Vol 19, No 4 (2023)
Research paper
Published online: 2023-05-09

open access

Page views 1047
Article views/downloads 479
Get Citation

Connect on Social Media

Connect on Social Media

ORIGINAL ARTICLE

Oncology in Clinical Practice

DOI: 10.5603/OCP.2023.0020

Copyright © 2023 Via Medica

ISSN 2450–1654

e-ISSN 2450–6478

Pathological complete response and survival of HER2-positive invasive breast cancer following docetaxel, carboplatin, and trastuzumab neoadjuvant therapy: a Vietnamese experience

Duc Thanh Le1Tu Anh Do1Lap Thanh Bui1Kien Hung Do1Chu Van Nguyen12
1National Cancer Hospital, Vietnam
2Hanoi Medical University, Vietnam

Address for correspondence:

Assoc. Prof. Nguyen Van Chu, MD, PhD

Department of Quan Su Pathology,

National Cancer Hospital, Vietnam

43 Quansu Street, Hangbong Commune,

Hoankiem District 100000, Hanoi, Vietnam

tel.: (+84) 916482277

e-mail: nguyenvanchu@hmu.edu.vn

Received: 12.10.2022 Accepted: 27.03.2023 Early publication date: 09.05.2023

ABSTRACT

Introduction. Neoadjuvant chemotherapy for HER2-positive breast cancer consists of a chemotherapy regimen plus trastuzumab with or without pertuzumab. The use of trastuzumab has been shown to improve pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). Purposes: To evaluate the efficacy and safety of neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) in the treatment of HER2-positive breast cancer in Vietnamese patients.

Material and methods. This retrospective study reviewed stage IIIII HER2-positive breast cancer patients who received neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) at the Vietnamese National Cancer Hospital. The primary endpoint was the pCR rate which was defined as the absence of invasive tumor in the breast and axillary nodes (ypT0/is, ypN0). The secondary endpoints were DFS, OS, and toxicities.

Results. The complete and partial clinical response of 51 patients were 33.3% and 58.8%, respectively. The pCR rate was 41.2%; there was a significantly higher response in cT1-2 patients compared to cT3-4 ones (61.1% vs. 39.3%, p = 0.033). Three-year estimated DFS and OS rates were 81.3% and 93.0%, respectively. Treatment was generally well tolerated. Grade 3/4 neutropenia and anemia were uncommon (21.6% and 7.8%). No symptomatic cardiac dysfunction occurred.

Conclusions. Neoadjuvant TCH, non-anthracycline chemotherapy with single anti-HER2 regimen achieved high efficacy, with a good pCR rate and favorable tolerability in stage II or III HER2-positive breast cancer patients.

Key words: breast cancer, HER2-positive, neoadjuvant chemotherapy, pCR, TCH

Oncol Clin Pract 2023; 19, 4: 235243

Introduction

Breast cancer (BC) is one of the most common cancers and the leading cause of malignancy-related mortality in women worldwide [1, 2]. In Vietnam, breast cancer is the most common cancer and the fourth leading cause of cancer-related death in women. The International Agency for Research on Cancer reported an estimated 21 555 new cases and 9 345 deaths of breast cancer in Vietnam [2]. Treatment for breast cancer is complex due to its heterogeneity and various molecular subtypes. Among them, newly diagnosed patients in the HER2 overexpression subtype, which was previously considered as an aggressive phenotype with poor prognosis [3–5], accounted for 1520% of patients.

Neoadjuvant chemotherapy (NAC) is commonly used for breast cancer patients not only with locally advanced stage but also patients in an early stage, especially with poor prognosis with triple-negative and HER2- -positive tumors [6, 7]. In addition to increasing the rate of breast-conserving surgery [8], NAC permits evaluation of the effectiveness of systemic treatments to guide adjuvant treatment [9]. Response to NAC also provides important prognostic information. Patients with pathological complete response (pCR) were reported to have better long-term outcomes [10–12]. NAC for HER٢-positive breast cancer consists of chemotherapy and HER2-directed therapy, specifically trastuzumab, with or without pertuzumab. The use of trastuzumab has been shown to improve pCR, disease-free survival, and overall survival [13]. Nevertheless, the addition of trastuzumab to standard therapy may increase toxicity, particularly cardiovascular toxicity [13, 14]. This toxicity is increased when trastuzumab is used concurrently with an anthracycline-containing chemotherapy regimen. Due to concerns about cardiotoxicity, anthracycline-free chemotherapy plus trastuzumab have been explored. The addition of carboplatin and docetaxel to trastuzumab (TCH regimen) was shown to have a synergistic effect in some studies [15–17]. The pCR rates achieved by the TCH regimen in the neoadjuvant setting ranged from 39% to 76% [17–20]. This regimen has less incidence of acute toxicity, cardiotoxicity, and more favorable tolerability. However, most evidence about the efficacy of this regimen was from the adjuvant setting or phase II studies [20–22]. In the GETN(A)-1 trial, a multicenter neoadjuvant study, 70 patients with HER2-positive breast cancer with diagnosed stage IIIII received trastuzumab 4 mg/kg (day 1), followed by 2 mg/kg weekly, plus docetaxel 75 mg/m2 every 3 weeks, and carboplatin (AUC 6) for six cycles before surgery. The pCR rate (ypT0/is ypN0) was 39%, and the objective response rate (ORR) was 95%. Sixty-four percent of the patients had breast conservation and no symptomatic cardiac dysfunction occurred [23]. However, the efficacy and safety of TCH regimens for neoadjuvant therapy have not been evaluated in Vietnamese women with HER2-positive breast cancer. Thus, we conducted this study to evaluate the pCR rates, toxicity profile as well as preliminary results for DFS and OS of the TCH regimen in HER2-positive breast cancer patients with stage IIIII in Vietnam.

Material and methods

Study design

In this single-center, retrospective study, 51 HER2-positive breast cancer patients with stage IIIII who were treated with a neoadjuvant TCH regimen from January 2015 to December 2021 at the Vietnamese National Cancer Hospital were recruited. The eligible patients need to meet all the following criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, histopathological diagnosis of invasive breast cancer and immunohistochemical result of HER2-positive, staging IIIII (cT1-4, cN0-3, M0), received neoadjuvant therapy with a TCH regimen, a baseline left ventricular ejection fraction (LVEF) of 50%, adequate hematologic, renal, and hepatic functions. Patients with the following criteria were excluded: bilateral breast cancer or metastatic breast disease; any previous treatment for breast cancer including surgery, radiation, chemotherapy, or endocrine therapy; pre-existing malignancy other than breast cancer; any prior treatment with cytotoxic drugs, in situ carcinoma, another breast malignancy (ex. malignant phyllode tumor). The diagnosis of BC was confirmed by histological evaluation of the biopsy specimens before treatment. An immunohistochemical (IHC) examination was performed before treatment. HER2-positive status was determined by IHC (3+) or IHC (2+) and positive fluorescence in situ hybridization (FISH) using the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 guidelines. This study was approved by the research committee of the National Cancer Hospital, Vietnam.

Treatment procedures

All patients had their clinical staging evaluated at diagnosis, using the 8th edition of the American Joint Committee on Cancer (AJCC). Physical examination, mammography, and ultrasound were usually performed at baseline and after every three chemotherapy cycles to evaluate clinical response. Treatment includes six cycles of docetaxel 75 mg/m2, carboplatin AUC6, and trastuzumab 6 mg/kg every 3 weeks (8 mg/kg loading dose). For each cycle, prophylactic G-CSF support was administered on days 2 to 5. Echocardiography to evaluate cardiac function was performed before initiation of therapy, after the third and sixth cycles. Then, LVEF assessments were carried out every 3 months and 1 year after the last cycle of treatment or whenever clinically indicated. After the completion of neoadjuvant chemotherapy, surgery was performed to remove the tumor by conservative surgery or modified radical mastectomy, combined with axillary lymph node dissection within 46 weeks after the final dose of chemotherapy. Following surgery, adjuvant endocrine therapy and radiotherapy were administered if indicated. Adjuvant trastuzumab (loading dose 8 mg/kg, followed by 6 mg/kg every 21 days) was continued postoperatively for up to 18 cycles.

Tumor response and toxicity assessment

Clinical response was evaluated by palpation after each treatment cycle and by mammary ultrasound, mammography, or magnetic resonance imaging before surgery, using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Following surgery, tumors were evaluated in their maximum diameter. Tumor and nodal samples were examined with histopathological tests to assess the pathological response. The pCR was defined as the absence of invasive tumor in breast and axillary lymph nodes (ypT0/is ypN0). Disease-free survival (DFS) was defined as the period between the date of surgery and the date of disease relapse (including distant metastases, local and regional recurrence) or death, whichever occurred first. Overall survival (OS) was measured from the date of the diagnosis to death due to any cause. Toxicities after and during six courses of chemotherapy were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.

Variables of interest

Variables used for analyzing include age (< 50 and 50 years), performance status (PS) (PS = 0 and PS = 1), menopausal status (premenopausal and postmenopausal), histologic grade (ductal carcinoma and others), clinical tumor stage (T1T2 and T3T4), clinical lymph nodal stage (N0N1 and N2N3), clinical stage (stage II and stage III), ER/PgR status (positive and negative), and pathological response (pCR and non pCR). All 51 patients were contacted via phone or messages to collect real-time information.

Statistics

All collected data were analyzed and measured by SPSS 20.0 software. Fisher’s exact test and Pearson Chi- -square test were used to evaluate impact of various factors on the pCR. Disease-free survival and overall survival were estimated by the Kaplan-Meier method. A 2-sided p value of <0.05 was considered statistically significant.

Results

Patient characteristics and treatment

Between February 2015 to December 2021 in the National Cancer Hospital, Vietnam, 51 patients with stage IIIII HER2-positive breast cancer were enrolled in the study. All patients received six courses of NAC chemotherapy. Table 1 shows the baseline clinicopathological features of patients. The median age was 46 years old and over half of the women were premenopausal. Considering the cTNM, BCs were staged in T3 and N2 which were the most common (43.1 and 52.9%, respectively). Therefore, BCs with stage IIIA (39.2%) and stage IIIB (35.3%) were more common than the other stages. Concerning pathological features, invasive ductal carcinoma, not otherwise specified (NOS) was the most common. Histological grade II was the most common (66.7%). Most patients (74.5%) were positive for hormone receptors (estrogen and/or progesterone receptor; HR) while 25.5% were HR-negative.

Table 1. Baseline characteristics of 51 patients with HER2+ invasive breast cancer carcinoma

Parameter

n

[%]

Age [years]

Median (range)

46.0 (2670 years)

< 50 years

30

58.5

50 years

21

41.2

Performance status

0

42

82.4

1

9

17.6

Menopausal status

Premenopausal

32

62.7

Postmenopausal

19

37.3

Histology

Invasive ductal carcinoma, NOS

39

76.5

Invasive lobular carcinoma

9

17.6

Invasive mucinous carcinoma

2

3.9

Invasive carcinoma, unclassified

1

2.0

Histological grade

1

1

2.0

2

34

66.7

3

16

31.4

Clinical tumor stage

T1

1

2.0

T2

17

33.3

T3

21

41.2

T4

12

23.5

Clinical nodal stage

N0

8

15.7

N1

12

23.5

N2

27

52.9

N3

4

7.8

Clinical stage

II

13

25.5

IIIA

22

43.1

IIIB

12

23.5

IIIC

4

7.8

ER/PgR status

Negative

13

25.5

Positive

38

74.5

Operation type

Mastectomy

44

86.3

Breast-conserving surgery

7

13.7

Clinical response

CR

17

33.3

PR

30

58.8

SD

4

7.8

PD

0

0.0

Pathologic response

pCR

21

41.2

Non-pCR

30

58.8

Clinical and pathological response

Based on the RECIST criteria, the clinical response and degree were investigated, complete response (CR), partial response (PR), and ORR were 33.3%, 58.8%, and 92.2%, respectively. Seven patients (13.7%) underwent breast-conserving surgery. Pathological complete response was achieved in 41.2% (Tab. 1). Table 2 presents the relationship between clinical and paraclinical features and pCR for HER2-positive BC. Pathological complete response rate was higher in hormone receptor-negative patients compared to hormone receptor-positive patients (61.5% vs. 34.2%, p = 0.084). Pretreatment tumor stage was significantly related to response to NAC. Lower cT-stage (cT1-2 vs. cT3-4) was a significant predictor of higher pCR rate (p = 0.033), i.e. pCR rates were 61.1% and 30.3% for cT1-T2 stage and cT3-T4 stage, respectively. In addition, the pCR rate was not significantly different irrespective of age groups, clinical lymph node status, histologic grade, and histologic type (p > 0.05).

Table 2. Factors associated with a pathologic complete response (pCR)

Factors

pCR

Analysis

p

No.

%

OR

95% CI

Age [years]

< 50 years

12

40.0

1 (reference)

50 years

9

42.9

0.889

0.2872.756

0.838

Histologic type

Ductal carcinoma, NOS

17

42.5

1 (reference)

Other

4

36.4

1.293

0.3265.137

0.714

Histologic grade

1 or 2

17

48.6

1 (reference)

3

4

25.0

2.833

0.76310.516

0.112

Clinical tumor stage

T1T2

11

61.1

1 (reference)

T3T4

10

30.3

3.614

1.08412.046

0.033

Clinical lymph node status

N0N1

8

40.0

1 (reference)

N2N3

13

41.9

0.923

0.2942.898

0.891

Clinical stage

II

6

46.2

1 (reference)

III

15

39.5

1.314

0.3694.679

0.673

ER/PgR status

Negative

8

61.5

1 (reference)

Positive

13

34.2

3.077

0.83611.323

0.084

Long-term outcomes

The median follow-up was 33.0 months. Eight of 51 patients (15.7%) had experienced at least one event. Five patients (9.8%) experienced local relapse (including local lymph node relapses), and 6 patients (11.8%) had metastatic relapses. Estimated 3-year DFS was 81.3% (Fig. 1). Patients who achieved pCR after NAC had better DFS than the ones with residual disease although the difference was not statistically significant (89.7% vs. 72.3%, p = 0.220) (Fig. 2). Additionally, DFS was not significantly different with age group, histologic type, histologic grade, clinical tumor stage, clinical lymph node stage, clinical stage and HR status (Tab. 3). Two patients (3.9%) died at 31 months and 34 months. One patient (1.9%) died of lung metastases and the other (1.9%) died of bone and brain metastases. Both patients (3.9%) did not achieve pCR after surgery. Estimated 3-year OS was 93.0% (Fig. 3).

Figure 1. Disease-free survival of HER2+ invasive breast cancers. Kaplan-Meier curve displayed the estimated 3-year disease-free survival (DFS) was 81.3%
Figure 2. Disease-free survival (DFS) of pathologic response status in HER2+ invasive breast cancers. The Log-rank test displayed that there was not a significant difference between these DFS curves of combination of pCR and non-pCR for infiltrating HER2+ breast cancers; CI confidence interval; HR hazard ratio; pCR pathologic complete response
Table 3. Factors affecting disease-free survival

Factors

No.

HR

95% CI

p

Age [years]

< 50 years

30

1 (reference)

50 years

21

0.331

0.0671.645

0.177

Histologic type

Ductal carcinoma, NOS

40

1 (reference)

Other

11

1.276

0.2606.262

0.764

Histologic grade

1 or 2

35

1 (reference)

3

16

0.287

0.0412.023

0.210

Clinical tumor stage

T1T2

18

1 (reference)

T3T4

33

0.716

0.1513.407

0.675

Clinical lymph node status

N0N1

20

1 (reference)

N2N3

31

0.913

0.519153.186

0.132

Clinical stage

II

13

1 (reference)

III

38

1.030

0.04423.930

0.985

ER/PgR status

Negative

13

1 (reference)

Positive

38

3.477

0.35633.962

0.284

Pathologic response

Non pCR

30

1 (reference)

pCR

21

0.246

0.0541.116

0.069

Figure. 3. Overall survival (OS) of HER2+ invasive breast cancers. Kaplan-Meier curve displayed the estimated 3-year OS was observed in 93.0%
Safety and tolerability

Toxicities in our patients are presented in Table 4. Anemia and neutropenia were the most common serious (grade 3/4) adverse events. All patients completed 6 cycles of planned chemotherapy, with 12 patients requiring dose adjustments due to toxicity. None of the patients had LVEF decline or clinical symptoms of heart failure. There were no deaths related to treatment.

Table 4. Selected adverse events on six-course chemotherapy

Event

All grade

Grade 3/4

n1

[%]

n2

[%]

Hematologic toxicities

Anemia

37

72.5

4

7.8

Neutropenia

23

45.1

11

21.6

Thrombocytopenia

10

19.6

2

3.9

Nonhematologic toxicities

Infection with neutropenia

0

0

0

0

Infusion reaction

6

11.8

0

0

Mouth ulcer

20

39.2

0

0

Anorexia

39

76.5

1

1.9

Vomiting

10

19.6

0

0

Diarrhea

17

33.3

0

0

Peripheral neuropathy

26

51.0

0

0

Renal toxicity

0

0

0

0

Cardiac toxicity

0

0

0

0

Hepatic dysfunction

18

35.3

0

0

Discussion

Breast cancer patients with HER2 overexpression typically demonstrate a poor prognosis due to high malignancy. In the adjuvant setting, this poor prognosis has been significantly improved by anti-HER2 therapy with trastuzumab [24]. In the neoadjuvant setting, the addition of a HER2-targeted therapy to chemotherapy has resulted in an increased rate of pCR and improved DFS and OS [25]. In recent years, the TCH regimen has been increasingly used in some countries but in Vietnam, this regimen has not been widely applied. Our study aimed to evaluate the safety and efficacy of the TCH regimen in a neoadjuvant setting for HER2-positive breast cancer in daily clinical practice. The ORR and pCR were obtained in 92.2% and 41.2% patients, respectively. This result was slightly lower than the results described in previous publications (Tab. 5 [15, 17, 23, 26, 27]). Sugitani et al. [17] reported on 50 HER2-positive patients with stage IIII invasive breast cancer, a pCR of 52% with the TCH regimen. Meanwhile, a retrospective analysis of Echavarria et al. [15] on 84 HER2-positive patients with stage IIII receiving the same regimen demonstrated that clinical characteristics were 2.4%, 65.5%, and 32.1% for stages I, II, and III, respectively, and the pCR rate was 47.6%. In another study of 39 BC patients who were treated with AC-TH or TCH regimens, Phung et al. [28] showed that clinical complete response (cCR) and pCR rate was obtained in 33.3% and 64.1%, respectively. This observed difference may be due to slightly different patient characteristics. Notably, our cohort had a lower proportion of patients with HR-negative disease (25.5%) as compared to Echavarria et al.’s [15] (45.5%) and Sugitani et al.’s [17] (50.0%) research, which is a subset known to be more sensitive to NAC. Additionally, in our study, another reason is that stage III patients were accounted for a higher percentage than in other studies.

Table 5. Clinical trials and observational analysis on the use of docetaxelcarboplatintrastuzumab regimen

n

cCR [%]

PR [%]

ORR [%]

ypT0/isN0 [%]

Design

Sugitani et al. [17]

50

10

56

66

52

Phase II trial

Echavarria et al. [15]

84

34.5

63.1

97.6

47.6

Retrospective analysis

Coudert et al. [23]

70

85

10

95

39

Phase II trial

Kolberg et al. [26]

78

43.6

Retrospective analysis

Bayraktar et al. [27]

65

58.9

19.6

78.5

43.3

Retrospective analysis

Previous meta-analyses demonstrated lower pCR rates in luminal/HER2 than in non-luminal/HER2 tumors. The KRISTINE trial showed that HR-negative breast cancer patients had up to 19% higher pCR rates than HR-positive patients [29]. This discrepancy might be explained that PIK3CA mutations are associated with reduced rates of pCR to anti-HER2 therapy in HER2-positive/HR-positive tumors [30, 31]. In our study, patients with hormone receptor-negative tumors also had a better response to chemotherapy than the ones with HR-positive tumors (61.5% vs. 34.2%). However, we did not observe a statistically significant difference in the pCR rate between two groups, which could be due to our relatively small sample size. Our results show that higher cT-stages have significantly lower pCR rates than lower cT-stages (cT3-4 vs. cT1-2; p < 0.033). The cT-stage is one of the most important predictors of pCR in breast cancer patients. A study by Caudle et al. [32] on 1 762 patients showed that the tumor stage was a predictive factor of disease progression. Jin et al. [33] also concluded that tumor size was an independent predictor of pathological complete response. The patients with larger tumor sizes were less likely to achieve pCR than those with smaller tumor sizes. The pCR rates for cT1, cT2, cT3, and cT4 were 23.6%, 13.6%, 11.9%, and 10.3%, respectively [33]. Goorts et al. [34] (n = 2 366) showed that for cT1, cT2, cT3, and cT4, pCR rates were 31%, 22%, 18%, and 17%, respectively. Lower cT-stage was a significant predictor of higher pCR rate (p < 0.001) [34]. So, clinicians should take cT-stage into account when estimating the likelihood of achieving pCR in an individual patient.

In our study, the median follow-up was 33.0 months. Two patients died at 31 months and 34 months and both of these patients did not achieve pCR after NAC. Estimated 3-year OS and DFS were 93.0% and 81.3%, respectively. In addition, 3-year DFS was better in the pCR group than in the non-pCR group (89.7% vs. 72.3%) although there was no significant difference, which may be due to the small study population and inadequate follow-up time. In addition, we found that patients who achieved pCR after NAC had better long-term outcomes despite not achieving statistical significance due to low event data [35].

The TCH regimen was generally well tolerated. Most adverse events were manageable. All the patients were able to complete the planned number of chemotherapy cycles. Anemia (7.8%), grade 3/4 neutropenia (21.6%), and thrombocytopenia (3.9%) were the most common adverse events. No patient experienced febrile neutropenia. In the TRYPHAENA trial, grade 3/4 neutropenia and febrile neutropenia were 46% and 17%, respectively. A study by Sugitani et al. [17] on breast cancer patients treated with a TCH regimen showed grade 3/4 neutropenia (36%), anemia (12%), thrombocytopenia (2%), and febrile neutropenia (6%). Echavarria et al. [15] reported febrile neutropenia and grade 34 neutropenia accounting for 6.0% and 16.7% of patients. Patients in our study had a considerably lower rate of adverse events presumably due to prophylactic administration of filgrastim to all patients.

None of the patients developed clinical congestive heart failure during the follow-up period. The safety of this regimen and reduced cardiac complication has also been demonstrated in previous studies in adjuvant and neoadjuvant settings [17, 18]. The BCIRG-006 study found that the anthracycline-free 1-year TCH regimen was associated with a lower risk of asymptomatic LVEF decline (9.4%) and congestive cardiac failure (CCF) (0.4%) compared to doxorubicin, cyclophosphamide, docetaxel, and trastuzumab (18.6% LVEF decline, 2% CCF) or doxorubicin, cyclophosphamide, and docetaxel (11.2% LVEF decline, 0.7% CCF) [24]. When compared to other regimens that do not contain anthracyclines, the TCH regimen generally has a more favorable safety profile with regard to neutropenia and febrile neutropenia. On the other hand, patients treated with TCH regimens were associated with a significant reduction of cardiotoxicity [17, 24]. A study in Poland on 34 breast cancer patients treated with Neoadjuvant Pertuzumab Plus Trastuzumab in Combination with Docetaxel and Carboplatin regimen confirmed that the regimen is safe and relatively effective. No patients with myocardial dysfunction or a significant decrease in LVEF were observed [36].

Our study has a few limitations. Besides the retrospective nature, the relatively small sample size and short follow-up period may have precluded more significant results regarding predictive factors of pCR, DFS, or OS. Further studies with larger sample sizes may need to be conducted to fulfill these limitations.

Conclusions

In conclusion, neoadjuvant chemotherapy with a TCH regimen showed promising efficacy in HER2- -positive breast cancer with high clinical and pathological CR rates while being safe and well-tolerated. This regimen should be used more in the neoadjuvant setting, especially in cases of concern with anthracycline toxicity.

Article Information and Declarations

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Ethics statement

This study was approved by the research committee of Vietnam’s National Cancer Hospital under number: 2147/QD-BVK.

Written informed consent was obtained for all patients before enrolling them in the study.

Author contributions

D.T.L.: should be considered the major author. He participated directly in diagnosis, treatment, and follow-up of the patients, performed the literature review, and assisted in drafting parts of the study and formatting the presented material.

K.H.D. and T.A.D.: took part in the diagnostic and treatment consultant and, assisted in the literature review.

L.T.B.: performed patient follow-up, review of patients’ records, literature review, and assisted in drafting parts of the study.

C.V.N.: performed diagnostic consultation on the HE stains and immunohistochemical staining, and assisted in the literature review, drafting parts of the study, and formatting the presented material.

Funding

By the authors.

Acknowledgments

The authors would like to thank the participants of this study.

Conflict of interest

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

  1. Jenkins C, Minh LN, Anh TT, et al. Breast cancer services in Vietnam: a scoping review. Glob Health Action. 2018; 11(1): 1435344, doi: 10.1080/16549716.2018.1435344, indexed in Pubmed: 29473488.
  2. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209249, doi: 10.3322/caac.21660, indexed in Pubmed: 33538338.
  3. Borg A, Tandon AK, Sigurdsson H, et al. HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res. 1990; 50(14): 43324337, indexed in Pubmed: 1973070.
  4. Gogia A, Deo SVs, Shukla NK, et al. Clinicopathological profile of breast cancer: An institutional experience. Indian J Cancer. 2018; 55(3): 210213, doi: 10.4103/ijc.IJC_73_18, indexed in Pubmed: 30693880.
  5. Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014; 106(5), doi: 10.1093/jnci/dju055, indexed in Pubmed: 24777111.
  6. Kaufmann M, von Minckwitz G, Bear HD, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007; 18(12): 19271934, doi: 10.1093/annonc/mdm201, indexed in Pubmed: 17998286.
  7. Kaufmann M, von Minckwitz G, Smith R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol. 2003; 21(13): 26002608, doi: 10.1200/JCO.2003.01.136, indexed in Pubmed: 12829681.
  8. Mieog JSD, van der Hage JA, van de Velde CJH. Neoadjuvant chemotherapy for operable breast cancer. Br J Surg. 2007; 94(10): 11891200, doi: 10.1002/bjs.5894, indexed in Pubmed: 17701939.
  9. Jackisch C, Harbeck N, Huober J, et al. 14th St. Gallen International Breast Cancer Conference 2015: Evidence, Controversies, Consensus - Primary Therapy of Early Breast Cancer: Opinions Expressed by German Experts. Breast Care (Basel). 2015; 10(3): 211219, doi: 10.1159/000433590, indexed in Pubmed: 26557827.
  10. Brandão M, Reyal F, Hamy AS, et al. Neoadjuvant treatment for intermediate/high-risk HER2-positive and triple-negative breast cancers: no longer an ‘option’ but an ethical obligation. ESMO Open. 2019; 4(3): e000515, doi: 10.1136/esmoopen-2019-000515, indexed in Pubmed: 31231570.
  11. Reyal F, Hamy AS, Piccart MJ. Neoadjuvant treatment: the future of patients with breast cancer. ESMO Open. 2018; 3(4): e000371, doi: 10.1136/esmoopen-2018-000371, indexed in Pubmed: 29862051.
  12. Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007; 25(28): 44144422, doi: 10.1200/JCO.2007.10.6823, indexed in Pubmed: 17785706.
  13. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014; 32(33): 37443752, doi: 10.1200/JCO.2014.55.5730, indexed in Pubmed: 25332249.
  14. Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012; 2012(4): CD006243, doi: 10.1002/14651858.CD006243.pub2, indexed in Pubmed: 22513938.
  15. Echavarria I, Granja M, Bueno C, et al. Multicenter analysis of neoadjuvant docetaxel, carboplatin, and trastuzumab in HER2-positive breast cancer. Breast Cancer Res Treat. 2017; 162(1): 181189, doi: 10.1007/s10549-016-4098-z, indexed in Pubmed: 28040858.
  16. Pegram MD, Konecny GE, O’Callaghan C, et al. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst. 2004; 96(10): 739749, doi: 10.1093/jnci/djh131, indexed in Pubmed: 15150302.
  17. Sugitani I, Ueda S, Sakurai T, et al. Neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin administered every 3 weeks for Japanese women with HER2-positive primary breast cancer: efficacy and safety. Int J Clin Oncol. 2017; 22(5): 880886, doi: 10.1007/s10147-017-1136-8, indexed in Pubmed: 28547525.
  18. Chen W, He J, Song S, et al. Efficacy of TCH/TEC neoadjuvant chemotherapy for the treatment of HER-2-overexpressing breast cancer. Oncol Lett. 2015; 9(4): 19221926, doi: 10.3892/ol.2015.2912, indexed in Pubmed: 25789069.
  19. Lin C, Chen DR, Chang KJ, et al. A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin and trastuzumab for T2 breast cancers. Cancer Chemother Pharmacol. 2012; 69(5): 13631368, doi: 10.1007/s00280-012-1841-y, indexed in Pubmed: 22349922.
  20. Shinde AM, Zhai J, Yu KW, et al. Pathologic complete response rates in triple-negative, HER2-positive, and hormone receptor-positive breast cancers after anthracycline-free neoadjuvant chemotherapy with carboplatin and paclitaxel with or without trastuzumab. Breast. 2015; 24(1): 1823, doi: 10.1016/j.breast.2014.10.008, indexed in Pubmed: 25467313.
  21. De Iuliis F, Salerno G, Corvino R, et al. Anthracycline-Free Neoadjuvant Chemotherapy Ensures Higher Rates of Pathologic Complete Response in Breast Cancer. Clin Breast Cancer. 2017; 17(1): 3440, doi: 10.1016/j.clbc.2016.06.010, indexed in Pubmed: 27435626.
  22. Tiwari SR, Mishra P, Raska P, et al. Retrospective study of the efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab (TCH-P) in nonmetastatic HER2-positive breast cancer. Breast Cancer Res Treat. 2016; 158(1): 189193, doi: 10.1007/s10549-016-3866-0, indexed in Pubmed: 27324504.
  23. Coudert BP, Largillier R, Arnould L, et al. Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial. J Clin Oncol. 2007; 25(19): 26782684, doi: 10.1200/JCO.2006.09.9994, indexed in Pubmed: 17515572.
  24. Slamon D, Eiermann W, Robert N, et al. Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011; 365(14): 12731283, doi: 10.1056/NEJMoa0910383, indexed in Pubmed: 21991949.
  25. Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010; 28(12): 20242031, doi: 10.1200/JCO.2009.23.8451, indexed in Pubmed: 20308678.
  26. Kolberg HC, Akpolat-Basci L, Stephanou M, et al. Neoadjuvant Chemotherapy with Docetaxel, Carboplatin and Weekly Trastuzumab Is Active in HER2-Positive Early Breast Cancer: Results after a Median Follow-Up of over 4 Years. Breast Care (Basel). 2016; 11(5): 323327, doi: 10.1159/000452079, indexed in Pubmed: 27920627.
  27. Bayraktar S, Gonzalez-Angulo AM, Lei X, et al. Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline- and nonanthracycline-based regimens for HER2-positive breast cancer. Cancer. 2012; 118(9): 23852393, doi: 10.1002/cncr.26555, indexed in Pubmed: 21953213.
  28. Phung HT, Nguyen HT, Nguyen TV, et al. Pathological Complete Response with Neoadjuvant Trastuzumab Combined with Chemotherapy in HER2 Positive Breast Cancer: A Single Institution Retrospective Analysis from Vietnam. Breast Cancer (Dove Med Press). 2020; 12: 117122, doi: 10.2147/BCTT.S268369, indexed in Pubmed: 33116816.
  29. Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018; 19(1): 115126, doi: 10.1016/S1470-2045(17)30716-7, indexed in Pubmed: 29175149.
  30. Loibl S, Majewski I, Guarneri V, et al. PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab. Ann Oncol. 2016; 27(8): 15191525, doi: 10.1093/annonc/mdw197, indexed in Pubmed: 27177864.
  31. Loibl S, von Minckwitz G, Schneeweiss A, et al. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 2014; 32(29): 32123220, doi: 10.1200/JCO.2014.55.7876, indexed in Pubmed: 25199759.
  32. Caudle AS, Gonzalez-Angulo AM, Hunt KK, et al. Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010; 28(11): 18211828, doi: 10.1200/JCO.2009.25.3286, indexed in Pubmed: 20231683.
  33. Jin Xi, Jiang YZ, Chen S, et al. A nomogram for predicting pathological complete response in patients with human epidermal growth factor receptor 2 negative breast cancer. BMC Cancer. 2016; 16: 606, doi: 10.1186/s12885-016-2652-z, indexed in Pubmed: 27495967.
  34. Goorts B, van Nijnatten TJA, de Munck L, et al. Clinical tumor stage is the most important predictor of pathological complete response rate after neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2017; 163(1): 8391, doi: 10.1007/s10549-017-4155-2, indexed in Pubmed: 28205044.
  35. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014; 384(9938): 164172, doi: 10.1016/S0140-6736(13)62422-8, indexed in Pubmed: 24529560.
  36. Jagiełło-Gruszfeld AI, Rosinska M, Meluch M, et al. Neoadjuvant Pertuzumab Plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2-Positive Breast Cancer: Real-World Data from the National Institute of Oncology in Poland. Cancers (Basel). 2022; 14(5), doi: 10.3390/cancers14051218, indexed in Pubmed: 35267525.