Multidisciplinary Symposium — Breast Cancer
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- Cancer Imaging [ 1740-5025 ] ; 2015.
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DOI: 10.1102/1470-7330/00/010018+07
PubMed: 18194883
PubMed Central: 4554692
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multidisciplinary Symposium — Breast Cancer</title></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18194883</idno><idno type="pmc">4554692</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554692</idno><idno type="RBID">PMC:4554692</idno><idno type="doi">10.1102/1470-7330/00/010018+07</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000D11</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D11</idno><idno type="wicri:Area/Pmc/Curation">000D10</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000D10</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Multidisciplinary Symposium — Breast Cancer</title></analytic><series><title level="j">Cancer Imaging</title><idno type="ISSN">1740-5025</idno><idno 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Kurtz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harris, Jr" uniqKey="Harris J">JR Harris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haffty, Bg" uniqKey="Haffty B">BG Haffty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fisher, B" uniqKey="Fisher B">B Fisher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clarke, Dh" uniqKey="Clarke D">DH Clarke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Tienhoven, G" uniqKey="Van Tienhoven G">G van Tienhoven</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haffty, B" uniqKey="Haffty B">B Haffty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Osborne, Mp" uniqKey="Osborne M">MP Osborne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Sh" 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sortKey="Montgomery, Rc" uniqKey="Montgomery R">RC Montgomery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hetelekidis, S" uniqKey="Hetelekidis S">S Hetelekidis</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Fisher, B" uniqKey="Fisher B">B Fisher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Silverstein, M" uniqKey="Silverstein M">M Silverstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fisher, Er" uniqKey="Fisher E">ER Fisher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Silverstein, M" uniqKey="Silverstein M">M Silverstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Silverstein, M" uniqKey="Silverstein M">M Silverstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thompson, Jf" uniqKey="Thompson J">JF Thompson</name></author><author><name sortKey="Uren, Rf" uniqKey="Uren R">RF Uren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beechey Newman, N" uniqKey="Beechey Newman N">N Beechey-Newman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giuliano, Ae" uniqKey="Giuliano A">AE Giuliano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krag, Dn" uniqKey="Krag D">DN Krag</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Albertini, Jj" uniqKey="Albertini J">JJ Albertini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giuliano, Ae" uniqKey="Giuliano A">AE Giuliano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Veronesi, U" uniqKey="Veronesi U">U Veronesi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giuliano, Ae" uniqKey="Giuliano A">AE Giuliano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roumen, Rm" uniqKey="Roumen R">RM Roumen</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Cancer Imaging</journal-id><journal-id journal-id-type="iso-abbrev">Cancer Imaging</journal-id><journal-title-group><journal-title>Cancer Imaging</journal-title></journal-title-group><issn pub-type="ppub">1740-5025</issn><issn pub-type="epub">1470-7330</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18194883</article-id><article-id pub-id-type="pmc">4554692</article-id><article-id pub-id-type="publisher-id">10010018</article-id><article-id pub-id-type="doi">10.1102/1470-7330/00/010018+07</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Multidisciplinary Symposium — Breast Cancer</article-title><subtitle>Monday 9 October 2000, 16.00–17.00</subtitle></title-group><pub-date pub-type="epub"><day>5</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2000</year></pub-date><volume>1</volume><issue>1</issue><fpage>18</fpage><lpage>24</lpage><permissions><copyright-statement>© International Cancer Imaging Society 2000</copyright-statement></permissions><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© International Cancer Imaging Society 2000</meta-value></custom-meta></custom-meta-group></article-meta></front><sub-article id="d30e99"><front-stub><title-group><article-title>Contemporary problems in the surgical management of breast cancer: the surgical/radiological interface</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Beechey-Newman</surname><given-names>Nicholas</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><aff id="Aff1">Guy’s Hospital, London, UK</aff></contrib-group></front-stub><body><sec id="Sec2"><title>Problems with breast-conserving surgery for invasive disease</title><sec id="Sec3"><title>The morbidity of axillary dissection</title><p>The immediate complications of axillary node surgery are relatively insignificant. It is very uncommon for any patient to sustain serious injuries such as brachial plexus nerve or axillary vein injury, and although seroma formation is a very frequent occurrence it is well tolerated and is rarely prolonged. Delayed complications and long-term morbidity are by contrast commonplace and impact on the lives of many individuals. The principle symptoms that may be encountered after axillary surgery are arm swelling, susceptibility to upper limb infections, shoulder stiffness, pain and altered sensation or numbness. Quality of life studies show that lymphoedema is the most troublesome complaint[<xref ref-type="bibr" rid="CR9">9</xref>].</p><sec id="Sec4"><title>Lymphoedema</title><p>Incidence: depends on degree of swelling that is used to define the condition.</p><p>Serious swelling that interferes with limb function = 2–8%[<xref ref-type="bibr" rid="CR1">1</xref>,<xref ref-type="bibr" rid="CR9">9</xref>]</p><p>Significant swelling that is well tolerated = 15–20%[<xref ref-type="bibr" rid="CR1">1</xref>–<xref ref-type="bibr" rid="CR4">4</xref>]</p><p>Objective arm swelling without symptoms = 40%</p><p>Transient early lymphoedema that resolved = 7.5%[<xref ref-type="bibr" rid="CR1">1</xref>]</p><p>Risk factors:
<list list-type="bullet"><list-item><p>Degree of axillary surgery (sample, level I, II or III)[<xref ref-type="bibr" rid="CR5">5</xref>]</p></list-item><list-item><p>Obesity predisposes[<xref ref-type="bibr" rid="CR1">1</xref>,<xref ref-type="bibr" rid="CR6">6</xref>]</p></list-item><list-item><p>Incidence increases with time[<xref ref-type="bibr" rid="CR1">1</xref>]</p></list-item><list-item><p>More common in older patients and possibly after wound infection[<xref ref-type="bibr" rid="CR7">7</xref>]</p></list-item></list></p></sec><sec id="Sec5"><title>Chronic pain</title><p>Incidence = 2.5%[<xref ref-type="bibr" rid="CR6">6</xref>]–25%[<xref ref-type="bibr" rid="CR3">3</xref>,<xref ref-type="bibr" rid="CR4">4</xref>]</p></sec><sec id="Sec6"><title>Numbness/paresthesia</title><p>Early post-op incidence = 70–77%[<xref ref-type="bibr" rid="CR3">3</xref>,<xref ref-type="bibr" rid="CR4">4</xref>,<xref ref-type="bibr" rid="CR6">6</xref>,<xref ref-type="bibr" rid="CR8">8</xref>]</p><p>Resolves in 20%, improves in 60–100%, remains in 20%[<xref ref-type="bibr" rid="CR6">6</xref>,<xref ref-type="bibr" rid="CR8">8</xref>]</p></sec><sec id="Sec7"><title>Shoulder stiffness</title><p>Abduction reduced by >15 degrees in 9% at 1 year, other movements unaffected[<xref ref-type="bibr" rid="CR3">3</xref>].</p></sec></sec><sec id="Sec8"><title>Local recurrence</title><sec id="Sec9"><title>Rate</title><p>Local recurrence following mastectomy approx. = 1%/year (incl. Regional)</p><p>Local recurrence following breast-conserving surgery approx. = 2%/year (incl. Regional)
<table-wrap id="Tab1"><label>Table 1</label><caption><p><bold><italic>Loco-regional recurrence rates in the larger trials of breast-conserving surgery</italic></bold></p></caption><table frame="hsides" rules="groups"><thead><tr><th>Authors</th><th><italic>n</italic></th><th>F/U years (median)</th><th>% Local recurrence</th><th>% Local recurrence/year</th></tr></thead><tbody><tr><td>M. D. Anderson</td><td>525</td><td>5</td><td>10.3</td><td>2.15</td></tr><tr><td>Institut Curie</td><td>518</td><td>13</td><td>18</td><td>1.3</td></tr><tr><td>Yale[<xref ref-type="bibr" rid="CR15">15</xref>]</td><td>278</td><td>7.5</td><td>17</td><td>2.3</td></tr><tr><td>Marseilles</td><td>1593</td><td>11</td><td>12.9</td><td>1.2</td></tr><tr><td>Harvard</td><td>733</td><td>6</td><td>13.3</td><td>2.2</td></tr><tr><td>Univ. Pennsylvania</td><td>1030</td><td>3</td><td>9.3</td><td>3.1</td></tr><tr><td>Marsden</td><td>211</td><td>10</td><td>22</td><td>2.2</td></tr><tr><td>NSABP[<xref ref-type="bibr" rid="CR16">16</xref>]</td><td>629</td><td>6.5</td><td>14.5</td><td>2.2</td></tr><tr><td>Westminster</td><td>356</td><td>5</td><td>13.5</td><td>2.7</td></tr></tbody></table></table-wrap></p></sec><sec id="Sec10"><title>Effects of local recurrence on survival</title><p>Most studies show no impact on survival in patients with isolated local recurrence[<xref ref-type="bibr" rid="CR10">10</xref>,<xref ref-type="bibr" rid="CR17">17</xref>,<xref ref-type="bibr" rid="CR19">19</xref>]</p><p>Local recurrence (intra-breast) is associated with a relative increase in the risk of metastatic disease (and therefore death) of 2.0–1.5 times[<xref ref-type="bibr" rid="CR11">11</xref>,<xref ref-type="bibr" rid="CR12">12</xref>,<xref ref-type="bibr" rid="CR16">16</xref>]</p><p>Increased risk of metastatic disease is principally confined to early recurrences (<5 years, and especially in recurrences <2 years after primary surgery)[<xref ref-type="bibr" rid="CR10">10</xref>,<xref ref-type="bibr" rid="CR12">12</xref>,<xref ref-type="bibr" rid="CR13">13</xref>,<xref ref-type="bibr" rid="CR19">19</xref>]</p><p>Overall survival following local recurrence = 50% @ 5 years[<xref ref-type="bibr" rid="CR12">12</xref>,<xref ref-type="bibr" rid="CR15">15</xref>,<xref ref-type="bibr" rid="CR19">19</xref>]</p><p>Local recurrence is controllable by mastectomy in 70–95%[<xref ref-type="bibr" rid="CR12">12</xref>,<xref ref-type="bibr" rid="CR20">20</xref>]</p><p>Overall survival following local recurrence in breast-conserving surgery is no worse than local recurrence following modified radical mastectomy[<xref ref-type="bibr" rid="CR18">18</xref>]</p></sec><sec id="Sec11"><title>Risk factors for local recurrence</title><p>Ninety per cent of local recurrences occur in the same quadrant of the breast suggesting that most represent residual disease.</p><p>Approx. 10% of patients undergoing breast-conserving surgery can be shown to have adjacent residual areas of multifocal disease[<xref ref-type="bibr" rid="CR24">24</xref>]</p><p>General: local recurrence is more frequent in younger patients[<xref ref-type="bibr" rid="CR21">21</xref>] and those with larger tumours</p><p>Surgical: moderately or extensively involved surgical margins are associated with increased rate of local recurrence[<xref ref-type="bibr" rid="CR22">22</xref>], close or focally involved margins are probably not[<xref ref-type="bibr" rid="CR23">23</xref>]</p><p>Pathological: local recurrence increased with extensive in-situ component, tumour grade[<xref ref-type="bibr" rid="CR17">17</xref>] and lymphatic/vascular invasion. Nodal status is a possible risk factor.</p></sec></sec></sec><sec id="Sec12"><title>Problems with breast-conserving surgery for DCIS</title><p>DCIS is often extensive in one area of the breast and may be multi-centric. The mainstay of treatment is complete surgical excision. The successful elimination of DCIS represents a chance to avoid potentially fatal invasive disease, but just as with invasive disease the earlier fashion of simple mastectomy has given way to breast-conserving surgery in many patients. A recurrence rate of approximately 1% @ 10 years can be expected after mastectomy compared with 12–20% for breast-conserving surgery. The factors associated with recurrence are the surgical margin, the presence of multifocal or multicentric disease, lesion size and the degree of differentiation of the in-situ change. DCIS is usually not palpable and the pre-operative assessment of extent and multicentricity are problematic given current imaging techniques.</p><sec id="Sec13"><title>Background</title><sec id="Sec14"><title>Prevalence</title><p>PM studies = 8.9%</p><p>15–20% of detected breast malignancy</p></sec><sec id="Sec15"><title>Distribution in the breast</title><p>Holland studied 82 mastectomy specimens in patients with DCIS and correlated the pathology with specimen radiology[<xref ref-type="bibr" rid="CR25">25</xref>]</p><p>DCIS associated with microcalcification in 94% of comedo necrosis and in 53% of micropapillary/cribiform</p><p>Histological grade not related to size</p><p>Microcalcification underestimates lesion size by >20mm
<list list-type="bullet"><list-item><p>12% of comedo necrosis DCIS</p></list-item><list-item><p>44% of micropapillary/cribiform</p></list-item><list-item><p>50% of mixed micropapillary/cribiform+comedo necrosis</p></list-item></list></p><p>True multicentric disease is uncommon — 1/82 breasts (1.2%)</p><p>Extensive disease is frequently found
<list list-type="bullet"><list-item><p>23% DCIS extends through >1 quadrant (90° sector)</p></list-item><list-item><p>33% DCIS measured >40 mm in diameter</p></list-item><list-item><p>i.e. complete surgical clearance difficult in >50%</p></list-item></list></p><p>A focus of DCIS was closely associated with the nipple in 52%
<list list-type="bullet"><list-item><p>in comedo DCIS there was a nipple area focus in 64%</p></list-item><list-item><p>in micropapillary/cribiform DCIS nipple area disease in 34%</p></list-item><list-item><p>DCIS involved the nipple itself in half of these cases 70% of disease close to the nipple is mammographically occult</p></list-item></list></p><p>In patients with clear excision margins (>1mm) 43% have residual DCIS[<xref ref-type="bibr" rid="CR33">33</xref>].</p></sec></sec><sec id="Sec16"><title>Relative recurrence rates</title><p>Recurrence at 5 years following mastectomy= 1–2% @ 10 years[<xref ref-type="bibr" rid="CR29">29</xref>,<xref ref-type="bibr" rid="CR35">35</xref>]</p><p>Recurrence at 5 years following breast-conserving surgery = 12–22%@5–10 years[<xref ref-type="bibr" rid="CR26">26</xref>]</p><p>Approximately 50% of all recurrences following any treatment modality are invasive and 50% represent further DCIS. Invasive recurrences occur later (2 vs. 5 years)[<xref ref-type="bibr" rid="CR27">27</xref>]</p><p>Cause-specific mortality of those treated by breast conservation = 0–2% @ 10 years[<xref ref-type="bibr" rid="CR27">27</xref>]</p><p>Recurrence rates after breast conservation are approximately halved by radiotherapy[<xref ref-type="bibr" rid="CR34">34</xref>]</p><p>NSABP-24 investigated the recurrence rates following surgery plus tamoxifen. The recurrence rate is reduced but the follow-up is too short to tell whether recurrence is being prevented or just delayed[<xref ref-type="bibr" rid="CR32">32</xref>].</p></sec><sec id="Sec17"><title>Risk factors</title><p>The following are recognized as being associated with recurrence following surgical excision of DCIS
<list list-type="bullet"><list-item><p>Close margins — most studies define ‘close’ as 1 or 2 mm. Risk is particularly high when the margin is <2 mm but decreases progressively with widening margins. By a margin of 10 mm the risk is down to 4% @ 7.5 years[<xref ref-type="bibr" rid="CR31">31</xref>,<xref ref-type="bibr" rid="CR34">34</xref>]</p></list-item><list-item><p>Large lesion diameter. As with the measurement of margins this may be very difficult for the pathologist to assess accurately. Areas of DCIS >4–5 cm are associated with high recurrence rates[<xref ref-type="bibr" rid="CR30">30</xref>]</p></list-item><list-item><p>High histological grade/poor cytological differentiation. Assessment is somewhat subjective. The intermediate grade is particularly inconsistent[<xref ref-type="bibr" rid="CR35">35</xref>]</p></list-item><list-item><p>Histological evidence of necrosis. This is related to higher histological grade[<xref ref-type="bibr" rid="CR34">34</xref>]</p></list-item><list-item><p>Atypical ductal hyperplasia or cancerization of lobules adjacent to lesion[<xref ref-type="bibr" rid="CR28">28</xref>].</p></list-item></list></p></sec><sec id="Sec18"><title>Predicting recurrence</title><p>The Van Nuys Prognostic Index (VNPI)[<xref ref-type="bibr" rid="CR36">36</xref>]</p><p>Has the advantage of being from a ‘single’ institution Combines the three most significant variables by multivariate analysis Log rank test to find cut off values that would divide the variable into three separate groups:
<table-wrap id="Tab2"><table frame="hsides" rules="groups"><thead><tr><th>Score</th><th>1</th><th>2</th><th>3</th></tr></thead><tbody><tr><td>Lesion size Histopathology</td><td><16 mm Not high grade, no necrosis</td><td>16–40 mm Not high grade, necrosis present</td><td>>40 mm High grade, necrosis present</td></tr><tr><td>Margin</td><td>>10 mm</td><td>1–9 mm</td><td><1mm</td></tr></tbody></table></table-wrap></p><p>Identifies three risk groups
<list list-type="bullet"><list-item><p>VNPI = 3 or 4 — low risk of Local recurrence, 3% recurrence @ 8 years</p></list-item><list-item><p>VNPI = 5,6 or 7 — intermediate risk of LR, 23% recurrence @ 8 years</p></list-item><list-item><p>VNPI = 8 or 9 — high risk of LR, 80% recurrence @ 8 years.</p></list-item></list></p></sec></sec><sec id="Sec19"><title>Sentinel node biopsy[<xref ref-type="bibr" rid="CR38">38</xref>]</title><sec id="Sec20"><title>Definition</title><p>There is some argument as to how the sentinel node is defined[<xref ref-type="bibr" rid="CR37">37</xref>]. Theoretically the sentinel node is the node or nodes in each of the sometimes multiple lymph node basins that receives the direct lymph drainage from the site of the lesion. Practically, the sentinel node is the node or nodes in each lymph node basin that receive a blue-stained lymphatic and/or accumulate sufficient tracer to be clearly discernable at surgery. In the case of radioisotope tracers local definitions involving the count ratio of the node and the nodal bed are often used. The ratio has been defined as anywhere between 2 and 10.</p><p>Sentinel node biopsy aims to predict the status of the regional lymph node basin draining a carcinoma by analysis of the sentinel node(s) only. There is strong evidence that if the sentinel node is free from metastasis then the rest of the lymph nodes in that nodal basin will also be tumour-free. These sentinel node-negative patients can then safely omit nodal clearance and the morbidity that is associated with it.</p><p>In breast cancer approximately two thirds of sentinel node-positive cases have metastases confined only to the sentinel node(s) with all non-sentinel nodes being tumour-free. At the present time patients with a sentinel node containing tumour all undergo further axillary treatment (clearance or radiotherapy).</p></sec><sec id="Sec21"><title>Methods</title><sec id="Sec22"><title>Tracer</title><p>Blue dye[<xref ref-type="bibr" rid="CR39">39</xref>], 99-m technetium labelled colloid[<xref ref-type="bibr" rid="CR40">40</xref>] (particles 50–500 nm diameter) or both[<xref ref-type="bibr" rid="CR41">41</xref>]</p></sec><sec id="Sec23"><title>Site of injection</title><p>This varies. The most common is around the tumour. Also popular is sub- or intra-dermal. Occasionally reported into the tumour</p></sec><sec id="Sec24"><title>Pre-operative lymphoscintigram</title><p>This is not an essential part of sentinel node biopsy but it does have two advantages:
<list list-type="order"><list-item><p>alerts the surgeon to drainage outside the axilla;</p></list-item><list-item><p>often shows the presence of multiple sentinel nodes.</p></list-item></list></p></sec></sec><sec id="Sec25" sec-type="results"><title>Results</title><sec id="Sec26"><title>Accuracy</title><p>Population accuracy = % of cases where the sentinel node biopsy correctly predicts the status of the nodal basin as a whole. (In series with 50–70% node-negative cases the population accuracy can never be worse than 50–70%)</p><p>Underlying accuracy = % of node-positive cases that were accurately predicted.
<table-wrap id="Tab3"><table frame="hsides" rules="groups"><thead><tr><th>Author</th><th>Method</th><th>ID rate</th><th>Population accuracy</th><th>Underlying accuracy</th></tr></thead><tbody><tr><td colspan="2">Early (1996–1998) results</td><td></td><td></td><td></td></tr><tr><td>Giuliano[<xref ref-type="bibr" rid="CR42">42</xref>]</td><td>Dye</td><td>93%</td><td>99%</td><td>98%</td></tr><tr><td>Albertini[<xref ref-type="bibr" rid="CR41">41</xref>]</td><td>Dye & isotope</td><td>92%</td><td>100%</td><td>100%</td></tr><tr><td>Veronesi[<xref ref-type="bibr" rid="CR43">43</xref>]</td><td>Isotope</td><td>98%</td><td>97.5%</td><td>95%</td></tr><tr><td colspan="2">Recent (1999–2000) results</td><td></td><td></td><td></td></tr><tr><td>Guenther</td><td>Dye</td><td>71%</td><td>97%</td><td>90%</td></tr><tr><td>Roumen</td><td>Isotope</td><td>69%</td><td>98%</td><td>96%</td></tr><tr><td>Morgan</td><td>Dye</td><td>73%</td><td>94%</td><td>80%</td></tr><tr><td>Institut Curie</td><td>Dye</td><td>87%</td><td>97%</td><td>92%</td></tr><tr><td>Imoto</td><td>Dye</td><td>74%</td><td>94%</td><td>86%</td></tr></tbody></table></table-wrap></p><p>The figures for the underlying accuracy do not appear in the published results but can be extracted from them. The underlying accuracy represents the number of patients who would benefit most from adjuvant chemotherapy but may miss out on it due to incorrect staging.</p></sec></sec><sec id="Sec27"><title>Benefits</title><sec id="Sec28"><title>Reduced morbidity</title><p>Can avoid axillary dissection and the associated arm morbidity in approx. 50–60% of patients with primary breast cancer.</p></sec><sec id="Sec29"><title>Facilitates the detection of micrometastases</title><p>Allows intense histological examination to be concentrated on the sentinel node(s) rather than spread between a large number of non-sentinel nodes. Nodes can be subjected to serial sectioning, immunohistochemistry and reverse transcriptase PCR</p></sec><sec id="Sec30"><title>Extra axillary nodes</title><p>Lymphoscintigraphy has demonstrated drainage to the internal mammary chain in approx. 10% of cases of primary breast cancer[<xref ref-type="bibr" rid="CR45">45</xref>]</p></sec><sec id="Sec31"><title>Improved axillary sampling</title><p>Sentinel node biopsy can be used in conjunction with axillary node sampling. This ensures that the sample is representative of the rest of the axilla.</p></sec></sec><sec id="Sec32"><title>Problems</title><sec id="Sec33"><title>False negatives</title><p>There are probably a small number of unavoidable false-negative results. Even when the sentinel node is clearly identified false-negative results seem to arise in approximately 5% of cases. This may be due to an inherent flaw in the convenient sentinel node theory. Current results (see above) indicate a 5–20% false-negative rate in node-positive patients. A small number of node-positive patients may undergo less intensive treatments in error, with potentially fatal results</p></sec><sec id="Sec34"><title>Upstaging</title><p>The more rigorous histological examination of the sentinel node is resulting in ‘up-staging’. This means that there is a larger percentage of node-positive patients in any series (e.g. 29% node positivity increased to 42% when the sentinel node was subjected to more sophisticated analysis)[<xref ref-type="bibr" rid="CR44">44</xref>]. The increase is largely due to the increased detection of micrometastases. The prognostic implications of these small micrometastases is unclear and optimal management will take many years of clinical trials to evaluate</p></sec><sec id="Sec35"><title>2-stage procedure</title><p>Attempts to analyse the sentinel node by frozen section during surgery have resulted in unacceptable inaccuracy[<xref ref-type="bibr" rid="CR43">43</xref>]. Presently, the sentinel node biopsy has to be done first and if axillary surgery is required a second operation is necessary</p></sec><sec id="Sec36"><title>Radiation exposure</title><p>The absorbed dose to the patient is 0.1 mSv</p><p>Absorbed dose to surgeon = 2–5µSv per case (maximum dose= 1mSv/year)</p><p>Absorbed dose to surgeon’s fingers = 100µSv per case, (maximum dose= 500mSv/year).</p></sec></sec></sec></body></sub-article><sub-article id="d30e1040"><front-stub><title-group><article-title>Is imaging mandatory for staging?</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>McWilliams</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="Aff2"></xref></contrib><aff id="Aff2">Guy’s and St Thomas’ NHS Trust, London, UK</aff></contrib-group></front-stub><body><p>Mammography is the primary imaging modality in the detection of breast cancer. However, the limited sensitivity and specificity of mammography in the radiographically dense or treated breast and in assessing response to chemotherapy has led to the development of adjunctive imaging techniques including Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Scintimammography (SMM). The role of each of these specialized investigations is yet to be defined, but it has been established that they should not replace the use of conventional mammography and ultrasound, but be reserved as complementary techniques for resolving specificdefined problems. One of their main benefits appears to be improved loco-regional staging. In the current era of breast-conserving surgery accurate staging is mandatory so that inappropriate conservative surgery is not performed. Adjuvant imaging will help define the local extent of disease pre-operatively and thereby reduce local recurrence rates.</p><sec id="Sec38"><title>Loco-regional staging</title><p>In the current era of conservative surgery for early breast cancer it is critical for accurate loco-regional staging to be carried out so that appropriate treatment can be selected. Breast cancer may have a multicentric, multifocal origin; in a radiographic-histologic evaluation of mastectomy specimens, Hollands <italic>et al.</italic> showed 41% of cases had remote cancer foci most of which were occult at mammography[<xref ref-type="bibr" rid="CR46">1</xref>]. Tumour size, multifocality, retroareolar tumours and in situ component need to be accurately detected so that optimal local tumour control is made and mastectomy performed as a one-stage procedure if indicated. Flanagan <italic>et al.</italic> claim mammography to be almost exact in assessing tumour size[<xref ref-type="bibr" rid="CR47">2</xref>], but ultrasound tends to be more accurate[<xref ref-type="bibr" rid="CR48">3</xref>].</p><p>MRI has recently been advocated as the most accurate method of assessing tumour size and extent and detecting extensive ductal carcinoma in situ due to its extreme sensitivity[<xref ref-type="bibr" rid="CR49">4</xref>–<xref ref-type="bibr" rid="CR55">10</xref>]. MRI of the breast using a surface coil and rapid dynamic contrast-enhanced gradient echo imaging shows almost all malignant lesions enhance rapidly, concomitant with early vascular enhancement[<xref ref-type="bibr" rid="CR56">11</xref>] and relative to normal breast parenchyma, and also have characteristic morphological appearances. Clinically and mammographically occult multifocal tumours are readily detected by MRI[<xref ref-type="bibr" rid="CR50">5</xref>–<xref ref-type="bibr" rid="CR54">9</xref>,<xref ref-type="bibr" rid="CR57">12</xref>] as shown in Table <xref rid="Tab4" ref-type="table">1</xref>. Orel[<xref ref-type="bibr" rid="CR58">13</xref>] and Morris[<xref ref-type="bibr" rid="CR59">14</xref>] showed MRI is very sensitive in patients with malignant axillary lymphadenopathy and unknown primary tumour for the detection of clinically and mammographically occult breast cancer. The main limitation with MRI is the poor specificity; Gilles showed that early contrast enhancement in 37 of 79 patients with benign lesions giving a specificity of 53%[<xref ref-type="bibr" rid="CR60">15</xref>]. Boetes found that assessing morphological appearance as well as the rate of enhancement increased specificity to 86%[<xref ref-type="bibr" rid="CR61">16</xref>].
<table-wrap id="Tab4"><label>Table 1</label><caption><p><bold><italic>Detection of multifocal tumours and assessment of tumour size by MRI: comparison with conventional imaging</italic></bold></p></caption><table frame="hsides" rules="groups"><thead><tr><th>Author</th><th>Conrad[<xref ref-type="bibr" rid="CR50">5</xref>]</th><th>Kerslake[<xref ref-type="bibr" rid="CR53">8</xref>]</th><th>Mumtaz[<xref ref-type="bibr" rid="CR52">7</xref>]</th><th>Orel[<xref ref-type="bibr" rid="CR51">6</xref>]</th><th>Boetes[<xref ref-type="bibr" rid="CR54">9</xref>]</th></tr></thead><tbody><tr><td>No of patients in study</td><td>40</td><td>50</td><td>90</td><td>64</td><td>60</td></tr><tr><td>Multifocal tumour detected by MRI but not BM</td><td>9</td><td>14</td><td>6+5</td><td>22</td><td>9</td></tr><tr><td>MR/histology tumour size correlation</td><td>Good</td><td>Good</td><td>Good</td><td>Good</td><td>Good</td></tr></tbody></table><table-wrap-foot><p>BM = bilateral mammogram.</p></table-wrap-foot></table-wrap></p><p>MR mammography as an adjunct to mammography and ultrasound reveals breast cancer with a higher confidence and sensitivity[<xref ref-type="bibr" rid="CR55">10</xref>], but with lower specificity. MR imaging-guided needle localization and biopsy systems have been developed to evaluate lesions identified by MR that are clinically and mammographically occult[<xref ref-type="bibr" rid="CR51">6</xref>]. Cost, lengthy imaging time and poor availability may restrict access to MRI.</p><p>Scintimammography (SMM) using technetium-99mm sestamibi has recently been evaluated as an adjunctive technique to mammography. <sup>99m</sup>Tc-MIBI accumulates in tumour cells and has been reported to be accurate in detecting breast cancer and can help differentiate benign from malignant lesions[<xref ref-type="bibr" rid="CR62">17</xref>–<xref ref-type="bibr" rid="CR65">20</xref>]. SMM can be especially useful in the mammographically dense breast and, therefore, the young. Khalkhali <italic>et al.</italic> first reported the usefulness of Tc-99m sestamibi imaging in the detection of breast cancer[<xref ref-type="bibr" rid="CR66">21</xref>]. Palmedo detected tumours as small as 9mm and detected 100% of palpable tumours and, including impalpable lesions, the overall specificity was 83% and sensitivity was 88%. Helbich compared MR to <sup>99m</sup>Tc-sestamibi in differentiating benign from malignant breast lesions[<xref ref-type="bibr" rid="CR62">17</xref>] (see Table <xref rid="Tab5" ref-type="table">2</xref>).
<table-wrap id="Tab5"><label>Table 2</label><caption><p><bold><italic>Differentiation of benign and malignant breast lesions: MR vs Tc-99m sestamammography[</italic></bold><xref ref-type="bibr" rid="CR62">17</xref><bold><italic>]</italic></bold></p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th>MR</th><th>Planar mibi</th><th>SPECT mibi</th></tr></thead><tbody><tr><td>Sensitivity</td><td>96%</td><td>62%</td><td>83%</td></tr><tr><td>Specificity</td><td>82%</td><td>88%</td><td>80%</td></tr></tbody></table></table-wrap></p><p>Whilst both MR imaging and scintimammography are useful in the evaluation of breast cancer, MR was found to be more sensitive and just as specific. MR is a shorter examination time to scintimammography, but claustrophobia in the magnet can often lead to early termination of the procedure. In this instance scintimammography is a good alternative and can also give important information about the axilla. Scintimammography has limited spatial resolution and therefore the size of the tumour affects detection that may account for the low sensitivity. The main problem with scintimammography currently is limited availability as a special prone coil that improves imaging is required. The suggested use of scintimammography is as an adjunct to conventional imaging in failed triple assessment, breast prosthesis and with axillary metastasis and unknown primary[<xref ref-type="bibr" rid="CR67">22</xref>].</p><p>Indications for scintimammography:
<list list-type="bullet"><list-item><p>Failed triple assessment</p></list-item><list-item><p>Previous surgery</p></list-item><list-item><p>Breast prosthesis</p></list-item><list-item><p>Negative biopsy of suspicious mass</p></list-item><list-item><p>Axillary nodes with occult primary</p></list-item></list></p><p>Several studies have addressed the imaging of breast cancer with PET. PET produces images that reflect the physiological and biochemical processes of tissues. The most widely used PET pharmaceutical is fluorine-18-fluorodeoxyglucose (FDG) which evaluates the glucose metabolic rates of tissues. Malignancies have exceptionally high rates of glycolysis compared with benign tissues. FDG-PET is suitable for detecting breast cancer and evaluating response to treatment. FDG is taken up by all malignant tissues and therefore whole body scanning can be undertaken with assessment of lymph node involvement and distant metastases. Wahl reported visualization of all 10 primary breast cancers using FDG-PET[<xref ref-type="bibr" rid="CR68">23</xref>] and Adler showed 96% sensitivity and 100% specificity for the detection of malignancy[<xref ref-type="bibr" rid="CR69">24</xref>]. A limited number of benign lesions were studied, but these had a lower uptake than malignant lesions. Given the high cost of PET and limited availability, this technique is unlikely to serve as a screening modality for breast cancer. As an adjunct to conventional imaging it can be used in the indeterminate mammogram, prior to biopsy, with axillary metastasis of an unknown primary to search the breast[<xref ref-type="bibr" rid="CR70">25</xref>] and to evaluate the axilla prior to axillary surgery.</p><p>FDG-PET may be used in circumstances where mammography is technically difficult.</p><p>This includes:
<list list-type="bullet"><list-item><p>Dense breasts</p></list-item><list-item><p>Breast implants</p></list-item><list-item><p>Lumpy breasts/ multifocal disease</p></list-item><list-item><p>Post-operative breast</p></list-item><list-item><p>Equivocal biopsy</p></list-item></list></p></sec><sec id="Sec39"><title>Assessment of tumour response to chemo-endocrine therapy prior to surgery</title><p>Adjuvant systemic therapy following surgery for primary breast cancer with Tamoxifen or chemotherapy can reduce the risk of relapse and mortality. Neoadjuvant chemo-endocrine therapy is also used as primary treatment prior to surgery. Assessment of response to treatment is an important role of imaging in the multidisciplinary approach to treatment of breast cancer.</p><p>Changes seen on mammography associated with tumour response include a decrease in size and density of the lesion, calcifications becoming more tightly packed and complete resolution of the lesion[<xref ref-type="bibr" rid="CR71">26</xref>]. The remaining mammographic lesion may not necessarily contain tumour cells. Ultrasound can be useful in monitoring tumour size and recording changes in Doppler signal. However, even in the presence of no detectable lesion on ultrasound the presence of a viable tumour cannot be eliminated[<xref ref-type="bibr" rid="CR72">27</xref>].</p><p>MR has recently been reported in the evaluation of response to neo-adjuvant chemotherapy. Gilles assessed residual active disease using dynamic contrast-enhanced MR, and the presence or absence of early contrast enhancement appeared to be a reliable diagnostic criterion for the presence of residual tumour[<xref ref-type="bibr" rid="CR73">28</xref>]. Abrahams, using rotating delivery of excitation off resonance (RODEO) with gadolinium enhancement, reported that changes in vascularity early in the course of chemotherapy help to predict response[<xref ref-type="bibr" rid="CR74">29</xref>]. They accurately evaluated residual disease and suggest MR is superior to conventional imaging in the assessment of response to chemotherapy. Conversely Rieber <italic>et al.</italic> found that post-neo-adjuvant chemotherapy MR led to some false-negatives and an underestimation of residual tumour volume in some, although MR could provide evidence of response after the first two cycles with a high degree of probability[<xref ref-type="bibr" rid="CR75">30</xref>].</p><p>FDG-PET is valuable for monitoring the effects of pre-operative chemotherapy in patients with locally advanced breast cancer, with better sensitivity for tumour and specificity for nodal metastasis than ultrasound[<xref ref-type="bibr" rid="CR76">31</xref>].</p></sec><sec id="Sec40"><title>Local recurrence</title><p>Radiation therapy is increasingly being utilized following breast conservation. Post-treatment follow-up is difficult as surgical and radiation changes can mimic recurrence. Mammographic radiation changes are well known and the late phase usually stabilizes by 12 months after completion of radiotherapy. If diagnosed early, recurrences are treated with mastectomy and do not impair survival of these patients. Previously, biopsy was performed to determine whether changes were radiation-induced or a recurrence. Several studies have shown promising results with MRI[<xref ref-type="bibr" rid="CR77">32</xref>]. FDG-PET and SSM may also have a role in diagnosing local recurrence. Hathaway reported the combined use of MR and FDG-PET[<xref ref-type="bibr" rid="CR70">25</xref>] and their complementary role: PET identified all cases of metastatic tumour, whereas MR was useful in determining the relationship of the tumour to the axillary and supraclavicular neurovascular structures. Orel reports a high positive predictive value for MR predicting residual tumour after excisional biopsy, which would complement traditional methods of margin evaluation[<xref ref-type="bibr" rid="CR78">33</xref>]. Patients underwent MR imaging 6–40 days after excision biopsy and results suggest that those with positive margins following surgery should undergo MR to assess for residual disease prior to re-excision.</p></sec><sec id="Sec41" sec-type="conclusion"><title>Conclusion</title><p>Imaging plays an important role in loco-regional staging in the current era of breast-conserving surgery otherwise local recurrence rates may be unacceptably high. MR, PET and SSM are being increasingly utilized as adjuvant imaging in loco-regional breast disease and the choice may depend on local availability. PET and SSM are not widely available and, due to increasing access to MR, this may be the favoured technique. MR, PET and SSM should only be used in specific problem-solving areas discussed by the multidisciplinary team. Further studies comparing all three imaging modalities are required.</p></sec></body></sub-article></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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