21% vs 15%)
65
Does addition of 5-yrs of letrozole after 5 years of tamoxifen or AI improve outcomes vs observation in post-menopausal early stage breast?
No, no additional DFS or OS benefit observed with addition of 5-years of letrozole (NSABP B-42)
66
What data exists for BCT vs MRM +/- RT in triple negative early stage breast cancer (T1-2N0)?
Cross Cancer Institute, Alberta, Canada: 768 pts, LRR better with BCT (96%) vs MRM w/o RT (90%), retrospective study
67
Are there differences in outcomes observed between radical and total mastectomy on NSABP B-04?
No, patients randomized to radical mastectomy vs TM+RT to axilla vs TM (cN- axilla), if cN+, radical mastectomy + TM+RT to axilla. No significant benefit in LF, DFS or OS out to 25 years with radical mastectomy. *notably no systemic therapy given in this trial
68
How does SLN+ guided ALND perform vs ALND in all patients (NSABP B-32)?
SLNBx had accuracy of 97.1%, false negative rate of 9.8%, NPV 96.1%
No difference in OS, DFS or LRC at 7-yrs with SLNBx guided approach
69
Is ALND required for 1-2 micromets or can these patients be observed?
IBCSG 23-01: 1-2 micromets (N1mi <=2mm), SLNBx followed by ALND or observation; not required, no difference in LRR, DFS or OS at 10-yrs, increased risk of lymphedema with ALND (13% vs 4%)
70
What was the design of ACOSOG Z0011?
T1-2, clinical N0, lumpectomy with 1-2 SLN+, randomized to completed ALND vs no ALND, RT given as WBRT tangents (RT to SCV or targeted axilla were prohibited)
71
What were the results of ACOSOG Z0011 in terms of LRR, DFS and OS?
OS worse at 10 years with ALND (83.6% vs 86.3%), no difference in 5-ur LRR, 5 or 10 yr DFS
Established that ALND is not required in T1-2 breast cancer with 1-2 SLN+ receiving WBRT and adjuvant systemic therapy
72
What are some of the concerns around interpretation of ACOSOG Z0011?
Surprisingly 21% in ALND had 3 or more nodes suggesting that RT can control nodal disease, OS favored group without ALND but not appropriately powered.
High tangents were used in some patients although no benefit was observed, but those that had high tangents had more nodes. Additionally 15% of patients received axillary RT despite it being a protocol violation
73
What is the trial design of AMAROS (EORTC)?
Noninferiority trial of ALND vs RNI to axilla (levels I-III) and medical SCV for SLNB+ patients after mastectomy or BCS
Optional RT to CW post-mastectomy. If in ALND group and >=4 nodes, RNI allowed.
74
What were the results of AMAROS trial in terms of recurrence, survival and lymphedema?
Axillary recurrences were non-inferior and rare in both arms. Doubling of lymphedema risk (28% vs 14%) at 5-yrs. NO difference in OS or DMFS at 10 years.
75
What is the role of sentinel lymph node biopsy with neoadjuvant chemotherapy (SENTINA)?
cN0: SLNB before neoadj. chemo, and if SLN+ another SLNB after chemo
cN+: neoadjuvant chemo, if ycN0 SLNB and ALND, yf ycN1, ALND with no SLNB
SLN detection rate before chemo if cN0: 99%, 52% false negative rate after chemo
cN+, ycN0: 80% detection rate, 14% false negatives, FNR <10% if 3+ nodes removed, 8.6% if using dual tracer
76
What are results of SLN after neoadjuvant CHT from ACOSOG Z1071?
Design: T0-4, cN1-2, M0, neoadjuvant chemo
SLN --> ALND (BCS or mastectomy)
cN1 disease with >=2 SLNs removed the false negative rate as 12.6% (exceeded 10% prespecified limit), improved with dual techniques and at least 3 nodes (closed early due to poor accrual)
77
What was benefit of PMRT in locally advanced patients from EBCTCG metanalysis? Did this depend on number of nodes involved?
Mastectomy + ALND to at least level II, N+ (included 22 trials from 1964-1986)
pN0 patient did not benefit
10-yr LRR reduced for 1-3 nodes (20% vs 4%) and >=4 nodes (32% vs 13%), BCM decreased at 20-yrs by ~10%, also reduced distant mets
78
What are some caveats to benefit of PMRT from EBCTCG analyses?
Old studies (no Her2 therapies, older surgical and RT techniques, older endocrine therapies)
Only included patients with full axillary dissections (ACOSOG Z0011 has shown that this is not necessary for 1-2 SLN+)
79
What was study design of Danish DBCG 82b study for locally advanced patients?
Premenopausal, high risk (axillary N+, >5 cm or invasion of skin or pec fascia)
Randomized to CMF + 48-50 Gy to CW and nodes vs CMF alone
80
What benefit of PMRT was observed in Danish 82b trial (premenopausal high risk locally advanced)?
"10-yr OS improved with PMRT (54% vs 34%)
Improved LRR at 10 yrs (9% vs 32%), ""good"" risk group had LC and BCM benefit with mortality benefit lost in high risk group
"
81
What was design of Danish DBCG 82c study?
Postmenopausal, <70 y/o with high risk (N+, >5 cm or invasion of sin or pec fascia)
TAM+RT 48-50 Gy to CW and nodes vs TAM alone
82
What were results (survival and LRR) of Danish DBCG 82c study (locally advanced post-menopausal)?
PMRT improved 10-yr OS (45% vs 36%), DFS and LRR (8% vs 35%)
83
What is design and question being answered of ongoing TAILOR RT trial?
Is there benefit to RNI for low Oncotype?
Oncotype <18, ER+, Her2-
1-3 LNs after LND, or 1-2 LNs ater SLNB + BCS, or 1 LN after SLNB + MRM
Randomzied to no RT (except WBRT for BCS) or WBRT + RNI or PMRT + RNI
No neoadjuvant chemo included
84
What evidence exists for hypofractionated PMRT with chemo?
British Columbia (Rogaz, JCNI 2005): premenopausal women s/p MRM with LN+ randomized to 1) CMF alone, or 2) CMF with 37.5 Gy/16 fx PMRT RNI to CW, SCV, axilla and bilateral IMNs
-Improved 20-yr LRF (26% vs 10%), 20-yr OS by 10% (37% vs 47%)
Higher cardiac toxicity with RT (0.6% vs 1.8%)
85
What is design and question being answered of ongoing SUPREMO trial for locally advanced breast?
Hypofractionated PMRT?
RT choice of 40 Gy/15 fx (70%), 45 Gy/20 fx or 50 Gy/25 fx
Low toxicity of hypofractionated RT at 2 year data cut
86
Is there benefit to PMRT in early stage triple negative patients?
China (Wang, Radiother Oncol, 2011): 681 pts stage I-II TNBC s/p MRM + chemo (80% of patients were node negative)
Improved 5-yr RFS and OS by about 10% each
87
Is there a benefit of chest wall boost with PMRT?
No, large retrospective review from MGH (IJROBP, 2019) of 746 pts demonstrated 10 Gy CW boost increased implant failures and skin toxicity without improving local control
*Retrospective analysis
88
What is design of ongoing Alliance RT CHARM study?
Stage IIa-IIIa with planned reconstruction after MRM (excludes T3, N3 or positive IMNs)
Randomized to 1) 42.56 Gy/16 fx RNI vs 50 Gy/25 fx RNI
89
What is design/question for ALLIANCE A011202 (ongoing)?
Similar to AMAROS but with neoadj. CHT (is ALND needed in N+ after CHT?)
cT1-3N1 --> NAC --> surgery --> SLNB (ypN+)
1) ALND + RNI vs 2) axillary RT and RNI
90
What is design/question of RTOG 1304/NSABP B-51 (ongoing)?
Is RNI needed for ypN0 after neoadj. CHT?
cT1-3N1 --> NAC --> surgery --> SLNB ypN0
Lumpectomy: WBRT vs WBRT + RNI
Mastectomy: observation vs PMRT + RNI
*Differentiate from Alliance A011202 (these are SLNB negative after NAC)
91
Is there benefit to regional nodal irradiation (from EBCTCG meta-analysis), and how did this depend on heart dose?
14 trials, 13132 pts
Trials 1989-2003: reduced BC recurrence, BCM and overall mortality
Trials 1961-1978: no benefit in BCR or BCM, OS worse
Older trials estimated to have heart doses >8 Gy and <85% dose to nodes (heart dose is important)
92
Do we need to cover IMN nodes with RNI (data from DBCG-IMN)?
Patients (operable BC, N+) randomized to no IMN RNI (left sided) vs +IMN RNI (right sided)
8-yr OS (72% vs 76%) and BCM (23% vs 21%) improved with inclusion of IMNs
93
What were results of EORTC 22922/10925 randomizing patients to no RNI vs RNI to IMN and medical SCV?
Included patients with medial tumors or any N+
Preserved 15-yr BCM benefit, but DM, DFS and OS benefit seen at 10-yrs disappears
*Note this shows potential benefit in N0 patients, which is contradicted in EBCTCG meta-analysis
94
Is there a benefit of RNI after breast conservation for N+ or high risk patients (>5 cm, >2 cm with <10 nodes removed with either ER-, Grade 3 or LVI) from MA.20?
s/p BC and SLNB/ALND and adjuvant chemo or ET with above features
1) no RNI vs 2) RNI to IMN, SCV, axillary levels III (plus I-II if <10 ndoes removed or >3 nodes +)
Improved 10-yr DFS (77% vs 82%), no diff in OS or BCM
Relatively low rates of pneumonitis and lymphedema
*benefit of inclusion of IMNs? (although this was no RNI vs IMN+ RNI)
95
What did Paris, Hennequin et al (IJROBP, 2013) study show in regards to inclusion of IMNs?
+Axillary nodes or medial tumor after mastectomy
*Powered to detect 10% improvement (MA.20 only showed 3% benefit)
96
What is primary risk for local recurrence after mastectomy for T1-2 tumors?
MSKCC (Mamtani et al, Cancer 2012): increasing tumor size in setting of NO chemotherapy was only significant predictor of local recurrence
97
Can Oncotype be utilized to predict LRR (from retrospective review of B-14 and B-20)?
Yes, 10-yr LRR low (4%), int (7.2%), high (16%)
98
Was Oncotype predictive of LRR risk from SWOG S8814 (post-menopausal, N+, ER/PR+, BCS or mastectomy)?
Yes, 10-yr LRR, low (10%), int-high (17%)
99
What are general predictors of LRR post-mastectomy (from multiple retrospective reviews) that may benefit from PMRT?
Young age, increased nodes positive, tumor size, +LVSI, grade, ER negative, decreasing nodes examined
100
What is most common site of LRR after mastectomy?
Chest wall (68%), SCV (41%) (MDACC, Katz 2000)
101
Describe patterns of failure for node + breast cancer s/p mastectomy without PMRT (NSABP meta-analysis).
10-yr LRF (with or without distant) 20%, isolated LRF 12%, 10-yr DF alone 43%
Predictors of LRF as first event: age, tumor size, premenopausal, LN+, # LN dissected
Large tumor and >=4 nodes high risk of local failure and probably greatest benefit from PMRT
102
Is there benefit to PMRT with T3N0 patients?
Low rates of LRF: 5-yr 7.6% (MDACC, Floyd IJROBP, 2006), higher rates with LVI
*Probably minimal benefit
103
Is there benefit to a neoadjuvant vs adjuvant chemotherapy approach in breast cancer?
No difference in OS, BCM or DM with higher rates of LRR with neoadj. (EBCTCG meta-analysis)
104
What was design of NSABP B-18?
T1-3N0-1, randomzied to neoadj. AC vs adjuvant AC
105
What were outcomes of neoadjuvant vs adjuvant CHT on NSABP B-18?
NAC allowed more BCS (68% vs 60%)
No difference in OS
*pCR predicts OS and DFS (OS at 9-yr 78% with CR, 67% with PR, 65% with no response)
106
What were arms on NSABP B-27?
T1c-T3 N0-1 or T1-3N1
1) neoadjuvant AC vs 2) neoadj. ACT vs neoadj. AC --> surgery --> T
107
What were outcomes with different NAC approaches in NSABP B-27?
Best pCR rates with neoadjuvant ACT (compared to AC alone), 13% vs 26%
108
What were predictors of LRR from NSABP B-18 and B-27 after neoadjuvant chemo?
T-stage, N-stage, tumor size and path response (after mastectomy)
Age, clinical tumor and nodal status, and chemo response (BCS)
109
What do retrospective analyses demonstrate in terms of benefit of RT after NAC?
Possible benefit of PMRT in stage III, T3-T4, or >=4 nodes (note that this contradicts DBCG and EBCTCG meta-analyses that demonstrated benefit for 1-3 nodes)
*Retrospective single institution or NCDB analyses (randomized trials including Alliance and B-51 are ongoing)
110
Is there benefit to dose escalation for inflammatory breast cancer?
Yes, based on MDACC retrospective experience for select patients
Dose escalation up to 66 Gy from 60 Gy gave LRC in patients with 1) partial response to NAC, 2) close, positive or unknown margins, or 3) <45 years old
Increased grade 3-4 toxicity (29% vs 15% with 60 Gy)
111
Is there a survival benefit with local treatment of the primary in metastatic breast cancer?
No, based on Tata memorial series (350 pts)
Locoregional treatment to primary and nodes, no differenc ein median OS, 2-yr OS with local treatment
112
What were inclusion criteria and outcomes for SABR-COMET?
<=5 oligometas (93% were 1-3), any histology with controlled primary after definitive treatment
Most patients were lung, breast, colorectal or prostate
Randomized to 1) SBRT + SOC, 2) SOC
Improved median OS 50 vs 28 months, and median PFS 12 vs 6 months
113
What is design of NRG-BR002 (breast oligomet trial) (ongoing)?
<=4 oligomets, size <5 cm amenable to surgery or SBRT, excludes brain mets
1) SOC chemo vs 2) SBRT or surgery
Primary endpoints of PFS and OS
114
Is there benefit to use of IMRT vs 2D or 3DCRT techniques in early stage breast?
Yes, reduced toxicity observed across small trials. No compromised outcomes
Erasmus Cancer Institute, Netherland (Pignol, Radiother, 2016): 2D vs IMRT, reduced moist desquamation, no difference in OS, LRFS, or DFS
Royal Marsden (Donovan, Radiother, 2007): IMRT vs 2D, less palpable induration
KROG 15-03: pT1-2N0M0, IMRT 57.4 Gy/28 fx with SIB vs 3DCRT 59.4 Gy/33 fx, reduced >= grade 2 toxicity with IMRT, better coverage and lower lung doses
115
Is there benefit to use of hyperthermia for chest wall recurrences for locally recurrent breast cancer?
Yes, Datta et al, IJROBP, 2016; meta-analysis of 2210 pts, demonstrated improved CR rates when combined with RT (60.2% combined vs 38.1% alone) with low toxicity
116
What evidence exists for re-irradiation outcomes for locally recurrent breast cancer?
RTOG 1014, local recurrence >1 yr from previous single tumor <3 cm
RT given as 45 Gy/30 fx BID with PBI EBRT
Grade 3 tox: 7%, no grade 4 or 5
5-yr IBTR low (5%), 5-yr mastectomy (10%), excellent DM and OS (95%)
117
What is the mean heart dose needed to maintain acute coronary event risk <5% with breast XRT?
From van den Bogaard et al, JCO 2017:
4-8 Gy, cumulative incidence of ACE increased 16.5% per each Gy, no threshold
118
What is risk of major coronary event per Gy from Darby breast XRT analysis?
7.4% per each Gy, no threshold
Absolute risk higher for those with risk factors
*Caveat: most of these patients were treated prior to 3DCRT, had to be virtually reconstructed to generate dosimetry
119
How does anthracycline based chemo perform compared to CMF in breast CA (from EBCTCG meta-analysis)?
194 randomized control trials of adjuvant CHT or hormones
Anthracyclines superior to CMF
*Better benefit in age <50, that is indepedent of TAM, nodal status or tumor features
120
What are the risks of late recurrence in breast cancer (after 5 years of endocrine therapy)?
EBCTCG, NEJM, 2017: 88 trials of women disease free after 5-yrs of endocrine therapy
Risk of distant recurrence remains that increases with increasing nodal involvement, T-stage and grade
*Best resource for chance of distant recurrence
121
Is there a benefit of chemotherapy in Oncotype intermediate (11-25) patients?
No, TAILORx demonstrated no change in 9-yr OS, DM, DFS, FFDM FF LRR/DM in score 11-25 pts
Benefit in age <50 in DFS, LRR+DM but not DM or OS
122
Is there benefit to addition of CHT to endocrine therapy in low-int. risk Oncotype with 1-3 nodes (RXPONDER)?
Yes, for premenopausal women (improved 5-yr IDFS 94% vs 89%), no difference in post-menopausal women
123
Is there benefit to adjuvant capecitabine in women with PR in breast after neoaj. chemo and surgery (CREATE-X)?
Yes, capecitabine imrpoved 5-yr DFS (74% vs 68%) and OS (89% vs 84%), particularly large benefit in TNBC patients
124
What were results of addition of pembrolizumab to neoadj. carbo/paclitaxel in KEYNOTE-522 (TNBC)?
Improved pCR (65% vs 51%) at interim analysis, PD-L1 had better pCR rates in both arms
*Awaiting OS data
*Awaiting OS data
125
Is there a benefit of addition of trastuzumab-emanstine (TDM-1) over trastuzumab for women with Her2+ BC after PR to NAC? (KATHERINE trial)
Yes, TDM-1 improves 3-yr invasive LR (88% vs 77%), DFS (HR 0.50), DM (11% vs 16%)
What is emtansine? (microtubule inhibitor)
126
Which patients with recurrent breast cancer benefit from chemotherapy?
CALOR: recurrent breast cancer, radical resection, chemo vs no chemo
Improved OS in ER negative patients only (no benefit in ER+, can be managed with endocrine therapy only)
127
Should adjuvant chemo be given before or after RT in patients after lumpectomy?
Doesn't matter (Harvard, Bellon, JCO 2005): adjuvant cyclophospmade, doxorubicin, methotrexate, fluorouracil and predisone
Randomized to CHT before or after RT
No differences in time to any event, DM or OS base
*High Oncotype may indicate increased risk of DM and may benefit from earlier CHT
128
How does fulvestrant perform vs anastrazole in patients with locally advanced or metastatic breast cancer (FALCON)?
Improved PFS (16.6 vs 13.8 months), higher rates of arthralgia with fulvestrant
129
How does pertuzumab-based neoadjuvant regimens perform relative to trastuzumab (NEOSPHERE)?
Locally advanced, inflammatory or early stage breast CA treated with NAC
1) Trastuzumab/docetaxel vs 2) pertuzumab/trastuzumab/docetaxel vs 3) pertuzumab/trastuzumab vs 4) pertuzumab/docetaxel
Improved PFS, DFS and pCR rates with addition of pertuzumab to trastuzumab + docetaxel
130
What is the optimal duration Her2 targeted therapy in Her2+ advanced breast cancer?
HERA BIG: 1 yr vs 2 yr Herceptin vs observation, improved 10-yrs DFS with Herceptin (69% vs 69% vs 63%), no benefit to 2 yrs of therapy
*1-yr of therapy is optimal
*1-yr of therapy is optimal
131
What is the addition survival benefit of Herceptin added to paclitaxel after AC (NSABP-31 and NCCTG analysis)?
Improved relative survival by 37%, 10-yr DFS and OS both increased by ~10% absolute
132
What was the design of the HER2CLIMB study and what novel molecule was used?
Metastatic Her2+ breast CA, s/p trastuzumab, pertuzumab and TDM1, brain mets allowed
Randomized to placebo vs trastuzumab, capecitabine and tucatinib
Improved PFS and OS with or without brain mets
Tucatinib is a small molecule Her2 inhibitor with BBB penetrance
133
Are there response or tolerability differences between AC and CMF for breast cancer non-responsive to TAM (Fisher, NSABP B-15)?
1) AC vs 2) CMF, no difference in DFS, DM or OS
AC complted sooner with less nausea, more alopecia with CMF
*AC is better option
