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Cambridge Breast Unit, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK n Tel.: +44 122 358 6577
n Fax: +44 122 358 6932 n john.benson@addenbrookes.nhs.uk

Second Kyoto Breast Cancer Consensus Conference (KBCCC)
Kyoto, Japan, 14–16 April 2011
This is the second of a two-part conference report and covers the other main
themes of the Second Kyoto Breast Cancer Consensus Conference (KBCCC)
including ductal carcinoma in situ, sentinel lymph node biopsy and therapeuticalgorithms for local management of breast cancer. Once again, this reportemphasizes conclusions from the consensus sessions that were a key feature of
the KBCCC.

John Forbes from the University of Newcastle,
Australia, provided an insightful overview ofthe biology and management of ductal carcinoma in situ (DCIS) and emphasized the needfor more information from reliable clinical trials containing randomized prospective data.
Although DCIS generally has a good prognosis, there is an increased risk for subsequentinvasive breast cancer dependent on tumor
extent, grade, HER2 expression and probablemammographic density. Local recurrence ofDCIS is influenced by margin status, which isa modifiable risk factor – the most importantcomponent of treatment for DCIS is excision
with clear surgical margins. It should be notedthat MRI does not accurately predict the extentof DCIS. When the size of DCIS on MRI is lessthan 2 cm, MRI can assist in surgical planning.
Otherwise, it can potentially overestimate theextent of disease in up to 50% of cases andmay increase mastectomy rates. MRI may playa role in the evaluation of patients with a strong
family history of breast cancer and those witha documented mutation in the breast cancer
susceptibility genes BRCA-1 and BRCA-2.
Forbes presented results of the recently published UK/Australia and New Zealand Ductal
Carcinoma In Situ (UK/ANZ DCIS) trial [1] .
No differences in rates of ipsilateral breast tumor
recurrence (IBTR) were found between low andintermediate nuclear grade DCIS, suggestingthat distinction between these categories may
be unnecessary and grading should be reclassified as low/intermediate, high and very high.
Cytonuclear grade should be accepted as thebasic method for assessing intrinsic biologicalaggressiveness. Surgical excision should aim fora minimum tumor-free radial margin of 2 mm.
Interestingly, in the UK/ANZ DCIS trial, the10.2217/FON.11.72 © 2011 Future Medicine Ltd

relative risk of IBTR for margins of 0–1 mm
was 1.0 compared with 0.47 for margins of1–2 mm. There was no additional improvement in local control beyond a margin of 1 mm.
Randomized trials have confirmed that both
radiotherapy and tamoxifen reduce the risk ofIBTR and the chance of any subsequent invasive breast cancer. In the UK Coordinating
Committee on Cancer Research (UKCCCR)
trial, patients in both the radiotherapy and noradiotherapy arms were randomized to receive
tamoxifen or no systemic therapy. Tamoxifen
yielded a 29% reduction in risk of recurrence,but for those patients receiving radiotherapy,
much of the benefit of tamoxifen disappeared.
Similarly, radiotherapy produced a 60% risk
reduction for both noninvasive and invasivecancer, with little additional benefit from concomitant tamoxifen. Nonetheless, tamoxifenhad a longer-­term preventative effect on disease in the contralateral breast. These findings
may limit the ability of the International Breast
Cancer Interventional Study (IBIS) II trial todetect any advantage of anastrozole over tamoxifen for post-menopausal women with hormonesensitive DCIS treated with breast-conserving
surgery (BCS; not mastectomy). For patientsnot receiving radiotherapy, local recurrence riskfor high- and low-density breasts was 40 and0%, respectively, suggesting that benefits in risk
reduction were confined to the group for whomtamoxifen decreased breast density.
Mehra Golshen, of the Dana Farber/Brigham
and Women’s Cancer Center, MA, USA, briefly
discussed sentinel lymph node (SLN) biopsy inthe context of DCIS and adamantly maintainedthat there was no indication for axillary staging
except for cases of DCIS mandating mastec­
tomy (both intermediate and high nuclear
Future Oncol. (2011) 7(8), 959–961

Conference Scene

John R Benson

Future Oncology

Diagnosis and local managementof breast cancer: part II

Keywordsn breast cancer n DCIS n MRI
n neoadjuvant therapy n PETn sentinel nodepart ofISSN 1479-6694959

Conference SceneBensongrade) where the chance of finding invasive disease was approximately 10%. He cited an incidence of only 0.8% for lymph node metastases
in DCIS and often only isolated tumor cells arefound in nodes. No groups of patients undergoing BCS for DCIS only on core biopsy (nomicro-/overt invasion) were considered appropriate for simultaneous SLN biopsy, which isassociated with some morbidity, including allergic reactions to lymphazuran (the most commonly employed blue dye tracer agent in theUSA), lymphedema (1–7%), seroma formation(13%) and infection (3%). SLN biopsy can be
performed as a delayed procedure when invasivecancer is found in a wide-excision specimen.
An exciting and topical area of discussion
and interest came from results of the Z0011
trial evaluating omission of completion axillary lymph node dissection (cALND) in SLN
biopsy-­positive patients [2] . This trial examined disease-free survival and overall survival
in a group of almost 900 patients undergoing BCS for relatively favorable T1 and T2tumors (80% estrogen receptor positive)
with macro- and micro-metastases in one or
two SLN nodes. Patients were randomized tocALND or observation only and all received
whole-breast irradiation and systemic therapy(chemo­therapy/hormonal therapy). At a medianfollow-up of 6.3 years, there was no differencein either 5‑year rates of locoregional recurrence(SLN biopsy alone = 1.6% [95% CI: 0.7–3.3%]
vs ALND = 3.1% [95% CI: 1.7–5.2%]; p = 0.11)
nor overall survival (SLN biopsy alone = 92.5%[95% CI: 90.0–95.1%] vs ALND = 91.8%[95% CI: 89.1–94.5%]) between the two arms.
The unadjusted hazard ratio for treatment-related
overall survival was 0.79 (90% CI: 0.56–1.11),
and when adjusted for age and adjuvant therapy
was 0.87 (90% CI: 0.62–1.93). It has been commented by Golshen (and others) that this trial
was seriously underpowered and failed to accrue
its target goal of 1900 patients. However, thetrial was terminated early due to a lower mortality rate than expected. Furthermore, patientsin the SLN biopsy-only arm had slightly better
prognostic factors overall, with a higher proportion of micrometastases in the SLN biopsy arm(45%) compared with the ALND arm (35%).
The group of patients within this trial had a low
burden of axillary disease, with minimal likelihood of having more than two positive nodes;
thus, the therapeutic value of SLN biopsy wassimilar to axillary clearance. Moreover, adjuvant
treatments may have partly compensated forundertreating the axilla surgically. Due to the960

Future Oncol. (2011) 7(8)limited follow-up, some consider it premature to
assume that the results from Z0011 will dramati­
cally change surgical practice [3] . However, thishas happened in some centers in the USA for
patients fulfilling relevant criteria, including
receipt of radiotherapy after BCS. On the basisof results to date, Forbes considered it highly
unlikely that any equivalence of outcomes would
be overturned by additional cases of locoregional
recurrences to reveal any clinically meaningful
survival benefit in the dissection group withlonger follow-up. Consensus opinion supported
omission of cALND in breast-conservation
therapy patients with T1/T2 tumors and micrometastases only in the SLN and perhaps macro­metastases when the metastatic ratio is low –say one out of two or two out of four nodes,
rather than one out of one or two out of twonodes. Nomograms devised for the estimationof non-SLN involvement are difficult to reliably
apply in practice and in particular may not betransferable to data sets generated from otherinstitutions [4,5] .
Kazuhiko Yamagami from Shinko Hospital,
Japan, discussed the application of indocyanine
green (ICG) fluorescence to breast cancer patientsin Japan, where blue dye is currently the mostcommon tracer agent used. He emphasized theproblems of radioisotopes, including mandatory
licencing and availability. SLN biopsy using blue
dye alone can be problematic, especially with a fatrich axilla. It is necessary to dissect through fatty
tissue to reach a node and the blue color is readily
obscured by a thin covering of fat. Pinpointing
the SLN can be difficult in a fatty axilla andextensive dissection (with consequent damage tolymphatics) may be necessary. An illumi­nated or
fluorescent node can direct dissection, permitting
a more direct approach to the SLN. A combination of blue dye and ICG are injected into thesubareolar region and fluorescent lymphatics arevisualized immediately. These delve deep into theaxillary tissues at the ‘fluorescent line’, which canhelp guide the site of the skin incision. A plastic
sphere can be used to visualize approximately
50% of nodes through the skin and thus marktheir location. This is difficult in obese patientswith a BMI >30 in whom the axillary skin mustbe first incised. Identification rates for the SLN
are reported to be 97.8% and the staining characteristics showed that almost 90% of nodes wereblue and fluorescent.
In an interesting study using triple localization, 86 out of a total of 145 nodes were blue,
hot and fluorescent, with all nodes containing
metastases being visualized with all three tracer
future science group

Diagnosis & local management of breast cancer: part IIagents. This approach is being investigated in
the author’s unit in the UK where nodal tracer
characteristics are being evaluated using a combination of blue dye, ICG and radioisotope.
This feasibility study is a prelude to a larger
trial comparing the dual localization techniqueswith either a combination of blue dye and isotope(conventional) or blue dye and ICG. Results ofthis trial will determine standard practices for
SLN localization in the future.
A central theme of the conference was the use oftreatment algorithms and alternating decision tree
development for the management of patients withprimary breast cancer. These are often based on
probabilities, and various decision-making tools
can be used to guide treatment recommendations
that depend on the risk of a particular factor being
present. In the future, it is likely that molecular profiling of tumors will assist in predicting
treatment responses to neoadjuvant therapies
Bibliography
1.

Cuzick J, Sestak I, Pinder SE et al. Effectof tamoxifen and radiotherapy in womenwith locally excised ductal carcinoma
in situ: long-term results from the UK/ANZ
DCIS trial. Lancet Oncol. 12(1), 21–29(2011).

future science group

Conference Scene

and absolute benefits from both adjuvant andneo­adjuvant chemotherapy in terms of diseasefree and overall survival. These technologies
also offer the potential to assess the risk of local
relapse when BCS is undertaken after primarychemotherapy; such information could be incorporated into a nomogram and indicate whether
mastectomy might be more appropriate than BCS(whatever the final imaging appearances).
Financial & competing interests disclosure

The author has no relevant affiliations or financial
involvement with any organization or entity with afinancial interest in or financial conflict with the subject matter or materials discussed in the manuscript.
This includes employment, consultancies, honoraria,
stock ownership or options, expert testimony, grants orpatents received or pending, or royalties.
No writing assistance was utilized in the productionof this manuscript.

2.

Giuliano AE, Hunt K, Ballman K et al.
Axillary dissection vs no axillary
dissection in women with invasive breast
cancer and sentinel node metastases:
a randomized clinical trial. JAMA 305,569–575 (2011).

3.

Jatoi I. Axillary vs sentinel lymph nodedissection for invasive breast cancer. JAMA
305(22), 2288 (2011).

www.futuremedicine.com

4.

Van Zee KJ, Manasseh DM, Bevilacqua JLet al. A nomogram for predicting the likelihoodof additional nodal metastases in breast cancer
patients with a positive sentinel node biopsy.
Ann. Surg. Oncol. 10, 1140–1151 (2002).

5.

Pal A, Provenzano E, Duffy SW et al. A model
for predicting non-sentinel lymph nodemetastatic disease when the sentinel lymph node
is positive. Br. J. Surg. 95, 302–309 (2008).

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