Journal of Cancer and Clinical Oncology

Vol. 3(1), pp. 024-030, February, 2019. © www.premierpublishers.org. ISSN: 5907-4449

Research Article

A Novel Immunohistochemical Signature with the Quantification of

HER2 Predicts the Complete Response in HER2-Positive Breast
Cancer
Anna Novell (PhD)1, Maria Alba Sorolla (PhD)1, Silvia Bielsa (MD, PhD)1,2, Gisela Urgel1,3, Joel
Veas (MD)3 and Antonieta Salud (PhD; MD)1,3
1ResearchGroup of Cancer Biomarkers (GReBiC), IRBLleida, Lleida, Spain
2Pleural
Medicine Unit, Department of Internal Medicine, Arnau de Vilanova University Hospital, Lleida, Spain
3Department of Medical Oncology, Arnau de Vilanova University Hospital, Lleida, Spain

Around 30% of HER2-positive breast cancer patients do not respond to neoadjuvant

chemotherapy (NAC) and anti-HER2 drugs. It is necessary to improve the selection system of
patients who will benefit from this treatment, with others biomarkers that could also predict the
response. HER2, ki67, ER, PR, LC45 and the HER family were quantified by immunochemistry in
HER2+ breast tumors from 99 patients treated with NAC and anti-HER2 drugs. The correlation
between the expression of these proteins and the response rate was evaluated through both an
area under the ROC curve and a logistic regression model analysis. HER2 score 3+ is a poor
predictive biomarker to NAC with anti-HER2 drugs, with an area under the ROC curve (AUC ROC)
HER2 score 3+ of 0.719. HER2 score 2+ with a curve of 0.438, is not associated with a response rate of
treatment. The optimal HER2 score 3+ cutoff point has been proven to yield 21% in HER2-enriched
tumors and 10% in HER2-luminal ones. The signature (AUC=0.809) formed by a high percentage
of HER2 score 3+, a high percentage of Ki67, a low Histo-score of ER and the absence of
involvement lymph nodes is a better predictive combination for response than HER2 score 3+
alone. HER2 status is a poor clinical biomarker. Our proposed signature will improve the selection
of patients who benefit from the neoadjuvant treatment.

Keywords: breast cancer, HER2 score 3+, predictive biomarker, trastuzumab, neoadjuvant chemotherapy.

ABBREVIATIONS

AUC = area under the ROC curve; BC= breast cancer; CI= confidence interval; ER= estrogen receptor; Hsc= histo-score;
IHC= immunohistochemistry; HER2+BC= HER2-positive Breast Cancer; LC45= leucocyte common 45; NAC=
neoadjuvant chemotherapy; O-R= odds-ratio; pCR= pathological complete response; PR= progesterone receptor; Se=
sensitivity; Sp= Specificity; TIL= tumor infiltrating lymphocytes

INTRODUCTION

Trastuzumab is effective in the treatment of HER2-positive
breast cancer (HER2+BC), but not all patients benefit from
it. Useful and robust biomarkers need to be identified in
order to select the most suitable anti-HER2 therapy for
every individual tumor feature. These biomarkers help to
decide the precise treatment for each patient and avoid
over-treatment.
HER2 status is an established biomarker used to select
the patients who will benefit from anti-HER2 therapy. This
therapy consists of chemotherapy combined with
trastuzumab or with a dual HER2 blockade (trastuzumab
in combination with either pertuzumab or lapatinib). In the
adjuvant setting, this therapy has improved patient
prognosis, increasing disease-free survival in 40-50% and
decreasing the dying risk in 33% (Triulzi et al. 2016). In
addition, around 60-70% of the pathological complete
response (pCR) rate has been achieved in the
neoadjuvant setting (Siravegna et al. 2017).

A Novel Immunohistochemical Signature with the Quantification of HER2 Predicts the Complete Response in HER2-Positive Breast Cancer
Novell et al. 025
HER2 expression status is mainly determined by
immunohistochemistry (IHC). The American Society of
Clinical Oncology (ASCO)/ the College of American
Pathologists (CAP) guidelines have defined three different
categories related to HER2 expression: a) Negative with
IHC 0 or 1+, b) Equivocal with IHC 2+ and c) Positive with
IHC 3+. ASCO/CAP 2013 recommendations consisted of
establishing HER2 positivity or IHC 3+ when tumors
exhibited at least 10% of the cells with intense complete
membrane staining (Wolff et al. 2018).
There is an increasing body of evidence indicating that the
simple detection of HER2 status seems insufficient to
predict patients who will benefit from anti-HER2 therapy.
Previous studies suggested that it is necessary to combine
the expression of HER2 with other biomarkers. Recently,
there are some biomarkers that have been described as
being implicated in the response grade of trastuzumab and
the different mechanisms of resistance to it (Pogue-Geile
et al. 2013).
On the one hand, it is necessary to find robust biomarkers
in the neoadjuvant setting, in order to stratify subjects who
are most likely to benefit from anti-HER2 therapy. A better
patient selection would limit the risk of side effects and
overtreatment, improving the outcome of all patients with
early-stage HER2+ BC (Nuciforo et al. 2015; Di Modica et
al. 2017; Varadan et al. 2016). On the other hand, the
accepted conclusion that “more HER2, more response” is
not clear. In fact, there are patients with high HER2
expression who do not obtain a good response (Joensuu
et al. 2011; Gullo et al. 2009).
The aim of our study was the assessment of the predictive
value of HER2 alone and together with other biomarkers
to predict the response rate when using a combination of
NAC and anti-HER2 therapy.
METHODS
Patients
A total of 99 patients, diagnosed with HER2+ BC and
treated at the Arnau de Vilanova University Hospital
(Lleida, Spain), collected from January 2010 to December
2017. The majority of patients were subjected to standard
preoperative treatment, consisting of one term of 4 cycles
of both anthracyclines and cyclophosphamide followed by
4 cycles of both taxanes and anti-HER2 drugs. The rest
were only treated with the combination of taxanes and anti-
HER2, due to treatment toxicity. Trastuzumab was the
anti-HER2 drug of choice in the majority of patients,
whereas the dual HER2 blockade was applied to the rest.
Patient response to treatment was evaluated according to
Miller-Payne classification. A complete response was
considered to be grade 4 (isolated tumor cell nests) and 5
(absence of tumor cells). Grades ranging from 1 to 3 (more
than 20% residual tumor) meant lack of response to the
neoadjuvant treatment.
A Novel Immunohistochemical Signature with the Quantification of HER2 Predicts the Complete Response in HER2-Positive Breast Cancer
Standardized surgery was performed after approximately
6 weeks of neoadjuvant chemotherapy (NTC). The
adjuvant radiotherapy (AR) was administered in the
patients subjected to conservative surgery in both breast
and tumoral bed. The axilla was treated with AR in those
patients having more than 3 involved nodes. Both axilla
and chest wall received AR when tumors were larger than
5 cm. Additionally, the patients with HER2-luminal tumors
received adjuvant hormonotherapy treatment. The
adjuvant anti-HER2 drugs were administered in every
patient of this study.
Follow-up time was calculated from the date of tumor
resection up to the date of death, or up to the last visit for
surviving patients. The last follow-up recording was
conducted in August 2018.
Immunohistochemical analysis
Formalin-fixed and paraffin-embedded breast tumors were
cut into 3 µm slices and dried 1h at 65°C. Sections were
dewaxed in xylene and rehydrated by decreasing the
concentrations of ethanol, and washed with PBS. Then,
slides were subjected to antigen retrieval for all antibodies
through heat treatment at 95°C for 20 min in buffer
(DAKO). Before staining, endogenous peroxidases were
blocked. Primary antibodies were: Ki67 (ready-to-use;
MIB; DAKO); Estrogen receptor (ER) (ready-to-use; 1D5;
DAKO); Progesterone Receptor (PR) (ready-to-use;
PgR636; DAKO); HER2 (Herceptest kit; Dako); EGFR
a(1/100; H11; DAKO); HER3 (1/50, DAK-H3-IC; DAKO) ;
HER4 (1/100, 111B2, Cell Signaling) and Leucocyte
Common 45 (LC45) (ready-to-use, PD7/26 + 2B11,
DAKO). Anti-LC45 recognizes both B and T lymphocytes,
as an indicator to tumor-infiltrating lymphocytes (TIL).
For all of these antibodies, the reaction was visualized with
Envision Flex (Dako). Sections were counterstained with
hematoxylin. Finally, in order to determine the specificity of
the immunostaining, primary lung cancer was used as a
positive control. As a negative control, the primary
antibody was omitted, replaced by non-immune serum.
Immunohistochemical (IHC) staining were evaluated and
scored independently by two investigators who reached, in
case of discrepancy, a final decision by consensus. The
immunostaining of each protein was scored using different
criteria. Ki67 and LC45 were calculated though the
percentage of staining nuclei. ER and PR were evaluated
though nuclear Histo-score (Hsc). Membrane EGFR and
HER4 were quantified for the percentage of membrane
staining. Cytoplasmic and nuclear HER3 and HER4 were
determined through Hsc. Finally, HER2 scores were
obtained by averaging 3 fields at 40x magnification, where
the percentage of stained tumoral cells over counted total
cells was considered. Specifically, score 2+ and score 3+
refers to moderate and strong complete membrane
staining, respectively.

Hsc provides semi-quantitative measurements of protein
expression by taking into consideration both the
percentage of positive cells and the intensity of their
staining. An Hsc ranges from 0 (no immune reaction) to
300 (maximal immunoreactivity).
Statistical analysis
Continuous and categorical variables were presented as
medians (25 – 75 quartiles) and number (percentages),
respectively. Between-group comparisons (responder and
non-responder tumor patients) were performed with the
Fisher’s exact and Mann-Whitney tests. Receiver
operating characteristic (ROC) curves assisted in the
selection of the best discriminating cut-off points of
expression proteins for predicting a complete response.
Measures of test efficacy included sensitivity and
specificity. For comparisons of AUC the Hanley & McNeil
method was used. To adjust for confounders, a backward
conditional stepwise logistic regression model estimated
the impact of each predictor of complete response;
variables which showed statistical significance in the
bivariate analysis were entered into the multivariate model.
Statistical significance was established at p<0.05.
Analyses were performed using SPSS version 24.0
(Statistical Package for the Social Sciences Inc, Chicago,
IL, USA) and for AUC comparisons with Epidat version 3.1
(Xunta de Galicia, Spain).
RESULTS
Clinical and pathological characteristics between
groups of responder and non-responder to
neoadjuvant treatment in HER2+BC
A total of 99 patients with a median age of 56 years (25
and 75 quartiles 47-69 years) were studied. The median
tumor sizes at diagnosis and after treatment were 3 cm (25
and 75 quartiles 0 - 8.6 cm) and 0 cm (25 and 75 quartiles
0 -6 cm), respectively. Approximately, half of the patients
had affected lymph nodes at diagnosis. The median follow-
up time was 29 months (ranging from 5 to 137) and there
were 9 metastatic events and 4 deaths reported. The
clinical characteristics of the patients are summarized in
Table 1.
The complete response to NAC with anti-HER2 therapy
was seen in 66.7% (grade 4 and 5; N=60) and a poor
response in 33.3% (grades ranging from 1 to 3; N=39).
According to Her2 intrinsic subtypes, 44% of tumors were
Her2-enriched and 56% were Luminal-Her2. The complete
response rate was significantly higher in HER2-enriched
than in HER2-Luminal. Nevertheless, the rate of
recurrences and deaths were higher in those which were
HER2-enriched. In particular, the 4 dead patients were
HER2-enriched, and half of these were responder tumors.
A Novel Immunohistochemical Signature with the Quantification of HER2 Predicts the Complete Response in HER2-Positive Breast Cancer
J. Cancer Clin. Oncol. 026
Related to treatment types, no differences were observed
in the complete response rate according to the regimen of
chemotherapy or anti-HER2 therapy types administered.
Determination of predictive HER2 value in response to
neoadjuvant treatment in HER2+BC
HER2 score 3+ had an AUCROC of 0.719, being
significantly higher than HER2 score 2+. The AUCROC of
HER2 score 2+ was of 0.438, not being associated with
the response grade. AUCROC values and confidence
intervals are shown in table 2. Both responder and non-
responder tumors have a similar percentage of stained
tumoral cells with HER2 score 3+ (table 2).
Based on our results, no significant differences between
the ROC curve of HER2-enriched tumors and Her2-
luminal (AUCROC HER2-enriched of 0.748; 95%CI 0.575-0.922
and AUCROC Her2-Luminal of 0.698; 95%CI 0.559 -0.839 with
p=0.66).
According to the AUCROC obtained from each molecular
subtype of HER2, distinct optimal cut-off values were
determined depending on the HER2 molecular subtype
while maintaining a good balance between sensitivity (Se)
and specificity (Sp). In this regard, the HER2-luminal tumor
cut-off value of the HER2 score 3+ was 10%, with a Se of
69.2% and Sp of 58.8%, same as the approved cut-off
point by ASCO/CAP 2013 for all HER2+BC. In HER2-
enriched tumors, HER2 score 3+ with a cut-off point of
10% had a Se of 77.8% and Sp of 40%. Regarding our
results, its optimal cut-off point was 21% with a Se of
72.7% and Sp of 80%.
Determination of other biomarkers that predict
response grade to neoadjuvant treatment in HER2+BC
Four proteins showed a differential expression in primary
tumor core biopsies between responder and non-
responder groups: the percentage of tumoral cells with
HER2 score 3+, Hsc of nuclear ER, percentage of Ki67
and percentage of membrane HER4. In addition, all these
variables displayed an AUCROC range between 0.6 and
0.72 (Table 2).
It was determined that the odss-ratio (OR) and p-value of
these predictive biomarkers had more potential to predict
a complete response, with their specific cut-off points:
namely, percentage of Her2 score 3+ ≥10 (OR =3.38,
p=0.005); Histo-score of ER <100 (OR=4.1, p=0.001);
percentage of Ki67 ≥30 (OR=3.1, 0.039); percentage of
membrane HER4 ≥1 (OR=4.9, p=0.012) and the absence
of affected lymph nodes (OR=3.3, p=0.018). The OR
confidence interval and p-values are shown in table 3.
Remarkably, the combination of 3 from these independent
continuous biomarkers (HER2 score 3+, ER and ki-67)
plus a clinical variable (absence of involvement lymph
nodes) compose a clinically relevant predictive signature
Novell et al. 027
to predict a complete response (Figure 1). The predictive
value of this multivariate model was significantly higher in
comparison with HER2 score 3+ alone (AUCROC signature
=0.81 versus AUCROC HER2 score 3+=0.72 with p=0.04).
DISCUSSION
In this study, the predictive value of HER2 status was
assessed in the complete response rate to the
combination of NAC and trastuzumab in HER2+BC
patients. A determination was made in the percentage of
tumoral cells with HER2 score 3+ and score 2+ by IHC.
This would seem to be the first study concluding that HER2
score 3+ is a poor predictive biomarker and HER2 score
2+ is not associated with the response grade.
It is known that the HER2-enriched tumor subtype shows
a higher pCR rate compared to the HER2-luminal one
(Portier et al. 2013; Sassen et al. 2009). Interestingly, it
was found that AUCROC of HER2 score 3+ was equal
independently the molecular subtype. According to our
results, it is believed that the cut-off point of HER2 score
3+ would have to be different for each molecular subtype
of HER2+BC. It was shown that the current clinical cut-off
point of HER2 score 3+ (>10%) is appropriate for the
HER2-Luminal group. Conversely, the optimal cut-off point
is >21% in the HER2-enriched subtype, having a similar
sensitivity, but a higher specificity than the current clinical
cut-off point.
There is a discrepancy in literature regarding whether a
positive or negative association exists between HER2
quantity and response grade in HER2-positive tumors
(Giuliano et al. 2015). Our results proved that there are no
major differences between responder and non-responder
groups according to the percentage of stained tumoral
cells with HER2 score 3+. Bear in mind, the benefit from
trastuzumab depends on a complex interaction between
HER2 and other known and unknown variables.
It is known that bidirectional HER/ER crosstalk contributes
to the resistance to anti-HER2 therapy (Duchnowska et al.
2012; Arpino et al. 2008; Pogue-Geile et al. 2013).
Giuliano et al. published a preclinical model that showed a
simultaneous increase in ER and Bcl2 expression in BC
xenografts treated with anti-HER2 therapies (Giuliano et
al. 2015). In the present results, low expression of ER is a
predictive biomarker of complete response with an
important OR of 4.4 and AUCROC of 0.72.
The relationship between baseline tumor-infiltrating
lymphocytes (TIL) and pCR rates in HER2+BC patients
(Solinas et al. 2017) has also been described. In this
regard, it was reported that patients with tumors enriched
in genes related to T and B cell responses, chemokine
signaling and inflammation have a better benefit from
trastuzumab (Di Modica et al. 2017; Bianchini and Gianni
A Novel Immunohistochemical Signature with the Quantification of HER2 Predicts the Complete Response in HER2-Positive Breast Cancer
2014). We did not find this association of TIL with the
complete response. We evaluated TIL through IHC of anti-
LC45 to provide information more easily on the complexity
of the tumor immune microenvironment. Nevertheless, our
assessment of TILs does not give information on the
composition and functional status of the immune infiltrate.
High levels of Ki-67 expression have also been described
as a good predictor of complete response to
chemotherapy in BC (Resende et al. 2018). In this study,
Ki-67 has a predictive value of NAC with anti-HER2 drugs
with OR of 3.1 and AUCROC of 0.612.
HER4 over-expression, in conjunction with the over-
expression of HER2, can be cross-activated to release
4ICD, enhancing the sensibility to trastuzumab (Portier et
al. 2013; Sassen et al. 2009). It was found that the
membrane HER4 expression was related to a complete
response with OR of 4.9 and AUC ROC of 0.617.
The most important contribution of this study is the
generation of a predictive signature of complete response
to neoadjuvant treatment in HER2+BC, because HER2
interacts and cross-regulates with other biomarkers, like
the aforementioned. This signature is composed of HER2
score 3+ together with Ki67, ER and lymph nodes
involvement state. Thanks to the combination of HER2
with other biomarkers, the prediction of response grade
has been improved. The AUCROC of the multivariate model
is higher than HER2 score 3+ alone, being 0.809. This
highlights that our signature is a clinically useful predictor,
which becomes a starting point for future studies for further
validation.
CONCLUSIONS
To sum up, this study is the first to show that HER2 score
3+ is a poor predictive biomarker of response to NAC and
anti-HER2 drugs in HER2+BC. In addition, we suggest
using a specific cutoff point of HER2 according to
molecular subtype of HER2+BC, being at least 10% of
stained tumoral cells in the HER2-luminal group and a 21%
in the HER2-enriched group.
We propose a novel and useful predictive signature of
complete response, which is composed by HER2, ER,
Ki67 and absence of lymph nodes. Remarkably, these
biomarkers are routinely determined in any pathology
laboratory and thus, our proposed model could easily be
translated in clinical practice.
ACKNOWLEGMENTS
Work supported by IRBLleida Biobank (B.0000682) and
Plataforma Biobancos PT/17/0015/0027.

COMPLIANCE WITH ETHICAL STANDARDS
Funding
This study was funded, in part, by the second edition of
Martí Via award from Vallformosa Fundation, Spain in the
year 2016.
Conflict of interest statement
We declare that we have no conflict of interest.
Ethical approval
The local Ethical Committee (CEIC- number 1232)
approved our study. All procedures performed in this
retrospective study involving human participants were in
accordance with the ethical standards of the institutional
and/or national research committee and with the 1964
Helsinki declaration and its later amendments or
comparable ethical standards.
Informed consent
Informed consent was obtained from all individual
participants included in the study. All patient data was
anonymized before the analysis.
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Novell et al. 029

APPENDIX

TABLES AND FIGURE

Table 1: Clinical and pathological characteristics of 99 patients with HER2+ breast cancer treated with neoadjuvant
chemotherapy and anti-HER2 therapy
Clinical characteristic N (%)
Age (years) 56 (47-69)*
Diagnostic tumor size (cm) 3 (2,2-4)*
Tumor with affected lymph node 54 (55)
M 7 (7)
Clinic TNM
I 8 (8)
II 31 (31)
III 54 (55)
IV 6 (6)
Tumor subtype
Her2-enriched 44 (44)
Her2-Luminal 55 (56)
Type of neoadjuvant anti-Her2 treatment
Trastuzumab 75 (76)
Doble-drug combination therapy 24 (24)
Chemotherapy
anthracycline plus taxane 67 (68)
taxane 30 (30)
anthracycline 2 (2)
Response Rate
Responder Tumor 60 (61)
Non-responder tumor 39 (39)
Recurrence 9 (9)
Dead 4 (4)
Data are presented as median (25-75 quartiles)* or n (%)

Table 2: Comparison of expression proteins between non-responder and responder HER2-positive primary tumors treated
with neoadjuvant chemotherapy combined with anti-Her2 drugs.
Biomarkers N Responder Tumors No-responder p- value AUCROC (95%CI)
Median (range) Tumors Median (range)
HER2 score 3+ (%) 99 40 (10-80) 7 (2-30) 0.001 0.719 (0.616-0.822)
ER (Hsc) 99 0 (0-238) 260 (40-290) 0.001 0.720 (0.614-0.826)
Ki67 (%) 99 42 (30-62) 40 (29-55) 0.073 0.612 (0.499-0.725)
Membrane HER4 (%) 72 0 (0-0) 0 (0-19) 0.010 0.617 (0.476-0.759)
Cytoplasmic HER3 (Hsc) 78 93 (35-109) 100 (50-130) 0.094 0.613 (0.481-0.744)
Total LC45 (%) 98 35 (20-45) 30 (15-40) 0.545 0.536 (0.42-0.652)
Estromal LC45 (%) 98 30 (15-40) 25 (10-40) 0.468 0.543 (0.427-0.659)
Intratumoral LC45 (%) 98 5 (0-10) 0 (0-10) 0.493 0.539 (0.421-0.657)
PR (Hsc) 99 0 (0-20) 10 (0-55) 0.100 0.587 (0.471-0.702)
Membrane EGFR (%) 77 0 (0-9) 0 (0-0) 0.445 0.540 (0.408-0.671)
Nuclear HER4 (Hsc) 72 0 (0-0) 0 (0-0) 0.236 0.543 (0.407-0.680)
Membrane HER3 (%) 78 10 (0-30) 10 (0-21) 0.751 0.521 (0.391-0.650)
Cytoplasmic HER4 (Hsc) 72 100 (58-133) 100 (15-160) 0.859 0.487 (0.339-0.636)
HER2 score 2+ (%) 99 38 (13-70) 50 (20-70) 0.302 0.438 (0.325-0.552)
The table 2 shows the expression of each possible predictive biomarker in both responder and no-responder groups. In
addition, the AUCROC indicates the association grade between the biomarker expression and the response to neoadjuvant
treatment. The biomarkers with values of AUCROC ≤0.5 are not associated with the response.
Notes: the bold values show significant differences of expression between responder and no-responder groups.
Abbreviations: N= number of analyzed cases; AUCROC= area under curve of ROC analysis; CI=confidence interval; Hsc=
histo-score.

A Novel Immunohistochemical Signature with the Quantification of HER2 Predicts the Complete Response in HER2-Positive Breast Cancer
 J. Cancer Clin. Oncol. 030

Table 3: Bivariate analysis for predictive biomarkers of complete response in HER2+ breast cancer patients.
Bivariate analysis
N Biomarkers with its cut-off point
Complete Response Proportion (%) OR 95% CI p-value
99 Her2 score 3+ (%) ≥10 vs <10 44/59 (75%) vs 18/39 (46%) 3.38 1.42-8.06 0.005
99 ER (Hsc) < 100 vs ≥100 * 35/60 (58%) vs 10/39 (26%) 4.1 1.70-98.0 0,001
99 Ki67 (%) >30 vs ≤ 30 44/60 (73%) vs 26/39 (67%) 3.10 1.02-9.40 0.039
72 Mem HER4 (%) ≥1 vs <1 44/48 (92%) vs 18/26 (69%) 4.9 1.3-18.3 0.012
99 Affected lymph nodes 0=N>1 33/45 (73%) vs 27/54 (50%) 3.3 1.3-8.3 0.018
The table 3 shows odds-ratio (OR) of biomarkers with its AUC>0.5, categorized according to the best discriminating cut-
off point of expression proteins for predicting a complete response or the value using in the clinical practice.
Notes: * The cut-off points of ER and PR are currently being used in clinical practice. Abbreviations: N= number of
analyzed cases, Mem= membrane; OR= Odds-Ratio, CI=confidence interval.

Figure 1. An immunohistochemical predictive signature of complete response in HER2+BC. A) Multivariate analysis.

Protein expression profile in primary tumor has a high predictive value to the complete response of neoadjuvant treatment.
The predictive signature is composed for 3 continuous biomarkers (HER2 score 3+, ER and Ki-67) and a clinical variable
(affected lymph nodes state). B) Representative IHC images of predictive signature of complete response.

AUTHORS INFORMATION Antonieta Salud (MD; PhD), Research Group of Cancer

Corresponding Author: Anna Novell (PhD) Research
Group of Cancer Biomarkers (GReBiC), IRBLleida,
Avinguda Alcade Rovira Roure, 80; 25198 Lleida, Spain.
Email: anovell@irblleida,cat Tel: +34973003747
CO-AUTHORS
Maria Alba Sorolla (PhD), Research Group of Cancer
Biomarkers (GReBiC), IRBLleida, Avinguda Alcade Rovira
Roure,80; 25198 Lleida, Spain.
Email: msorolla@irblleida.cat; Tel: +34 973 00 37 47
Silvia Bielsa (MD, PhD), Research Group of Cancer
Biomarkers (GReBiC), IRBLleida and Pleural Medicine Unit,
Department of Internal Medicine, Arnau de Vilanova
University Hospital, Avda. Alcalde Rovira Roure, 80; 25198
Lleida, Spain.
Email: silviabmartn@hotmail.com; Tel: +34 625 78 44 23
Gisela Urgel, Research Group of Cancer Biomarkers
(GReBiC), IRBLleida and Department of Medical Oncology,
Arnau de Vilanova University Hospital, Avda. Alcalde Rovira
Roure, 80; 25198 Lleida, Spain.
Email: gurgel@irblleida.cat; Tel: +34 608 69 15 39
Joel Veas (MD), Department of Medical Oncology, Arnau de
Vilanova University Hospital, Avda. Alcalde Rovira Roure, 80;
25198 Lleida, Spain.
Email: joelveas@gmail.com; Tel: +34 635 81 29 17
A Novel Immunohistochemical Signature with the Quantification of HER2 Predicts the Complete Response in HER2-Positive Breast Cancer
Biomarkers (GReBiC), IRBLleida and Department of Medical
Oncology, Arnau de Vilanova University Hospital, Avda.
Alcalde Rovira Roure, 80; 25198 Lleida, Spain.
Email: asaluds@hotmail.com; Tel:+34 659 96 51 37
Accepted 11 February 2019
Citation: Novell A, Sorolla MA, Bielsa S, Urgel G, Veas J,
Salud A (2019). A Novel Immunohistochemical Signature
with the Quantification of HER2 Predicts the Complete
Response in HER2-Positive Breast Cancer. Journal of
Cancer and Clinical Oncology 3(1): 015-023.
Copyright: © 2019 Novell et al. This is an open-access
article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium,
provided the original author and source are cited.