
==== Front
World J Surg Oncol
World J Surg Oncol
World Journal of Surgical Oncology
1477-7819
BioMed Central London

3535
10.1186/s12957-024-03535-x
Research
Clinicopathological characteristics and survival analysis of different molecular subtypes of breast invasive ductal carcinoma achieving pathological complete response through neoadjuvant chemotherapy
Xiao Cheng
Guo Yao
Xu Yang
Huang Junhua
Li Junyan drli_jy@163.com

https://ror.org/03gxy9f87 grid.459428.6 Cancer Prevention and Treatment Institute of Chengdu, Department of Thyroid and Breast Surgery, Chengdu Fifth People’s Hospital (Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), NO.33 Ma Shi Street, Wenjiang District, Chengdu, 611137 China
16 9 2024
16 9 2024
2024
22 25028 3 2024
9 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma.

Methods

Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan–Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots.

Results

This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan–Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05).

Conclusions

Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12957-024-03535-x.

Keywords

Breast invasive ductal carcinoma
Pathologic complete response
Overall survival
Cancer-specific survival
Neoadjuvant chemotherapy
issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

The incidence rate of breast cancer has shown an annual increase in recent years. According to statistics from the Global Cancer Center in 2020, the incidence rate of breast cancer among women has surpassed that of lung cancer, becoming the most common cancer. Breast cancer is also the leading cause of cancer death among women [1]. Chemotherapy can significantly improve the prognosis of breast cancer. It plays a crucial role in the treatment regimen for breast cancer. Depending on the timing of chemotherapy and surgery, it can be divided into adjuvant chemotherapy (post-operative chemotherapy) and neoadjuvant chemotherapy (pre-operative chemotherapy). Studies show that for early breast cancer, both adjuvant and neoadjuvant chemotherapy have no significant difference in distant recurrence and breast cancer mortality rates, and both offer similar survival benefits [2]. However, neoadjuvant chemotherapy can reduce the size of the tumor and downstage it, increasing the opportunity for breast-conserving therapy. Moreover, neoadjuvant chemotherapy can serve as a means for drug sensitivity testing, allowing for the understanding of the tumor’s individual sensitivity to a specific regimen, and thereby providing a basis for adjusting the treatment plan among other advantages.

The selection of neoadjuvant chemotherapy regimens is closely related to the molecular subtyping of breast cancer. According to the ASCO guidelines and the St. Gallen International Breast Cancer Expert Consensus, based on the immunohistochemical expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67, breast cancer is classified into four molecular subtypes, including HR + /HER-2 + , HR + /HER-2-, HR-/HER-2 + , and HR-/HER-2- [3]. Based on the RECIST criteria for solid tumors, studies have shown that breast cancer patients achieving pCR after neoadjuvant chemotherapy have a longer disease-free survival and overall survival compared to those who do not reach pCR, especially in HER-2 positive and triple-negative breast cancer cases [4]. However, there is limited research on the survival differences among various molecular subtypes in breast cancer patients who achieve pCR after neoadjuvant chemotherapy. In this study, we conducted a retrospective analysis of patients with invasive ductal carcinoma who achieved pCR after neoadjuvant chemotherapy, using data from the SEER (Surveillance, Epidemiology, and End Results) database from 2010 to 2019, to investigate the correlation between different molecular types and patient prognosis.

Material and methods

Data collection

This study extracted case data of patients with invasive ductal carcinoma of the breast from the SEER database. Inclusion criteria were: (I) Pathologically confirmed invasive ductal carcinoma, (II) Female patients, (III) Pathological complete response after neoadjuvant chemotherapy, and (IV) Cases from the year 2010 to 2019. The exclusion criteria included: (I) Male patients, (II) Patients with unknown molecular subtypes, (III) Patients who had not undergone surgery after neoadjuvant chemotherapy, (IV) Cases with distant metastasis, and (V) Missing survival or other critical variable data. After the screening process, a total of 9,380 patients met the inclusion criteria and were subsequently included in the study. The data selection process is detailed in Fig. 1.Figure1 Flowchart of data filtering process in the SEER database

Study variables

For each patient, we collected data on the age at diagnosis, race, histological grade, TNM staging (according to the 8th edition of the AJCC staging system), estrogen receptor (ER) status, progesterone receptor (PR) status, HER-2 status, surgical treatment, radiation therapy, survival time, overall survival and cancer-specific survival. Based on the status of ER, PR, and HER-2, patients were classified into four molecular subtypes: HR + /HER-2 + , HR + /HER2-, HR-/HER2 + and HR-/HER-2-. The prognostic indicators are overall survival (OS) and cancer-specific survival (CSS).

Statistical analysis

Statistical analysis was conducted using Stata 17.0, R studio 4.0.3, and SPSS 23.0 (Chicago, Illinois, USA). Categorical variables were presented as counts and frequencies (%), analyzed using Fisher’s exact test or Pearson’s chi-square test. The Kaplan–Meier method was used for survival analysis between different subgroups, with the log-rank test applied to calculate the differences in survival rates between groups. Univariate and multivariate Cox regression analyses were utilized to identify independent prognostic factors. Propensity score matching (PSM) was adopted to minimize potential confounders and selection bias. After psm, the forest plot was used to evaluate differences in OS between subgroups of HR + /HER-2 + and HR + /HER-2- patients. A two-tailed P-value of less than 0.05 was considered statistically significant.

Results

This study included a total of 9380 patients with invasive ductal carcinoma of the breast, with a median follow-up time of 35 months and a maximum follow-up time of 119 months. The study population comprised White, Black, and other races (including American Indian, Asian, or Pacific Islander), with the highest prevalence among Whites at 73.31%. Furthermore, the proportions of patients under 50 years old in the HR + /HER2-, HR-/HER2 + , HR + /HER2 + , and HR-/HER2- groups were 54.67%, 40.2%, 50.35%, and 51.82%, respectively, with the highest proportion in the HR + /HER2- group (p < 0.01). Of the cases above, 4211 patients underwent breast-conserving surgery, while 5169 received a mastectomy. Aside from the application of radiotherapy, statistical differences (p < 0.05) were observed in the distribution of patient age, race, histological grade, T stage, N stage, and surgery approach among different molecular subtypes. The baseline characteristics of the patients are provided in detail in Table 1. Significant differences were observed in pathological complete response rates among different molecular subtypes after neoadjuvant chemotherapy (p < 0.01). The pCR rates for HR + /HER-2 + , HR + /HER-2-, HR-/HER-2 + , and HR-/HER-2- molecular subtypes were 37.89%, 15.49%, 54.88%, and 36.88% (with details in the supplementary materials). Table 1 Clinicopathological characteristics of different molecular subtypes

Characteristics	All patients
n = 9380	HR + /HER-2 + 
n = 2721	HR + /HER-2-
n = 1661	HR-/HER-2 + 
n = 2082	HR-/HER-2-
n = 2916	P value	
Age(Mean ± SD)	51.04(± 11.95)	50.91(± 11.90)	49.59(± 11.99)	53.14(± 11.48)	50.49(± 12.10)	 < 0.01	
 ≤ 50(%)	4626(49.32)	1370 (50.35)	908 (54.67)	837 (40.20)	1511 (51.82)		
 > 50(%)	4754(50.68)	1351 (49.65)	753 (45.33)	1245 (59.80)	1405 (48.18)		
Race,n(%)						 < 0.01	
 Black	1311(13.98)	257 (9.45)	263 (15.83)	227 (10.90)	564 (19.34)		
 Others	1192(12.71)	405 (14.88)	180 (10.84)	332 (15.95)	275 (9.43)		
 White	6877(73.31)	2059 (75.67)	1218 (73.33)	1523 (73.15)	2077 (71.23)		
T stage,n(%)	
 T1	2136(22.77)	636 (23.37)	372 (22.40)	457 (21.95)	671 (23.01)	 < 0.01	
 T2	5329(56.81)	1521 (55.90)	948 (57.07)	1118 (53.70)	1742 (59.74)		
 T3	1260(13.43)	383 (14.08)	209 (12.58)	333 (15.99)	335 (11.49)		
 T4	655(6.99)	181 (6.65)	132 (7.95)	174 (8.36)	168 (5.76)		
N stage,n(%)						 < 0.01	
 N0	4882(52.05)	1377 (50.61)	745 (44.85)	999 (47.98)	1761 (60.39)		
 N1	3716(39.62)	1147 (42.15)	730 (43.95)	902 (43.32)	937 (32.13)		
 N2	396(4.22)	102 (3.75)	104 (6.26)	81 (3.89)	109 (3.74)		
 N3	386(4.11)	95 (3.49)	82 (4.94)	100 (4.80)	109 (3.74)		
Grade,n(%)						 < 0.01	
 1	160(1.71)	69 (2.54)	55 (3.31)	25 (1.20)	11 (0.38)		
 2	2200(23.45)	959 (35.24)	385 (23.18)	526 (25.26)	330 (11.32)		
 3	7020(74.84)	1693 (62.22)	1221 (73.51)	1531 (73.54)	2575 (88.30)		
Radiation,n(%)						0.06	
 No	3530(37.63)	1073 (39.43)	588 (35.40)	783 (37.61)	1086 (37.24)		
 Yes	5850(62.37)	1648 (60.57)	1073 (64.60)	1299 (62.39)	1830 (62.76)		
Surgery,n(%)						0.02	
 Breast conserving	4211(44.89)	1207 (44.36)	720 (43.35)	905 (43.47)	1379 (47.29)		
 Mastectomy	5169 (55.11)	1514 (55.64)	941 (56.65)	1177 (56.53)	1537 (52.71)		
Cancer-specific death,n(%)						 < 0.01	
 No	9065(96.64)	2680(98.49)	1557(93.74)	2025(97.26)	2803(96.12)		
 Yes	315(3.36)	41(1.51)	104(6.26)	57(2.74)	113(3.88)		
Overall survival,n(%)						 < 0.01	
 No	387(4.13)	59 (2.17)	123(7.41)	72(3.46)	133(4.56)		
 Yes	8993(95.87)	2662(97.83)	1538(92.59)	2010(96.54)	2783(95.44)		

In the univariate analysis, molecular subtype, T stage, N stage, radiation therapy, and surgery approach were related to OS and CSS, while age is only associated with the OS. Multivariate analysis identified molecular subtype as an independent risk factor for OS and CSS in patients (Table 2). Compared to patients in the HR + /HER-2 + positive group, other molecular subtypes of breast cancer exhibited poorer CSS, with the HR + /HER-2- subtype displaying the lowest OS (HR = 2.95, 95%CI:2.16–4.02, P < 0.05) and CSS (HR = 3.68, 95%CI:2.57–5.29, P < 0.05). The Kaplan–Meier (KM) curves based on molecular subtypes were presented in Fig. 2. Table 2 Univariate and multivariate cox regression analyses of CSS and OS

Characteristics	Cancer-specific survival	Overall survival	
Univariate	Multivariate	Univariate	Multivariate	
HR (95%CI)	P	HR (95%CI)	P	HR (95%CI)	P	HR (95%CI)	P	
Age	
  ≤ 50	ref		-		ref		ref		
  > 50	1.16(0.93–1.45)	0.189	-	0.102	1.43(1.16–1.75)	 < 0.01	1.02(1.01–1.03)	 < 0.01	
Race	
 Black	ref		-		ref		-		
 Others	0.65(0.41–1.03)	0.067	-		0.69(0.46–1.07)	0.099	-		
 White	0.87(0.64–1.17)	0.360	-		0.86(0.72–1.47)	0.761	-		
Subtype	
 HR + /HER-2 + 	ref		ref		ref		ref		
 HR + /HER-2-	3.68(2.57–5.29)	 < 0.01	3.52(2.45–5.05)	 < 0.01	2.99(2.19–4.09)	 < 0.01	2.95(2.16–4.02)	 < 0.01	
 HR-/HER-2 + 	1.82(1.22–2.73)	 < 0.01	1.78(1.19–2.66)	 < 0.01	1.61(1.14–2.27)	 < 0.01	1.49(1.06–2.10)	0.024	
 HR-/HER-2-	2.51(1.75–3.59)	 < 0.01	2.91(2.03–4.17)	 < 0.01	2.04(1.49–2.77)	 < 0.01	2.33(1.71–3.17)	 < 0.01	
T stage	
 T1	ref		ref		ref		ref		
 T2	1.30(0.93–1.83)	0.12	1.18(0.84–1.65)	0.345	1.31(0.97–1.77)	0.074	1.22(0.91–1.65)	0.187	
 T3	1.62(1.08–2.42)	0.02	1.20(0.79–1.81)	0.401	1.62(1.08–2.42)	0.033	1.25(0.86–1.83)	0.239	
 T4	4.27(2.93–6.22)	 < 0.01	2.17(1.45–3.25)	 < 0.01	4.06(2.89–5.70)	 < 0.01	2.32(1.61–3.35)	 < 0.01	
N stage	
 N0	ref		ref		ref		ref		
 N1	2.31(1.75–3.05)	 < 0.01	2.04(1.53–2.72)	 < 0.01	1.98(1.56–2.51)	 < 0.01	1.81(1.41–2.31)	 < 0.01	
 N2	4.32(2.88–6.47)	 < 0.01	3.11(2.05–4.74)	 < 0.01	3.09(2.11–4.52)	 < 0.01	2.29(1.55–3.41)	 < 0.01	
 N3	8.63(6.14–12.13)	 < 0.01	6.21(4.31–8.95)	 < 0.01	6.40(4.69–8.74)	 < 0.01	4.71(3.37–6.58)	 < 0.01	
Grade	
 I	ref				ref				
 II	1.65(0.52–5.25)	0.369	-		1.21(0.49–2.99)	0.674	-		
 III	1.90(0.61–5.94)	0.269	-		1.40(0.58–3.38)	0.458	-		
Surgery	
 Breast conserving	ref		ref		ref		ref		
 Mastectomy	1.81(1.42–2.31)	 < 0.01	1.44(1.09–1.89)	0.008	1.44(1.17–1.78)	 < 0.01	1.26(0.99–1.60)	0.042	
Radiotherapy	
 No	ref		ref		ref		ref		
 Yes	1.71(1.33–2.19)	 < 0.01	1.38(1.05–1.81)	0.019	1.54(1.23–1.92)	 < 0.01	1.25(0.99–1.59)	0.063	

Figure. 2 Kaplan–Meier plots for patient outcomes. A Cancer-specific survival for patients in different molecular subtypes (p < 0.001). B Overall survival for patients in different molecular subtypes (p < 0.001)

This study discovered significant prognostic differences across molecular subtypes in patients with breast invasive ductal carcinoma after achieving a pathologic complete response (pCR) through neoadjuvant chemotherapy. HR + /HER-2- group was associated with the poorest outcomes, and patients with HR + /HER-2 + showed the highest OS and CSS (p < 0.05). To address potential selection biases highlighted by significant differences in baseline characteristics in our retrospective analysis, we applied propensity score matching for age, race, T stage, N stage, histological grade, radiation therapy, and surgery approach between the HR + /HER-2- and HR + /HER-2 + groups. After propensity score matching, both the HR + /HER2- and HR + /HER2 + groups had 1,647 patients. Following this matching (with details in the supplementary materials), Kaplan–Meier analysis indicated that OS and CSS in HR + /HER-2 + patients were significantly higher than HR + /HER-2- patients (p < 0.05) (Fig. 3). Subgroup analysis forest plots revealed that the HR + /HER-2 + group exhibited a higher OS in White, histological grades II and III, T2 stage, N0 and N1 stages, and across all age groups, surgery approach, and radiation therapy subgroups (p < 0.05) (Fig. 4).Fig. 3 A Overall survival in the HR + /HER-2 + group compared to the HR + /HER-2- group. B Cancer-specific survival in the HR + /HER-2 + group compared to the HR + /HER-2- group

Fig. 4 The forest plot of OS for different subgroups between HR + /HER-2 + and HR + /HER-2- after propensity score matching

Discussion

Neoadjuvant chemotherapy is a pivotal component in the management of breast cancer, with its efficacy significantly correlated to the molecular subtype and stage of the disease. It is administered to approximately 17–40% of patients with early-stage breast cancer, aiming for the optimal outcome of a pathological complete response (pCR) [5, 6]. Nonetheless, the pCR rates after neoadjuvant chemotherapy vary across different molecular subtypes of breast cancer. Reports suggest that HER-2 + patients have a pCR rate of around 40%, triple-negative breast cancer exhibits a pCR rate of approximately 23%, and HR + /HER-2- breast cancer has a notably low pCR rate of only 9.1% [7–10]. Despite these differences, there is a paucity of research on the prognostic implications post-pCR across these molecular subtypes. Our study, utilizing a comprehensive retrospective analysis of the SEER database, indicates that HR + /HER-2 + patients exhibit the best OS and CSS following pCR achieved through neoadjuvant treatment, outperforming other molecular subtypes. Conversely, the prognosis for HR + /HER-2- patients is significantly poorer.

Nadia Howlader et al. conducted a retrospective analysis through the SEER database on the overall 4-year survival rate of 196,094 female patients with invasive breast cancer from 2010 to 2014. They found that the survival rates for patients with HR + /HER2- and HR + /HER2 + subtypes were similar, at 92.5% versus 90.3% respectively. Moreover, among patients with initial stage IV disease, those with the HR + /HER2 + subtype had a better survival rate compared to those with the HR + /HER2- subtype (45.5% vs 35.9%) [11]. The Kaplan Meier survival curve in our study indicated that patients with invasive ductal carcinoma who received neoadjuvant chemotherapy and achieved the pCR had a higher CSS rate in the HR + /HER-2 + group. This could be associated with the use of targeted treatment drugs for patients with HER-2 + . In the KRISTINE phase 3 trial, a pathological complete response was achieved by 55.7% in the docetaxel, carboplatin, and trastuzumab plus pertuzumab neoadjuvant therapy group [12]. In the CLEOPATRA clinical trial, 402 patients with HER-2 + metastatic breast cancer treated with Pertuzumab, Trastuzumab, and Docetaxel had a median survival of nearly 5 years (57.1 months), significantly exceeding the early estimated median survival of about 2 years [13]. In addition, other drugs targeting HER-2, such as Lapatinib, Pyrotinib, and T-DM1, have been incorporated into clinical guidelines and practice. These drugs can be combined with endocrine therapy, chemotherapy, or each other, making the treatment options for HR + /HER2 + subtypes more extensive than those for other types of breast cancer. This might explain the higher OS and CSS we observed.

Several studies report that HER-2 + and triple-negative patients have a high neoadjuvant response rate, achieving significant survival benefits after reaching pCR [14–16]. However, HR + /HER-2- early invasive cancer patients show a low response rate to neoadjuvant chemotherapy, and clinicians often prioritize surgery, followed mainly by endocrine therapy postoperatively [17]. Although HR + /HER-2- is the most common type of invasive breast cancer clinically, accounting for 60–70% of all breast cancer classifications [18]. Unlike other subtypes of breast cancer, the recurrence risk of HR + breast cancer extends from 5 years post-diagnosis to at least 20 years, with some patients potentially relapsing even 30 years after diagnosis [19]. Despite HR + /HER-2- breast cancer having a higher endocrine treatment response rate, the 5-year tumor-specific mortality rate still exceeds 30% in some high-recurrence risk patients [20]. The recurrence and metastasis of HR + /HER-2- breast cancer is closely related to intertumoral heterogeneity and endocrine resistance [21]. To enhance the precision treatment effectiveness for HR + /HER2- breast cancer, Zhi-Ming Shao et al. utilized multi-omics technologies to classify HR + /HER-2- type invasive breast cancer into four subtypes: canonical luminal subtype (SNF1), immunogenic subtype (SNF2), proliferative subtype (SNF3), RTK-driven subtype (SNF4). It was found that among these four subtypes, patients with the RTK-Driven type had the worst prognosis, with endocrine therapy being almost ineffective [22]. This may also result in a subset of HR + /HER-2- patients having a poor prognosis despite achieving pCR through neoadjuvant chemotherapy, followed by standardized surgery and endocrine therapy.

In addition to molecular subtypes, lymph node staging is also an important prognostic risk factor [23, 24]. Approximately 30% of breast cancer patients experience regional lymph node (LN) metastasis, which is associated with early recurrence and poor clinical prognosis. Elevated lymph node staging is frequently correlated with worse prognosis [25, 26]. Similar to previous studies, in the multivariable analysis of tumor-specific survival for invasive ductal carcinoma in this study, the hazard ratio for N3 significantly increased compared to N0 (HR = 6.17, 95%CI:4.28–8.89, P < 0.05), this suggested a deterioration in prognosis with increasing N staging. After neoadjuvant chemotherapy, patients whose axillary lymph nodes reached pCR had a better prognosis than those who did not reach pCR. However, there are differences in the pCR rates of axillary lymph nodes among patients with invasive breast cancer of different molecular subtypes. Sanaz Samiei et al. conducted a pooled analysis, encompassing 33 studies and a total of 57,531 patients. The results showed that the pCR rate in axillary lymph nodes was lowest for the HR + /HER-2- subtype of breast cancer, at 16%. For HR + /HER-2 + , HR-/HER-2 + , and HR-/HER-2- subtypes, the axillary lymph node pCR rates were 45%, 57%, and 47% respectively [27]. Rene Flores et al. discovered that, in comparison to other molecular subtypes, patients diagnosed with HR + /HER-2- breast cancer exhibited the greatest risk of their axillary lymph nodes failing to achieve a pathological complete response (pCR) following neoadjuvant chemotherapy (OR = 1.57, CI:1.41–1.74, p < 0.001) [28]. Among the four subtypes of invasive ductal carcinoma patients who achieved pathological complete response (pCR) after neoadjuvant chemotherapy, the HR + /HER-2- group had the highest proportion of N2 + N3, reaching 11.2%. Patients with the HR + /HER-2 subtype exhibited higher N staging and lower lymph node response rates to neoadjuvant chemotherapy, which may also be related to the observed lower overcomes.

Surgery approach is also an independent risk factor for OS and CSS. According to univariate analysis, comparing with breast-conserving surgery, total mastectomy had a worse OS(HR = 1.44, CI:1.17–1.78) and CSS (HR = 1.81, CI:1.42–2.31, p < 0.05). Yu-Chun Song et al. conducted a retrospective analysis of data from 730 patients who underwent neoadjuvant chemotherapy between 2000 and 2014, finding that patients in both the total mastectomy and breast-conserving surgery groups had similar 5-year rates of locoregional recurrence (LRR), distant metastases (DM), and disease-free survival (DFS). However, the breast-conserving surgery group had a significantly higher 5-year breast CSS (98.9% vs. 90.4%, p = 0.005) and OS (98.9% vs. 90.1%, P = 0.003) rates [29]. It is well-known that breast cancer patients undergoing mastectomy often present with larger tumors and a higher frequency of lymph node metastases compared to those who opt for breast-conserving surgery. To balance the baseline differences in factors other than the surgical method among breast cancer patients, Sungchan Gwark et al. utilized propensity score matching to evaluate 1641 patients undergoing neoadjuvant chemotherapy. Their findings indicated that breast-conserving surgery combined with radiotherapy leads to superior disease-free survival (DFS, p < 0.05), distant metastasis-free survival (DMFS, p < 0.05), and overall survival (OS, p < 0.05) in comparison to mastectomy [30]. Combining the results of this study with the latest related research, we found that choosing breast-conserving surgery after neoadjuvant chemotherapy offers better benefits in survival prognosis for patients.

This study has certain limitations. It is a database-based retrospective analysis, and the conclusions may be subject to potential unknown biases or confounding factors. There is a lack of data on the application of HER-2 + targeted drugs and endocrine therapy for HR + patients. Additionally, the SEER database has a short record time for neoadjuvant chemotherapy, lacking longer follow-up data. Moreover, there is a lack of external data validation and data on Disease-Free Survival (DFS) and Local Recurrence Rate (LRR), and this may have also affected the results of our systemic treatment analysis.

Conclusions

This study discovered that there are differences in the clinicopathological characteristics of different molecular subtypes of invasive ductal carcinoma of the breast that achieve pCR through neoadjuvant chemotherapy. Patients in the HR + /HER-2- group are typically younger, present with a more advanced lymph node stage, and exhibit the lowest survival rates. In contrast, patients in the HR + /HER-2 + group demonstrate the highest OS and CSS rates. Following the achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy, patients who undergo breast-conserving surgery significantly improved OS and CSS compared to those who undergoing mastectomy.

Supplementary Information

Supplementary Material 1.

Acknowledgements

None.

Authors’ contributions

XC and GY participated in study design. LJY and HJH undertook the research and performed the analyses. XC wrote the manuscript. XY contributed for overall editing and visualization. All the authors read and approved the final manuscript.

Funding

This work was supported by the Chengdu High-level Key Clinical Specialty Construction Project.

Availability of data and materials

In this study data are available from the Surveillance, Epidemiology, and End Results (SEER) database.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Ethical approval was waived by the Ethics Committee of Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine and The General Hospital of Western Theater Command in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

Competing interests

The authors declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Sung H Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries CA Cancer J Clin 2021 71 3 209 249 10.3322/caac.21660 33538338
Sung H, 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):209–49.33538338 10.3322/caac.21660
2. Early Breast Cancer Trialists' Collaborative, G. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27–39.
3. Waks AG Winer EP Breast cancer treatment: a review JAMA 2019 321 3 288 300 10.1001/jama.2018.19323 30667505
Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300.30667505 10.1001/jama.2018.19323
4. Hayashi N The prognostic effect of changes in tumor stage and nodal status after neoadjuvant chemotherapy in each primary breast cancer subtype Clin Breast Cancer 2018 18 2 e219 e229 10.1016/j.clbc.2017.09.013 29138067
Hayashi N, et al. The prognostic effect of changes in tumor stage and nodal status after neoadjuvant chemotherapy in each primary breast cancer subtype. Clin Breast Cancer. 2018;18(2):e219–29.29138067 10.1016/j.clbc.2017.09.013
5. Heil J Eliminating the breast cancer surgery paradigm after neoadjuvant systemic therapy: current evidence and future challenges Ann Oncol 2020 31 1 61 71 10.1016/j.annonc.2019.10.012 31912797
Heil J, et al. Eliminating the breast cancer surgery paradigm after neoadjuvant systemic therapy: current evidence and future challenges. Ann Oncol. 2020;31(1):61–71.31912797 10.1016/j.annonc.2019.10.012
6. Haque W Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy Breast Cancer Res Treat 2018 170 3 559 567 10.1007/s10549-018-4801-3 29693228
Haque W, et al. Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy. Breast Cancer Res Treat. 2018;170(3):559–67.29693228 10.1007/s10549-018-4801-3
7. Shubeck S Response to treatment, racial and ethnic disparity, and survival in patients with breast cancer undergoing neoadjuvant chemotherapy in the US JAMA Netw Open 2023 6 3 e235834 10.1001/jamanetworkopen.2023.5834 36995711
Shubeck S, et al. Response to treatment, racial and ethnic disparity, and survival in patients with breast cancer undergoing neoadjuvant chemotherapy in the US. JAMA Netw Open. 2023;6(3):e235834.36995711 10.1001/jamanetworkopen.2023.5834
8. Myers SP Association of tumor molecular subtype and stage with breast and axillary pathologic complete response after neoadjuvant chemotherapy for breast cancer Ann Surg Oncol 2021 28 13 8636 8642 10.1245/s10434-021-10195-8 34142288
Myers SP, et al. Association of tumor molecular subtype and stage with breast and axillary pathologic complete response after neoadjuvant chemotherapy for breast cancer. Ann Surg Oncol. 2021;28(13):8636–42.34142288 10.1245/s10434-021-10195-8
9. Teshome M Kuerer HM Breast conserving surgery and locoregional control after neoadjuvant chemotherapy Eur J Surg Oncol 2017 43 5 865 874 10.1016/j.ejso.2017.02.002 28284519
Teshome M, Kuerer HM. Breast conserving surgery and locoregional control after neoadjuvant chemotherapy. Eur J Surg Oncol. 2017;43(5):865–74.28284519 10.1016/j.ejso.2017.02.002
10. Choi HJ Factors affecting pathologic complete remission in patients with hormone receptor-positive and human epidermal growth factor receptor 2-Negative breast cancer receiving neoadjuvant chemotherapy Oncology 2022 100 10 529 535 10.1159/000526155 35882211
Choi HJ, et al. Factors affecting pathologic complete remission in patients with hormone receptor-positive and human epidermal growth factor receptor 2-Negative breast cancer receiving neoadjuvant chemotherapy. Oncology. 2022;100(10):529–35.35882211 10.1159/000526155
11. Howlader N Differences in breast cancer survival by molecular subtypes in the United States Cancer Epidemiol Biomarkers Prev 2018 27 6 619 626 10.1158/1055-9965.EPI-17-0627 29593010
Howlader N, et al. Differences in breast cancer survival by molecular subtypes in the United States. Cancer Epidemiol Biomarkers Prev. 2018;27(6):619–26.29593010 10.1158/1055-9965.EPI-17-0627
12. Hurvitz SA 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 1 115 126 10.1016/S1470-2045(17)30716-7 29175149
Hurvitz SA, 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):115–26.29175149 10.1016/S1470-2045(17)30716-7
13. Swain SM Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study Lancet Oncol 2020 21 4 519 530 10.1016/S1470-2045(19)30863-0 32171426
Swain SM, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519–30.32171426 10.1016/S1470-2045(19)30863-0
14. Stankowski-Drengler TJ Breast cancer outcomes of neoadjuvant versus adjuvant chemotherapy by receptor subtype: a scoping review J Surg Res 2020 254 83 90 10.1016/j.jss.2020.04.011 32422430
Stankowski-Drengler TJ, et al. Breast cancer outcomes of neoadjuvant versus adjuvant chemotherapy by receptor subtype: a scoping review. J Surg Res. 2020;254:83–90.32422430 10.1016/j.jss.2020.04.011
15. Salim DK Molecular types and neoadjuvant chemotherapy in patients with breast cancer- while molecular shifting is more common in luminal a tumors, the pathologic complete response is most frequently observed in her-2 like tumors Asian Pac J Cancer Prev 2014 15 21 9379 9383 10.7314/APJCP.2014.15.21.9379 25422228
Salim DK, et al. Molecular types and neoadjuvant chemotherapy in patients with breast cancer- while molecular shifting is more common in luminal a tumors, the pathologic complete response is most frequently observed in her-2 like tumors. Asian Pac J Cancer Prev. 2014;15(21):9379–83.25422228 10.7314/APJCP.2014.15.21.9379
16. Chen D Analysis of neoadjuvant chemotherapy for breast cancer: a 20-year retrospective analysis of patients of a single institution BMC Cancer 2023 23 1 984 10.1186/s12885-023-11505-x 37845617
Chen D, et al. Analysis of neoadjuvant chemotherapy for breast cancer: a 20-year retrospective analysis of patients of a single institution. BMC Cancer. 2023;23(1):984.37845617 10.1186/s12885-023-11505-x
17. Murphy BL Neoadjuvant chemotherapy use in breast cancer is greatest in excellent responders: triple-negative and HER2+ Subtypes Ann Surg Oncol 2018 25 8 2241 2248 10.1245/s10434-018-6531-5 29786125
Murphy BL, et al. Neoadjuvant chemotherapy use in breast cancer is greatest in excellent responders: triple-negative and HER2+ Subtypes. Ann Surg Oncol. 2018;25(8):2241–8.29786125 10.1245/s10434-018-6531-5
18. Lee JH Predicting the response of neoadjuvant chemotherapy in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer with axillary lymph node metastasis by multigene assay J Breast Cancer 2022 25 6 473 484 10.4048/jbc.2022.25.e49 36479604
Lee JH, et al. Predicting the response of neoadjuvant chemotherapy in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer with axillary lymph node metastasis by multigene assay. J Breast Cancer. 2022;25(6):473–84.36479604 10.4048/jbc.2022.25.e49
19. Pedersen RN The incidence of breast cancer recurrence 10–32 years after primary diagnosis J Natl Cancer Inst 2022 114 3 391 399 10.1093/jnci/djab202 34747484
Pedersen RN, et al. The incidence of breast cancer recurrence 10–32 years after primary diagnosis. J Natl Cancer Inst. 2022;114(3):391–9.34747484 10.1093/jnci/djab202
20. Lipsyc-Sharf M Circulating tumor DNA and late recurrence in high-risk hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer J Clin Oncol 2022 40 22 2408 2419 10.1200/JCO.22.00908 35658506
Lipsyc-Sharf M, et al. Circulating tumor DNA and late recurrence in high-risk hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. J Clin Oncol. 2022;40(22):2408–19.35658506 10.1200/JCO.22.00908
21. Pan H 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years N Engl J Med 2017 377 19 1836 1846 10.1056/NEJMoa1701830 29117498
Pan H, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–46.29117498 10.1056/NEJMoa1701830
22. Jin X Molecular classification of hormone receptor-positive HER2-negative breast cancer Nat Genet 2023 55 10 1696 1708 10.1038/s41588-023-01507-7 37770634
Jin X, et al. Molecular classification of hormone receptor-positive HER2-negative breast cancer. Nat Genet. 2023;55(10):1696–708.37770634 10.1038/s41588-023-01507-7
23. Huang X Exploring the most appropriate lymph node staging system for node-positive breast cancer patients and constructing corresponding survival nomograms J Cancer Res Clin Oncol 2023 149 16 14721 14730 10.1007/s00432-023-05283-z 37584708
Huang X, et al. Exploring the most appropriate lymph node staging system for node-positive breast cancer patients and constructing corresponding survival nomograms. J Cancer Res Clin Oncol. 2023;149(16):14721–30.37584708 10.1007/s00432-023-05283-z
24. Chang JM Axillary nodal evaluation in breast cancer: State of the art Radiology 2020 295 3 500 515 10.1148/radiol.2020192534 32315268
Chang JM, et al. Axillary nodal evaluation in breast cancer: State of the art. Radiology. 2020;295(3):500–15.32315268 10.1148/radiol.2020192534
25. Teng J Bayesian inference of lymph node ratio estimation and survival prognosis for breast cancer patients IEEE J Biomed Health Inform 2020 24 2 354 364 10.1109/JBHI.2019.2943401 31562112
Teng J, et al. Bayesian inference of lymph node ratio estimation and survival prognosis for breast cancer patients. IEEE J Biomed Health Inform. 2020;24(2):354–64.31562112 10.1109/JBHI.2019.2943401
26. Singh D Mandal A The prognostic value of lymph node ratio in survival of non-metastatic breast carcinoma patients Breast Cancer Res Treat 2020 184 3 839 848 10.1007/s10549-020-05885-y 32852709
Singh D, Mandal A. The prognostic value of lymph node ratio in survival of non-metastatic breast carcinoma patients. Breast Cancer Res Treat. 2020;184(3):839–48.32852709 10.1007/s10549-020-05885-y
27. Samiei S Axillary pathologic complete response after neoadjuvant systemic therapy by breast cancer subtype in patients with initially clinically node-positive disease: a systematic review and meta-analysis JAMA Surg 2021 156 6 e210891 10.1001/jamasurg.2021.0891 33881478
Samiei S, et al. Axillary pathologic complete response after neoadjuvant systemic therapy by breast cancer subtype in patients with initially clinically node-positive disease: a systematic review and meta-analysis. JAMA Surg. 2021;156(6):e210891.33881478 10.1001/jamasurg.2021.0891
28. Flores R Discordant breast and axillary pathologic response to neoadjuvant chemotherapy Ann Surg Oncol 2023 30 13 8302 8307 10.1245/s10434-023-14082-2 37606840
Flores R, et al. Discordant breast and axillary pathologic response to neoadjuvant chemotherapy. Ann Surg Oncol. 2023;30(13):8302–7.37606840 10.1245/s10434-023-14082-2
29. Song YC Breast-conserving surgery versus mastectomy for treatment of breast cancer after neoadjuvant chemotherapy Front Oncol 2023 13 1178230 10.3389/fonc.2023.1178230 37496664
Song YC, et al. Breast-conserving surgery versus mastectomy for treatment of breast cancer after neoadjuvant chemotherapy. Front Oncol. 2023;13:1178230.37496664 10.3389/fonc.2023.1178230
30. Gwark S Survival after breast-conserving surgery compared with that after mastectomy in breast cancer patients receiving neoadjuvant chemotherapy Ann Surg Oncol 2023 30 5 2845 2853 10.1245/s10434-022-12993-0 36577865
Gwark S, et al. Survival after breast-conserving surgery compared with that after mastectomy in breast cancer patients receiving neoadjuvant chemotherapy. Ann Surg Oncol. 2023;30(5):2845–53.36577865 10.1245/s10434-022-12993-0
