Breast Cancer Flashcards
What is the incidence for DCIS and Invasive breast cancer?
DCIS: Incidence (Australian statistics)
- 1600 cases annually
- Incidence increasing (detection bias due to screening, 90% screen detected)
- 20% of breast cancers
Increasing incidence with increasing age: - Mean age 55 years
Invasive Breast cancer:
Incidence (Australian statistics)
- 20000 cases annually
- 2nd most common cancer overall (after NMSC)
- Most common cancer in women (2nd most common cause of death - after lung)
Rising incidence since 1990s
- Likely due to early detection (screening programs)
- Change in reproductive patterns (less children and use of OCP/HRT)
- Obesity
Marked female predominance 99% female. (approx 200 male cases annually)
Mean age is 65 years
Ethnic differences
- Incidence higher in white women (USA, Australia, NZ)
Mortality higher in black women (more likely to be LA or TNBC)
What are the risk factors for developing breast cancer?
1) Advancing age
2) Hormonal factors (increasing oestrogen exposure)
a. Early menarche
b. Late menopause
c. Nulliparity & late first pregnancy (progesterone associated with pregnancy)
d. No breastfeeding
e. OCP or HRT use (Combination worse than estrogen alone)
f. Estrogen also affects triple neg risk
3) Metabolic syndrome
a. Obesity (aromatase –> oestrogen in fat)
b. Lack of exercise
4) Alcohol
5) Smoking
6) Other breast pathology
a. In-situ disease
b. Atypical hyperplasia
7) Genetic & family history
a. BRCA 1 (50-60% lifetime risk) or BRCA 2 (40-50% lifetime risk)
b. PALB2
c. Li-Fraumeni (p53)
d. Hereditary diffuse gastric cancer (CDH1 - lobular)
e. Cowden syndrome (PTEN)
f. Peutz-Jeghers syndrome (STK11), HNPCC, CHEK2
Previous radiation (e.g. Hodgkin lymphoma 20-30% risk) before the age of 30
Describe the pathological features of DCIS.
- Risk of progression to IDC at 10 years for LCIS/ DCIS of 10-40%
- Macroscopic
○ Majority of lesions are non-palpable (identified via microcalcification on MMG only)
○ Most often, no gross mass on cross-section
-May be a firm gritty region with yellow punctate flecks (comedonecrosis) - Microscopic
○ Abnormal epithelial cells situated within the myoepithelial cell layer (duct)
○ Architecture (MPSCC)
- Micropapillary (papillary structures/fronds without fibrovascular cores, infrequent mitoses)
- Papillary (branching fronds/papillary intraluminal projections with a central fibrovascular core)
- Solid (tumour cells in sheets- no evidence of papillations or necrosis)
- Cribriform (fenestrated proliferations with a punched out appearance)
- Comedo (high grade nuclei, pleomorphic, central necrosis), most aggressive
○ Pagets- DCIS involving the nipple
- Crusting/eczematous change of nipple or areolar complex.
- Associated with IDC ~90% of the time.- ~50% of women will have a palpable mass. ○ Can demonstrate comedonecrosis - Central expansile necrosis with cellular debris ○ Nuclear grade is dependent on N:C ratio, nuclear/nucleolar pleomorphism, mitoses, necrosis ○ Most growth for low-grade DCIS is discontinuous, vs high grade which has continuous growth (paradoxical).
- Immunohistochemistry
○ POS = E-cadherin, ER/PR
○ NEG = HMWCK, CK5/6 - Risk stratification
○ Loss of HMW keratin
○ Comedo subtype
○ Necrosis - Low grade (I)
○ Small, round nuclei. Rare mitosis - Moderate grade (II)
○ Pleomorphic cells, coarse chromatin, infrequent mitoses - High grade (III)
○ Prominent pleomorphic cells, large and prominent nucleoli, frequent mitoses, comedo necrosis
- Macroscopic
Describe the pathological features of LCIS.
- Less common than DCIS
- High degree of multicentric or bilateral involvement marker for bilateral breast cancer
- Not cancer: Risk of invasive disease = 1% annually, 20% lifetime risk
○ Invasive disease can be ductal or lubular - Doesn’t need clear margin. Considered as a risk factor to developing invasive breast cancer, but not a pre-malignant lesion.
- Macroscopic
○ Typically no gross lesion
○ Usually no calcifications - Microscopic
○ Proliferation of monomorphic, poorly cohesive cells in lobules and terminal ducts (marbles in a bag)
○ Growth is within lobular units = Fill >/= 50% of acini in lobule
○ Cells are small with uniform nuclei and prominent cytoplasm (occasionally can have signet ring cells)
○ Rare mitoses
○ Pleomorphic subtype hard to differentiate from DCIS = treat like DCIS - Immunohistochemistry
○ POS = HMWCK, ER/PR, mucin
NEG = E-cadherin
What are the prognostic factors for DCIS?
Patient Factors
- Age and performance status
- Palpable lesion (vs screen detected)
- Family history
Tumour Factors
- Size (typically >25mm)
- High-grade
- Presence of comedonecrosis
- ER/PR (predictive of Tamoxifen benefit)
- Genomic testing (DCISion-RT)
Treatment Factors
- Extent of resection (margins)
Van Nuy prognostic index = MAGS, not widely used
Score for risk of local recurrence
Margins >10, 1-10, <1mm
Age 60, 40-60, <40
Grade –necrosis/high grade
Size 15, 15-40, >40mm
What are the indications for mastectomy?
- MULTICENTRIC- Multicentric disease (different quadrants of breast)
- TISSUE TUMOUR RATIO -Tumour/breast volume ratio (technical feasibility)
- DIFFUSE CHANGES -Presence of diffuse mammographic changes (e.g. calcifications)
- T4 disease
- RT -Previous radiotherapy to chest
- POSITIVE MARGINS- Positive margins despite multiple attempts at resection
- FIRST TRIMESTER PREGNANCY
- PREFERNECE- Patient preference
- Other relative: □ Pacemaker in-field (needs to be moved) □ T3 (can use neoadj CTx to downstage) □ Connective tissue disorder eg ?active lupus, scleroderma (RA is ok) □ Rel CI to RT: cardiac/lung disease; poor shoulder mobility, radiosensitivity syndromes BRCA1/2 (survival c/w mastectomy but need to accept high rate new primary)
What is the evidence for hypofractionation and Boost in DCIS?
BIG-3 Boost trial (Chua, 2022 (TROG07.01)
- 1608 women with high-risk DCIS were randomised in a 2x2 fashion
○ Boost (16Gy/8F) vs no boost
○ 50Gy/25F vs 42.5Gy/16F
- Age <50 or Age ≥50 + at least one High risk feature (palpable disease, multi-focality, >15mm, int/high grade, necrosis, close margin <10mm)
- Outcomes (5-year)
○ Improved local control with boost (97% vs 93%)
§ Half of local recurrences were invasive
§ Improvement in all subgroups
○ No difference in local control between 50Gy vs 42.5Gy arms (94% vs 94%)
○ Grade ≥2 Induration 14% vs 6%
○ Grade ≥2 Breast pain 14% vs 10%
What is the evidence for adjuvant radiotherapy in DCIS?
Meta-analysis (EBCTCG, 2010)
- 3729 patients with DCIS across 5 major RCTs
- Outcomes
○ RT associated with halving of risk of ipsilateral recurrence (HR 0.46) at 10 years
- 50% of these recurrences were invasive
-No difference in CSS or OS
What is the pathogenesis for a Luminal breast cancer?
- Increased oestrogen exposure leads to increase in proliferative signalling
○ Rapid proliferation increases the risk of mutation
○ Accumulation of 1p gain and 16q loss; PI3K mutation- Development of pre-malignant lesions
○ Atypical ductal/lobular hyperplasia
○ DCIS/LCIS -often surrounds tumour
○ Then invasive (low grade) - Luminal B cancers often acquire a TP53 or BRCA 2 mutation which accounts for their aggressive biology
Low ER 10% -still get effect from endocrine therapy
- Development of pre-malignant lesions
List the differential diagnosis for a breast lesion
- Malignant
○ Epithelial: IDC, ILC, tublar, papillary, micropapillary, adenoid cystsic, mucinous, medullary, metaplastic, DCIS, LCIS
○ Stromal: angiosarcoma, RMS, liposarcoma, LMS, malignant phyllodes
○ Haem: DLBCL, MALT, FL, Burkitts - Benign:
○ Epithelial: fibrocystic change, proliferation +/- atypia
○ Stromal: fibroadenoma, phyllodes
Non-neoplastic: infectious mastitis, breast abscess, fat necrosis
Describe the pathological features of ductal carcinoma
- By far, the most common type of breast cancer
- Macroscopic
○ Hard, grey-white gritty (fribrosis/calcification) masses with characteristic irregular stellate shape from invasion
- Fibrotic/scirrhous/desmoplastic stromal reaction
○ Typically radiodense on MMG - Microscopic
○ Can present as sheets, nests, cords or individual neoplastic cells
○ No myoepithelial lining (invasive disease)
○ Common features
- Gland/Tubular formations are preserved in low-grade tumours
- Desmoplastic stroma is a prominent feature
- Calcification is common
- Associated DCIS is common
○ LVSI may be seen - Immunohistochemistry
○ POS = CK7, E-Cadherin, GATA3, CEA
○ NEG = CK20, p63 (basal cells)
○ Variable ER/PR/HER2 as per subtype
- Macroscopic
Desccribe the grading of invasive breast cancers.
Nottingham modification of Bloom-Richardson scoring
○ TNM (tubular formations, nuclear pleomorphism, mitoses (in hotspot))
○ Each factor is scored 1-3 and added up
○ Grade 1- low grade. Cells infiltrate stroma as glands. Nuclei uniform with little/no mitoses.
○ Grade 2- intermediate grade. Some gland formation, nuclear pleomorphism + mitoses.
* Grade 3- high grade. Solid nests of cells without gland formation. Marked nuclear pleomorphism and frequent mitoses.
Describe the pathological features of Lobular carcinoma
- Second most common form of breast cancer
- More likely to be multifocal or bilateral
- Tendency towards unusual metastases (e.g. leptomeningeal, peritoneal, etc.)
- Macroscopic
○ Lesions can be much less well defined and insidiously infiltrate breast
- May be unidentifiable on gross pathology
○ Often minimal desmoplastic reaction
- Less likely to be radiodense - Microscopic
○ Hallmark is discohesive cells infiltrating as individual cells or single file
- Often lack marked atypia
- Mitoses or desmoplasia are uncommon
○ Can have signet ring cell appearance
○ Pleomorphic variant
- Increased N:C ratio (typically G2-3)
- More aggressive phenotype (ER/PR neg, HER pos, p53 pos) - Immunohistochemistry
○ POS = GATA3, ER/PR (majority), HMWCK
○ NEG = E-cadherin
Classical lobular mostly luminal A
What are the clinical, radiological and microscopic features of inflammatory breast cancer?
Clinical
- Rapid onset (<6 months)
- Enlarged/erythematous breasts (Occupies at least 33% of the breast)
- Peau d’orange (oedema secondary to dermal plugging of lymphatic vessels)
- May or may not have mass ( typically not palpable due to rapid spread to lymphatics and distant sites)
Radiological
- MMG: Extensive skin and trabecular thickening. May include tumour mass with microcalcifications and/or diffusely increased breast density
- US: Skin thickening, muscle or axillary involvement, hypoechoic mass, identify region for biopsy
- MRI: Irregular, confluent mass, internal enhancement. MRI demonstrates skin thickening.
Microscopic - Tumour cells in dermal lymphovascular spaces - Most associated with high grade invasive ductal carcinoma NST, DCIS often absent - T4d, T stage does not change following neoadjuvant treatment ypT4d IHC GATA 3 (often supports breast origin) -Cd31/ERG supports intralymphatic space involvement
What are the differences between Oncotype DX, PAM50 and MammaPrint?
What are the prognostic factors for invasive breast cancer?
Patient Factors
- Age & performance status (younger age increases recurrence risk)
- Menopausal status
- Smoking
- Screen vs clinical detection
Tumour Factors
- TNM staging
○ Tumour size predicts LN involvement
○ Including exact pattern of nodal involvement
○ Especially Nodal macromets –predicts DFS
○ LN ECE
- Histologic Grade
- Histological Type
○ Positive = tubular, mucinous, encysted papillary
○ Negative = inflammatory, metaplastic
- LVI
- ER/PR and HER2 expression
- Ki67 (proliferation index)
- Tumour infiltrating lymphocytes
○ High = Good prognostic marker for DFS. Body is fighting the cancer.
- Multifocality
- PDL-1 –in immune cells in sample
- Genomic profile (eg. OncotypeDX)
○ Above tests aid in:
i. Molecular subtyping
ii. Likelihood of treatment benefit (chemotherapy, extension of endocrine therapy)
iii. Patient prognosis
iv. Staging (oncotype Dx)
○ Prognostic and predictive to guide chemo
○ Gives 10 year recurrence score out of 100 based on tumour genes (21)
○ Used for early stage ER+ breast cancer
○ MAMMAPRINT –can be ER neg as well, max 5cm tumour size
○ PAM50
○ ENDOPREDICT
Treatment Factors
- Resection margin
○ Positive margin bad (tumour on ink)
○ Close margin 1-2mm = 10% recurrence
- Addition of RT to BCS
- Boost
- Response to neoadj chemo
What are the options for breast reconstruction after mastectomy?
*** Prosthesis (silicon, saline) **
○ Saline implant - tissue expander under pectoral muscle, inject saline over wks/months till desired volume obtained. Tissue expander replaced by permanent implant.
* Oncoplastic reconstruction (volume displacement/replacement)
* Autologous reconstruction (flap)
○ TRAM (transverse rectus abdominis myo-cutaneous) flap or latissimus dorsi flap, main 2 options. TRAM needs woman to have “spare tissue” to ensure both sides look even after procedure.
○ DIEP flap – preserves rectus abdominus but takes ‘skin and soft tissue’ from abdo (!)
○ Can be done immediately or after radiotherapy
- Decision making:
○ Pt: anatomy, body habitus, comorbidity, size/configuration, contra breast, prior surgery, quality of chest wall, smoking, pt preference
○ Tumour: site
○ Treatment: planned oncological tx like RT - Timing of reconstruction:
○ NCCN:
▪ Implant: initial tissue expander at oncological surgery, implant later
▪ Autologous: delay to post-RT
○ Immediate:
▪ Adv: dec cost, 1 procedure, psych benefit, normal landmarks preserved
▪ Disadv: prolonged OT, necrosis, RT cosmesis, SE
▪ Relative CI:PMRT, stg 3 or higher, comorbidities
○ Delayed:
▪ Adv: path return, post adj RT, better perfusion flaps
▪ Dis: 2x surgeries, cosmesis poorer, RT affects ability to perform recon
Recommendation:
○ If no adjuvant XRT expected to be indicated by path, then immediate reconstruction
○ If PMRT likely to be indicated, reconstruction should be delayed. Immediate reconstruction affects technical delivery of XRT
▪ RT to implant-based reconstruction may result in higher rates of late contraction, capsular fibrosis, implant fixation and poor aesthetic outcome
□ Similar effects with autologous reconstruction but less severe
□ Effects: haematoma, infection, wound dehiscence, flap necrosis, flap loss, capsular contracture, implant malposition, implant leakage/rupture/deflation, seroma
* Evidence for implant vs autologous reconstruction for adj RT: (J Natl Can: 2018)
○ A prospective multicenter cohort study: showed autologous reconstruction appears to yield superior patient-reported satisfaction and lower risk of complications than implant-based approaches among patients receiving postmastectomy radiotherapy.
○ 2-year reconstruction failure rates were 18.7% and 1.0% among irradiated patients with implants and with autologous reconstruction, respectively. (unirradiated 3-4%)
○ 2-year major breast complications rates were 33.2% and 17.6% among irradiated patients with implants and with autologous reconstruction, respectively.
(unirradiated were 15% and 23 %
What are the aims of WBRT after breast lumpectomy?
Eradicate microscopic residual disease
Rationale:
- achieve LC rates similar to Mx
- preservation of breast
- improved OS
- all groups benefit, but absolute benefit depends on RF (LVI, age, grade etc)
What is the rational and the indications for post-mastectomy RT?
- Rationale:
w ↓ LRR - most common sites of LR= CW and SCF
w ↑ DFS.
w Increase breast cancer specific survival/ Decrease BCM
w Improve OS by 5 % (only if N2)- ESMO guidelines: PMRT in node positive pts reduce the 10yr risk of recurrence (local or distant) by 10% and the 20-year risk of breast cancer related mortality by 8%.
- Patterns of LRR post-MT + adequate ALND
w CW (50-75%)
w SCF (20-40%)
w Axilla (2-4%)
w IMC (uncommon).
Predictors for LRR after mastectomy:
w Size >5cm (>15% LRF).
w Invasion of skin/CW (pT4) (>15% LRF).
w Positive/close <5mm deep margins.
w Positive ALN (inc. # pos: 1-3 10%; 4-9 20%; 10+ 30%).
w No of LN dissected (need 10+ for accurate Ax + staging).
w Others: LVSI, high grade, multicentricity, young age (early 40s).
2+ RF→ close to 20% risk LRF (PG).
ECE not an independent predictor of LRR.
Indications for PMRT:
* Absolute indications: women at high risk of locoregional failure (eVIQ):
* pT3 N+ [pT3N0 is controversial].
* pT4 N0
* pTx N2/3.
* SM+
* Inflammatory breast
* Consider For intermediate risks: pT1/2 N1, pT3N0 depending on # of additional RFs: w Multifocal/multicentricity. w High grade. w Presence of LVSI. w ER negative. w Nodal burden. w Young age <50yo * TNBC is controversial (Chinese RCT).-
When would you consider a tumour bed boost for invasive breast cancer? What is the rational?
Rational:
- Reduced LR rates
- Most recurrences occur near lumpectomy site
- All patients under 50 years old
- Age 51-70 years with high risk features or positive margin
- High risk features:
- Grade 3
- LVI
- Close margins
- ER negative
What are the indications for partial breast irradiation and describe suitable treatment options.
○ Consider Partial Breast Irradiation if (ASTRO):
○ > 50 years of age
○ pT1 and pN0
- Consider if size up to 3cm
○ Clear surgical margins (>3mm)
○ G1-2
○ No LVI (ESTRO)
○ Modest DCIS component (no extensive intraductal)
○ ER pos and HER2 neg
- Both BT and EBRT are reasonable options
○ Some concerns about use of IORT
○ Interstitial brachytherapy
- 34Gy/10F BD over 7 days
○ IMPORT-LOW (EBRT-based) - 40Gy/15F - Volume to include entire radial breast, limited in craniocaudal direction only □ CTV = tumour-bed + 15mm □ PTV = CTV + 10mm - Requires fiducials implanted into tumour bed
What should be considered when omitting adjuvant breast radiotherapy in elderly patients?
- Magnitude of benefit may be less in some subgroups (eg. Elderly)
○ Studies of BCS +/- XRT- no sub group of pts in whom XRT could be avoided but magnitude of benefit may be less
○ XRT ↓ RR within treated breast regardless of endocrine tx. (EBCTCG Lancet 05)
○ Tumour biology of elderly patients tends to be more favourable
○ Some studies in older pts with early stage breast cancer, looking at TAM Rx as an alternative to XRT. Still see sig benefit of XRT in terms of LR.- Patient selection:
o >65 years
o T<3cm (mainly T1)
o N0
o ER/PR +
o Margins >2mm
- Patient selection:
What are the indications for adjuvant chemotherapy when treating breast cancer?
- Consider adjuvant chemotherapy if:
○ All patients with N2 or greater (4 or more LN)
○ N1 (1-3 LN) with a high-risk genomic score (Oncotype Dx)
○ Luminal B-like (high Ki67)
○ ER negative disease (including HER2+ or TNBC)
○ G3
○ PREDICT nomogram may assist in calculating benefit
What are the options for endocrine therapy in breast cancer treatment and how do they work?
○ Pre-menopausal
- Tamoxifen
□ SERM- anti-oestrogen effect on breast cancer cells
□ A competitive oestrogen receptor binder, blocks binding of estrogen.
□ Acts as antagonist in breast, partial agonist in bone, CVS, CNS, agonist in uterus.
- Zoladex (ovarian suppression) + aromatase inhibitor
□ Ablation: inhibitors endogenous estrogen production from ovaries via surgery or RT
□ Suppression: temporary inhibition of oestrogen
○ Post-menopausal
- Aromatase inhibitor (preferred)
□ Blocks aromatase (cytochrome p450 protein) which is needed for synthesis of oestrogen from angrodens and adipose tissue
□ Anastrozole, Letrozole→ nonsteroidal.
□ Exemestane→ steroidal AI.
- Tamoxifen
What should be considered when treating breast cancer in pregancy?
- Definition: breast cancer in pregnancy, one year post partum, or any time during lactation
- In general manage similar to non-pregnant if possible, whilst minimising risk to fetus
- Modified staging (CXR with fetal shielding, USS/MR Liver, MRI spine - no GAD, NO CT)
- Discuss MDT, patient, obstetician
- Same prognosis as non-pregnant women.
- 1st trimester: Discuss termination. TM + ALND→ Chemo in 2nd trimester→ delivery→ RT→ Tam.
- 2nd trimester: Surgery can include BCS and ALND (no SLNB).
- Systemic therapy
○ Chemo safe in 2nd/3rd trimester –> Assoc with intrauterin growth restiction, prematurity, LBW in 50%
- If indicated, should advise not to delay once pregnancy safely reaches 2nd/3rd trimester
- 1st trimester (0-13 weeks) - organogenesis; highest risk of congen and chromosomal abnormalities, stillbirth and M/C
- Non-taxane based chemo in 2nd and 3rd trimesters: AC, FAC most common.
- FAC: 5-FU, doxorubicin, cyclophosphamide. Non-taxane chemo, most common for pregnant women.
- Suspend 3-4 weeks prior to delivery to avoid neonatal myelosupression/sepsis/death
○ No Tam/AI: assoc w/ vaginal bleeding, M/C, congenital malform and fetal death
○ No HER2 therapy
○ No immunotherapy - No SLN dye during pregnancy.
- No RT in any trimester.
What is the evidence for hypofractionation in invasive breast cancer?
- Rationale:
w Reduce treatment course
w improve patient convenience
w reduce cost
w increase access to RT.
w Increase dose/# to give equivalent BED.
w Low a/b ratio ~4-5.
START-A and -B trials explored hypofractionation in the UK
- START-B involved 2215 women and compared 40Gy/15F (over 3 weeks) with 50Gy/25F
- Outcomes
○ No difference in 10 year LR (4.3% vs 5.5%; p=0.21)
○ Less acute toxicity in hypofractionated arm and late cosmetic effects (breast shrinkage, telangiectasia, breast oedema)
Canadian trial (Whelan, 2010)
- 1234 women with node-negative breast cancer were randomised to
○ 50Gy/25F whole breast irradiation
○ 42.5Gy/16F whole breast irradiation
- Outcomes
○ Local recurrence unchanged between arms (6.7% vs 6.2%)
○ No change in long-term cosmesis (71.3% vs 69.8%)
What is the evidence for ultra-hypofractionation?
- FAST-FORWARD, UK(Lancet, 2020):
○ 4096 pt, multicentre, non-inferiorty trial, phase 3,
○ >18, pT1-3N0-1, lump or mast: 40Gy/15# or 27Gy/5# (daily) or 26Gy/5# (daily)
○ Primary endpoint: ipsilateral breast tumour relapse
○ Median FU 6 years
○ 26Gy/5# non-inferior to 40Gy/15#, no diff in s/e, local control
○ Treated breast/CW alone
Interpretation: 26Gy/5# is NON-inferior to 40Gy/15# for local tumour control and safe in terms of normal tissue toxicity up to 5 years
What is the evidence for boost in invasive breast cancer?
- Rationale:
w Reduced LR rates.- absolute benefit decrease with age (4-10% LRR)
w Most recurrences occur near lumpectomy site.
w NO OS benefit.
w Decrease rate of subsequent mastectomy- Caveat: worse cosmesis with 5% fibrosis
- Dose:
w 10Gy/5#
w 16Gy/8#
* This is standard of care in the boost trials.
w Photons or electrons.
w SIB - Indications:
w High grade
w Close margins < 2mm
w Age <50 (maybe <60)
w Unfavourable Histo feat. Eg HER2+, triple negative, LVSI, ↑ Ki-67, larger primaries, ER-, N+.
Summary
- Mature evidence, All women benefit from a boost
○ Diminishing benefit when age > 60-65 years
- SIB is a reasonable approach (toxicity is reasonable) as per import high
EORTC boost trial (Bartelink, 2015) ○ Involving 5318 women with negative margins and 17 year median follow-up ○ Population: ○ Intervention/Control: 50Gy +- 16Gy boost ○ Outcomes - Reduction in 5, 10, 20-year local recurrence (9% vs 13%) - Benefit greatest in younger women <40 (and <50 years) □ If <50 years with DCIS, LR was 15% vs 31% - No 20-year OS or CSS benefit - Increased severe fibrosis at 20 years (5.2% vs 1.8%) IMPORT-HIGH (Coles, 2023 Lancet) ○ 2617 women with breast cancer (early and LA stages) were randomised to - 40Gy/15F with sequential boost 16Gy/8F - 36Gy/15F whole breast + 40Gy/15F to partial breast with SIB to 48Gy vs 53Gy ○ Outcomes (at 3 years) - 15% vs 11.5% breast induration with 53Gy SIB - No change in toxicity for sequential 16Gy vs SIB 48Gy □ Potential for improved cosmesis with 48Gy SIB ○ 5 year IBTR -1.9% whole breast, 2% 48Gy, 3.2% 53G
What is the evidence for withholding radiotherapy in breast cancer?
- Studies of BCS +/- XRT— no subgroup of pts in whom RT could be avoided but magnitude of benefit may be less.
- Tumour biology of elderly patients tends to be more favourable.
- Some studies in older pts with early-stage breast cancer, looking at TAM Rx as an alternative to RT-> Still see sig benefit of RT in terms of LR. But no Change in CSS, OS, or DM.
w In early invasive breast ca there is a risk of 20-30% of recurrence. Tamoxifen alone may bring this to 15%. RTx brings it down an extra 8-10%. Therefore, RTx offers SS benefit and can be omitted only in poor performance patients. - Offer RT as long as fit enough + LE ≥5yrs.
w Rationale: treating LR in older pts more difficult, also if give hormonal tx alone, hard to justify stopping after 5yrs (but then morbidity with long-term hormone tx). - Consider omission of RT IF:
w T <3cm, N0
w reduced life expectancy
w ER or PR +;
w Margin –
w willing/ able to take 5 years endocrine therapy
w accept modest higher local recurrence. - CALGB/RTOG/ECOG [Hughes NEJM ‘04, ‘12]: BCS→ Tam x5y ± WBRT. 600 pts, >70yrs, Stage I, ER+. MFU 5yrs.
- LRR (p<0.001): TAM- 4%; -TAM + XRT- 1%.
- Sig reduction in 10yr FU LRR 9% (TAM) vs. 2% (RT and TAM)à Interpreted by authors as acceptable risk 9% in elderly patients with early breast cancer -> need to consider co-morbidities.
- No difference in time to mastectomy, time to DM, BCSS or OS.
- Conclusion: Tamoxifen alone is reasonable option for women >70 years as no adv in OS, DFS or breast preservation with addition of adj RT.
- PRIME II trial [Kunkler Lanc Onc ‘15, 🐦 SABCS ‘20]: BCS→ Tam x5y ± RT.. 1000pts, >65yr, ER+, LN-, low grade, <3cm size, G3 or LVSI but not both
w Sig reduction in IBTR with RT at 5yr (4.1% vs 1.3%) and 10yr (10% vs 1%)
w No diff in regional recurrence, OS or DM at 5yr or 10yr.
w Conclusion: adj RT+tam provides sig reduction in IBTR but the rate of IBTR is probably low enough for omission of RT to be considered for some patient.
What is the evidence for partial breast irradiation?
Meta-analysis (Viani, 2020)
○ 14436 patients from 11 RCTs were included
○ Outcomes
- Overall cohort demonstrated higher LR in partial breast arm (HR1.46)
- Subgroup analysis
□ Higher LR if IORT approach utilised
□ No difference between PBI and WBRT if BT or EBRT used
- No difference in overall mortality
NSABP B-39 (Vicini, 2019) ○ 4216 women with early-stage breast cancer were randomised to - Whole breast irradiation (50Gy/25F) - Partial breast with BT (34Gy/10F) - Partial breast with EBRT (38.5Gy/10F) ○ Equivalence methodology ○ Outcomes - 10 year local recurrence was 4.6% vs 3.9% - Criteria to declare equivalence was not met □ However, absolute difference between arms was small and clinically not significant
What is the evidence for nodal irradiation in clinically N0, but SLNB positive patients?
SLNB negative-> No further treatment.
SLNB + (ITC)-> Treat as node negative.
SLNB micromets:
* Low risk: no regional LN treatment required. (As per Milan IBCSG: ALND vs obs in T1-2, Nmi-> NO diff in OS, DFS. More toxicity with RT)
* High risk: consider high tangents/regional LN RT (as per Z0011-> no diff in OS, DFS, or axillary recurrence. But RT arm used high tangent)
w Need to consider other high risk features, number of micromet etc
SLNB+ 1-2 nodes macromets
Options:
* ALND +/- adj RT as indicated.
* RNI (AX, SCF, IMC) ***
w LVH/North Shore: Safe to omit completion ALND if 1-2 SLN+ or micromets only and treated with RNI (as per AMAROS SLN+/- ALND vs RNI. No diff in OS, DFS, or axillary recurrence. Decreased toxicity with RNI)).
Mx of nodes >3+ nodes macromets
* Need to consider full extent of axillary nodal burden uncertain in this situation.
* Possible that given many SLN+ -> possible to harbour more.
* Need to manage axilla definitively à RT or ALND.
w Prefer ALND: diagnostic information.
* If 2-3 nodes involved with macro mets post-SLNBx, chance of >4 total is 60-80% (MSK nomogram).
NCCN: if >4 positive nodes = suggest regional nodal RT (SCF, infraclavicular fossa, IMC and part of axilla that may be suspicious).
Summary:
- There is no need for ALND for cN0 (SNB positive) patients
- Uncertain regarding optimal role of RT for macrometastases. Could give:
○ No axillary irradiation (Z11)
○ High-tangents (Z11)
○ Comprehensive nodal irradiation (AMAROS) similar to ALND
- No RT indicated for micrometastases (IBCSG)
American Z0011 trial (Giuliano, 2017) ○ Randomised 900 women to ALND vs proceed to breast RT - Inclusion = pT1-2 and 1-2 positive sentinel nodes (cN0) ○ Outcomes - No difference in 5-year locoregional recurrence (97% vs 96%) □ Only 1 further regional recurrence in SLNB arm between 5-10 years - No difference in DFS (80.2% vs 78.2%) - OS was non-inferior in SLNB alone arm (86.3% vs 83.6%) □ Non-inferiority margin of HR 1.3 - Limitations: - Early closure due to accrual - Large numbers received nodal irradiation despite protocol (either high tangents - within 2cm of humeral head)[approx. 50% in both arms] or off-protocol formal treatment [19% across both arms, including SCV]) - AMAROS (EORTC 22023) non-inferiority trial 2023 - Randomised 1425 patients to ALND vs breast + axillary RT - Inclusion = pT1-2 (<3cm) cN0 disease with positive sentinel node - RT = whole breast + axilla I-III and medial SCF - Non-inferiority margin = 5-year axillary recurrence <4% with RT (presume 2% in ALND arm) - Outcomes - Preliminary 10-year follow-up data (presented at 2018 Breast Cancer Symposium – Rutgers, et al.) published 2023 - Axillary recurrence = 1.82% (RT) vs 0.93% (ALND) HR 1.71; p=0.37 - DMFS = 78.2% (RT) vs 81.7% (ALND) HR 1.18; p=0.19 - OS = 81.4% (RT) vs 84.6% (ALND) HR 1.17; p=0.26 - Micrometastasis - IBCSG 23-01 trial (Galimberti, 2018) - Randomised over 900 women to ALND vs proceed to breast RT - Inclusion = micromets (<2mm) on SNB (pT1-2 cN0 disease) - Outcomes - No difference in DFS, locoregional recurrence or OS
- EORTC 22922 trial (Poortmans, 2015)
- Randomised trial involving over 4000 women
- Stage I-III Breast cancer. Centrally or medially located tumour irrespective of axillar involvement or lateral tumour with axilla involvement.
- mastectomy or BCS + ALND
- 50Gy/25# to whole breast/ CW +/- regional nodal irradiation (medial SCV, IMN)
- Outcomes
- Improvement in CSS (p=0.02), DMFS (p=0.02) and DFS (HR 0.89; p=0.04) with regional irradiation
- No OS benefit (HR 0.57; 95% CI 0.76 - 1.00)
What are the indications for SCF RT post ALND?
- For high-risk patients, there may be a benefit to supraclavicular nodal RT (even post-ALND) if:
- pT3N+ OR N2+ (absolute indication)
pT1-2N1 OR pT3+N0 OR pT2N0 with <10 nodes in ALND (dependent on risk factors G3, LVI+, ER neg, young age, etc.)
- pT3N+ OR N2+ (absolute indication)
What is the evidence for nodal RT in clinical N1 patients?
- MA20 trial (Whelan, 2015)
- 1800 women recruited with inclusion:- Lumpectomy + ALND
- WBRT +/RNI (SCF, IMN, high axilla)
- pN1+ (90% of cohort 1-3 nodes = 85% & >3 nodes = 5%)
- pN0 with high risk features (pT3 OR <10 nodes in ALND, with at least one of: G3, LVI+, ER neg)
- Outcomes
- No OS or CSS benefit
- DFS was improved with nodal irradiation 82% vs 77% (HR 0.76; p=0.01)
- 92% vs 95% locoregional (HR 0.59)
- Distant 86 vs 82% (HR 0.76)- Danish IMC study (Thorsen, 2016)
- 3089 patients with early-stage node positive breast cancer were included, <70 yo
- Prospective collection of non-randomised data
- 3089 patients with early-stage node positive breast cancer were included, <70 yo
- Danish IMC study (Thorsen, 2016)
- WBRT/CW RT + SCF + high axilla +/- IMN
- If left-sided cancer, IMC were omitted; If right-sided cancer, IMC were included- Outcomes
- IMC irradiation was associated with improved OS (8 year OS = 75.9% vs 72.2%)
- Improved CSS and DMFS
- Equal numbers of IHD death
- Patients with lateral disease and 1-3 LN did not appear to benefit.
- Outcomes
What would be your radiotherapy technique for adjuvant whole breast RT (Hypofractionated)?
Patients
1) All patients receiving whole breast RT (without nodal RT)
Pre-simulation
MDT discussion
Pathology review (margin status)
Ensure wound healing
Aim commencement 4-8 weeks post-operatively
Simulation
Supine with arms above head
- Breast board
- Knee block
- Vac bag
DIBH if left-sided
Mark-up
- Wire scars
- Wire palpable breast
- Field borders marked
Generous CT (2mm without contrast)
- Upper cervical spine to below diaphragm
Fusion
N/A
Dose prescription
Hypofractionated
- 42.5Gy/16F
- -40.05Gy/15F
Boost
- SIB 48Gy
- Sequential 10Gy in 4/5F
- 16Gy/8#
Tangential IMRT technique
9/10 days per fortnight
Volumes
CTVbreast
- Entire breast (based on clinical mark-up and CT)
PTVbreast
- CTV + 5mm
CTVboost
- Tumour bed + 5mm
PTVboost
- CTV + 5mm
Target Verification
Daily CBCT
OARs
Ipsilateral lung
- V16 < 15%
- V5 < 50%
Contralateral lung
- V5 < 10%
Heart
- Mean < 4Gy
- V20Gy <5%
LAD
- Dmax < 32Gy
Contralateral Breast
- V4.1Gy <5% or ALARA for VMAT
What would be your radiotherapy technique for adjuvant whole breast + Nodal RT?
1) All patients where nodal irradiation is required
Pre-sim
MDT discussion
Pathology review (margin status)
Ensure wound healing
Aim commencement 4-8 weeks post-operatively
SIM
Supine with arms above head
- Breast board
- Knee block
DIBH if left-sided
Mark-up
- Wire scars
- Wire palpable breast
- Field borders marked
Generous CT (2mm without contrast)
- Upper cervical spine to below diaphragm
- Add contrast if treating LN
Fusion: N/A
Prescription
Conventional fractionation
- 50Gy/25F
Boost
- SIB 57Gy
- Sequential 10Gy in 4/5F
- 16Gy/8#
Accept 80% coverage to IMC (40Gy)
Tangential IMRT technique
9/10 days per fortnight
Volumes
CTVbreast
- Entire breast (based on clinical mark-up and CT)
PTVbreast
- CTV + 5mm
CTVboost
- Tumour bed + 5mm
PTVboost
- CTV + 5mm
CTVnodal
- Level 3 + SCF + IMC
- See ESTRO guideline
PTVnodal
- CTV + 5mm
Treatment verification
Daily CBCT
OARs
Ipsilateral lung
- V20 < 30%
- V5 < 60%
Contralateral lung
- V5 < 10%
Heart
- Mean < 5Gy
- V25<10
LAD
- Dmax < 32Gy
Contralateral Breast
- ALARA
Spinal Cord
- Dmax < 45Gy
Oesophagus
- ALARA
What would be your radiotherapy technique for partial breast RT via brachytherapy?
1) Suitable early-stage patients
Pre-SIM
MDT discussion
Pathology review (margin status)
Ensure wound healing
Perform US simulation
- Ensure suitable tumour cavity is present
Aim commencement 4-8 weeks post-operatively
- Consent
- GA
- Prophylactic ABx (cephazolin)
SIM
- US-guided injection of contrast into cavity
- Application of template
- US-guided catheter implantation
* Ensure coverage around cavity
- CT simulation
- Mapping of catheters
- Treatment planning and optimisation
- Treatment delivery
- Removal of catheters after final fraction
Prescription
34Gy/10F BD to cover tumour cavity
- D90% > 100% PTV
I-192 via afterloader
Volumes
CTV
- Seroma/tumour bed
PTV
- CTV + 20mm
○ Surgical margins are accounted for in this process
○ Minimum expansion is 5mm
Treatment verification
US-guided implantation
OARs
PTV has a minimum 5mm margin from skin and ribs
Ensure active source dwell positions are at least 5mm from skin
What is the 5 year local control and overall survival for Stage 1, 2, 3, 4 Breast cancer?
Local Control 5 year Overall Survival
Stage I >90% 100%
Stage II 85-90% 95%
Stage III 80-85% 80%
Stage IV 32%
Describe BRCA1 and BRCA2 mutations in regards to breast cancer
- HRR uses undamaged sister chromatid as template for DNA repair in late S/G2 phase. Mutations of the BRCA gene results in defective DNA DS repair mechanisms and increased cancer risk (chromosomal instability and accelerating tumorgenesis)
BRCA 1 Tumour Suppressor Gene(Chromosome 17)
- More common than BRCA 2
- 3% of breast carcinomas are due to germline mutation in BRCA 1
- Often high grade infiltrating ductal carcinoma NST
- Associated with triple negative breast cancer
- In BRCA1 mutation, high risk of developing cancer
- Poor response to hormone therapy
- Breast and ovarian cancer
BRCA 2 Tumour Suppressor Gene (Chromosome 13)
- Less common than BRCA 1
- Associated primarily with post-menopausal breast cancer
- In BRCA 2 mutation, risk of developing cancer relatively less than BRCA 1
- Highly responsive to hormone treatment
- Pancreas, prostate, stomach, bile duct, gall bladder, melanoma
Describe IHC and FISH
IHC
- Formalin fixed tissue biopsy
- Combing with an antibody and bound antibody detected by immunoenzyme technique
- Cells visualised by light microscopy
- Positive staining indicates expression of relevant antigen
- Fluorescent probe applied and hybridised for 1-24 hours, a fluorescent signal can be observed with the chromosomal morphology.
- Detect ER and PR and proportion of HER 2 receptors
FISH
- Visualises specific genes
- Sensitive for cytogenetic testing chromosomal abnormalities (deletions, translocations, duplications)
- Performed on either interphase nuclei or metaphase chromosomes to detect specific DNE sequences. Can only detect aberrations withing the target region of the probe applied.
More accurate at detecting a HER 2 amplification
What is the work up for a patient with a breast lesion?
- Breast imaging
○ MMG + US
○ MR breast
- Funded if conventional imaging is indeterminant
- Screening if <50 years old and high-risk (e.g. BRCA pos, high-risk family history)- Core biopsy of lesion
- FNA/core of axillary node +- clip
- Staging imaging
○ CT CAP + WBBS
- Only if T3 or cN+
○ FDG PET-CT
- Funded if locally advanced/stage III disease
- For the evaluation of suspected locoregional recurrence or metastatic disease of breast carcinoma - Sentinel node biopsy
Fertility preservation/ family planning
Genetic counselling
What is the TNM staging for breast cancer
What is the rational for neoadjuvant chemotherapy with breast cancer? What are the disadvantages?
Approach to neoadjuvant chemotherapy:
1. Cytoreduction - downstage/size primary/node - reduce operation/lymphoedema risk eg. BCS
2. Early control of distant micrometastatic disease
3. Test drive systemic therapy to assess response to therapy
No survival difference on metanalysis of 10 trials
* EBCTCG MA [McGale Lancet Onc '18]: NAC vs. Adjuvant chemo. 4756 women. 10 RCTS w No sig differences distant recurrence (15-year rate of 38%in both arms) or BCM (34% in both arms) or overall mortality (15yrs rate ~41%). w NACT was associated with an increased BCS (65 vs 49 %) and increased risk of local recurrence (15-year LC rate, 21.4 vs 15.9 %; rate ratio 1.37, 95% CI 1.17-1.61), which has been attributed to the increased use of BCS. NAC with 30% CR, 40% PR. More than 2/3 respond to NAC.
Disadvantages:
1. Lack of pathological staging
2. May progress
3. Toxicities may preclude further treatment
4. Overtreatment
What are the indications and regimens of neoadjuvant breast chemotherapy for: Luminal cancers, HER2 +ve cancers, Triple negative cancer?
What are the predictors for LRR post mastectomy and what is the rational for PMRT?
Predictors for LRR after mastectomy:
o Size >5cm (>15% LRF)
o Invasion of skin/CW (pT4) (>15% LRF)
o Positive ALN (inc. no positive: 1-3 10%; 4-9 20%; 10+ 30%)
o No of LN dissected (need 10+ for accurate Ax + staging)
o Positive/close <5mm deep margins
o Others: LVSI, high grade, multicentricity, young age (early 40s)
2+ RF→ close to 20% risk LRF (PG)
ECE not an independent predictor of LRR.
What is the evidence for hypofractionation in PMRT?
What is the toxicity after PMRT?
As per Van den Bogaard retrospective analysis: can keep risk of acute coronary event <5% if Mean heart dose <4-8Gy
Discuss the use of hormone therapy for breast cancer.
- Use endocrine therapy if ER+ AND tumour > 0.5 cm (consider for tumours ≤ 0.5 cm).
- ER and PR should be considered positive if at least 1% positive tumour nuclei (ASCO)
○ As of 2020, there is a new category of “Low Positive” for 1-10% positivity.
○ The more hormone receptor-positivity the better, meaning those with ER(+)PR(-) and especially ER(-)/PR(+) breast cancers are not as favourable as ER/PR +ve. - When stopping tamoxifen at 5y for T1N0 disease, there is still at least a 10% chance of DM at 20 years! This suggests that certain patients should be selected for extended therapy (e.g. greater than 5y of hormone therapy)
5 years of tamoxifen has the most significant reduction in BCM not only during years 0-4, but also years 5-9 and 10-14 (i.e., after discontinuation). Overall mortality was little affected, despite small absolute increases in thromboembolic or uterine cancer mortality (both in women older than 55y of age) - EBCTCG
Describe the boundaries of nodal contouring in breast cancer for level 1, 2, 3, 4 and IMC
LVL1
-Caudal: Where the pectoralis major muscle inserts onto the ribs
-Cranial: Level I ends where axillary Level II begins; where the AVs pass the lateral edge
of the pectoralis minor muscle
-Anterior: Lateral edge of pectoralis major muscle
-Posterior: Imaginary straight line between edge of latissimus dorsi muscle and the
intercostal muscles.
-Lateral: Imaginary line from just inside the lateral edge of the pectoralis major to just
inside the antero-medial edge of the latissimus dorsi muscle (caudally)/deltoid
muscle (cranially).
-Medial: Caudal: ribs and intercostal muscles. Cranial: lateral border of the pectoralis minor muscle.
LVL2:
-Caudal: Where AVs pass lateral edge of pectoralis minor muscle
-Cranial: 5mm above AV/subclavian vein
-Anterior: Posterior aspect of pectoralis major muscle, to include rotter’s nodes
-Posterior: Ribs and intercostal muscles.
-Lateral: Lateral edge of the pectoralis minor muscle
-Medial: Medial edge of the pectoralis minor muscle
LVL3:
-Caudal: Where AVs pass medial edge of the pectoralis minor muscle
-Cranial: 5mm cranial to subclavian vein
-Anterior: Posterior aspect of pectoralis major muscle
-Posterior: Ribs and intercostal muscles
-Lateral: Medial edge of the pectoralis minor muscle (contiguous with Level II)
-Medial: Clavicle/ribs or lower SCV contours
What are the indications for neoadjuvant chemotherapy in breast cancer?
- Not suitable
- Poorly defined extent of tumor.
- Patients with extensive insitu disease when extent of invasive component not well known.
Patients with not palpable or clinically assessable tumours.
Discuss the role of predictive tools in the post-operative setting for this woman?
i. Predictive tools can be used in the clinic setting when discussing adjuvant treatment options with patients. Predictive tests report the likelihood of response to treatment. Predictive tools include:
1. Models correlating specific patient and tumour factors with relevant oncological outcomes such a locoregional control, disease free survival and overall survival e.g. Sloan Kettering Nomogram for DCIS recurrence (Van Nuys superseeded) , IBTR! Ipsilateral breast cancer recurrence.
2. Genomic testing on tumour predicting risk of distant recurrence and benefit from adjuvant treatments e.g. DCISionRT
ii. Compare and contrast 2 predictive tools that are commonly used in assessing patients with DCIS
The women if referred with a request for adjuvant radiotherapy to completed in 3 weeks noting she is a country patient
i. Discuss and justify your recommended dose and fractionation for this patient
Would discuss with patient accessibility to attend radiotherapy daily. If being regionally located means increased time off work, time away from family and travel to/from centre would discuss a hypo-fractionated course of breast radiotherapy.
Recommend a course of hypo-fractionated radiotherapy 42.4Gy in 16 fractions to the left whole breast 2.65 Gy per fraction 9-10 fractions in a fortnight. Results of the BIG-3/TROG 7.01 trial provide the best evidence to support the use of hypofractionation in pure DCIS, demonstrating no difference in locoregional control in comparison to conventional 50Gy in 25 fractions. ASTRO guidelines support use of hypofractionation in DCIS.
I would discuss a boost 10Gy in 4 fraction sequential boost based on patient age and BIG-3.TROG 7.01 demonstrating a benefit in locoregional control with a boost. I would omit a boost if the surgical margins are clear and no other high risk features, as patient is older then 50 years and the lesion is 12mm and intermediate grade.
a) Describe your initial management
Summary: Young woman, at least cT2 left breast ca in third trimester
In general treat according to guidelines for non-pregnant patients whilst minimising risk to fetus
○ History § Including progress of pregnancy/hx to date/fertility/family planning § Locoregional symptoms, distant metastatic disease § Co-morbidities and contraindications to treatment § FmHx ○ Examination: features of primary (size, fixation, skin/CW involvement, multifocality/centricity), evidence of nodal, metastatic disease ○ Bloods including FBC, UEC, CMP, LFT, Hep B/C/HIV Serology (chemo) ○ Appropriate staging within limits of pregnancy § USS bilateral breast, axilla, neck, consider MRI breast in young female (dense breasts) +/- single MLO with shielding § Core bx of mass plus axillary LN including receptor status § CXR with abdominal shielding; and USS/MRI liver, MRI spine § Can consider whole body MRI without GAD (ESMO guidelines) § No PET/CT/WBBS ○ Discussion at MDT, patient, and obstetrician § Weigh risk of breast cancer & treatment in context of stage of pregnancy vs. risk to fetus ○ Generally in third trimester § Can consider early delivery if feasible § Surgical management can include TM + ALND or BCS + SLNB or ALND, No blue dye, ok to do lymphoscintigraphy, need to d/w nuclear medicine § Can treat with chemotherapy in 2nd/3rd trimester if required § RT should be delayed until after delivery
Notes:
o Should manage as similar to non-pregnant patient, if possible
o Modified staging
o Locoregional treatment as for non-pregnant (with exception of RT)
Assuming no other adverse/ high risk factors (eg. extranodal extension, perinodal LVI) then this patient with a G2 pT2N2 has had appropriate management of the axilla (>10 nodes, <50% nodal burden).
Does not require further axillary nodal irradiation
Given young age, HER2 positive disease (intermediate prognosis), and node positive would offer adjuvant whole breast radiotherapy plus boost with treatment of Level III, SCF and IMC for locoregional control and DFS benefit based on MA20, EORTC22922 and Danish IMC studies.
MA20: 5% benefit in DFS and DM at 10 years; treated high axilla, SCF, IMC
EORTC 22922: RNI reduces LRR and DM
Danish IMN: benefit of IMN irradiation greatest for node positive medial/central disease; and >=4 LN regardless of location; reduction in distant mets, breast cancer mortality and OS
Prescribe 50Gy/25Fx to whole breast, SCF and IMC with 10Gy sequential tumour bed boost.
Presim: consent, referral to lymphoedema clinic, genetics
Simulation: Supine, breast board, arms above head, wire scars and breast, CT sim 2mm axial slice with DIBH
Volumes: CTV = whole breast based on clinical mark-up and CT based anatomy (as per ESTRO contouring guidelines), tumour bed boost, IMC and SCF CTV
with 5mm isotropic expansions to PTV
PTV V95>95 ICRU 62/83
OAR constraints: lung V20<30, V5<60; contral lung V5<10, heart mean<5, Contral breast ALARA, V3<10, Spinal cord Dmax <45, oesophageal ALARA
Treatment with tangential VMAT or IMRT, 6MV photons, daily CBCT soft tissue match
Evidence to suggest hypo-fractionated schedules for breast and nodal irradiation eg. 42.4Gy/16Fx is safe with equivalent locoregional control, however younger populations under-represented in trials.
· The aims of adjuvant whole breast RT after WLE are to:
o Without further treatment, the risk of IBTR would be ~20-25% at 10 years.
o Avoid mastectomy (Breast conservation)
o Decrease the risk of ipsilateral breast tumour recurrence (by ~2/3).
o Decrease breast cancer specific mortality
· Evidence that supports this:
EBCTG Meta-analysis of multiple RTCs which showed a marked reduction in 10 year locoregional recurrence with the addition of RT to breast conserving surgery. It also found that 1 breast cancer death at 15 years was avoided for every four local recurrences avoided at 10 years.
· VMAT/IMRT
o More conformal, less heart dose
o More low dose wash
o Longer to plan
· 3DCRT
o Included standard tangent and anterior beam, partial wide tangential
o Quicker to plan, but less conformal
o Issues with junctioning
· Photon/ Electrons mixed field
o reverse hockey stick,
o Dedicated electron field targeting IMC, matched to adjacent photon tangents.
o Associated with higher mean heart doses
o ossues with junctioning
Can decrease heart dose further with DIBH
i. Most studies are collected from animal data, human data exists in populations following nuclear disasters such a Japan atomic bomb. The effects are relate to the dose/dose rate, gestational age and radiation type. 1st trimester embryos are undergoing organogenesis. The effects of ionising radiation exhibit the greatest intrauterine growth retardation. After first 6 weeks much higher doses of radiation are required to cause lethality, mostly effects for permanent growth retardation, fertility deficit and decreased IQ.
Embryo stage (organogenesis up to 6 weeks)
100mSv –nil effect
100mSv-1Gy -major malformations, miscarriage
=1-2Gy 100% malformations (similar timing to thalidomide, rubella)
Eg. Small organ, missing organ
+ Intrauterine growth retardation (can catch up post delivery)
Death could occur at birth (due to malformed organs, low weight)
0.25Gy = no Threshold: effect in rats
i. ii. Dose delivered/dose rate (duration of radiation exposure, distance to source) Presence of shielding, field size,distance from edge of field Type of radiation (brachytherapy vs electrons vs photons) Radiation energy Use of portal imaging as additional radiation exposure iii. Estimate dose received by abdomen Use of phantom to estimate dose TLD with bolus on abdo/pelvis for next fraction iv. 8 weeks gestational age, Dose <0.1 Gy likely safe 0.1-0.5 Gy potential growth restriction in early trimester, health effects unlikely in 2nd and 3rd trimester >0.5 Gy growth restriction incidence higher, lower IQ, probability of miscarriage increases with dose Doses of >2 Gy can lead to high rates of neonatal death
