Early-stage (I-II) Breast Cancer Flashcards
What histologic subtypes of IDC are associated with favorable outcomes?
Tubular, medullary, mucinous (colloid), papillary
What is a phyllodes tumor of the breast?
Ranges from benign to malignant. Rare tumor, leaflike, lobulated appearance on microscopic section. Treated with surgery, wide local excision or total mastectomy. No role for RT
What is Paget disease of the breast?
Malignant epithelial cells infiltrating the epidermis of the nipple-areolar complex. Presents with crusting, scaling, itching, and redness of the skin. 80-90% is associated with underlying DCIS or invasive breast cancer
What percent of invasive breast cancers are invasive lobular carcinomas?
10-15%
What percentage of women with clinically negative axilla were found to have axillary metastases on LND in NSABP B04?
40% of clinically node negative patients had positive nodes on LND
In NSABP B04, what percentage of women with a clinically negative axilla who did not undergo LND eventually developed a clinically positive axilla?
20% of women with initially negative nodes developed positive nodes
Workup for early-stage invasive breast cancer?
H&P (hormone use, ob/gyn hx, family or personal hx of breast/ovarian ca), diagnostic bilateral mammogram +/- ultrasound, pathology w/ ER/PR and HER2 status, CBC/CMP
When should bone scan or CT abdomen/pelvis be performed?
Bone scan only if localized bone pain or elevated alk phos
CT a/p if elevated alk phos or LFTs, abdominal sx, abnormal exam
When should breast MRI be used in screening/workup?
Women with >20% increased lifetime breast cancer risk based on family history and genetics
How should ER/PR and HER2 status be determined and reported?
ER/PR is positive if >1% of tumor cell nuclei are reactive via IHC
HER2 is positive if evidence of protein overexpression (3+) or gene amplification. If 2+, should get reflex testing using ISH
How should axilla and primary be evaluated prior to surgery or preoperative systemic thearpy?
If detected radiologically (mammo or axillary US), should get core biopsy
If LN-, SLNBx
If LN+, ALND if surgery planned or SLNBx following systemic therapy
Which trial shows SLNBx as an alternative to ALND for sentinel node negative patients?
NSABP B32: randomized 5611 patients to SLNBx + immediate completion axillary LND vs. SLN Bx alone; OS, DFS and regional control were similar between groups. Also shows decreased risk for lymphedema and arm numbness with SLNBx
What should be done is SLNBx is positive?
If T1/T2 or 1-2+ SLN, WBI after lumpectomy is appropriate without systemic chemo. ACOSOG Z0011 randomized ALND vs. no dissection for SLNBx+ treated with WBI and found noninferior 5yr OS, DFS, and LRR; 10yr OS also noninferior
What can be done in high risk patients with 1-2+ axillary SLNBx who do not undergo ALND?
High tangents (cranial tangent border >2cm from humeral head)
List the T-staging cutoffs for T1 and T2 breast cancers per 8th edition of AJCC
(c/p)T1mi: ≤1 mm (c/p)T1a: >1 mm but ≤5 mm (c/p)T1b: >5 mm but ≤10 mm (c/p)T1c: >10 mm but ≤20 mm (c/p)T2: >20 mm but ≤50 mm
What is clinical nodal staging for N1 disease?
cN1: mets to movable ipsilateral level I and level II axillary nodes
cN1mi: micromets (>0.2mm but <2.0mm)
What is the pathologic staging for N0-N1 disease?
pN0(i+): ITCs only (malignant cell clusters ≤0.2 mm)
pN0(mol+): Pos molecular findings by RT-PCR; no ITCs detected
pN1mi: Micromets (<0.2 mm but ≤2.0 mm)
pN1a: Mets in 1–3 axillary LNs, at least 1 with >2.0 mm
pN1b: Mets in ipsi IM SLNs, excluding ITCs
pN1c: pN1a and pN1b combined
What T and N groupings make up stage IA, IB, IIA, IIB?
IA: T1N0
IB: T0N1mi, T1N1mi
IIA: T0N1, T1N1, T2N0
IIB: T2N1, T3N0
What is the bioscore incorporated into the AJCC 8th edition staging system>
Multivariate model that incorporates grade, ER status, HER2 status and pathologic stage to assess DSS which ranges from 0 to 7
Which biomarker panel has level I evidence for breast cancer and what is it used for?
Oncotype DX recurrence score. A low oncotype DX score downgrades a biologically low-risk T2N0 from stage II to stage I
What percentage of breast cancer patients are diagnosed with stages 0 to II disease?
80%
What are the management options for early stage breast cancers?
- Lumpectomy w/ surgical axillary staging + RT
- Total mastectomy w/ surgical axillary staging +/- reconstruction
- If T2 or T3 and otherwise meets criteria for BCS can consider systemic chemo
When do you use adjuvant chemotherapy for early stage node negative breast cancer?
Triple negative or Her2+ with tumor > 1cm
ER+, Her2- with tumor > 0.5cm, consider oncotype
What does oncotype dx score tell you?
Risk of distant recurrence within 10 years of diagnosis with 5 years of endocrine therapy alone in ER+, N0 patients that undergo upfront surgery
Low <18, adjuvant endocrine alone
Intermediate 18-30, adjuvant endocrine +/- chemo
High >=31, adjuvant endocrine + chemo
When should you use adjuvant endocrine therapy in early stage breast cancer?
ER+ and tumor > 0.5cm
General principles for administering adjuvant endorine therapy?
If premenopausal, tamoxifen x 5 yrs (consider additional 5 yrs vs. switching to AI)
If postmenopausal, AI x 5 yrs
Major contraindication to using AI
Premenopausal status as AIs are ineffective in women with estrogen producing ovaries
Major side effects of tamoxifen and AIs
Tamoxifen: blood clots, strokes, uterine cancer, cataracts
AIs: bone loss, osteoporosis, joint pain, stiffness
Major chemo agents used in breast cancer
Doxorubicin (A), epirubicin (E), cyclophosphamide or carboplatin (C), paclitaxel or docetaxel (T), 5FU (F), trastuzumab (H)
Major chemo regimens for HER2- tumors
ddAC = doxorubicin + cyclophosphamide, q2w x 4
followed by
paclitaxel q2 wk x4
Major chemo regimens for HER2+ tumors
AC (doxorubicin + cyclophosphamide) plus trastuzumab followed by single agent trastuzumab
What data support the equivalence of BCT (lumpectomy +RT) vs mastectomy with regard to survival?
Several RCTs (NSABP B06, Milan III, Ontario, Royal Marsden, EORTC 10801). B06: No difference in 20 year DFS, OS or DM
What percentage of patients are eligible for BCT for early stage breast cancers?
75-80%
What are the contraindications for BCT for patients with early stage breast cancer?
Prior RT to the chest, disease extent that makes excision difficulty, diffuse microcalcifications, pregnancy, persistently positive margin, homozygous ATM mutation
Is there a contraindication for BCT in patients with a positive family history of breast cancer?
No
What are the dose fractionation schedules for WBI?
Standard 50Gy in 2 Gy fx or 45-50.4 Gy in 1.8 Gy fx
Hypofractionated: 42.56 in 2.66 Gy fx or 40.05 in 2.67 Gy fx
What data support the use of hypofractionated WBI?
4 RCT with >10 year f/u suggest same outcomes with potentially better side effect profile (Canadian, START pilot, START A/B trials)
Canadian (Whelan) - 42.56/16fx vs 50/25fx, T1-2N0, excluded women with >25cm breast width - no difference in LR, DFS or cosmesis
British (START A/B): 40/15fx vs 50/25fx, T1-3N0-1, no difference in IBTR, better cosmesis with hypofractionation
Per ASTRO guidelines, who can be offered hypofractionated WBI?
> 50y, pT1-2N0, treated with BCS, no systemic chemo, good dose homogeneity
What data support the use of a tumor bed boost?
2 studies demonstrate improved LC rate with 10-16 Gy boost after initial 45-50 Gy WBI
EORTC boost trial: RCT 50 Gy vs. 50+16 Gy (-margins) or 26 Gy (+margins). 10yr LF rate 6.2% boost vs. 10% w/o boost. No difference in 20yr OS
Lyon boost trial: RCT 50Gy vs 50+10Gy, 3y LF rate 3.6% vs. 4.5%
Should you boost to higher dose in patients with incomplete excision after BCS?
No. EORTC boost trial showed no difference in LC or survival between 10 Gy and 26 Gy boosts
What is next step in management of patient who has lumpectomy with focal positive margin?
Ideally, re-excision in order to decrease LR risk to baseline
Is there a subset of women whose LR risk is not influenced by margin positivity after BCS?
Age < 40 y/o women have worse 5 yr LR rate (37%) if margins are positive
Should T1-2N0 women treated with mastectomy found to have +margin be treated with adjuvant RT?
British Columbia retrospective study had 94 women with positive mastectomy margins, half treated with RT. Suggests women >50, T2 tumor, grade III, and +LVI may have LR benefit with PMRT
What is EIC?
Extensive intraductal component: DCIS both admixed and adjacent to invasive disease and comprising 25% of total tumor mass
Does EIC have prognostic significance in the LR risk of patients treated with BCT?
Yes, but dependent on margin status. If there is a close or positive margin, EIC is associated with higher risk of recurrence
What data suggests that the results of BCT can be further improved with tamoxifen?
NSABP B21 - 3 arm RCT tam alone vs. RT alone vs. tam + R. 8 yr IBTR 16.5% tam alone, 9.3% RT alone, 2.8% RT + tam
Are there patient subgroups with low risk of LR that can be treated with BCS and systemic therapy alone without radiation?
Yes. Age > 65-70, ER+, T1N0
Toronto: >60 w/ <1cm tumor, risk 1.2% vs. 0% with RT
CALGB 9343/Intergroup: >70y, T1, cN0, ER+ tamoxifen vs. tamoxifen + RT - no difference in time to mastectomy, DM, OS
Prime II: >65y T1-T2N0 ER+ on tamoxifen WBI vs. no RT, IBTR 1.3% vs. 4.1%
Can RT be used for treating axillary nodes in place of surgery in ALND not performed?
AMAROS trial randomized SLN+ to completion ALND vs nodal RT. No significant difference in LRR, DM or OS and better arm function in the RT group
Are there data supporting WBI + RNI for early stage breast cancer after BCS?
2 RCTs (MA.20 and EORTC 22922/10925)
MA.20 - Whelan - LN+ or high risk LN- patients, decreased regional recurrence (2.7 vs. 0.7%) with addition of nodal irradiation
EORTC - decreased regional recurrence (4.2 vs. 2.7%) and decreased DM rate (19.6% vs. 15.9%)
no OS benefit in either
How should chemo be sequenced with radiotherapy after BCS?
JCRT sequencing trial (“upfront-outback” trial)
5yr results better in chemo 1st arm but 11yr results show no difference in DFS, LR, DM, or OS
Either sequence is acceptable
What US trial investigated the role of accelerated partial breast irradiation?
NSABP B39/RTOG 0413 - randomized women with stage 0, 1 or 2 with tumors <3cm and <3 LN+ to WBI vs APBI (interstitial, intracavitary or EBRT)
PUBLICATION PENDING
What is the dose and duration of treatment for APBI from B39/RTOG0413?
All given BID over 5 days
34Gy in 3.4Gy BID fractions for interstitial/intracavitary treatment
38.5 Gy in 3.85 Gy BID fx for EBRT
Who can be offered PBI?
> 50y, Tis, T1, with DCIS allowed if low/intermediate grade, <2cm and margins >3mm
Is there evidence to support using IMRT for WBI for early stage breast cancer?
Data suggests benefit in acute effects and late cosmesis
Canadian study: reduced moist desquamation
British study: cosmesis improved (OR 0.68) and reduced skin telangiectasia
Are there subsets of women who undergo mastectomy for early stage breast cancers that may benefit from PMRT?
NCCN guidelines: no RT if -axillary nodes, tumor <5cm, margins >1mm
Otherwise, risk factors including close/+ margins, extensive LVSI, central/medial tumors, young age can be taken into consideration
How do you manage breast cancer in pregnant woman?
Chemo can be used to delay surgery until after delivery - non-taxane chemos (FAC) are appropriate in 2nd and 3rd trimesters. Chemo is held 3 weeks before due date to reduce risk of infetion and bleeding. RT must be deferred until pospartum
