Early Stage Breast Cancer Flashcards
What is the T staging for breast cancer?
- 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!
What is the MOA of palbociclib?
Selective inhibitors of CDK4 and 6
What are letrozole and anastrozole?
Reversible non-steroidal aromatase inhibitors
What is the usual dose of anastrozole?
1 mg QD
What is tamoxifen?
- Selective Estrogen Receptor Modulator (SERM)
– Antagonist in breast
– Agonist in bone, uterus, etc
What is the usual dose of tamoxifen
20 mg QD
What is exemestane?
- ExemeSTane:
– Irreversible STeroidal aromatase inhibitor
What were the findings of the Paloma-2 study (NEJM 2016) for metastatic breast cancer (MBC)?
- 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
Do you use a bolus w/ PMRT? Why? What kind?
- 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
What is unique to a bolus being used for PMRT?
- 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
What is the suggested workup for a new dx of DCIS?
- 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
What is gestational breast cancer?
- Gestation breast cancer is a cancer that develops:
– Throughout pregnancy
– During lactation
– The first post-partum year
What is the approach to the evaluation/management of axilla for a newly dx gestational breast cancer undergoing BCS?
- 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
What is the brand name for pembrolizumab?
- Keytruda
- Hence many studies with pembro are name KEYnote
Per Keynote-522, how should IO (Keytruda) be sequenced w/ RT for breast cancer pts undergoing BCS?
- 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
What are the NCCN definitions of menopause?
- 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
What are the 10-yr LR and DM rates for a Phyllodes tumor?
- 10-yr LR: 8%
- 10-yr DM: 13%
What factors for Phyllodes tumor make it more likely to metastasize?
- Size ≥ 7 cm
- Stromal overgrowth
- Increased stromal cellularity
- Infiltrative borders
- High mitotic count
- Necrosis
What is the preferred management of recurrent Phyllodes tumors?
- Excision w/ wide-margins
- w/o LN staging
- can consider PORT (Category 2B)
Are tangents considered 3d-CRT?
Yes
What were the randomization and tx arms of the Wang et al., JCO 2020 trial for breast cancer?
- 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)
If a young woman is dx w/ TNBC, what mutation does she likely carry?
BRCA1
What were the pt populations, tx arms, results and conclusions of the Florence trial (Liv et al. 2015)?
- 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
What were the tx arms of the FAST trial for breast cancer?
- 50Gy in 25 fx QD
- 30Gy in 5 fx once-weekly
- 28.5Gy in 5 fx once-weekly
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
Which gene is generally lost in LCIS?
- CDH-1 → loss of E-cadherin
- Benign but predisposes pts to breast cancer
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
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
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
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
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
Can prophylactic contralateral breast irradiation be considered for BRCA carriers?
- Yes, per phase II data
- May reduce development of breast cancer by ~10%
Is LCIS a unilateral or b/l process?
B/l in 35-60% of the cases
Which ET is preferred in high-risk women w/ breast cancer?
Exemestane + ovarian suppression
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)
What are the borders of IM nodes?
- Borders:
– Sup: Cranial aspect of the 1st rib
– Inf: Cranial aspect of the 4th rib
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).
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
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
How much anterior breast flash is used for tangents?
2 cm
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%
What prophylactic intervention has a demonstrated benefit for decreasing the risk of lymphedema in breast cancer pts s/p ALND?
Compression Sleeves
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%
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)
What can be used for chemoprevention for breast cancer?
- Premenopausal - tamoxifen
- Postmenopausal: Raloxifene/tamoxifen/aromatase inhibitor
How do outcomes compare between male and female breast cancer pts?
Males have worse outcomes across all stages
What are the minimum established criteria for inflammatory breast cancer?
- Rapid onset of breast erythema, edema, peau d’orange, or warm breast with or without an underlying palpable mass.
- Flattening, crusting, or retraction of the nipple (not always present).
- Diagnosis of mastitis not responding to antibiotics for > 1 week.
- Symptom ≤ 6 months.
- Erythema ≥ 1/3 of the breast.
- Pathologic confirmation of invasive breast cancer from a biopsy of the breast.
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
What is the ASTRO treatment algorithm for the tx of early-stage breast cancers?
Which pts are appropriate for APBI?
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%
What were the arms of the START A trial?
- 50 Gy in 25 fx
- 41.6 Gy in 13 fx or 39 Gy in 13 fx
* 10 Gy boost was allowed
What were the arms of the START B trial?
- 50 Gy in 25 fx
- 40 Gy in 15 fx
* 10 Gy boost was allowed
Between all the arms of START A and B, which arm had the best cosmetic outcome
40 Gy in 15 fx
What % of pts in START A or B received a boost?
~50% balanced across all the arms
What were the arms of the NSABP B-06 trial?
- Total mastectomy
- Lumpectomy
- Lumpectomy plus adjuvant RT
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%
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
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
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)
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%
What is the general tx paradigm for inflammatory breast cancer?
- Neoadj. CHT
- Mastectomy + ALND (Lvl I, II)
- RT to CW + SCL LNs
What is the % increase in major coronary events w/ each additional Gy of mean heart dose?
- 7.4%
- No threshold
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
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
How does the benefit of an RT boost for breast cancer depend on a pts age?
What kind of side effects are a/w an RT boost for breast cancer?
Increased rates of moderate and severe fibrosis
What is a common side effect of anastrozole frequently requiring a switch to tamoxifen?
- Myalgias
- Arthralgias
- Vaginal sx
What factors are prognostic for a pt w/ DCIS?
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)
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
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%
Beyond what cut-off post-BCS does survival start to decrease w/ delays in starting RT?
20 weeks
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)
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
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)
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
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
Which malignancies besides breast and ovarian cancers are more common in BRCA2 vs. BRCA1 carriers?
- Prostate
- Pancreas
- Uveal melanoma
- Male breast cancer
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
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
Which systemic CHT has demonstrated efficacy for brain mets from breast cancer?
trastuzumab deruxtecan
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
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
What are the rates of lymphedema a/w SLNBx vs. ALND?
- SLNBx: 5-10%
- ALND: 15-20%
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)
What % of cases of LCIS have multicentric disease? What % are b/l?
- Multicentric: 90%
- Bilateral: 35-59%
When is pre-op RT indicated in the tx of inflammatory breast cancer?
- In those pt w a poor response to CHT
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
What is the BID fractionation scheme for pre-op RT for inflammatory breast cancer?
- 51 Gy in 34 fx (BID)
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
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%
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%
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%
Is there a benefit to routine resection of additional margins from the lumpectomy cavity?
- Yes
- decreases +margin rates: 34% → 19%
- Chagpar, NEJM 2015