Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.

0.23 MB·English

by  Delpech, Y

FULL PAPER
British Journal of Cancer (2013) 108, 285–291 | doi: 10.1038/bjc.2012.557
Keywords: breast cancer; lobular carcinoma; neoadjuvant chemotherapy; pathological complete response;
clinical response; margins
Clinical benefit from neoadjuvant
chemotherapy in oestrogen receptor-positive
invasive ductal and lobular carcinomas
Y Delpech1,2, C Coutant3, L Hsu1, E Barranger2, T Iwamoto1, C H Barcenas4, G N Hortobagyi1, R Rouzier5,
F J Esteva1 and L Pusztai*,1,6
1DepartmentofBreastMedicalOncology,TheUniversityofTexasMDAndersonCancerCenter,Houston,TX,USA;2Department
of Gynecology and Obstetrics, Lariboisiere Hospital, AP-HP, Paris, France; 3Department of Surgical Oncology, Georges
FrancoisLeclercCancerCenter,Dijon,France;4DepartmentofHematologyandOncology,TheUniversityofTexasMDAnderson
CancerCenter,Houston,TX,USA;5DepartmentofGynecologyandObstetrics,TenonHospital,AP-HP,Paris,Franceand6Section
of Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, 333 Cedar Street, PO Box 208032, New Haven,
CT06520-8028, USA
Background:Theaimofthisstudywastocompareclinicalandpathologicaloutcomesafterneoadjuvantchemotherapybetween
oestrogen receptor(ER)-positive invasivepure lobular carcinoma (ILC) andinvasive ductal carcinoma (IDC).
Methods:Thisanalysisincluded1895patients(n¼177ILC;n¼1718IDC),withstageI–IIIbreastcancer,whoreceivedneoadjuvant
chemotherapy.Clinicalandpathologicalresponserates,thefrequencyofpositivesurgicalmarginsandrateofbreast-conserving
surgerywere compared.
Results:TherewasatrendforfewergoodclinicalresponsesinILCcomparedwithIDC.Tumourdownstagingwassignificantlyless
frequent in ILC. Positive or close surgical resection margins were more frequent in ILC, and breast-conserving surgery was less
common(Po0.001).Theseoutcomedifferencesremainedsignificantinmultivariateanalysis,includingtumoursize,nodalstatus,
age,gradeandtypeofchemotherapy.Invasivepurelobularcarcinomawasalsoassociatedwithasignificantlylowerpathological
completeresponse(pCR)rateinunivariateanalysis,butthiswasnolongersignificantafteradjustingfortumoursizeandgrade.
Conclusion: Neoadjuvant chemotherapy results in lower rates of clinical benefit, including less downstaging, more positive
margins and fewer breast-conserving surgeries in ER-positive ILC compared with ER-positive IDC. Pathological complete
responses arerare inboth groups,but donot significantly differ after adjusting forother variables.
Pureinvasivelobularcarcinomas(ILCs)accountfor10–15%ofall margins after breast-conserving surgery (Porter et al, 1999;
breast cancers and are almost invariably oestrogen receptor (ER)- Molland et al, 2004; Waljee et al, 2008; Boughey et al, 2009).
positiveandtendtohavelowhistologicalgrades(gradesIandII) Theratesofpathologicalcompleteresponse(pCR)toneoadjuvant
(Fisher et al, 1975; Wellings et al, 1975; World Health chemotherapy are also significantly lower in ILC compared with
Organisation, 1982). Invasive pure lobular carcinoma is charac- invasive ductal carcinomas (IDCs) (Cristofanilli et al, 2005).
terisedbysmall,roundcellswithscantcytoplasmthatinfiltratethe SeveralinvestigatorshavesuggestedthatILChistologyisarelative
stroma in single files, which makes it more difficult to palpate or contraindication for preoperative chemotherapy because the
detectthistypeofcancerwithmammogram(Katzetal,2007).This expected benefit is modest because of less frequent clinical
histologicalfeaturemayalsoleadtohigherratesofpositivesurgical responses, low pCR rates and more frequent positive surgical
*Correspondence:ProfessorLPusztai;E-mail:[email protected]
Received24August2012;revised19November2012;accepted20November2012;publishedonline8January2013
&2013CancerResearchUK.Allrightsreserved0007–0920/13
www.bjcancer.com|DOI:10.1038/bjc.2012.557 285
BRITISHJOURNAL OF CANCER Neoadjuvanttherapy of ILC andIDC
margins(Katzetal,2007;Bougheyetal,2009;Purushothametal, PR and HER2 measurements (World Health Organisation, 1982).
2010). Oestrogen receptor and PR positivity were defined as nuclear
Comparing outcomes between ILC and IDC in general has staining X10% and HER2 positivity was defined as 3þ staining
substantial limitations because of the uneven distribution of on immunohistochemistry or gene amplification by FISH.
confounders, including histological grade and ER status between Histological grade was assessed following the modified Black’s
these two distinct histological subtypes. The question whether nuclear grading system.
histology itself, after adjusting for differences in grade and ER, After completion of neoadjuvant chemotherapy, 1827 (96.4%)
remains a predictor of lower response rates and higher rates of patients underwent primary breast surgery and 1826 (96.5%) had
positivemarginsremaincontroversial.Previousstudiesperformed axillary lymph node staging (level I and II dissection or sentinel
multivariate analysis to address this question and most results lymph node biopsy). If invasive or in situ carcinomas were seen
suggestedthathistologyremainsanimportantindependentfactor. within 2mm of the surgical margin on microscopic examination
However, Boughey et al (2009) and Wagner et al (2009) reported (i.e. positive or close tumour margins), a second operation was
frequent clinical responses in ILCs to preoperative chemotherapy performed to achieve clear margins. Pathological complete
and margin positivity rates after breast-conserving surgery were response was defined as no evidence of invasive carcinoma in
similar between patients who received neoadjuvant chemotherapy the breast and axillary lymph nodes.
and those who did not. In this study, we compare rates of
Statistical analysis. The w2 test (or Fisher’s exact test when the
pathological response, surgical margin status and rates of breast-
sample size was small) was used to evaluate associations between
conservingsurgerybetweenER-positiveILCandIDCthatreceived
categorical variables and histological subtype. The Student’s t-test
neoadjuvant chemotherapy. We excluded ER-negative tumours
was used for continuous variables. We also performed stratified
from the analysis to eliminate an important confounder.
analysisbyhistologicalgrade(gradeI/IIvsIII).Univariatelogistic
regressionswereperformed,includinghistologicalsubtype,nuclear
grade, nodal status tumour size, multifocality, age, race, meno-
PATIENTS ANDMETHODS
pausal status, HER2 status, Ki-67 score and the type of
neoadjuvant chemotherapy as variables to identify predictors of
Patientpopulation. Patientswereidentifiedforthisstudyfroma
breast-conserving therapy, positive margins and pCR. From this
prospectively maintained clinical database of the University of
model,anoddsratio(OR)foreachvariablewasdeterminedwitha
Texas MD Anderson Cancer Centre. Patients were selected for
95% confidence interval (CI). All significant variables from the
inclusion if they had ER-positive stage I–III breast cancer
univariate analysis were included in a subsequent multivariate
diagnosed between 1990 and 2010 and received neoadjuvant
analysis. Median overall survival and distant disease-free survival
chemotherapy. This search initially identified 2592 patients. After
were determined using the Kaplan–Meier methods. All analyses
reviewing the medical records, the following patients were
were performed using R package with Survival, Design, Hmisc,
excluded: male breast cancer (n¼12), patients with axillary
Rpart and Lexis libraries (http://lib.stat.cmu.edu//R/CRAN/).
metastasis without an identifiable primary breast tumour
(n¼13), metastatic disease at diagnosis (n¼13), patients who
received preoperative radiation therapy alone (n¼10) or under-
RESULTS
went partial excisional biopsy before neoadjuvant chemotherapy
(n¼214). We also excluded patients with rare or mixed
PatientcharacteristicsaresummarisedinTable1:177patientshad
histological subtypes (n¼224) to focus on the comparison of
ILC (9%), and 1718 patients had IDC (91%). Patients with ILC
pure lobular vs pure ductal carcinomas. Patients with over-
were older, had larger and lower grade (grades I/II) tumours and
expression of human epidermal growth factor receptor-2 (HER2)
had fewer HER2-positve cancers compared with IDC. Anthracy-
were also included. Review of medical records also revealed
cline-based or taxane and anthracycline combination regimens
miscoding of ER and progesterone receptor (PR) results in 21
were used equally frequently in both histological groups, but
patientswhohadhormonereceptor-negativebreastcancerandin
trastuzumab use was more common in IDC (Table 1).
189 patients who received neoadjuvant endocrine therapy alone.
Significantdownstagingwasobservedinbothhistologicaltypes
A total of 1895 patients were included in the final analysis
(Supplementary Figure 1). (Po0.0001)(SupplementaryFigure2A),butitwasmorecommon
amongIDC.Forty-onepercentofILCshadlowertumourTstage
The patients received neoadjuvant chemotherapy with anthra-
after neoadjuvant chemotherapy compared with baseline, whereas
cycline-based regimen (n¼236), with a taxane-based regimen
(n¼137) or with a combination of an anthracycline and taxane similar downstaging occurred in 64% of IDCs (Po0.0001)
(Supplementary Figure 2B).
(n¼1515);263patientsalsoreceivedtrastuzumabincombination
Positive or close surgical resection margins were significantly
with neoadjuvant chemotherapy. Postoperatively, 451 patients
more frequent in ILC patients (19 vs 11%; P¼0.001) and this
(24%) received adjuvant chemotherapy and 1522 (81%) received
remained significant even after multivariate analysis, including
adjuvanthormonaltherapy.TheInstitutionalReviewBoardofthe
tumour size and grade (OR¼1.82; 95% CI, 1.13–2.93; P¼0.01).
University of Texas MD Anderson Cancer Centre (MDACC) in
At the end, breast-conserving surgery was less frequent in ILC
Houston approved this study.
patientsthaninIDCpatients(19vs34%;Po0.001)(Table2)and
Assessment of clinical and pathological outcomes. The pre- histology remained an independent predictor of mastectomy
treatment tumour size was determined by physical examination (OR¼1.86; 95% CI, 1.15–2.99; P¼0.01) even after adjusting for
andmammography.Ifthetwomethodsyieldeddiscordantresults, age, tumour grade, initial tumour size, multifocality, nodal status
the radiological measurement was used as the tumour’s size. Pre- and clinical stage (Table 3).
treatmentlymphnodestatuswasevaluatedwithacombinationof Invasive lobular histologywasalso associatedwithsignificantly
clinical and ultrasonographic examination. If ultrasonogram lower pCR rates (3.5 vs 14%; Po0.001) (Table 2). In univariate
showed suspicious lymph nodes, a diagnostic fine-needle aspira- analysis, multifocal tumour, higher tumour size, node-positive
tion was performed. Post-treatment, residual cancer size was status and lower nuclear grade were also significantly associated
determined by pathological examination. All outside pathology withlowerpCRrates.Inmultivariateanalysis,includingtheabove
reportsandslideswerereviewedbyadedicatedbreastpathologist variables, histology was no longer significant (Table 4). Similarly,
atMDACCtoconfirmdiagnosisandtoassesstheadequacyofER, in an analysis stratified by grade, pCR rates were no longer
286 www.bjcancer.com|DOI:10.1038/bjc.2012.557
Neoadjuvanttherapy of ILCandIDC BRITISH JOURNALOF CANCER
Table1.Patientdemographicandtreatmentclinicalcharacteristics
ILC(n¼177) IDC(n¼1718)
Demographicorclinicalcharacteristics No.ofpatients % No.ofpatients % v2P-value
Age(years)
Median 54 50 o0.001
Range 35–62 21–83
Race
Asian 6 3 96 6 0.51
Black 19 11 223 13
White 150 85 1375 80
Other 2 1 24 1
Menopausalstatus
Yes 114 64 899 52 0.003
Concurrentbilateralbreastcancer
Yes 16 9 74 4 0.008
Tumoursize(cm)
Median 4.5 3.4 o0.001
Range 0.4–12 0.4–20
Multifocaltumour
Yes 42 24 326 19 0.1
Tstage
T1–2 99 56 1187 69 o0.001
T3–4 78 44 529 31
Nstage
N1orsup 102 58 1089 63 0.15
AJCCstage
I/II 111 63 1076 63 0.94
III/IV 66 37 641 37
HER2status
Negative 84 47 793 46 0.006
Positive 13 7 288 17
Nucleargrade
I–II 145 82 722 42 o0.001
III 24 14 980 57
Ki-67scorea
o20 48 27 224 13 o0.001
X20 28 16 518 30
Neoadjuvantchemotherapyregimenb
Anthracyclineandtaxanebased 137 77 1378 80 0.4
Anthracycline-basedonly 27 15 209 12 0.5
Taxane-basedonly 13 7 124 7 1
Trastuzumab 9 5 254 15 o0.001
Neoadjuvanthormonotherapyincombinationwithchemotherapy 3 2 54 3 0.4
Adjuvantchemotherapy 32 18 419 24 0.07
Adjuvanthormonotherapy 146 82 1382 80 0.6
Adjuvantradiotherapy 146 82 1311 76 0.08
Abbreviations:A¼adriamycin;AJCC¼AmericanJointCommitteeonCancer;C¼cyclophosphamide;E¼epirubicin;F¼5-fluorouracil;H¼herceptin;HER2¼humanepidermalgrowth
factorreceptor2;IDC¼invasiveductalcarcinoma;ILC¼invasivelobularcarcinoma;T¼taxane.
aKi-67scorewereavailablein76patientsinILCgroupandin742IDCgroup.
bThemostcommonregimenconsistedofT,F,AorEandC(T/FACorFEC),n¼1106;FACorFEC,n¼230;FACorFEC±HandTH(TH/FACorFEC±H),n¼218;ETorAT,n¼74;Talone,
n¼91.
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BRITISHJOURNAL OF CANCER Neoadjuvanttherapy of ILC andIDC
significantly different between ILC and IDC (Supplementary
DISCUSSION
Table 1).
Disease-free survival andoverallsurvivalwereevaluatedwitha
medianfollow-uptimeof44months(range,1–221months).Inall, We examined if patients with pure ILC benefit differently from
290 patients had developed a recurrence (222 distant recurrences neoadjuvant chemotherapy than patients with IDC. Approxi-
only, 19 local recurrences only, 49 distant and local recurrences), mately, 30–40% of IDCs are ER-negative and these cancers have
and 262 had died. Histological type was not associated with different chemotherapy sensitivity and clinical behaviour com-
significant difference in overall survival (hazard ratio¼1.01; 95% pared with ER-positive IDCs (Arpino et al, 2004; Rouzier et al,
CI, 0.7–1.47; P¼0.9), disease-free survival (hazard ratio¼0.92; 2005).Previousstudiestriedtoadjustforthevariabledistribution
95% CI, 0.66–1.28; P¼0.13) (Figure 1) or local recurrence-free of ER status by performing multivariate analysis. However,
survival (hazard ratio¼0.8; 95% CI, 0.36–1.90; P¼0.65) multivariateanalysishaslimitationsparticularlywhenconfounders
(Supplementary Figure 3). are only partially independent (Katz, 2003). In this study, we
excluded ER-negative IDCs from the current analysis to address
directly whether histology confers significant differences in
sensitivitytoneoadjuvantchemotherapy.Chemotherapysensitivity
Table2.Surgicalandpathologicaloutcomes
was measured by pathological tumour response rates and therate
of breast-conserving surgery.
ILC(n¼177) IDC(n¼1718) Similartopreviousreports,weobservedlowpCRratesinboth
histological subtypes, IDC (14%) and ILC (3.5%) (Cocquyt et al,
No.of % No.of % v2P-value 2003; Mathieu et al, 2004; Cristofanilli et al, 2005; Tubiana-Hulin
patients patients etal,2006;Katzetal,2007;SullivanandApple,2009;Huoberetal,
2010; Straver et al, 2010). However, pCR rates were not
Finalsurgicaloutcome
significantly different by histological type after adjusting for
Conservative 33 19 576 34 o0.001 differences in tumour grade. This is different from earlier reports
Mastectomy 139 79 1078 63 that suggested significantly lower pCR rates in ILC. Our results
Nosurgery 5 3 64 4 show that low- and intermediate-grade ILC and IDC both have
similar, very low pCR rates. This result supports the idea that
Pathologicalresponse
response to neoadjuvant chemotherapy in terms of pCR is more
NopCR 165 93 1404 82 o0.001 relatedtointrinsictumourcharacteristics,reflectedtosomeextent
pCR 6 3 246 14 in grade than histology itself (Lips et al, 2012). Pathological
completeresponseisapowerfulearlysurrogateofgoodsurvivalin
Abbreviations:IDC¼invasiveductalcarcinoma;ILC¼invasivelobularcarcinoma;pCR¼
ER-negativeandHER2-positivecancers,butitsprognosticvalueis
pathologicalcompleteresponse.
less important in ER-positive cancers because many patients with
Table3.Predictorsofmastectomyafterneoadjuvantchemotherapy
Univariateanalysis Multivariateanalysis
Factor ORa 95%CI P-value ORa 95%CI P-value
Age(years) 0.99 0.98–1.00 0.02 0.99 0.98–1.00 0.02
Multifocaltumour o0.001
No 1.00 — — 1.00 — —
Yes 4.6 3.28–6.46 3.85 2.70–5.48 o0.001
Tumoursize(cm) 1.42 1.33–1.51 o0.001 1.30 1.21–1.40 o0.001
Nstage
N0 1.00 — — 1.00 — —
N1orsup 2.03 1.66–2.48 o0.001 1.39 1.09–1.77 0.007
AJCCstage
I/II 1.00 — — 1.00 — —
III/IV 3.51 2.78–4.41 o0.001 1.89 1.41–2.54 o0.001
Nucleargrade
I 1.00 — — 1.00 — —
II 0.81 0.47–1.37 0.43 1.43 0.75–2.69 0.27
III 0.51 0.35–1.00 0.05 0.85 0.44–1.62 0.61
Histologicalsubtype
IDC 1.00 — — 1.00 — —
ILC 2.25 1.52–3.33 o0.001 1.86 1.15–2.99 0.01
Abbreviations:AJCC¼AmericanJointCommitteeonCancer;CI¼confidenceinterval;IDC¼invasiveductalcarcinoma;ILC¼invasivelobularcarcinoma;OR¼oddsratio.
aOR¼1isthereference;ORo1,factorassociatedwithlowermastectomyrate;OR41,factorassociatedwithhighermastectomyrate.
288 www.bjcancer.com|DOI:10.1038/bjc.2012.557
Neoadjuvanttherapy of ILCandIDC BRITISH JOURNALOF CANCER
Table4.Predictorsofpathologicalcompleteresponse
Univariateanalysis Multivariateanalysis
Factor ORa 95%CI P-value ORa 95%CI P-value
Age(years) 0.99 0.98–1 0.2 1 0.99–1.01 0.8
Multifocaltumoura
No 1.00 — — 1.00 — —
Yes 0.69 0.48–1 0.05 0.75 0.5–1.12 0.15
Nucleargrade
I 1.00 — — 1.00 — —
II 4.91 0.67–36.14 0.1 2.91 0.38–22.56 0.31
III 20.33 2.81–147.17 0.002 11.26 1.47–86.39 0.01
BaselineTstage
T1–T2 1.00 — — 1.00 — —
T3–T4 0.69 0.51–0.93 0.01 0.65 0.46–0.92 0.01
BaselineNstage
N0 1.00 — — 1.00 — —
N1orsup 0.73 0.56–0.96 0.02 0.66 0.49–0.9 0.008
Histologicalsubtype
IDC 1.00 — — 1.00 — —
ILC 0.21 0.09–0.47 o0.001 0.5 0.19–1.3 0.1
Neoadjuvantchemotherapyregimen
Taxanebasedb 2.67 1.56–4.59 o0.001 2.14 1.2–3.84 0.01
Traztuzumabc 6 4.44–8.12 o0.001 5.03 3.64–6.95 o0.001
Abbreviations:CI¼confidenceinterval;IDC¼invasiveductalcarcinoma;ILC¼invasivelobularcarcinoma;OR¼oddsratio;pCR¼pathologicalcompleteresponse.
aOR¼1isthereference;ORo1,factorassociatedwithlowerpCRrate;OR41,factorassociatedwithhigherpCRrate.
bTaxane-basedregimenwascomparedwithnotaxane-basedregimen.
cTrastuzumabregimenwascomparedwithnotrastuzumabregimen.
A B
1.0 1.0
y
bility 0.8 babilit 0.8
a o
prob 0.6 al pr 0.6
Overall survival 00..24 P=0.9 ease free surviv 00..24 P=0.13
s
Invasive lobular carcinoma Di Invasive lobular carcinoma
Invasive ductal carcinoma Invasive ductal carcinoma
0.0 0.0
0 12 24 36 48 60 72 84 96 108 120 0 12 24 36 48 60 72 84 96 108 120
Months from diagnosis Months from diagnosis
Figure1.(A)Overallsurvivalprobabilityand(B)disease-freesurvivalprobabilitybyhistologicalsubtype.
extensive residual cancer continue to do well probably because of recurrencerateswoulddiffersignificantlybyhistologyamongER-
thebenefitfromadjuvantendocrinetherapy(vonMinckwitzetal, positive cancers.
2012). Our findings confirm that survivals were similar for both An important clinical benefit from neoadjuvant chemotherapy
ER-positiveIDCandILC.Werecognisethatamedianfollow-upof is clinical tumour response that leads to downstaging and smaller
44 months is short for ER-positive breast cancers, which is a surgicalresectionvolume(Fisheretal,1998;Bougheyetal,2006).
limitation of the current analysis. However, it is unlikely that late Tumourresectionmarginsweremorecommonlypositiveorclose
www.bjcancer.com|DOI:10.1038/bjc.2012.557 289
BRITISHJOURNAL OF CANCER Neoadjuvanttherapy of ILC andIDC
(p2mm) in ILC (19 vs 11%) and the rate of breast-conserving KuererHM(2006)Impactofpreoperativeversuspostoperative
surgery was also lower (19 vs 34%). These differences in clinical chemotherapyontheextentandnumberofsurgicalproceduresinpatients
benefit remained significant after adjusting for other clinical treatedinrandomizedclinicaltrialsforbreastcancer.AnnSurg244(3):
variables,includinggradeandtumoursize.Theseobservationsare 464–470.
consistentwiththemajorityoftheliteraturethatreportslowrates BougheyJC,WagnerJ,GarrettBJ,HarkerL,MiddletonLP,BabieraGV,
Meric-BernstamF,LucciA,HuntKK,BedrosianI(2009)Neoadjuvant
of breast conservation therapy for patients with ILC following
chemotherapyininvasivelobularcarcinomamaynotimproveratesof
neoadjuvant chemotherapy (Soucy et al, 2008; Boughey et al,
breastconservation.AnnSurgOncol16(6):1606–1611.
2009). These results collectively indicate that clinical benefit from
CataliottiL,BuzdarAU,NoguchiS,BinesJ,TakatsukaY,PetrakovaK,Dube
neoadjuvant chemotherapy in operable ER-positive ILC is less
P,deOliveiraCT(2006)Comparisonofanastrozoleversustamoxifenas
compared with ER-positive IDCs due to the inherently lower preoperativetherapyinpostmenopausalwomenwithhormonereceptor-
chemotherapy sensitivity of these cancers and their unique positivebreastcancer:thePre-Operative‘Arimidex’Comparedto
anatomicalfeatures,whichmakedeterminationofcancermargins Tamoxifen(PROACT)trial.Cancer106(10):2095–2103.
more difficult intraoperatively. CocquytVF,BlondeelPN,DepypereHT,PraetMM,SchelfhoutVR,SilvaOE,
OurstudyisthelargestreportofoutcomesofILCsubtypeafter HurleyJ,SerreynRF,DaemsKK,VanBelleSJ(2003)Differentresponses
neoadjuvant chemotherapy, but there were some limitations. As a topreoperativechemotherapyforinvasivelobularandinvasiveductal
retrospective survey there was heterogeneity in our population, breastcarcinoma.EurJSurgOncol29(4):361–367.
CristofanilliM,Gonzalez-AnguloA,SneigeN,KauSW,BroglioK,Theriault
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RL,ValeroV,BuzdarAU,KuererH,BuccholzTA,HortobagyiGN(2005)
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Invasivelobularcarcinomaclassictype:responsetoprimary
available. However, nuclear grade may be considered as a crude
chemotherapyandsurvivaloutcomes.JClinOncol23(1):41–48.
surrogate for proliferation activity.
EiermannW,PaepkeS,AppfelstaedtJ,Llombart-CussacA,EreminJ,
However, a simple conclusion that ILC does not respond to VinholesJ,MauriacL,EllisM,LassusM,Chaudri-RossHA,DuganM,
neoadjuvantchemotherapywouldrepresentanoversimplification. BorgsM(2001)Preoperativetreatmentofpostmenopausalbreastcancer
Forty-one per cent of ILCs had lower tumour T stage compared patientswithletrozole:arandomizeddouble-blindmulticenterstudy.Ann
with baseline after neoadjuvant chemotherapy. What further Oncol12(11):1527–1532.
complicates clinical decision-making for patients with ILC is that EllisMJ,SumanVJ,HoogJ,LinL,SniderJ,PratA,ParkerJS,LuoJ,
clinical response rates over 50% have also been reported with the DeSchryverK,AllredDC,EssermanLJ,UnzeitigGW,MargenthalerJ,
use of 3–6 months of neoadjuvant endocrine therapy alone BabieraGV,MarcomPK,GuentherJM,WatsonMA,LeitchM,HuntK,
OlsonJA(2011)RandomizedphaseIIneoadjuvantcomparisonbetween
(Eiermannetal,2001;Cataliottietal,2006;Semiglazovetal,2007;
letrozole,anastrozole,andexemestaneforpostmenopausalwomenwith
Mlineritschetal,2008;Mustacchietal,2009;Ellisetal,2011).In
estrogenreceptor-richstage2to3breastcancer:clinicalandbiomarker
addition, the majority of patients with ILC have a low or
outcomesandpredictivevalueofthebaselinePAM50-basedintrinsic
intermediate recurrence score (Oncotype DX, Redwood, CA,
subtype–ACOSOGZ1031.JClinOncol29(17):2342–2349.
USA), which is associated with no or very modest benefit from FisherB,BryantJ,WolmarkN,MamounasE,BrownA,FisherER,
adjuvantchemotherapyintermsofimprovedsurvival(Kellyetal, WickerhamDL,BegovicM,DeCillisA,RobidouxA,MargoleseRG,Cruz
2010; Mook et al, 2010; Allison et al, 2012). Taking all this Jr.AB,HoehnJL,LeesAW,DimitrovNV,BearHD(1998)Effectof
information together, it is reasonable to conclude that most preoperativechemotherapyontheoutcomeofwomenwithoperable
patients with ILC are unlikely to derive substantial short-term breastcancer.JClinOncol16(8):2672–2685.
clinicalbenefit(substantialtumourreductionwithclearmarginsor FisherER,GregorioRM,FisherB,RedmondC,VelliosF,SommersSC(1975)
pathological CR) from neoadjuvant chemotherapy. However, ILC Thepathologyofinvasivebreastcancer.Asyllabusderivedfromfindings
oftheNationalSurgicalAdjuvantBreastProject(protocolno.4).Cancer
may derive similar long-term survival benefit from neoadjuvant
36(1):1–85.
chemotherapy as ER-positive IDCs, but this benefit is likely to be
HuoberJ,vonMinckwitzG,DenkertC,TeschH,WeissE,ZahmDM,BelauA,
modest.
KhandanF,HauschildM,ThomssenC,HogelB,Darb-EsfahaniS,Mehta
K,LoiblS(2010)Effectofneoadjuvantanthracycline-taxane-based
chemotherapyindifferentbiologicalbreastcancerphenotypes:overall
ACKNOWLEDGEMENTS resultsfromtheGeparTriostudy.BreastCancerResTreat124(1):133–140.
KatzA,SaadED,PorterP,PusztaiL(2007)Primarysystemicchemotherapy
Funding Support, Grants from ‘La Fondation de France’ and ofinvasivelobularcarcinomaofthebreast.LancetOncol8(1):55–62.
KatzMH(2003)Multivariableanalysis:aprimerforreadersofmedical
‘La Fondation pour la Recherche Me´dicale’ was provided to Yann
research.AnnInternMed138(8):644–650.
Delpech, and Lajos Pusztai was supported by the Breast Cancer
KellyCM,KrishnamurthyS,BianchiniG,LittonJK,Gonzalez-AnguloAM,
Research Foundation.
HortobagyiGN,PusztaiL(2010)UtilityofoncotypeDXriskestimatesin
clinicallyintermediateriskhormonereceptor-positive,HER2-normal,
gradeII,lymphnode-negativebreastcancers.Cancer116(22):5161–5167.
CONFLICT OF INTEREST LipsEH,MukhtarRA,YauC,deRondeJJ,LivasyC,CareyLA,LooCE,
Vrancken-PeetersMJ,SonkeGS,BerryDA,Van’tVeerLJ,EssermanLJ,
WesselingJ,RodenhuisS,ShelleyHwangE(2012)Lobularhistologyand
The authors declare no conflict of interest.
responsetoneoadjuvantchemotherapyininvasivebreastcancer.Breast
CancerResTreat136(1):35–43.
MathieuMC,RouzierR,Llombart-CussacA,SiderisL,KoscielnyS,Travagli
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