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Radiation Oncology Residency > Locally advanced breast cancer > Flashcards

Locally advanced breast cancer Flashcards

1
Q

What is locally advanced breast cancer?

A

Typically refers to stage III disease (T3N1, N2-3, or T4) but can also refer to stage IIB (T3N0) and inflammatory breast cancer. Does not include metastatic disease.

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2
Q

What are the trends in incidence of LABC?

A

T3-T4 disease incidence has decreased by 27% from 1980 to 1987 due to institution of mammography. SEER database review 92-99 revealed LABC 4.6% of all breast cancers and IBC 1.3%

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3
Q

What are diagnostic criteria for inflammatory breast cancer?

A

Rapid onset of breast erythema, edema, and/or peau d’organge and/or warm breast with or without an underlying palpable mass
Duration of hx no more than 6 months
Erythema occupying at least 1/3 of breast
Pathologic confirmation of invasive carcinoma

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4
Q

What is the pathognomonic feature more characteristic of IBC than other forms of LABC?

A

Tumor emboli (dermal lymphatic invasion) in the dermis of the skin overlying the breast

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5
Q

What is the prevalence of IBC?

A

1-4% of breast cancer cases are IBC, 70% present with regional disease and 30% with distant disease

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6
Q

What are the histologic subtypes of LABC?

A

Same as earlier stage disease: invasive ductal carcinomas, tubular, medullary, mucinous

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7
Q

Are there genetic/molecular factors associated with LABC?

A

No marker is used to define LABC but HER2+, BRCA+, triple negative are associated with aggressive phenotypes.

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8
Q

Workup for locally advanced invasive breast cancer

A

H&P, CBC, LFT, ER/PR/HER2, bilateral diagnostic mammogram, imaging with US, CT, PET, bone scan and MRI are optional per NCCN 2018

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9
Q

What are the 5 regional LN stations for breast cancer?

A

Station I: nodes inf/lat to pectoralis minor muscle
Station II: nodes deep to pectoralis minor and the interpectoral Rotter nodes
Station III: nodes sup/med to pectoralis minor
Station IV: SCV nodes
Station V: IM nodes

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10
Q

What are the most important factors that predict LRR for LABC?

A

Increasing number of LNs+, tumor size

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11
Q

What are the basic principles for treating LABC?

A

Inoperable LABC: neoadjuvant chemo to shrink the tumor and potentially conver to operable
Operable LABC: neoadj or adj chemo are used with mastectomy. PMRT indicated for all stage III disease. Hormonal therapy if ER+ or trastuzumab if HER2+

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12
Q

What is a Halsted radical mastectomy?

A

Resection of all breast parenchyma with overlying skin and major/minor pectoral muscles en bloc with axillary lymph nodes

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13
Q

What is spared with a modified radical mastectomy?

A

MRM spares the pectoralis muscles

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14
Q

What is spared with a total or simple mastectomy?

A

In total/simple mastectomy only the breast tissue is removed with overlying skin. Axillary LNs are not dissected.

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15
Q

What is considered an adequate axillary LND for purposes of staging and clearance?

A

Resection of levels I-II. The LNs and axillary fat pad need to be removed en bloc. Axillary LND is considered full if >10 LN are removed without neoadj chemo. LN yield is often less after chemo. If suspicious nodes are palpable intraoperatively then level III dissection may be indicated.

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16
Q

Which trial demonstrated that not all patients with SLNBx+ need completion axillary LND?

A

ACOSOG Z11 - patients with 1-2 SLNBx+ nodes randomized to completion ALND + RT vs RT alone. No difference in breast or axillary recurrence

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17
Q

Do clinically node+ patients always need ALND?

A

Yes. No matter what upfront treatment (surgery, neoadjuvant chemo) full axillary LND is indicated. Omission of ALND only on protocols.

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18
Q

What is standard systemic chemotherapy for LABC?

A

Antrhacycline and taxane based regimen (doxorubicin/cyclophosphamide (AC) and paclitaxel)

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19
Q

Does adding paclitaxel to standard AC chemo improve outcomes for patients with LABC?

A

Yes. Improved response rates, DFS and OS seen on NSABP B27 (improved pCR in group receiving preop AC+T), CALGB 9344 (improved DFS and OS), ECOG E1199 (improved DFS and OS)

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20
Q

Which meta-analysis shows benefit of anthracyclines?

A

EBCTG/Oxford overview: antrhacyclines > CMF > no chemo

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21
Q

What does “dose-dense” chemo mean?

A

Dose-dense chemo is administered q2wks as opposed to q3wks

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22
Q

Has dose-dense chemo been proven to be superior in a prospective randomized trial?

A

Yes. Intergroup C9741 randomized patients to q2wk vs q3wk AC+T and found improved 4yr DFS (75% to 82%)

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23
Q

What is the rationale for the use of neoadjuvant chemotherapy for LABC?

A

To convert patients from unresectable LABC to resectable. Can also make less extensive surgeries possible.

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24
Q

Which patients have inoperable disease and need neoadjuvant chemotherapy?

A

Women with fixed axillary LN (stage N2a), major skin involvement (stage T4b-T4d) +/- CW involvement

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25
Q

What major study determined whether neoadjuvant chemotherapy improves survival compared to adjuvant chemotherapy in LABC?

A

NSABP B18 - compared preop AC to postop AC. 16yr follow up w/o significant difference in OS or DFS but there is a trend for women <50y for improved DFS and OS in the preop group

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26
Q

What procedures should be done prior to starting neoadjuvant chemotherapy for LABC?

A

Core biopsy and clip localization of breast tumor (in case pt has a CR to chemo). If clinically node+, also place clip in involved LN prior to chemo

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27
Q

In NSABP 18 and 27, did pCR at time of surgery correlate with good OS and DFS outcomes?

A

Yes. Both NSABP 18 and 27 showed correlation between pCR and improved OS and DFS compared to non-pCR patients

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28
Q

What other seminal neoadjuvant chemo trials (beyond NSABP 18 and 27) adressed neoadjuvant vs. adjuvant chemotherapy and its role regarding BCS?

A

EORTC 10902 randomized patients with early stage BC to preop vs. postop chemotherapy. No difference at 10 yr f/u in OS or LRR but improved rates of BCS were seen in neoadjuvant chemo arm.

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29
Q

In EORTC 10902, was there a difference in the # of BCS between arms?

A

BCS increased from 22 to 35% in the preop chemo arm.

30
Q

Why did PMRT fall out of favor in the 1980s?

A

Historically PMRT was offered because patients presented at later stages and no chemo was given. Historical series failed to demonstrate a survival benefit, but did show improved local control. Updated results in 1994 showed increased PMRT increased cardiac mortality and decreased BC mortality.

31
Q

What are some criticisms of older PMRT data and meta-analysis?

A

Significant heterogeneity of surgical and RT techniques, old RT techniques with increased risk for cardiac or pulmonary toxicity and lack of systemic chemotherapy.

32
Q

What 3 randomized prospective trials are considered to represent the modern PMRT experience?

A

Premenopausal danish trial (DBCG 82b), Postmenopausal danish trial (DBCG 82c) and the British Columbia PMRT trial

33
Q

Study design and outcomes of premenopausal danish trial?

A

1708 women randomized to mastectomy and adj CMF +/- RT. Cumulative LRR was 32% without PMRT and 9% with PMRT. Benefit was seen for all patients regardless of nodal status.

34
Q

What are some criticisms of the DBCG 82b trial?

A

inadequate surgical treatment of axilla (median 7 nodes removed), excess LF in the axilla (44% in CMF arm) and outdated chemo (CMF)

35
Q

What were design and trial outcomes of postmenopausal danish trial 82c?

A

1375 postmenopausal women randomized to postmastecomy tamoxifen x 1 yr vs. tamoxifen + PMRT. PMRT significantly improved LRR (35% vs. 8%), DFS (24% vs. 36%) and OS (24% vs 45%) at 10 year f/u

36
Q

What are some criticisms of the postmenopausal danish trial 82c?

A

Inadequate surgical treatment of the axilla (median 7 LN removed) and suboptimal duration of tamoxifen (1 yr vs. 5 yr)

37
Q

What surgery was performed in the Danish 82b and 82c trials?

A

Total mastectomy + ALND (removing at least 5 LN, full dissection not required)

38
Q

How was RT given in the Danish 82b and 82c trials?

A

82b: PMRT after cycle 1 of CMF and 3-5 wks postop
82c: PMRT 2-4 wks postop
Does: 48-50 Gy in 22-25 fx with anterior photon fields to cover the SCV, ICV and undissected axillary nodes and anterior electron field to cover the IM nodes and chest wall. Posterior axillary boost (PAB) used for patients with a large AP diameter

39
Q

What was the design of the British Columbia PMRT trial?

A

318 premenopausal, high risk patients with positive axillary LNs randomized to CMF chemo x 6-12m vs. CMF + RT. Surgery was total mastectomy with ALND (median 11 LN). RT was Co-60 to 37.5 in 16 fx using a 5 field technique

40
Q

What are the relevant outcomes of the British Columbia PMRT trial?

A

20 year f/u: adjuvant RT improved LRR before DM (13% vs 39%), DFS (48% vs. 31%) and OS (47% vs. 37%). Benefit seen in group with 1-3 LN+ and >4 LN+

41
Q

What are some criticisms of the British Columbia PMRT trial?

A

LRF was high compared to current series, CMF chemo is out of date, RT fields included en face photons for IM nodal coverage

42
Q

What was demonstrated by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) RT meta-analysis?

A

Included 78 RCTs, 42,000 women.

BCS, node negative: RT reduced 5 year LR from 22.9% to 6.7% and reduced 15yr breast cancer mortality from 31.2 to 26.1%.

BCS, node positive: RT reduced 5 yer LR from 41% to 11% and reduced 15yr breast cancer mortality from 55 to 47.9%

Mastectomy, node negative: RT reduced 5 yr LR 6.33 to 2.3% but INCREASED 15yr mortality 27.7% to 31.3%

Mastectomy, node positive: RT reduced 5 yr LR 22.8 to 5.8% and reduced 15 yr BC mortality 60 to 54%

Use of tamoxifen x 5 yrs reduced LR risk by ~50% in ER+ patients

43
Q

Are there any prospective RCTs evaluating PMRT in patients treated with neoadjuvant chemotherapy?

A

No. Trials are currently ongoing.

44
Q

What was demonstrated in the retrospective series from MDACC regarding PMRT in patients treated with neoadjuvant chemotherapy?

A

Huang et al.(2004) - 542 patients treated with neoadjuvant chemo, mastectomy, and RT - CSS improved in patients treated with PMRT in stage IIIB, SCV LN+, cT4 tumors, and >4 LN+. LRR improved in clinical stage III, SCV LN+ dz with pCR on chemo

45
Q

What is the LRR without LN RT for patients with LN+ disease with pCR following neoadjuvant chemotherapy?

A

NSABP B18 and B27 show 9-13% LRR for patients treated without regional nodal irradiation (but receiving whole breast irradiation)

46
Q

What are the NCCN guidelines for PMRT?

A

Category 1 recommendation for patients with >4 +LNs and strongly considered for 1-3 +LNs. Considered for LN- patients with large tumors (T3, N0)

47
Q

What are arguments for providing PMRT to patients with 1-3LN positive

A

All 3 modern RCTs (Danish 82b, 82c and British Columbia) showed OS benefit with PMRT, even in subgroup analyses. EBCTCG meta-analysis had similar reduction in LR and BC mortality regardless of nodal extent. EORTC 22922 trials showed DFS benefit in patients treated with regional nodal RT (1/4 of which were postmastectomy)

48
Q

Do LF rates with N1 disease in Danish and British columbia trials represent typical US experience?

A

No. US studies have LF rates 4-13%

49
Q

For patients undergoing mastectomy with 1-3 LN+, what other clinicopathologic factors should be considered when recommending PMRT?

A

LVI, high grade, younger age, <10 LN examined, >20% LN+, larger tumor size (T2 or >4cm) and close margins

50
Q

Under what circumstances should regional LN be treated along with the chest wall (comprehensive PMRT)?

A

Patients with higher LRR risk. All stage III patients. Per NCCN guidelines, strongly consider in 1-3LN+ population, T3, or margin +

51
Q

Should IM nodes be included in all comprehensive PMRT fields?

A

NCCN 2018 states that “the NCCN panel recommends irradiation of ICV and supraclavicular areas, IM nodes, and any part of the axillary bed that may be suspicious (category 1 for ≥4 positive nodes; 2A for 1-3 positive nodes).”

52
Q

Should patients with T3N0 breast cancer who have had a mastectomy without neoadjuvant chemotherapy be treated with PMRT?

A

Controversial - traditionally these patients have bene treated with PMRT but 2 recent retrospective studies have shown low LF rates with mastectomy + adj chemo

53
Q

How should stage II patients with LN+ BC s/p neoadjuvant chemo and MRM be managed?

A

If pCR in LN and breat, LF rate is 0-10% without RT (NSABP B18 and MDACC data), so omission of PMRT can be considered. If pCR in LN but residual disease in breast, LF rate is 10-13% and discussion can be had regarding +/- PMRT. If +LN after neoadj chemo, LF rate is 15-20% and PMRT should be given

54
Q

How should stage II patients with LN+ BC s/p neoadjuvant chemotherapy and BCS be managed?

A

pCR in LN and breast will still need WBI. If persistent disease in breast, consider RNI in young patients. If LN+ despite neoadj chemo, will need WBI + RNI

55
Q

What question is the NSABP B-51 trial asking?

A

Randomizing women with cT1-3N1 BC with biopsy proven axillary LN mets who convert to pN0 after neoadjuvant chemo to +/- RNI. BCS patients all received WBI and are randomized to +/- RNI and mastectomy patients are randomized to no RT vs. CW+RNI.

56
Q

What question is the Alliance A011202 trial asking?

A

Randomizing women with cT1-3N1 BC with biopsy proven axillary LN mets who remain pN1 after neoadjuvant chemotherapy to ALND vs. axillary RT

57
Q

How is inflammatory breast cancer managed?

A

Combined modality treatment with neoadjuvant chemotherapy, MRM and comprehensive PMRT

58
Q

What are 2 acceptable PMRT schedules for IBC?

A

Conventional: 50Gy in 25 fx with 10-16 Gy CW boost
MDACC: hyperfractionated 1.5Gy BID to 51 Gy followed by 15 Gy in 10 fx BID to 66 gy

59
Q

In the MDACC retrospective analysis, which IBC patients benefited from escalation of postmastectomy RT from 60 Gy to 66 Gy?

A

Patients with unknown/close/+margins, less than pCR to neoadjuvant chemo, and age <45y

60
Q

What options for patients with poor response and unresectable disease after induction chemotherapy for IBC?

A

Alternative chemo. If still unresectable, can do preoperative RT.

61
Q

For patients who want breast reconstruction after mastectomy, when should reconstruction be done relative to the rest of the adjuvant treatment?

A

Tissue expander can be placed at time of surgery and exchanged for permanent implant either before or after RT. If autologous reconstruction is planned, this should occur after RT due to impaired cosmesis of autologous tissue from RT.

For T4b-d patients, reconstruction should be delayed 6-12 months after RT

62
Q

What is typical follow up schedule for patients treated for invasive breast cancer?

A

Interval H&P 1-4x/yr x5 years, then annually
Bilateral mammogram annually starting >=6m post-RT
Annual gyn exam - if tamoxifen
Bone health assessment at baseline and periodically - if AI

63
Q

For patients with large breasts and large medial to lateral separation, what techniques can improve dose homogeneity?

A

Photon energy >10 MV

64
Q

What are acute and late toxicities of whole breast RT?

A

Acute: RT dermatitis, hyperpigmentation, pneumonitis

Late: ST fibrosis, breast size change, telangiectasias, lymphedema, pulmonary fibrosis, precocious cardiovascular disease, secondary malignancy

65
Q

What randomized trials demonstrated superiority of 3D IMRT compared to 2D treatment approaches for minimizing cosmetic changes to the breast?

A

Royal Marsden (2007) showed significant improvement in cosmetic outcomes with 3D IMRT plans. No difference in QOL.

66
Q

What is the risk of secondary malignancy in patients treated for early BC with RT?

A

WECARE study: women <40y receiving >1Gy to contralateral breast had a RR of 3.

Sarcomas (angiosarcomas) within the RT field <1% (10 in 10,000) within 10-30 years

67
Q

What is the risk of lymphedema in patients treated for breast cancer?

A

~5% after SLN dissection and 10-25% after level I-II ALND. Comprehensive nodal RT after ALND further increases risk to 15-35%

68
Q

What is the risk for brachial plexopathy for a patient treated for breast cancer?

A

Median time to developing plexopathy is 10-12 months. Risk depends on RT dose and use of chemo. If dose <50Gy, risk is <1% without chemo and ~4.5% with chemo. If dose >50 Gy the risk is 5.6%

69
Q

What is the risk of cardiac toxicity after BCT for BC?

A

Rates of ischemic heart disease are proportional to mean heart dose and increase linear 7.4% per 1 Gy mean heart dose. Risk begins 1-2 years after RT and continues > 20 years. Mean heart dose therefore should be limited.

70
Q

What is the risk of pulmonary toxicities such as lung fibrosis and symptomatic pneumonitis after BCT for BC?

A

Pulmonary fibrosis occurs in everyone on imaging in the treated pleura but the risk of clinical pneumonitis is low. 0.2% pneumonitis after WBI and 1.2% after WBI+RNI

Radiation Oncology Residency (44 decks)

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