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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 first of a two-part conference report and focuses primary on newer
technologies (e.g., molecular methods for intraoperative nodal assessment andMRI/PET imaging) and surgical management in the context of neoadjuvantchemotherapy. A notable feature of the Second Kyoto Breast Cancer Consensus
Conference was a consensus session for which a series of key clinical questionsin the aforementioned areas formed the basis for discussion. Preconference
questionnaires had been issued to all delegates and the final consensus sessions
focused on more controversial and problematic areas where there is divergenceof opinion and clinical management.

The opening session of the second Kyoto Breast
Cancer Consensus Conference (KBCCC)
addressed some of the leading-edge technologies that are being employed in the diagnosis andmanagement of breast cancer. Seigo Nakamura
from the Breast Center of Showa University
Hospital, Tokyo, Japan, pointed out problemsof a lack of consistency, limited sampling of
nodal tissue and the time-consuming natureof conventional histopathological methods for
intraoperative node assessment. Nakamura
reported sensitivity and specificity for the onestep nucleic acid amplification (OSNA) systemof 95.0% (95% CI: 75.1–99.9%) and 97.1%(95% CI: 91.8–99.4%), respectively, and validation of the assay against routine histopathological examination revealed a concordance rate of
92.9% (95% CI: 90.1–95.1%), with only four
false-positive cases reported. Unlike the breastlymph node assay (Genesearch™ Breast Lymph
Node Assay [Veridex], Warren, NJ, USA), which
is binary, OSNA is semiquantitative and candifferentiate between macrometastases, micrometastases and isolated tumor cells. This raises
the intriguing possibility that OSNA values may
have independent prognostic significance andmay ultimately permit molecular diagnostics tosupercede histopathology.
Nonetheless, there are lingering concerns
regarding potential false positivity, and eventhe fundamental need for intraoperative nodeassessment has been questioned in a recent editorial by Benson and Wishart, which formed thebasis for a conference presentation [1] . Following
this, a significant proportion of delegates (almosta third) conceded that intraoperative nodal
assessment may not be essential in a modern
10.2217/FON.11.71 © 2011 Future Medicine Ltd

breast practice that incorporates sentinel lymph
node (SLN) biopsy prior to both immediate
breast reconstruction and primary chemo­
therapy (PC), preoperative axillary ultrasound(with or without nodal biopsy) and selectiveomission of completion axillary lymph nodedissection (cALND) in SLN biopsy-positivecases. These factors collectively reduce the absolute numbers of isolated cALNDs, particularly
when up to half of patients have cALND performed alongside definitive or additional breast
surgery. Intraoperative node assessment may
further reduce these low recall rates for isolated
cALND (~10%), but may not be cost-effective
nor logistically feasible within many healthcare
systems [2] .
The role of PET in breast cancer continues
to evolve, but dedicated breast PET scanners
have much improved sensitivity and resolution
compared with conventional whole-body PETcameras. It is unlikely that PET will ever replace
surgery for axillary staging due to innate limitations in resolution at the microscopic level, but
for selective cases of a positive SLN biopsy, anegative PET scan could increase confidence inany decision to omit cALND.
Mitsuhiro Tozaki from the Kameda MedicalCenter, Kamogawa, Japan, reviewed the current status and value of preoperative breast
MRI among Japanese women. MRI hasenhanced sensitivity for the detection of invasive cancer compared with mammography
and is useful for imaging the denser breasts ofyounger women and those with a strong family history of breast cancer. MRI can generate
false-­p ositive results and a degree of ‘overcall’ may have inadvertently increased rates of
Future Oncol. (2011) 7(8), 955–957

Conference Scene

John R Benson

Future Oncology

Diagnosis and local managementof breast cancer: part I

Keywordsn breast cancer n DCIS n MRI
n neoadjuvant therapy n PET
n sentinel nodepart ofISSN 1479-6694

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Bensonmastectomy in recent years [3,4] . Tozaki cautioned against interpretation of results fromthe Comparative Effectiveness of MRI in Breast
Cancer (COMICE) trial that involved a verylarge number of centers and, consequently,
limited individual experience and no MRIguided biopsies [5] . Technological advances have
improved the specificity of MRI and facilitatedmore widespread use of MRI biopsies, butthere are concerns regarding the costs of MRI,
and MRI-guided biopsies take approximately
1 h to perform. MRI has an established rolein evaluating the extent of disease and assessing suitability for breast-conserving surgery(BCS). However, routine preoperative use of
MRI has not been shown to reduce rates of
ipsilateral breast tumor recurrence following
BCS [6] . When nipple-sparing mastectomy isbeing considered, the absence of any enhancement patterns immediately beneath the nipple isreassuring and has a high false-negative predictive value. It was agreed that MRI is generally
poor at predicting residual cancer after PC, andit can be difficult to ascertain from the MRI
images whether a tumor has shrunk concentrically (and hence may be amenable to BCS) or ina ‘dendritic’ (or honeycomb) fashion, whereby
resection of the original tumor bed volume isindicated (and hence mastectomy is more likely
to be the appropriate surgical option dependingon the initial tumor:breast size ratio). The sensitivity and specificity of MRI for the assessmentof pathological complete response is 63.1 and98.5%, respectively. It was concluded that theoverall cost:benefit ratio of MRI in monitor­
ing patients during neoadjuvant therapy andimproving outcomes remains to be established.
John Robertson from Nottingham University,UK, discussed PC from a surgical perspective,
which prompted more questions than answers.
This treatment strategy was originally devisedon the premise that upfront chemotherapy
might improve disease-free and overall survival.
However, clinical trials (including the National
Surgical Adjuvant Breast and Bowel Project[NSABP] B-18) have shown equivalence of outcomes for adjuvant and neoadjuvant regimens.
There is evidence for a survival benefit for thosepatients who receive a complete pathologicaltumor response after chemotherapy. Althoughneoadjuvant trials of chemotherapy have shown
increased rates of BCS, this was not the main
purpose of these trials and indeed BCS wasadopted post-induction chemotherapy without adequate justification from clinical trials.
Within the B-18 trial, 60% of patients receiving
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Future Oncol. (2011) 7(8)postoperative (adjuvant) chemotherapy underwent BCS compared with 68% of those having a preoperative schedule of chemotherapy.
Despite an increase of 8% in the BCS rate, thelocal recurrence rate (ipsilateral breast tumor
recurrence) actually doubled (p < 0.001). Thus,
rates of local relapse are higher for PC, andmany patients in these studies were considered
suitable for BCS even before PC. Robertson
pointed out that few if any neoadjuvant trials
were speci­fically designed to assess local control
as an end point. Any apparent lack of detrimentin terms of long-term survival might be attributable to effective rescue treatments, but could
also be due to a ‘type II error’ due to limited
numbers of patients and length of follow-up. It
can take up to 15 years for local recurrence toimpact on overall survival, and studies of PC andBCS have only 6.5 years of follow-up. An overview of 11 randomized controlled trials foundthat only 18% of patients who were initiallydeemed unsuitable became amenable to BCS
following PC. Moreover, BCS following neoadjuvant treatment was associated with a 50%
increase in risk of local recurrence, which wasinvariably higher in premenopausal women whooften request BCS. This risk of local recurrence
continues to increase for up to 10 years, withestrogen receptor-positive tumors and lobularcancers having much lower response rates toPC compared with estrogen receptor-negative
tumors (5 vs 20%, respectively). For patients
undergoing BCS after PC, it is often unclear
how much tissue should be resected. Should avolume corresponding to the original tumor
size be removed? Basically, we do not know
the answer to this crucial question, for which
there are no data from randomized trials. If atumor shrinks concentrically and appears small(<3 cm) and unifocal on follow-up MRI, thenthe volume of resected tissue should correspondto the final tumor size on imaging. The tumor
bed should be localized with a clip irrespectiveof surgical intent, and when a complete response
has occurred clinically and radiologically, tissue
around the clip (~2 cm radius) should resected.
Ultimately, only pathological examination candetermine whether the whole tumor is likely tohave been resected after BCS.
Robertson cautioned against overinterpretation of the current data and recommended
that issues such as the chance of BCS and local
recurrence risk should be discussed with patientsembarking on neoadjuvant therapy. Randomized
controlled trials are needed in order to elucidate
factors that are predictive of local recurrence,
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Diagnosis & local management of breast cancer: part I

pathological complete response and BCS to facilitate a better understanding of the relationshipbetween local recurrence and overall survival.
Sentinel lymph node biopsies can be carriedout either before or after PC. The former provides potentially valuable information on staging, which may guide subsequent treatment
decisions (e.g., for radiotherapy). Current trends
favor SLN biopsy following PC, for which falsenegative rates are approximately 11% (compar­
able to routine SLN biopsy). Mehra Golshen
from Harvard Medical School, MA, USA,further explored the timing of SLN biopsy inrelation to PC, citing 100% identification rates
when performed before chemotherapy comparedwith 81% post-chemotherapy. Image-guided
node biopsy can be carried out with either core
biopsy or fine needle aspiration cytology andpreferably at the time of breast core biopsy inorder to avoid the possibility of enlarged reactive
nodes being found. Secondary nodal changes
can occur in response to recent breast coreneedle biopsy. Nonetheless, concomitant nodal
Bibliography
1.

2.

Benson JR, Wishart GC. Is intra-operative
nodal assessment essential in a modern breastpractice? Response to correspondence.
Eur. J. Surg. Oncol. 37, 453 (2011).

future science groupassessment is only appropriate when the index
of suspicion for breast malignancy is relatively
high. Patients who are initially node positive(based on either needle core biopsy/fine needle
aspiration cytology or SLN biopsy) shouldhave an ALND after PC. The Z1071 trial isevaluating either SLN biopsy or ALND after
chemotherapy at the time of definitive surgery
and will incorporate lymphedema and qualityof life measurements. A clip can be deployed ina lymph node at the time of biopsy and hence
the response to chemotherapy can be assessed.
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.

3.

Mameri CS, Kemp C, Goldman G et al.
Impact of breast MRI on surgicaltreatment, axillary approach and systemic
therapy for breast cancer. Breast J. 14,236–244 (2008).

4.

Morrow M. Magnetic resonance imaging in
the breast cancer patient: curb yourenthusiasm. J. Clin. Oncol. 26, 352–353(2008).

Benson JR, Wishart GC. Is intra-operative
nodal assessment essential in a modern breastpractice? Eur. J. Surg. Oncol. 36, 1162–1164(2010).

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5.

Turnbull L, Brown S, Harvey I et al.
Comparative effectiveness of MRI in breast
cancer (COMICE) trial: a randomised trial.
Lancet 375, 563–571 (2010).

6.

Solin LJ, Orel SG, Hwang WT et al.
Relationship of breast magnetic resonanceimaging to outcome after breast conservation
treatment with radiation for women withearly stage invasive breast carcinoma or ductalcarcinoma in situ. J. Clin. Oncol. 26, 386–391(2008).

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