Observational Study Medicine ®

Changes in HER2 status and survival outcomes in

patients with non-pathological complete response
after neoadjuvant targeted treatment
Xiaofei Ren, MSa,b, Xiangmei Zhang, MD, PhDa,c, Xiangmin Ma, MDd, Chao Yang, MDa,b, Jingping Li, MDa,b,
Beichen Liu, MDa,e, Chao Shi, MDa,b, Yunjiang Liu, MD, PhDa,b,*

Abstract
To study the changes in human epidermal growth factor receptor 2 (HER2) expression in patients with HER2-positive breast
cancer before and after neoadjuvant treatment. The clinicopathologic data of 499 patients with HER2-positive breast cancer
who completed neoadjuvant treatment and surgery at the Fourth Hospital of Hebei Medical University from 2018 to 2021 were
retrospectively analyzed. According to the new adjuvant regimen, 298 patients were divided into the trastuzumab + pertuzumab
combined chemotherapy group (dual target group), and 201 patients were divided into the trastuzumab combined chemotherapy
group (single target group).The effect of different neoadjuvant regimens on HER2 status was analyzed by comparing HER2
expression before and after treatment. A total of 255 of 499 neoadjuvant patients with HER2-positive breast cancer achieved a
pathological complete response (pCR). pCR was achieved in 60.07% (179/298) of the dual target group and 37.81% (76/201)
of the single target group, and the difference was statistically significant (χ² = 23.795, P < .001). Among 244 cases of HER2-
positive breast cancer that did not reach pCR (non-pCR), there was a certain negative conversion rate of HER2 expression after
neoadjuvant treatment, and the overall negative conversion rate was 13.11% (32/244). The negative conversion rates of the dual
target group was 17.65% (21/119) and single target group was 8.80% (11/125), (χ² = 4.188, P = .041). The DFS of 499 patients
in the pCR group was 98.43% (251/255), which was significantly higher than that in the non-pCR group 92.21% (225/244), (χ²
= 8.536, P = .003). Only 2 (0.20%) of 32 patients with negative HER2 had recurrence and metastasis. Neoadjuvant treatment
had an effect on the expression status of HER2, especially in the dual target group. For patients with negative HER2, the optimal
treatment strategy remains to be explored, but continued anti-HER2 treatment is still recommended.
Abbreviations: DFS = disease free survival, FISH = fluorescence in situ hybridization, HER2 = human epidermal growth factor
receptor 2, HR = hormone receptor, IHC = immunohistochemistry, ISH = in situ hybridization, OS = overall survival, pCR =
pathologic complete response, TNBC = triple negative breast cancer.
Keywords: breast cancer, human epidermal growth factor receptor 2, neoadjuvant treatment, pathological complete response,
targeted treatment

1. Introduction HER2, can significantly improve the prognosis of HER2-

According to the latest data on the 2020 global burden of can-
cer, breast cancer has surpassed lung cancer to become the most
common malignant tumor.[1] Human epidermal growth factor
receptor 2 (HER2)-positive breast cancers account for 20%
to 30% of all breast cancers, with biological characteristics
such as a high degree of malignancy, insensitivity to traditional
chemotherapy and poor clinical prognosis.[2,3] Trastuzumab,
a humanized monoclonal antibody that specifically targets
positive breast cancer.[4] Neoadjuvant chemotherapy is the
standard treatment for locally advanced breast cancer. On the
one hand, it can achieve the effect of local control, downstag-
ing surgery or tumor shrinkage to achieve breast conservation.
On the other hand, it can be used as in vivo drug sensitivity
test to guide subsequent treatment and improve prognosis and
long-term survival.[4] For patients with HER2-positive breast
cancer, neoadjuvant chemotherapy combined with targeted
treatment is superior to chemotherapy alone, and improves the

This work was supported by Project of “100 Foreign Experts Plan of Hebei
Province,” China (No. 2022001) and Hebei Province Key Research and
Development Program Project Funding (No. 21377793D) and Natural Science
Foundation of Hebei Province (No. H2022206378).
The authors have no conflicts of interest to disclose
The datasets generated during and/or analyzed during the current study are
available from the corresponding author on reasonable request.
a
Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance,
Hebei Medical University, Shijiazhuang City, Hebei, China, b Department of Breast
Center, Fourth Hospital of Hebei Medical University, Shijiazhuang City, Hebei,
China, c Department of Hematology, Fourth Hospital of Hebei Medical University,
Shijiazhuang City, Hebei, China, d Research Center, Fourth Hospital of Hebei
Medical University, Shijiazhuang City, Hebei, China, e Department of Breast Surgery,
Handan Central Hospital, Handan City, Hebei, China.
*Correspondence: Yunjiang Liu, Department of Breast Center, Fourth Hospital
of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei
Province, China (e-mail: lyj818326@outlook.com).
Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
How to cite this article: Ren X, Zhang X, Ma X, Yang C, Li J, Liu B, Shi C,
Liu Y. Changes in HER2 status and survival outcomes in patients with non-
pathological complete response after neoadjuvant targeted treatment. Medicine
2023;102:39(e34903).
Received: 25 March 2023 / Received in final form: 1 August 2023 / Accepted: 3
August 2023
http://dx.doi.org/10.1097/MD.0000000000034903

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Ren et al. • Medicine (2023) 102:39Medicine
pathologic complete response (pCR) of the breast and lymph
nodes.[5] However, for non-pCR patients, the probability of
recurrence and metastasis in a short period of time is signifi-
cantly increased, and intensive treatment after neoadjuvant
and surgical treatment has important clinical significance. At
present, there is a certain negative conversion rate of HER2
in non-pCR patients after neoadjuvant treatment with trastu-
zumab, and it is controversial whether postoperative adjuvant
treatment should be intensified for the negative conversion
population.[6] The aim of this study was to analyze the clinico-
pathological data of 499 patients with HER2-positive breast
cancer and to investigate the changes in HER2 expression sta-
tus in patients with HER2-positive breast cancer after neoad-
juvant treatment.
2. Patients and methods
2.1. Study design and patients
The clinicopathological data of breast cancer patients who
completed neoadjuvant treatment and surgical treatment in
the Breast Center of the Fourth Hospital of Hebei Medical
University from 2018 to 2021 were collected. The inclusion
criteria were as follows: pathological examination con-
firmed breast cancer before neoadjuvant treatment, HER2
(+++) was detected by immunohistochemistry before neoad-
juvant treatment, HER2 (++) was detected by fluorescence
in situ hybridization (FISH), no distant metastasis, and com-
pletion of the scheduled 6 to 8 cycles of neoadjuvant chemo-
therapy. Exclusion criteria were as follows: previous history
of other malignant tumors, previous history of endocrine
treatment, targeted treatment and radiotherapy, and other
immunohistochemical subtypes. A total of 499 patients met
the inclusion criteria. All patients were female, aged from
23 to 70 years, with a median age of 51 years. According to
the 2017 American Joint Committee on Cancer clinical stag-
ing criteria. According to the neoadjuvant regimen, patients
were divided into a dual target group (298 cases) and a
Figure 1. Flow chart of case screening.
2
single-target group (201 cases). The drug usage and dos-
age were determined according to the 2017 Chinese Society
of Clinical Oncology breast cancer diagnosis and treatment
guidelines.
HER2 testing was performed according to the 2018
American Society of Clinical Oncology/College of American
Pathologists guidelines. HER2 status was first determined
by immunohistochemistry (IHC), and patients with IHC 3 +
tumors were diagnosed as HER2 positive; for patients with
HER2 IHC 2 + tumors, HER2 was identified as positive by
FISH. The detection of ER and PR was based on the 2020
American Society of Clinical Oncology/College of American
Pathologists guidelines, and tumors were classified as hormone
receptor (HR) positive if ≥1% of tumor cells stained for ER
and/or PR.
This study was approved by the Ethics Committee of the
Fourth Hospital of Hebei Medical University (Ethics number:
2020048) (Fig. 1 and Table 1).
2.2. Statistical analysis
The primary endpoint was the HER2-negative conversion rate,
defined as among HER2-positive breast cancer after neoadju-
vant treatment that did not reach pCR (non-pCR), there was
the proportion of HER2 expression turned negative. Secondary
study measures were pathologic complete response (pCR),
defined as noninvasive carcinoma in the primary breast lesion
(possibly ductal carcinoma in situ) and lymph nodes in the neg-
ative area (ypT0 or Tis N0M0), or residual cancer burden grade
0. Disease free survival (DFS) is the time from breast cancer
diagnosis to the recurrence of ipsilateral local or regional inva-
sive breast cancer, distant metastasis, noninvasive breast cancer,
or death from any cause. Overall survival (OS) was defined as
the time between primary diagnosis and death from any cause.
The survival time was calculated from the time of pathological
diagnosis. The end date of follow-up was October 14, 2022,
and the end event was the death of the patient. SPSS 26.0 was
Ren et al. • Medicine (2023) 102:39www.md-journal.com

Table 1 difference was statistically significant (χ2 = 38.812, P < .001)

Basic characteristics of 499 patients with HER2 positive breast
(Table 2).
cancer (N [%]).
Clinical Single target Dual target 3.2. Changes in HER2 expression after neoadjuvant
characteristics group N = 201 group N = 298 χ² P treatment
Age 0.132 .716 A total of 244 patients with HER2-positive breast cancer did
 <50 91 (45.27) 130 (43.62) not achieve pCR after neoadjuvant treatment, including 119
 ≥50 110 (54.73) 168 (56.38) patients in the dual target group and 125 patients in the single
Menopause 2.631 .105 target group. There was a negative conversion rate of HER2
 Yes 89 (44.28) 154 (51.68) expression status after neoadjuvant treatment in patients with-
 No 112 (55.72) 144 (48.32) out pCR, and the overall negative conversion rate was 13.11%
Clinical stage 4.912 .555 (32/244). The negative conversion rates of HER2 expression in
 IIA 25 (12.44) 31 (10.40) the dual target group and the single target group were 17.65%
 IIB 62 (30.85) 103 (34.56) and 8.80%, respectively, and the difference was statistically sig-
 IIIA 35 (17.41) 63 (21.14)
 IIIB 27 (13.43) 34 (11.41)
nificant (χ2 = 4.188, P = .041). In the HER2-positive HR-negative
 IIIC 52 (25.87) 67 (22.48) groups, the negative conversion rates of HER2 expression in the
T stage 1.149 .765 dual target group and the single target group were 12.90% and
 T1 21 (10.45) 23 (7.72) 7.00%, respectively, and the difference was not statistically sig-
 T2 120 (59.70) 185 (62.08) nificant (P = .394). In the HER2-positive HR-positive group, the
 T3 24 (11.94) 37 (12.42) negative conversion rates of HER2 expression in the dual target
 T4 36 (17.91) 53 (17.79) group and the single target group were 19.32% and 9.76%,
N stage 2.311 .510 respectively, and the difference was statistically significant (P <
 N0 17 (8.46) 19 (6.38) .001). Among 244 patients who did not achieve pCR, the nega-
 N1 95 (46.77) 154 (51.67) tive conversion rate of HER2 3 + and HER2 2 + FISH(+) before
 N2 36 (17.91) 59 (19.79) neoadjuvant therapy was 6.19% (12/194) and 40% (20/50),
 N3 53 (26.37) 66 (22.15)
respectively, with a significant difference (P <.001). (Table 3).
Hormone 0.086 .769
receptor
 HR positive 118 (58.71) 171 (57.38)
 HR negative 83 (41.29) 127 (42.62) 3.3. Immunohistochemistry of HER2 after turning negative
HER2 status 2.925 .087 Among the 32 patients with negative conversion, 7 cases were
 HER2 3+ 184 (91.54) 258 (86.58) the HER2-positive HR-negative before neoadjuvant treatment,
 HER2 2 + 17 (8.46) 40 (13.42) 6 cases (18.75%) became triple negative breast cancer (TNBC)
FISH+ and 1 case (3.125%) became Luminal B after neoadjuvant treat-
Ki-67 2.868 .090 ment, and 25 cases were the HER2-positive HR-positive before
 ≤20 52 (25.87) 58 (19.46)
neoadjuvant treatment. After neoadjuvant treatment turned
 >20 149 (74.13) 240 (80.54)
negative, 1 case (3.125%) became TNBC, 2 cases (6.25%) were
HER2 = human epidermal growth factor receptor 2. Luminal A and 22 cases (68.75%) were Luminal B. After neo-
adjuvant therapy, Ki-67 expression decreased in 24 cases (75%),
remained unchanged in 3 cases (9.375%), and increased in 5
cases (15.625%).
used for statistical processing. The number of cases (%) was
expressed by χ2 test, Fisher exact test, and Log-Rank test. Test
level α = 0.05 (dual-tailed). 3.4. Prognosis condition
Among the 499 HER2-positive patients, the follow-up data
were complete, and the follow-up time ranged from 7 to 55
3. Results months, with a median follow-up time of 22 months. All
patients continued targeted therapy for 1 year after surgery,
3.1. Clinical efficacy of HER2-positive breast cancer and endocrine therapy and radiotherapy were supplemented
After neoadjuvant treatment, 255 patients achieved pCR, with according to the surgical method, postoperative pathological
a total PCR rate of 51.10%. The pCR rates of HR- group and results, lymph node metastasis and postoperative HR status.
HR + group were 64.76% (136/210) and 41.18% (119/289), Among the 255 patients with pCR, 4 (0.40%) had recurrence
respectively, and the difference was statistically significant (χ2 or metastasis, and 2 (0.40%) died. Among 244 non-pCR
= 27.075, P < .001). The pCR rates of the dual target group patients, 19 patients (2.61%) had recurrence or metastasis, and
and single target group were 60.07% (179/298) and 37.81% 6 patients (1.20%) died of brain metastasis or bone metastasis.
(76/201), respectively, and the difference was statistically The DFS of the pCR group was 98.43% (251/255), which was
significant (χ2 = 23.795, P < .001). In the HER2-positive significantly higher than that of the non-pCR group 92.21%
HR-negative group, 136 cases (64.76%) achieved pCR, of (225/244), Log-Rank test, χ2 = 8.536, P = .003. However,
which 96 cases (75.59%) in the dual target group and 40 cases there was no significant difference in OS between the 2 groups
(48.19%) in the single target group, and the difference was (99.22% vs 97.54%), Log-Rank test, χ2 = 1.248, P = .264. Of
statistically significant (χ2 = 16.511, P < .001). In the HER2- the 32 patients who were HER2 negative after neoadjuvant
positive HR-positive group, 119 patients (41.18%) achieved treatment, 2 (0.20%) had recurrence and metastasis. The DFS
pCR, including 83 patients (48.54%) in the dual-target group of the HER2-negative group was 93.75% (30/32), which was
and 36 patients (30.51%) in the single-target group, and the not significantly different from that of the HER2-nonnegative
difference was statistically significant (χ2 = 9.370, P = .002). group 91.98% (195/212) (Log-Rank test, χ2 = 0.023, P = .880).
Among the 255 patients who achieved pCR, the pCR rate of However, there was no significant difference in OS between the
the HER2 3 + group was 56.11% (248/442), and the pCR rate 2 groups (100% vs 97.17%), Log-Rank test, χ2 = 0.703, P =
of the HER2 2 + FISH (+) group was 12.28% (7/57), and the .402 (Figs. 2 and 3).

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Ren et al. • Medicine (2023) 102:39Medicine

Table 2 the HER2 2 + FISH (+) group (12.28%), which was consistent
with previous reports.[12,13] It indicates that HR status and HER2
Efficacy of neoadjuvant treatment in 499 cases of HER2-positive
protein expression level also have important effects on pCR.
breast cancer (N [%]).
Previous studies have shown that HER2 expression becomes
N pCR non-pCR χ² P negative in patients with HER2-positive breast cancer after
neoadjuvant treatment, and the negative conversion rate
Hormone receptor 27.075 <.001 of HER2 expression ranges from 9.4% to 40%. Mittendorf
(n = 499) et al[14] found that among the patients who did not achieve
 HR-negative 210 136 (64.76) 74 (35.24) pCR after neoadjuvant trastuzumab treatment, there were 25
 HR-positive 289 119 (41.18) 170 (58.82)
patients with sufficient residual cancer tissue to retest HER2
Neoadjuvant regimen 23.795 <.001
expression status, and 8 (32%) of them were negative. Guarneri
(n = 499)
 Dual target group 298 179 (60.07) 119 (39.93)
et al[15] found that HER2 expression turned negative in 19 of
 Single target group 201 76 (37.81) 125 (62.19) 69 residual cancer tissues after neoadjuvant treatment, with
HER2-positive HR-negative 16.511 <.001 a negative conversion rate of 27.5%. Yoshida et al[16] found
(n = 210) that 33 (33%) of 99 patients with HER2-positive breast can-
 Dual target group 127 96 (75.59) 31 (24.41) cer without pCR turned negative, among whom trastuzumab
 Single target group 83 40 (48.19) 43 (51.81) neoadjuvant treatment had the highest negative conversion
HER2-positive HR-positive 9.370 .002 rate of 70% (23/33). Wang et al[17] found that anti-HER2
(n = 289) neoadjuvant targeted treatment is more likely to become turn
 Dual target group 171 83 (48.54) 88 (51.46) negative. The negative conversion rate of the PCH (paclitaxel,
 Single target group 118 36 (30.51) 82 (69.49) carboplatin, trastuzumab) regimen was 19.8%, while that of
HER2 status (n = 499) 38.812 <.001 the PC (paclitaxel, carboplatin) regimen was 9.4%, and the
 HER2 3+ 442 248 (56.11) 194 (43.89) difference was statistically significant. This study showed that
 HER 2 + FISH + 57 7 (12.28) 50 (87.72) in 499 patients with HER2-positive breast cancer after neo-
HER2 = human epidermal growth factor receptor 2, HR = hormone receptor, pCR = pathological adjuvant treatment, 32 of 244 cases (13.11%) that did not
complete response, non-pCR = non-pathological complete response. achieve pCR turned HER2 negative. Among them, 21 cases
(17.65%) in the dual target group turned HER2 expression
negative, which was higher than 11 cases (8.80%) in the sin-
Table 3 gle target group. In the HER2-positive HR-negative group and
HER2-positive HR-positive group, the negative conversion
Changes of HER2 expression before and after new adjuvant
rate of HER2 expression status in the dual target group was
treatment in 244 non-pathological complete response (non-PCR)
also higher than that in the single target group. Especially in
patients (N [%]).
the HER2-positive HR-positive group, the negative conversion
Positive to rate of the dual target group was as high as 19.32%, suggest-
N negative Positive χ² P ing that patients have a higher negative conversion rate after
dual target neoadjuvant treatment.
4.188 .041 Previous studies have shown that neoadjuvant treatment
Dual target group 119 21 (17.65) 98 (82.35) with trastuzumab plus chemotherapy results in a higher rate
Single target group 125 11 (8.80) 114 (91.20)
HER2-positive 0.727a .394
of HER2-negative conversion than neoadjuvant treatment
HR-negative (n = 74)
with chemotherapy alone. However, in this study, the HER2-
 Dual target group 31 4 (12.90) 27 (87.10) negative conversion rate of dual target neoadjuvant treatment
 Single target group 43 3 (7.00) 40 (93.00) was higher than that of the single-target group. The reason
HER2-positive 39.880* <.001 for this inconsistency is that the previous studies did not use
HR-positive (n = 170) dual target neoadjuvant treatment as a comparison. A second
 Dual target group 88 17 (19.32) 71 (80.68) possibility is the use of different criteria for HER2 testing of
 Single target group 82 8 (9.76) 74 (90.24) residual tumors. The mechanism of HER2 reversion to nega-
HER2 status 39.891 <.001 tive status after neoadjuvant treatment is unclear. Among 244
 HER2 3+ 194 12 (6.19) 182 (93.81) patients who did not achieve pCR, the negative conversion
 HER 2 + FISH + 50 20 (40.00) 30 (60.00) rates of HER2 3 + and HER2 2 + FISH (+) before neoadjuvant
HER2 = human epidermal growth factor receptor 2, HR = hormone receptor.
treatment were 6.19% (12/194) and 40% (20/50), respectively
*Fisher exact probability test. (P < .001). Some studies have shown that HER2 2 + heteroge-
neity is more obvious.[18] HER2-negative conversion after neo-
adjuvant treatment may be related to tumor heterogeneity and
drug resistance, suggesting that there is HER2 heterogeneity
4. Discussion within the tumor, HER2-positive tumor cells are effective to
Tumor heterogeneity refers to the differences in the characteris- chemotherapy and targeted treatment, residual HER2-negative
tics of tumor cells caused by the existence of different genotype tumor cells, or HER2 positive tumor cells are resistant to
cells in the same tumor.[7] HER2-positive breast cancer has poor trastuzumab.
differentiation ability and strong tumor invasiveness, which can Among 32 HER2-positive patients, 7 (21.875%) became
increase the risk of breast cancer recurrence and metastasis, and TNBC after neoadjuvant therapy, 2 (6.25%) became Luminal A
has significant heterogeneity.[8] For HER2-positive breast cancer, and 23 (3.125%) became Luminal B. Braso-Maristany et al[19],
neoadjuvant targeted treatment can greatly improve the prog- in HER2 overexpression, showed that trastuzumab and lapati-
nosis of patients and prolong their survival.[9,10] However, breast nib treatment can induce low proliferation of Luminal A type.
cancer with HER2 heterogeneity has a poor prognosis and is The subtype switch from HER2 overexpression to Luminal A
not sensitive to anti-HER2 treatment.[11] The pCR rate was may provide an opportunity for treatment with agents known
51.10% (255/499) in 499 patients with HER2-positive breast to be active in Luminal A, such as endocrine treatment or
cancer after neoadjuvant treatment. Among, pCR was more CDK4/6 inhibitors. Therefore, when HER2 becomes negative
easily obtained in HR−/HER2-positive group after neoadjuvant and becomes a different molecular subtype, it may be necessary
therapy than in HR+/HER2-positive group. Moreover, the pCR to add new treatment options to push HER2 targeted treatment
rate of the HER2 3 + group (56.11%) was higher than that of to a higher level.
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Figure 2. Kaplan–Meier disease free survival curves according pathologic complete response (pCR) status after neoadjuvant treatment.

Figure 3. Kaplan–Meier disease free survival curves (A) and overall survival curves (B) were plotted according to the HER2 status of residual tumors in Non-
pathological complete response (non-pCR) patients after neoadjuvant targeted treatment.

In this study, 32 patients with HER2 positive turned nega-
tive after neoadjuvant treatment, and the immunohistochemi-
cal indexes of these 32 patients before and after neoadjuvant
treatment were observed, it was found that Ki-67 generally
showed a downwards trend, of which 24 cases decreased (75%),
3 cases remained unchanged (9.375%), and 5 cases increased
(15.625%). Gahlaut et al[20] found that Ki-67 changes after neo-
adjuvant treatment were statistically significant. Studies have
shown that Ki-67 expression is significantly decreased after
neoadjuvant treatment, and high Ki-67 expression in resid-
ual tumors is associated with poor DFS and OS. Therefore,
decreased Ki-67 expression after neoadjuvant treatment in
breast cancer patients indicates a better prognosis.[21]
A total of 499 HER2-positive patients were followed up, and
it was found that patients who achieved pCR had a better prog-
nosis, which was consistent with previous studies.[11] Two of 32
patients (0.20%) with HER2 negative conversion had recurrence
and metastasis, and there were no deaths. Its low recurrence and
metastasis rates show a good prognosis trend, which may be
related to the continued targeted treatment and other intensive
treatments after surgery. Some studies have shown that HER2
positive conversion after neoadjuvant treatment is not associated
with 5-year RFS or OS, and these patients are recommended to
continue to complete targeted adjuvant treatment.[22] In addition,
the KATHERINE study showed the efficacy of T-DM1 in the
treatment of HER2-negative residual invasive disease. Among

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Ren et al. • Medicine (2023) 102:39Medicine
70/845 (8.3%) patients with HER2-negative residual disease
reviewed at surgery, 11 of 42 (26.2%) patients treated with tras-
tuzumab had IDFS events. However, there was no IDFS event in
the 28 patients treated with T-DM1, indicating that T-DM1 treat-
ment should not be discontinued in this patient population.[23]
However, the sample size of this study is small and has certain
limitations. In the future, the sample size should be expanded,
and the heterogeneity of HER2 and the potential impact of tar-
geted drugs on HER2 biology should be further understood, as
well as the resistance mechanism of anti-HER2 treatment. In
addition, the optimal treatment strategy for patients with HER2
turning negative still needs to be explored, but at present, it is
still recommended to continue anti-HER2 treatment clinically.
Author contributions
Writing – original draft: Xiaofei Ren, Xiangmei Zhang.
Data curation: Xiangmin Ma, Chao Yang, Jingping Li, Beichen
Liu, Chao Shi.
Writing – review & editing: Yunjiang Liu.
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