[ROQs] Breast Flashcards
What are the borders of the breast when treating w/ tangential fields?
- Ant: 2 cm flash on breast
- Sup:
– 1 cm margin (superiorly) on the palpable breast tissue
– radiographically, the inferior edge of the sternoclavicular junction. This is also the match line when using a 3 field technique - Inf: 2-3 cm inferior to IM fold
- Med: midline
- Lateral:
– 1 cm margin on all the breast tissue
– Usually, mid-axillary line to posterior axillary line
What are the borders of the CW contours per the RTOG breast atlas?
- RTOG:
– 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 pectoralis muscles, chest wall muscles, and ribs)
– Lat: clinical reference + mid-axillary line (typically excludes latissimus dorsi muscle)
– Med: sternal-rib - Compare to:
– ESTRO: CW CTV does not include the pectoralis muscle or ribs
– RADCOMP: ribs are excluded
What are the known side effects of tamoxifen?
- ↑ risk Endometrial Ca 2/2 agonist acitivity in the endometrial tissue
- ↑ risk of PE
- ↑ risk of cataracts
- Trend towards ↑ risk of DVT/Stroke
Note: Fracture risk actually ↓ in women on tamoxifen
What are the known side effects of anastrozole?
- ↑ risk of MSK effects (Arthralgias + Myalgias)
- trend to ↑ fracture risk 2/2 ↓ bone mineral density
- ↑ risk of ischemic heart disease
- If side effects of anastrozole are intolerable, can switch to tamoxifen
What is the rule of thumb for the depths of various IDLs for e-?
- Rule of 5, 4, 3, 2, 1
– Dmax → 1/5 x e- energy
– 90% IDL → 1/3.2 x e- energy
– 80% IDL → 1/2.8 x e- energy
– Range → 1/2 x e- energy
Is pure LCIS considered benign or malignant? How is it treated?
- Benign; no longer considered a true premalignant lesion
– Per NCCN, observation and close follow-up alone; 15% risk of developing inv ca
– Risk reduction w/ chemoprevention: tamoxifen or raloxifene to reduce 5 yr risk fo disease
– No role for upfront surgery, WBRT or CHT
– If several risk factors (young age, diffuse disease, FH of breast ca, BRCA mutations) → can consider b/l mast
In the past, LCIS was considered a rare pre-malignant lesion and thus was treated accordingly.
What were the findings of the TAILORx trial for breast cancer?
Breast cancer, ER/PR+, Her2-, LN-
- Randomization:
– Oncotype Intermediate risk (score 11-25) →chemo+endocrine therapy vs.🏆 endocrine therapy
– Oncotype high risk (score > 25) → chemo+endocrine therapy
Results:
- Intermediate risk (score 11-25)
– No change in 9-yr OS, DM, DFS, FFDM, FF LRR/DM
– 9-yr OS 94%, DFS ~83%, FFDM 95%, FF LRR/DM ~92%
– Benefit in age <50 in DFS, LRR+DM, but not DM or OS
- High risk (score >25)
– 5-yr DM 7%, FF LRR/DM 91%, OS 96%
- Cognitive QOL
– Chemo+ET causes cognitive decline.
– ET alone also causes cognitive decline, though less so.
- Post-hoc subanalysis of “Lower” vs. “higher” risk (low risk: grade 1 size ≤3 cm, grade 2 ≤2 cm, grade 3 ≤1 cm): CHT + ET vs. ET alone
– 9-yr DM in age <50, lower risk: <5% both
– 9-yr DM in age <50, higher risk: 12% vs. 6% - Conclusions:
– Women older than 50 years with hormone-receptor positive, HER2-negative, lymph node-negative breast cancer and a 21-gene recurrence score of 0 to 25.
– Women 50 years or younger with hormone-receptor positive, HER2-negative, node-negative breast cancer and a 21-gene recurrence score of 0 to 15.
What were the results of the KATHERINE trial?
- Breast cancer, Her2+, who had PR after neoadjuvant taxane-based chemo & trastuzumab and surgery
- trastuzumab-emtansine (TDM-1) vs. trastuzumab”
– 3-yr Invasive LC 88% vs. 77%
– Invasive DFS improved, HR 0.50
– 3-yr DM 11% vs. 16%
– ↑ pneumonitis: 1.5% vs. 0.7%
Conclusion: Trastuzumab-emtansine improves invasive LC and DFS in partial responders to neoadjuvant chemo in HER2+.
What were the results of the Create X trial?
Breast cancer, HER2-, who had PR after neoadjuvant chemo and surgery
- →capecitabine vs. none
- Capecitabine improved DFS
– 5-yr DFS 74% vs. 68%
– 5-yr OS 89% vs. 84%
– Among triple negative:
– 5-yr DFS 70% vs. 56%
– 5-yr OS 79% vs. 70%”
Conc:
- Capecitabine improves DFS and OS in Her2- breast cancer with PR after neoadjuvant chemo.
- The effect is primarily in triple-negative patients.
What are the systemic therapy tx options for women w/ PR to their neoadj CHT for their HER2+ or TNBC?
- KATHERINE: T-DM1 improves 3y DFS by 10% over trastuzumab for HER2+ breast cancer wresidual dz after NAC.
- CREATE-X: Capecitabine improves 5y OS by ~5% for HER2- (10% for TNBC) breast cancer w residual dz after NAC.
Upon local recurrence of breast ca after tx, which factors predict a ↑ risk of concurrent distant mets?
Per Shen et al, Ca ‘05, the MDACC experience
- Initial LN+
- Skin involvement at IBTR
Per Galper et al, IJROBP ‘05:
- Invasive histology at the time of recurrence
- Local therapy for the recurrence (mastectomy vs. breast-conserving surgery vs. none)
- Shorter time to recurrence
- Age at initial diagnosis
What were the results of the NSABP B-27 trial for breast cancer?
- T1c-T3 N0-1 or T1-3 N1. It must be palpable.
- Randomization: Lumpecomty + ALND or masectomy, TAM in all
– neoadjuvant AC vs.
– neoadj ACT, then surg vs.
– neoadj AC, then surg, then T - Results: AC vs. ACT vs. AC-Surg-T:
– pCR 13% vs. 26% vs. 13% → Neoadj ACT led to best pCR
– ↑ Gr 4 tox: 10% vs. 23.4% (AC vs AC-T)
– negative nodes 51% vs. 58% (AC vs AC-T)
– Did not improve DFS or OS - Conc: addition of T improves cCR and pCR rates, but does not improve DFS and OS
What are the findings of the UK FAST FORWARD trial?
- pT1-3, N0-1, M0 s/p BCS or mastectomy (93% had BCS)
- Noninferiority
– 40 Gy/ 15 fx QD vs. 27 Gy/ 5 fx QD →🏆 26 Gy/ 5 fx QD
– Boost of 10 or 16 Gy in ~25% - Results: 40/15 vs. 27/5 vs. 26/5 → Recurrence and survival were noninferior
– 5-yr IBTR 2.3% vs. 2.0% vs. 1.5%
– 5-yr LRR 3.2% vs. 2.6% vs. 2.1%
– 5-yr DM 4.3% vs. 5.0% vs. 5.6%
– Any breast ca event 8.7% vs. 8.2% vs. 8.3%
– All cause mortality 6.8% vs. 7.7% vs. 6.6% - Tox: 40/15 vs. 27/5 vs. 26/5
– cosmetic effects worse in 27 Gy
– moderate/marked skin & CW effects: 9.9% vs. 15.4% vs. 11.9%
– Patient and photo assessments:: Worse in 27 Gy, noninf in 26 Gy vs. 40 Gy - Conc:
– 26/5 fractions to the whole breast/CW is noninferior to 40/15.
– 27/5 was noninferior in LC, but cosmetic effects were worse.
What are the findings of the UK FAST trial?
- pT1-2 pN0 s/p BCS, excluded: boost, RNI, mastectomy, chemo
- 50 Gy/ 25 fx vs. 30 Gy or 28.5 Gy/ 5 fx once weekly
- Outcomes: longer fu compared to FAST FORWARD
– LR 1% with all doses (at 9.9 yrs f/u)
– 10-yr cosmetic effects were worse with 30 Gy, and not different between 50 Gy and 28.5 Gy - Conc:
– At 10 year f/u, there is no difference in cosmetic effects between 50 Gy and 28.5 Gy/ 5 fx in once weekly fractions. Cosmesis with 30 Gy was worse. Local recurrence was very low in all arms.
What are the findings of the UK START A&B trials for breast cancer?
- pT1-3a, N0-1, s/p BCS and/or mastectomy
- START A:
– 50 Gy/25fx 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 (given in 61%)
– Nodal and CW RT allowed - Results:
– 10-yr LRR 4-6% (NS)
– Less cosmetic changes in 39 Gy and 40 Gy group (HR 0.77).
– In the 15% receiving RT to LNs, there was no difference in arm and shoulder toxicity at 10 years. No difference in lung or heart toxicity. - Conclusion:
– Hypofx results in favorable outcomes and low toxicity compared to conventional RT.
– Late cosmetic effects are reduced.
What are the findings of the Canadian hypofx trial (Whelan et al. NEJM 2010) for breast cancer?
- pT1 or T2, N0, -margin, s.p BCS and ALND
– 🏆 42.5 Gy / 16 fx vs. 50 Gy / 25 fx
– No boost - Outcomes:
– 5-yr LR ~3%
– 10-yr LR ~6% - Eq cosmetic outcomes
- Grade 3 tox favored conventional RT (contrast w/ START Α/Β, which did not show this)
What are the findings of the Univ of Florence trial of PBI for early stage BCa?
- Age >40, size <2.5cm, IDC or DCIS
- 30 Gy/ 5 fx QOD IMRT PBI vs. WBRT 50 Gy/ 25 fx + 10 Gy boost
- CTV = Cavity + 1-1.5 cm (limited to 3 mm from skin)
- PTV = CTV + 1 cm (limited to 3 mm from skin; allowed to go 4 mm into the lung)-
- Results:
– 5-yr IBTR ~1.5% (NS)
– 10-yr IBTR 3.7% vs. 2.5% (NS)
– 10-yr OS ~92% (NS)
– 10-yr BCSS 98% (NS) - Tox:
– ABPI had improved acute toxicity, late toxicity, and patient and physician assessed cosmesis
What are the findings of the CCP/planning objectives per Univ of Florence APBI trial?
What +LN ratio for pts w/ 1-3 +LNs is considered a cut-off point for delivering RNI for breast cancer?
- 20%, per Katz et al, IJORBP 2001
- 25%, per Truong et al, Cancer 2005
What were the results of the TEXT-SOFT trials investigating adjuvant ET for breast cancers
- Premenopausal primary breast cancer
- SOFT:
– TAM vs. TAM+ovarian suppression (OS) vs. exemestane+OS
– TEXT was similar w/o the TAM only arm - SOFT: TAM vs. TAM+ovarian suppression (OS) vs. exemestane+OS
– 8-yr DFS 79% vs. 83% vs. 86% (SS)
– 8-yr OS 91.5% vs. 93.3% vs. 92.1% (SS for TAM vs. TAM+OS)
if still premenopausal, 85% vs. 89% vs. 87% - Combine results: exem + OS vs. TAM vs. OS
– 8-yr DFS: 87% vs. 83%
– 8-yr freedom from distant recurrence: 92% vs. 90%
– 8-yr OS: 93% vs. 93% - Conc: In premenopausal breast cancer, adding ovarian suppression to TAM improved DFS and OS. Adding exemestane leads to an even better FFR. The highest risk patients may receive up to 10-15% reduction in DM. However, ovarian suppression has notable adverse effects.
What are the findings of the NSABP B-04 trial, NEJM 2002?
- Clinically (-) axilla and clinically (+) axilla
– cN- axilla: Rad mastectomy vs.🏆 TM+RT to axilla vs.TM + ALND
– cN+ axilla: Rad mastectomy vs. TM+RT to axilla 🏆 - Results: no diff in LF, DFS, or OS
- Conc: There is no benefit to radical mastectomy compared to total mastectomy.
What is the difference between radical and total mastectomy?
A radical mastectomy, also known as the Halsted mastectomy, involves the removal of the entire breast, the pectoralis major and minor muscles, and the axillary lymph nodes. This procedure was historically the standard treatment for breast cancer but has largely been replaced by less extensive surgeries due to advancements in understanding the disease and its spread.
In contrast, a total mastectomy (also known as a simple mastectomy) involves the removal of the entire breast tissue, including the nipple-areolar complex, but does not include the removal of the underlying chest muscles or the axillary lymph nodes unless a separate axillary dissection is performed.
Per the Taghian et al. JCO 2004 analysis, how does 10-yr LRF depend on the # of LNs and tumor size for patients who undergo mastectomy and systemic therapy w/o adjuvant RT?
Compare w/ the EBCTCG MA
Per the EBCTCG MA Lancet 2014, how are 10 and 20-yr outcomes for post-mastectomy patients affected by PMRT when broken down by pathologic LN staging and # of LNs?
- Conc:
– no benefit with RT for recurrence or BCM
– PMRT improves LRR and BCM in those with 1-3 nodes and ≥4 nodes.
What is the NCCN def. for a post-menopausal female?
- History of bilateral oophorectomy
- Age >60 years
- Age <60 and amenorrheic for ≥12 months 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 were the results of the EBCTCG MA for DCIS, JNCI 2010 w/ respect to ipsilateral breast tumor recurrence, BCM, and overall mortality?
BCS alone vs BCS + RT for DCIS
- 10-yr risk of ipsilateral breast tumor recurrence: 28.1% → 12.9% (SS)
– ↓ 50%!
- 10-yr breast cancer mortality: 4.1% vs. 3.7% (NS)
- 10-yr overall mortality: 8.2% vs. 8.4% (NS)
When is APBI recommended, conditionally recommended, conditionally not recommended, and not recommended for invasive cancers per ASTRO guidelines?
When is APBI recommended, conditionally recommended, conditionally not recommended, and not recommended for DCIS per ASTRO guidelines?
For whom is APBI suitable, cautionary, and unsuitable per ASTRO 2016 guidelines?
What are the cosmetic findings of the RAPID trial for APBI (Olivotto et al, JCO 2013)?
- Non-inferiority trial; ≥ 40 yrs; DCIS or IDC (tumor size <= 3 cm) s/p BCS w/ -margins, -LNs
- Rand: WBI [42.56/16 or 50/25 ± boost (3DCRT or IMRT)] vs. APBI [38.5/10 BID]
– CTV: Tumor bed + 1 cm [excluding CW, pec maj, 5 mm from skin]. PTV = CTV + 1 cm - Cosmesis Eval:
– Assessed by trained nurses, a patient questionnaire, and radiation oncologists
– At baseline, 3, and 5 years via digital photographs of both breasts.
– Global cosmetic scores: 0, excellent or no difference; 1, good or small difference; 2, fair or moderate difference; and 3, poor or large difference.
– Adverse cosmesis was defined as the proportion of patients with a “fair” or “poor” global cosmetic score. - Adverse Cosmesis Results: APBI vs. WBI
– Baseline: ~18%
– 3 yrs: APBI had sig worse cosmesis
– 5 yrs, APBI had sig worse cosmesis (32.8% vs 13.4%).
– APBI had sig more telangiectasia, breast induration, and fat necrosis (3% vs 0.9%, p = 0.01) - Clin Pearl:
– APBI increased rates of adverse cosmesis and late radiation toxicity compared to standard WBI.
– This sig differs from the findings of the Eur APBI trials, including Florence.
What are the findings of the NSABP B06 trial (Fisher et al. NEJM 1985) for breast cancer?
- Early stage Breast Ca:
– Total mast, segmental mastectomy alone, and segmental mastectomy f/b RT
– All underwent ALND - Results, ipsi breast recurrence: Seg. mast vs. Seg. mast + RT
– 8-yr: 10% v 29% (SS)
– 12-yr: 10% v 35% (SS)
– 20-yr: 14.3% v 39.2% (SS) - Results: DFS & OS: Mast vs.BCS vs. BCS+RT
– 20-yr DFS: 36% vs., 35% vs. 35%
– 20-yr OS: 47% vs. 46 %vs. 46% - Subsequent retrospective analysis revealed that 78 patients had DCIS
– DCIS results, Ipsi recurrence: seg. mast +RT vs. seg. mast vs. total mast
– 7% vs. 43% vs. 3.6% - Pearl:
– No randomized trials intentionally comparing outcomes for these interventions for DCIS patients alone
– This is the only randomized trial whose subanalysis compared mast vs. lump ± RT for DCIS
What are the findings of the NSABP B17 trial (Fisher et al. NEJM 1993) for breast cancer?
- DCIS s/p BCS w/ -margin → obs. vs. 🏆 50 Gy WBRT (6% boost)
- Results:
– 12-yr IBTR 32% vs. 16%
– 12-yr non-invasive IBTR 15% vs. 8%
– 12-yr invasive IBTR 17% vs. 8%
– All cohorts benefitted from RT
– 12-yr EFS: 50% vs. 64%
– 12-yr OS: ~86% for both - Conc:
– BCS + WBRT reduces IBTR
What are the findings of the NSABP B24 trial (Fisher et al. NEJM 1999) for breast cancer?
- DCIS s/p WLE for DCIS (16% had +margin) → 50 Gy alone vs. 🏆 50 Gy + TAM x 5yrs
– 38.5% Boost - Results: 50 Gy alone vs. 🏆 50 Gy + TAM x 5yrs
– 15-yr Cl of DCIS IBTR: 8.3% vs. 7.5%
–15-yr invasive IBTR: 10% vs. 8.5%. - Pearl:
– TAM added to RT reduces invasive breast cancer recurrence (among all patients before ER was assessed)
– When testing ER, ER+ tumors had reduced total invasive breast cancer events with TAM, although isolated effects were small.
What are the predictors of local recurrence after mast vs. BCS based on the nomogram by Mamounas et al., JCO 2012 (combined analysis of B-18 and B-27)?
- neoadj ACT f/b BCS, predictors of recurrence
– Age
– Clinical nodal status (before chemotherapy)
– Response to chemotherapy - neoadj ACT f/b mast, predictors of recurrence
– Tumor size before chemotherapy
– Nodal status before chemotherapy
– Pathologic response to chemotherapy.
What are the preferred neoadj and adj CHT regimens for locally advanced breast cancer?
Preferred:
- Dose dense doxorubicin/cyclophosphamide (ddAC) followed by paclitaxel (T)
- AC q3weeks x4C, f/b T q3weeks x4C
- Docetaxel and cyclophosphamide (AC)
- For Her-2+:
– ACT and trastuzumab +/- pertuzumab
– Docetaxel, carboplatin, and trastuzumab +/- pertuzumab
What were the results of the Chinese phase III trial (Wang et al, Lancet Onc 2019) investigating hypofx PMRT?
- Breast cancer s/p mastectomy + ALND, non-reconstructed, T3-T4 or ≥4 nodes
– 🏆 43.5 Gy/ 15 fx vs. 50 Gy/ 25 fx to CW and RNI - Results: hypofx vs. convfx
– No differences in LRR, DFS, OS, or late skin toxicity
– 5-yr LRR 8%, DFS 74%, OS 84% both arms - Tox:
– Acute skin tox, Gr 3: 3% vs. 8% (SS)
– All other acute and late tox were the same
– Lymphedema: G1-2 → ~20%. ≥ G3 → 1%. - Caveats:
– CW radiated w/ e-, SCV radiated w/ photons
– RT CHARM is investigating hypofx in the reconstructed breast
– Menomonic: Chinese are focused on function, not form → did not allow reconstruction
What were the results of the RT CHARM trial (Poppe et al, Lancet Onc 2019) investigating hypofx PMRT?
- Stage IIa-IIIa with planned reconstruction → 🏆 42.56 Gy/ 16 fx RNI vs. 50 Gy/ 25 fx RNI
– Excluded: T4, N3, positive IMN node - Results: Convfx vs. hypofx
– 3-yr LRR: 2.3% vs. 1.5%
– 2-yr reconstruction complications: 12% vs. 14%
– Complications less with autologous vs. implant only, OR 0.5
– acute and late toxicity not different
What were the results of the FABREC trial (Wong et al, JAMA 2023) investigating hypofx PMRT?
- Breast cancer s/p mastectomy and immediate expander or implant reconstruction Stage I-III
– → 🏆 42.56 Gy/ 16 fx vs. 50 Gy/ 25 fx
– Optional RNI allowed to SCV and IMN (given in ~90%); No boost
– Bolus allowed at discretion over scar or entire CW
– ~90% had RNI, 42% IMRT. 59% were prepectoral, ~20% were implants, and ~80% were expanders. All had immediate reconstruction. - Results: Median f/u 40 mos
– Physical well-being QOL was not superior with hypofx, but appeared not different
– Grade ≥3 chest wall toxicity 10.0% vs. 9.5% (further specifics not outlined)
– Recurrence rates were similar - Conc: QOL, chest tox Gr ≥ 3, and recurrence not diff
What were the findings of the dose-escalation MDACC inflammatory breast cancer retrospective study (Liao et al., IJORBP 2000)?
Studied the effect of dose-escalation for inflammatory breast cancer
- Tx seq: NACT → mastectomy → Adj. CHT + Adj. RT to CW and lymphatics
– 1977-1985: 60 Gy QD or BID (45-50 Gy to CW/LNs + 10 Gy boost to CW, either QD or BID)
– After 1986, the majority were dose-escalated: 66 Gy BID (45-51 Gy/1.5 Gy +15 Gy e- boost to CW)
Results:
- For BID patients only, 66 Gy BID vs. 60 Gy BID
– 5-yr LRC: 84% vs. 58%
– 10-yr LRC: 77% vs. 58%
– Long-term complications were comparable
What were the findings of the dose-escalation MDACC inflammatory breast cancer retrospective study (Bristol et al., IJORBP 2008)?
- Retrospective MDACC study of dose-escalation for inflammatory breast cancer, to identify which patients benefit from dose escalation
- Doses, PMRT:
– 1977-1981: 60 Gy QD: 50 Gy/25 fx + 10 Gy CW boost
– After 1982: 66 Gy BID: 45-51 Gy in 1.5 Gy/fx + 15 Gy boost, both BID -
Doses, Pre-op RT w/o boost
– 1977-1985: 45 Gy BID or 50 Gy in 25 fx Gy
– After 1985: 51 Gy with BID - Overall Results: Completed entire course vs. not able to complete whole therapy
– 5-yr LRC: 84% vs. 51%
– 5-yr DMFS: 47% vs. 20%
– 5-yr OS: 51% vs. 24% - Dose escalation from 60 → 66 Gy lends a 5-yr LRC benefit for:
– < 45 yrs old: 86% vs. 65%
– Less than partial response to neoadjvant chemo: 60% vs. 32%
– close, positive, or unknown margins: 83% vs. 60% - Tox: 66 Gy BID vs. 60 Gy
– Gr 3-4 tox: 29% vs.15%
– Lymphedema: 9% vs 2%.
– Fibrosis: 6% vs 4%.
– Brachial plexopathy: 2% vs 0%. - Conc(s):
– Completion of mastectomy, RT, and chemo leads to high LC.
– Dose escalation to 66 Gy appears to mitigate failure in partial responders, young age, or positive or close margins.
Per MDACC inflammatory breast cancer retrospective study (Bristol et al., IJORBP 2008), which factors predict clinical outcomes for inflammatory breast cancer patients?
- Response to chemotherapy: CR or PR vs. less than a partial response
- ER+ are better performers than ER-
- Surgical margin status
- Number of nodes pathologically involved (0-3 vs. ≥4)
- Whether or not a taxane was used.
What were the results of the ECOG 5194 (Hughes et al JCO 2009) study?
What is the ROT for recurrence after excision alone for DCIS?
- Low-G DCIS: 1%/yr
- High-G DCIS: 2%/yr
What are the results of the RTOG 0413/NSABP B-39 trial for breast cancer?
- Stage 0-II who underwent lumpectomy, tumor <3 cm, ≤3 nodes
– 50 or 50.4 Gy, optional 10-16 Gy boost
– vs. APBI, 34 Gy/ 3.4 BID w/ HDR/mammosite (interstitial, Rx to 1.5 cm. Intracav. Rx to 1 cm)
– vs. APBI, 38.5 Gy/ 3.85 BID with EBRT (CTV 1.5 cm, PTV 1 cm) - Results: APBI (EBRT: 73%, HDR: 27%) vs. WBRT
– 10-yr IBTR: 4.6% vs. 3.9%
– No difference in DM, DFS, or OS
– Gr 1 tox: 40% vs. 31%
– Gr 2 tox: 44% vs. 59%
– Gr 3 tox: 10% vs. 7%
– Patient assessed cosmesis not different; MD assessed cosmesis equivalent - Conc:
– PBI (EBRT or mammosite) is not equivalent to WBRT. However, the absolute difference is <1%.
– APBI had slightly worse Gr1 and Gr 3 tox.
– Cosmetic outcomes were not different.
What are the results of the NSABP B-21 (Fisher et al. JCO 2002) trial for breast cancer?
- Early strage breast; ≤1cm s/p WLE, any ER status
– →TAMx5 yrs only vs. 🏆 TAM+50 Gy vs. 50 Gy only
– Boost optional - Results: TAM only vs. RT only vs. TAM+RT
– 8-yr IBTR: 17% vs. 9% vs. 3% (SS)
– 14-yr IBTR: 29% vs. 11% vs. 10%
– 14-yr OS 78-82% (NS) - Conc:
– RT and TAM improve IBTR in tumors ≤1 cm.
– At longer-term f/u at 14 years, the IBTR benefit of TAM added to RT disappears, becoming similar to RT alone.
MNEMONIC: 2 therapies RT+TAM) are better than 1 (RT or TAM alone0
What are the findings of the MA.20 trial (Whelan et al., NEJM, 2015) for breast cancer?
-
BCS and SLNB or ALND and adjuvant chemo (90%) or ET (66%) with:
– LN+: 90%
— N1 (1-3): 85%
— N2 (4-9): 5%
– high risk LN-: 10%
— 1%: T3 (tumor >5 cm)
— cT2 (size>2 cm) with < 10 axillary nodes removed with either ER-, Grade 3, or LVI - Randomization to: WBI (50/25); RNI was 45/25
– →no RNI vs. 🏆 RNI to IMN, SCV, axilla level III (plus levels I-II if <10 nodes removed or >3 nodes+) - Findings: WBRT alone vs. WBRT + RNI
– 10-yr DFS 77% vs. 82% (SS)
– 10-yr BCM 10% vs. 12% (NS)
– 10-yr OS 82% vs. 83% (NS) → Some say that there is a trend towards OS benefit - Tox:
– Radiation pneumonitis 0.2% vs. 1.2% (SS)
– Lymphedema 4.5% vs. 8.4% (SS)
– No increase in brachial plexopathy. - Tidbits: NO OS benefit, still
– On interaction analysis, ER/PR- had improved DFS with RNI but not ER/PR+.
– ER- had a trend to improve OS by 83% vs. 74%, p=0.05.
– There were no interactions for # nodes. But note that the trial is not powered explicitly for this
What is the preferred treatment for Phyllodes tumor of the breast?
- Wide excision w/o axillary staging
– 10 yr LR: 8%
– 10 yr DM: 13% - For recurrence, surgery is preferred if it can be done. Adj. RT can be considered.
- Lumpectomy and tumor > 2 cm, or mastectomy and tumor > 10 cm may benefit from RT
Per the Morrow et al. Meta-analysis, J Clin Onc 2016, what is considered an adequate margin for DCIS?
- For DCIS being treated w/ WBRT: > 2 mm
- For APBI, per ASTRO, or omission of RT: > 3 mm
What % of males or females w/ BRCA1 or BRCA2 mutations will develop breast cancer?
Incidence of breast cancer:
- BRCA1: F 65%, M 1%
- BRCA2: F 45%, M 7%
What were the findings of NSABP B-18 trial (Fisher et al. JCO 1997, Wolmark et al. JNCI 2001) for breast cancer?
- T1-3N0-1 operable, palpable, and non-fixed
– NAC AC x4C vs. adj AC x4C - Results: NAC vs. adj.
– Ability to undergo BCS: 67% vs. 60% (SS)
– At the time of surgery, LN+: 41% vs. 57% (SS) - Findings: There is no OS difference between NAC and adjuvant chemo. NAC allowed more breast conservation. However, LR was increased if planned mastectomy was converted to BCS. Response predicts OS.
What are the findings of the PRIME II trial (Kunkler et al, Lancet Oncol, 2015; Kunkler et al, NEJM, 2023) for breast cancer?
- Age ≥65, T1-T2 ≤3 cm, ER/PR+, ≥1 mm margins, s/p lumpectomy AND SLNBx or ALND
– Median Age: 70
– One of grade 3 or LVSI, but not both
– (~12% were T2, 3% grade 3) - Randomized →ET + RT 40-50 Gy / 15-25 fx vs. ET alone
– 16% had boost - Findings, Median FU 9.1 yrs: ET vs. RT+ET
– 5-yr IBTR: 4% vs. 1%
– 10-yr IBTR: 10% vs. 1%
– 10-yr IBTR for ER-low (ER ≤ 50%): 19% vs. 0%
– Higher risk of IBTR if ET stopped early, HR 4.66
– 10-yr DM 3% vs. 1.6%, not different
– 10-yr OS ~81%, not different - Conc:
- WBRT in elderly with low-risk tumors improves IBTR. There is no benefit in OS or DM. Observation may be reasonable in some populations. Treatment should be individualized.
- RT should be recommended in ER low and those declining endocrine therapy or discontinuing it early.
- Results may not apply to Gr3 or T2.
- The trail was done when RT was given over 6 weeks. Equivalent hypofx and APBI regiemns are much easier for even the elderly to go through.
- MNEMONIC:
– PRIME Il starts with a P and requires pNO staging; it had broader inclusion criteria
– CALGB starts with a C and only requires a cNO axilla; it had less broad inclusion criteria
What are the findings of the CALGB 9343 trial (Hughes et al, JCO 2013) for breast cancer?
- Age ≥70, pT1 pN0, ER+, any grade, s/p lumpectomy
- →TAM with RT 45 Gy + 14 Gy boost vs. TAM alone
- Results: TAM vs. RT+TAM
– 5-yr LRR: 4% vs. 1%
– 10-yr LRR 10% vs. 2%
– 10-yr DM 5% in both arms
– 10-yr OS ~67% in both arms
– Tam compliance was not reported - Conc:
– RT improves LRR, but no change in OS or DM - MNEMONIC:
– PRIME Il starts with a P and requires pNO staging; it had a broader inclusion criteria
– CALGB starts with a C and only requires a cNO axilla, it had a less broad inclusion criteria
What workup is necessary for the complete staging of DCIS, per NCCN?
- History and physical
- Diagnostic bilateral 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 are the findings of the TATA memorial study (Badwe et al. Lancet Onc 2015)?
- Metastatic breast cancer at presentation
- Locoregional treatment to primary and axilla nodes vs. not
– Mast vs. BCS + ALND → RT; Induction chemo given if unresectable initially - Results: Locoregional tx vs. not
– Median LR PFS: Median not achieved vs. 18.2 mos (SS)
– Only 10% of the LR tx group required palliative surgery at the time of progression
– Median OS: 19.2 mos vs 20.5 mos (NS)
– 2-yr OS 42% vs 43% (NS)
– No difference in OS on adjustment for stratification factors, pre/post menopausal, or Her2
– QOL not compared - Conclusion: Local treatment of the primary tumor in metastatic breast cancer did not improve OS, and should not be offered routinely.
Contrast this with the Turkish study, MF07-01 (Soran et al., JACS 2021), which showed that locoregional therapy for denovo metastatic breast cancer decreased the hazard of death by ↓ 38%
How does a delay in adjuvant RT for breast cancer impact locoregional recurrence risk?
- Every month delay → ↑0.5% in absolute LRF; ↑8% in relative risk of LRF (Systemic review and MA: Gupta et al CLin Onc 2016)
- Inferior outcomes (LRF, DFS, BRSS) for delays beyond 20 weeks only (Olivotto et al., JCO 2009)
What are the absolute and relative contraindications to BCS approach to breast cancer, per the NCCN?
What are the absolute and relative recommendations for mastectomy versus the BCS approach to breast cancer, per the NCCN?
Which patients were excluded from the Canadian hypofx trial for breast cancer?
- +margins
- size > 5 cm
- Separation > 25 cm
Which patients are candidates for hypofractionated whole-breast RT?
Note that per the HypoG-01 phase III Univancer trial, hypofx RT to regional nodes is safe!, which has not been incorporated into the ASTRO guidelines yet.
What is the primary feared toxicity of trastuzumab?
- Cardiotoxicity, including CHF, in 3%
- Risk increased further if given alongside doxorubicin
What is the primary toxicity of Docetaxel?
Fluid accumulation
What are the primary toxicities of Taxanes?
Peripheral neuropathy, allergic reactions, myalgias, arthralgias
What is the primary toxicity of 5FU?
Mucositis/Stomatitis
What kind of a beam is used to treat a spraclav field for breast cancer?
Contralateral anterior oblique
What were the findings of the TARGIT-A clinical trial investigating PBI IORT vs. WBRT w/ EBRT?
- Test the non-inferiority of TARGIT-IORT [± WBRT w/o boost (based on adv. features on path)] vs. EBRT WBRT [± boost, as indicated]
– IOT delivered pre-path confirmation right after lumpectomy
– If adverse features are confirmed on the path, IORT pts got WBRT w/o boost - Summary of 2014 and 2020 updates:
– 5 y LR 2.1% (IORT ± WBRT) v 0.95% (WBRT) (difference = 1.2% but SS)
— LR is < 2.5% (low in both arms), so it maintains non-inferiority of TARGIT-IORT to WBRT w/ EBRT per trial design
– No diff in survival
– TARGIT IORT reduced non-breast cancer mortality by 4% - Hazard Ratios (BMJ, 2020 update):
– Local recurrence-free survival HR 1.13, NS
– Mastectomy-free survival HR 0.96, NS
– Distant disease-free survival HR 0.88, NS
– Overall survival HR 0.82,NS
– Breast cancer mortality HR 1.12, NS
– Mortality from other causes HR 0.59, SS - Criticisms:
– There is an SS ↑ in LR w/ IORT ± WBRT
– Some patients received EBRT after IORT, but the criteria were very non-uniform
How does the risk of major coronary events increase w/ increase in mean heart dose?
- ↑7.4% relative per Gy, w/ no threshold (Darby et al. NEJM 2013)
- However, the absolute risk in women w/o cardiac risk factors is still very low
Which factors are used in calculating the Nottingham histologic grade for IDC of the breast?
_ EORTC 10853 (Bijker er al. JCO 2006)
– Comedians are the worst!
What are the findings of the EORTC 22922 (Poortmans et al. NEJM 2015)?
- Does comprehensive RNI improve OS in:
– Any medial or central tumor, or any N+,
– s/p BCS (76%) or mastectomy (24%)
– 44% N0; 56% N+ - 50 Gy breast/CW + [no RNI vs. 🏆 RNI to IMN, SCV, and Axillary]
- 15-yr Results: no RNI vs. RNI
– OS: 70.9% vs. 73.1% (NS)
– DFS: 59.9% vs. 60.8% (NS)
– Distant DFS: 68.2% vs. 70.0% (NS)
– Any recurrence: 27.1% vs. 24.5% (SS)
– Death from breast cancer: 19.8% vs. 16.0% (SS) - Conc: RNI improves BC recurrence and mortality but NOT OS.
What are the findings of the AMAROS trial (Donker et al. Lanc Onc 2015)?
- cT1-2N0, s/p BCS or mastectomy. Lobular allowed
– ~14% lobular, ~18% mastectomy. 5% had ≥3 LN+. Only 1 T3 - Noninferiority. BCS or mastectomy, If SLNB+:
– →ALND vs. 🏆 RNI to axilla levels I-III and medial SCV (No IMN)
– RT was given to axilla in ALND group if ≥4 nodes positive. - Results:: ALND ± RT vs. RT
– 5-yr axilla recurrence: 0.41% vs. 1.04%
– 10-yr axilla recurrence: 0.93% vs. 1.82%
– 10-yr LRR: 3.4% vs. 3.8%
– 1-yr lymphedema 40% vs. 22%
– 5-yr lymphedema 25% vs. 12%
– 10-yr 2nd primary: 8.3% vs. 12.1% but CIs overlap
– Contralateral BTR 8% vs. 11% (SS)
– 10-yr OS 85% vs. 81% (NS)
– 10yr DFS: 77% vs. 82% (SS)
– DM 12% vs. 15% - Conc:
– ALND is not required in T1-2 SLNB+ when RT is directed to the axilla. The secondary endpoints of OS and DM are similar.
– Although the trial statistically did not reach noninferiority, overall axillary recurrences are low at 1% or less in each group.
How does a + margin (tumor on ink) affect IBTR?
- +margin → 2 fold increase in IBTR
- No tumor on ink is acceptable for a -margin
[Moran et al. IJROBP 2014]
What were the findings of RTOG 9804 (McCormick et al, JCO 2015) aimed at identifying women w/ DCIS who may not require adj. RT?
- Good-risk DCIS: low- or intermediate-grade DCIS, <2.5 cm, with margins ≥ 3 mm.
– → Lumpectomy alone vs. Lumpectomy + RT
– RT to 50/25, 50.4 Gy in 1.8 Gy fractions, or
42.5 Gy in 16 fractions. Boost radiation was not allowed on the study.
– Tamoxifen was optional, but 62% of women did receive tamoxifen. - Median follow-up of 7.17 years, the study demonstrated:
- An improvement in local failure (LF) with radiation therapy (7 year LF=0.9% vs. 6.7%, p<0.001).
- The risk of a contralateral breast recurrence was 3.9% in the RT arm and 4.8% in the observation arm, (p=0.88).
- The mastectomy rate at 7 years was 2.8% in the observation arm and 1.5% in the RT arm.
- There was no difference in overall survival or disease free survival with the addition of radiation therapy.
In terms of toxicity, grade 1-2 toxicity was seen in 30% of patients in the observation arm compared with 76% of patients in the RT arm. However, grade 3-4 toxicity was 4% with observation and 4.2% with RT. Late RT toxicity was as follows: 30% grade 1, 4.6% grade 2, 0.7% grade 3. - Memory hook: 9804 → kinda like brain, spare the brain!
What were the findings of the KEYNOTE 522 trial (Schmidt et al, NEJM 2020 and 2022) for CHT + IO for breast cancer?
- Phase III trial investigating the addition of IO to CHT for TNBC
– NAC CHT (carbo/taxol f/b doxorubicin or epirubicin and cyclophosphamide) +/- NAC pembrolizumab and adjuvant pembrolizumab up to 9 cycles for a completion of 1 year of immunotherapy - Results: CHT+IO vs. CHT only
– pCR ↑15% : 64.8% vs. 51.2% - 15-mo disease progression: 7.4% vs. 11.8%
– 3 yr EFS: 84.5% vs. 76.8% - Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.
– ≥ Gr 3 AEs: 78.0% vs. 73.0%
– Death: .4% (3 patients) and 0.3% (1 patient) - Notes:
– Pembro can be delivered concurrently w/ RT or started 2 weeks thereafter
–Dosing: 200 mg q3weeks, or 400 mg q6weeks
Which factors predict ↑ risk of LRF after mastectomy?
- – 0 +LN: 4%
– 1-3 +LN: 10%
– 4-9 +LN: 21%
– ≥10 +LN: 22%
– > 2mm ENE
– T stage - – Tumor size ≥ 2 cm
– Close/positive margins
– Age < 50
– LVSI|
– No systemic therapy - Risk:
– 0 risk factors →2.0%,
– 1 risk factor → 3.3%
– 2 risk factors → 5.8%
– ≥ 3 risk factors → 19.7% - Thus, patients w/ 3 or more risk factors are advised to undergo PMRT
In cN0 breast cancer patients, what are the advantages of doing SLNBX before vs. post-CHT at the time of surgery?
The advantages of doing the procedure before chemotherapy include:
1. Accurate assessment of the initial involvement of the axilla.
2. It may help counsel the patient on needing post-mastectomy RT or regional irradiation.
3. It may affect systemic therapy decisions.
The advantages of doing a sentinel lymph node biopsy after chemotherapy are:
1. Only one procedure is done.
2. Provides an assessment of the response to chemotherapy.
3. If patients become node negative, fewer patients may need an axillary dissection.
4. There is no delay in initiating chemotherapy.
Which patients derive the most significant benefit from the breast boost EORTC breast boost trial (Bartelink et al. JCO 2007)?
- Boost: 16 Gy in 8 fx
- LRC: All groups benefit, but younger (≤ 40 yrs) benefit the most
- 10-yr OS is the same: 82%
How do typical breast tumors present on a mammogram?
- Cysts (fibroadenomas) → well circumscribed
- LCIS → not visible
- DCIS → micro-calcifications (linear branching →High G DCIS)
- Spiculated → cancers
What % of Paget’s disease patients have an underlying palpable breast mass?
- Palpable → ~50%
– If present, 90% are invasive cancers - For surgery, removal of the nipple-areolar complex is indicated
What were the findings of ACOSOG Z0011 trial for early-stage breast cancer?
- cT1-2 cN0 but 1-2 +SLN on bx → ALND (Lvl I, II) vs. no further surgery → WBRT
– Exc: ≥ 3 +LNs, matted LNs, gross ENE, NACT
– All received adj. WBRT w/ tangents
– RT to SCV or targeted axilla prohibited → BUT 15% received SCV RT and 50% received high tangents
– ALND removed a median of 17 LNs
– In the ALND cohort, 27% had additional LNs, and 21% had ≥ 3 +LNs - Results, no diff in outcomes at 5 or 10 yrs
– 10 yr DFS: ~80%
– 10-yr OS: 84% vs. 86% (SS) - Conc(s) + Caveats:
– ALND not required after 1-2 +LNs
– Mnemonic: Z001+1 → only 2 +LNs allowed
What CHT regimen is the most effective for inflammatory breast cancers?
FAC → Paclitaxel (5FU + AD→T)
- 5-FU/Doxorubicin/Cyclophosphamide → Paclitaxel
- ↑ median PFS (18 → 27 mos), ↑ median OS (32 → 54 mos)
What are the most important, paradigm-shifting trials for DCIS?
- Notable NSABP DCIS trials: B-06, B-17, B-24.
– TL;DR - Hypothesis for BCS/BCT in DCIS per B-06, confirmed BCT in B-17, add tamox per
Is there any benefit to doing chemo prior to or after RT?
Bellon, JCO 2005
- No benefit to any particular sequencing
What are the borders of a typical 3D SCV field?
Superior border: Cricoid cartilage
Inferior border: Inferior clavicular head
Lateral border: Coracoid process (sometimes brought to the lateral edge of humerus)
Medial border: Ipsilateral vertebral pedicals
What are the borders of a typical 2 field breast technique?
What are the borders of a typical 3 field breast technique?
What are the borders of a typical 4 field breast technique?
What are the borders of a typical monoisocentric breast technique?
What are the borders of a typical dual isocentric breast technique?
What is considered good-risk DCIS, per RTOG 9801?
- Low to Int grade
- Size < 2.5 cm
- Margins ≥ 3 mm
What are the borders of a typical IMN coverage technique?
What is considered good-risk DCIS, per the ECOG study Hughes et al 2009?
- Two Cohorts: Evaluate the incidence of ipsilateral recurrence (events) in DCIS pts tx w/o adj. RT
– Low risk, 1: Low- or int-grade DCIS; size ≤ 2.5 cm, SM ≥ 3 mm, no residual calcifications on their post-excision
– High risk, 2: high-grade DCIS; size ≤1 cm, SM ≥ 3mm, no residual calcifications on their post-excision mammograms - Findings: Cohort 1 vs. 2
– 5-yr all LF rate: 6.1% vs. 15.3% (SS)
– 12-yr all LF rate: 14.4% vs. 24.6% (SS)
– 12-yr invasive LF rate: 7.5% and 13.4% (NS) - Contrast: ECOG had a broader def. for those who could avoid RT
What is the MOA of palbociclib (Ibrance)?
- CDK4 and CDK6 inhibitor
- Paloma-2 Study (Finn et al. NEJM 2016)
– Post-menopausal, ER+/HER-, metastatic breast cancer (prior CHT and ET allowed) → Palbociclib and letrozole vs. letrozole alone: PFS 24.8 vs. 14.5 mos (HR 0.58)
– Similar results in the MONALEESA-2 study
What is the MOA of Fulvestrant?
Complete ER antagonist
What is the MOA of Erlotinib?
EGFR inhibitor
What is the MOA of Exemestane?
irreversible steroidal inhibitor
What is the MOA of anastrozole and letrozole?
Competitive aromataste inhibitor
When should bolus be used in PMRT patients?
- Bolus recommendations are controversial; NO LC benefit demonstrated in any studies
- Per ESTRO, when skin needs full dose:
– T4b disease
– inflammatory breast cancer
What are the risk factors for DCIS development?
What outcomes does adding herceptin to ACT CHT improve?
Perez et al., JCO 2014, combined analysis of hte NCCTG N9831 and NSABP B-31 trials
- 10-yr DFS: 62% → 74%
- 10-yr OS: 75 → 82%
What were the findings of the ACOSOG Z1071 trial?
FNR of SLNBx in pts w/ an initial bx-proven cN1 disease who underwent NACT f/b surg w/ SLNBx and ALND
- 12.6 % (higher than the expected threshold of 10%)
- 6.8% if the LN was clipped prior to NACT
Which dosimetric factor is a/w increased risk of reconstruction complications ain pts undergoing PMRT?
- Dose heterogeneity
– Minimize it by keeping V107% < 11%
– Rate of complications 12%
– if you exceed this, rate of complications jumps to 42%
What were the main findings of the Danich DBCG-IMN (Thorsen et al. JCO 2022)?
-Adj. RT w. vs. w/o IMN RT
– 15-yr distant recurrence: 36% vs. 29% (SS)
– 15 yr OS: 60% vs. 55% (SS)
– Conc: IMN RT improves distant recurrence and OS
Which SLNBx trials allowed BCS vs. mastectomy?
In the NSABP report on lumpectomy alone for LCIS (Fisher et al, Cancer 2004), what were the IBRT and CBTR at 12 yrs?
- 12-yr results:
– IBRT: 14%
– CBTR: 8% - Given “low” recurrence risk, lumpectomy alone has been deemed sufficient for LCIS ny the NCCN
What are the findings of the HYPORT and HYPORT V studies (Chatterjee et al. IJORBP 2023)?
- Metabolic response is a response seen on a PET/CT scan.
Are HER2-directed therapies used in DCIS?
- No, HER2-directed therapies are not currently recommended for DCIS patients. They should receive endocrine therapies only.
- B43, Cobleigh et al JCO 2021, was a -ve trial (trial of pure DCIS rand to RT ± T): did not achieve a 36% reduction in IBRT.
Which targeted therapies can be used in metastatic breast cancer patients w/ ESR1 mutation, which can lead to a ligand-independent activation of ER?
- Elacestrant: Selective ER degreder (SERD)
- EMERALD Trial (Bidard et al. JCO 2022): PFS 2 mos → 4 mos
Which hypofx trail has included patients w/ pure DCIS?
- DBCG HYPO
- All other hypofx trials have excluded pts w/ pure DCIS
How many pts w/ LCIS have multicentric or bilateral disease?
- LCIS:
– Multicentric: 90%
– B/l invovlement: 50%
– Tamoxifen can ↓ progression to invasive disease
What is the difference between luminal A and B cancers?
Luminal A breast cancers are characterized by:
* Estrogen receptor (ER) positive
* Progesterone receptor (PR) positive
* HER2 negative
* Low proliferation index, typically measured by a low Ki67 index (less than 14%).
Luminal B breast cancers are characterized by:
* ER positive
* PR negative or low
* HER2 negative or positive
* High proliferation index, typically measured by a high Ki67 index (14% or higher).
Luminal A tumors generally have a better prognosis and respond well to endocrine therapy alone. In contrast, luminal B tumors have a higher proliferation rate, poorer prognosis, and may benefit from additional chemotherapy.
What does the presence of CHEK2 mean for a patient’s breast cancer risk, and what are the recommendations for screening?
- Increased risk of b/l breast cancers
– CHEK 2 → Check both breasts!
What is the risk of complications and capsular contracture for patients being planned for PMRT?
- 20-25%
- Thus, a two-stage breast reconstruction process is recommended for patients receiving PMRT
What additional therapies should be given to women receiving ET for their early stage breast cancers w/ signs of osteoporosis?
- Vitamin D (800 IU)
- Calcium (1200 mg)
- Bisphosphonate or Denosumab
- Z-score of ≤ -2 is considered below the expected range
How should mometasone be prescribed for radiation dermatitis prevention in pts receiving RT?
- Mometasone 0.1% BID QD during RT and 1-2 weeks after
For which women can chemoprevention be used to prevent breast cancer?
Note: IF ADH is identified on bx, surgical excision is recommended 2/2 increased risk of identifying occult DCIS.
Should additional “shave margins” be taken during lumpectomy?
Yes! It decreases the +margin rate by 50% (34% → 19%)
Chagpar et al, NEJM 2015)
What are the findings of the DANISH post-mastectomy trials (82b & c)?
- s/p TM+ALND, high-risk: axillary N+, size >5 cm, or invasion of skin or pectoralis fascia
- Danish 82b: premenopausal → mastectomy + CHT ± RT
- Danish 82c: postmenopausal → mastectomy + TAM ± RT
Results:
- In the group of patients with 1-3 positive lymph nodes, outcomes were still beneficial.
– 15-year locoregional failure was 4% (with RT) vs. 27% (no RT), p<0.001.
– 15-year overall survival (OS) was 57% (with RT) vs. 48% (no RT), p=0.03.
- In patients with ≥4 lymph nodes involved, RT was also beneficial.
– 15-year locoregional failure was 10% (with RT) vs. 51% (no RT) vs. p<0.001.
– 15-year overall survival (OS) was 21% (with RT) vs. 12% (no RT), p=0.03.
For which patients is the 21 gene pannel recommended?
- Get 21-gene panel for:
– ER+
– Her2-
– Size >0.5cm
– pN0
The risk of developing which cancers is higher in the BRCA2 population compared to BR?
- BRCA2 carriers appear to have an elevated incidence of the following malignancies vs. BRCA1 carriers:
– Prostate (Kote-Jarai et al. Br J Cancer 2011)
– Pancreas (Ferrone et al. J Clin Oncol 2009).
– Uveal melanoma (Moran et al. Fam Cancer 2012)
– Male breast cancer (Evans et al. J Med Genet 2010)
What are the standard doses for tamoxifen and anastrozole?
- TAM: 20 mg QD
- Anastrozole: 1 mg QD
Which genetic mutation is most strongly a/w lobular breast cancer?
- CHD1
- also a/w gastric cancer
Do large-breasted women have poor outcomes with hypofractionated RT?
- No, per a study by Shaitelman JCO 2018
- Study was designed to address concerns of people that women with large breasts should not undergo hypofx RT
What are the rates of distant recurrence for women w/ T1-2, N0-9, M0, ER+ breast cancers tx w/ local therapy (lump vs. mast) f/b ET x5yr alone?
These findings should make us question a cookie cutter 5-year ET plan for breast cancer patients and suggest a need for more individualized treatment practices.
What was the main finding of the EUROPA trial for breast cancer?
- EUROPA, Lancet Onc 2025:
– Endocrine therapy was associated with a more significant reduction in health-related quality of life (HRQOL) compared to radiotherapy at 24 months in women aged 70 years and older with luminal A-like early breast cancer who had undergone breast-conserving surgery. These findings suggest that radiotherapy might better preserve HRQOL in this patient population
