Skip to main content
Erschienen in: BMC Cancer 1/2020

Open Access 01.12.2020 | Research article

Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer

verfasst von: Takaaki Oba, Kazuma Maeno, Daiya Takekoshi, Mayu Ono, Tokiko Ito, Toshiharu Kanai, Ken-ichi Ito

Erschienen in: BMC Cancer | Ausgabe 1/2020

Abstract

Background

The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).

Methods

We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed.

Results

In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042).

Conclusions

High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.
Begleitmaterial
Hinweise

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12885-020-6647-4.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
AC
Anthracycline
Alb
Serum albumin level
BMI
Body mass index
DOC
Docetaxel
EC
Epirubicin and cyclophosphamide
ER
Estrogen receptor
FEC
Fluorouracil, epirubicin, and cyclophosphamide
HER2
Human epidermal growth factor receptor type 2
HG
Histological grade
NAC
Neoadjuvant chemotherapy
NLR
Neutrophil/lymphocyte ratio
pCR
Pathological complete response
PgR
Progesterone receptor
PNI
Prognostic nutritional index
PTX
Paclitaxel
ROC
Receiver operating characteristics
TNBC
Triple-negative breast cancer

Background

Despite recent improvements in early detection and progress in surgical techniques, chemotherapy, molecular targeting therapy, and endocrine therapy, breast cancer remains the leading cause of cancer death for women [1]. That is why some patients with breast cancer still develop recurrence even after curative resection and neoadjuvant/adjuvant therapy. Therefore, prevention of recurrence and accurate prediction of prognosis are needed to improve patient survival and fully inform patients.
Accumulating evidence suggests that nutritional status has a strong impact on the outcome of cancer treatment [2]. The prognostic nutritional index (PNI), which is calculated via a simple formula using only serum albumin level and lymphocyte cell count in the peripheral blood, is among the most commonly used parameters to evaluate nutritional status [3]. It has been demonstrated that a preoperative low PNI status is both a risk factor for postoperative complications and a predictive factor for poor prognosis among patients with various malignant tumors including gastric, colorectal, lung, pancreatic, and renal cell cancer undergoing surgery [410]. However, only few nutritional studies in the treatment for breast cancer have been conducted [11, 12]. Therefore, the significance of PNI in breast cancer still remains unclear.
Neoadjuvant chemotherapy (NAC) has become widely used for patients with locally advanced breast cancer because it has been shown to significantly elevate the rate of breast-conserving surgery by reducing the tumor volume. Further, the prognosis of the patients who underwent NAC is not inferior to those treated with postoperative chemotherapy [13]. In addition to these clinical benefits, NAC also provides important prognostic information such as pathological complete response (pCR) rate, which has been demonstrated to be a prognostic marker in human epidermal growth factor receptor type 2 (HER2)-positive or triple-negative breast cancer (TNBC) [14]. In this regard, NAC could have potential to present other various prognostic markers as well as pCR and we focused on PNI.
It has been reported that chemotherapy leads to malnutrition due to its gastrointestinal adverse effects including anorexia, nausea, vomiting, stomatitis, and diarrhea [15]. Migita et al. reported that a decrease of PNI during NAC in patients with gastric cancer is associated with a worse long-term outcome [16]. However, to date, there has been no study on the impact of changes in PNI on postoperative prognosis in patients with breast cancer who underwent NAC.
As such, the present study aimed to evaluate the prognostic impact of PNI and other nutritional indices in patients with breast cancer. Towards this goal, we evaluated the changes in PNI and other nutritional factors (e.g., serum albumin level and neutrophil/lymphocyte ratio (NLR)) and body mass index (BMI) during NAC and investigated the association between them and patient outcomes.

Methods

Patients and study design

This retrospective, single-center study evaluated patients with breast cancer who underwent NAC and subsequent surgery in Shinshu University Hospital between 2005 and 2016. Patients who could not provide detailed laboratory data and those who could not complete NAC or required a treatment delay of ≥2 weeks due to chemotoxicity were excluded.

Data collection

Data on clinicopathological characteristics, including age, sex, clinical stage at diagnosis, histological type, histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR), HER2 status, NAC regimens, operation procedure, pathological responses to NAC, and presence of recurrence, were collected from the patients’ medical records. Disease-free survival was defined as the time from surgery to the date of locoregional relapse or distant metastases, whichever occurred first.
PNI, the serum albumin level (Alb) (g/dl), NLR, and BMI were used as nutritional parameters in this study. Pre- and post-NAC blood examination data were also obtained. In addition, both body weight and height were obtained at the same day when blood samples were collected. Pre-NAC nutritional values were collected more than 1 week before the beginning of NAC, while post-NAC values were collected at more than 4 weeks after the last administration of NAC. PNI values were calculated using the following formula: 10 × serum albumin value (g/dl) + 0.005 × total lymphocyte counts in the peripheral blood/mm3 [3]. NLR values were as the total neutrophil count divided by the total lymphocyte counts, while BMI as patient’s weight (in kilograms) divided by the square of height (meters) [17, 18]. ΔPNI, ΔAlb, ΔNLR, and ΔBMI were calculated as each value on pre-NAC minus that on post-NAC. The receiver operating characteristic (ROC) curve of each prognostic parameter was analyzed to determine the best cut-off value for disease-free survival.

NAC regimens and surgical methods

Two different NAC regimens were mainly used: (1) anthracycline-based regimens (AC) including EC (60–75 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide) or FEC (500 mg/m2 fluorouracil, 75–100 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide) administered every 3 weeks and (2) taxane regimens including triweekly administered docetaxel (DOC) 75 mg/m2 or weekly administered paclitaxel (PTX) 80 mg/m2. Most of the patients who underwent four cycles of AC were then administered a further four cycles of DOC or PTX. In HER2-positive patients who received taxane regimens, 6 mg/kg (triweekly) or 2 mg/kg (weekly) trastuzumab was simultaneously administered. Surgery was performed within 4–7 weeks after NAC completion. All patients underwent axillary lymph node dissection. The efficacy of NAC was pathologically examined in the surgical specimens. pCR was defined as no evidence of residual invasive carcinoma in the breast tissue regardless of the axillary lymph node status.

Adjuvant trastuzumab, endocrine, and radiation therapy after surgery

Following surgery, extensional adjuvant trastuzumab (initially 8 mg/kg, followed by 6 mg/kg) was administered every 3 weeks for 12 months to patients with HER2-positive breast cancer. Whole breast irradiation of 50–60 Gy was performed for the patients who underwent breast-conserving surgery, while chest wall and regional lymph node irradiation of 50–60 Gy was performed for the patients with more than three nodal metastases on the postoperative pathological examinations or preoperative imaging examinations including ultrasonography, magnetic resonance imaging, and 18 F-fluorodeoxyglucose positron emission tomography. In addition, postmenopausal patients with positive ER or PgR status were treated with aromatase inhibitors for more than 5 years, whereas premenopausal patients were treated with tamoxifen or tamoxifen with luteinizing hormone-releasing hormone agonist.

Statistical analysis

Categorical and continuous variables were analyzed using Fisher’s exact test and two-sided tests, respectively. Survival curves were estimated using the Kaplan–Meier method, and significant differences in survival were assessed using the log-rank test. Univariate and multivariate analyses with a Cox proportional hazards model were performed to determine significant factors. All statistical analyses were carried out using StatFlex ver.6 (Artech Co., Ltd., Osaka, Japan), and p < 0.05 was considered statistically significant.

Results

Clinicopathological characteristics and nutrition parameter of patients

In total, 191 patients with a mean age (± standard deviation) of 51.2 ± 10.4 were evaluated. The patient characteristics are shown in Table 1. With respect to clinical stage at diagnosis, 1 (0.5%), 118 (61.8%), and 72 (37.7%) patients had stage I, II, and III disease, respectively. For the pathological classification, 171 patients (89.5%) had invasive ductal carcinoma; 12 patients (6.3%), invasive lobular carcinoma; and 8 patients (4.2%), other special types. As for intrinsic subtype, 107 cases (56.0%) were luminal (ER+ and/or PgR+/HER2-), 37 cases (19.4%) were luminal HER-2 (ER+ and/or PgR+/HER2+), 24 cases (12.6%) were HER2 enriched (ER- and PgR- / HER2+), and 23 cases (12.0%) were TNBC (ER- and PgR−/HER2-). Eleven patients (5.8%) were treated with AC without taxane; 91 patients (47.6%), AC followed by weekly PTX and/or trastuzumab; and 89 patients (46.6%), AC followed by triweekly DOC and/or trastuzumab. Regarding chemotoxicity, 14 patients (7.3%) required a dose reduction of < 20% during NAC. Mastectomy was performed for 128 patients (67.1%), while breast-conserving surgery was performed for 63 patients (32.9%). pCR was obtained in 37 patients (19.4%). The median follow-up period after surgery was 51 months (range, 1–151 months), and 38 patients (19.9%) developed recurrence.
Table 1
Clinicopathologic characteristics in patients
Variables
 
Total
low ΔPNI
high ΔPNI
 
  
n = 191 (%)
n = 91 (%)
n = 100 (%)
p value
Age(mean ± SD)
 
51.2 ± 10.4
50.9 ± 9.26
51.5 ± 11.3
0.68
Sex(Male/Female)
 
0/191
0/91
0/100
 
Pre-NAC clinical stage
I
1 (0.5%)
1 (1.1%)
0 (0%)
0.67
 
II
118 (61.8%)
52 (57.2%)
66 (66.0%)
 
 
III
72 (37.7%)
38 (41.7%)
34 (34.0%)
 
 
IV
0 (0%)
0 (0%)
0 (0%)
 
Histological type
IDC
171 (89.5%)
81 (89.0%)
90 (90.0%)
0.89
 
ILC
12 (6.3%)
7 (7.7%)
5 (5.0%)
 
 
Special type
8 (4.2%)
3 (3.3%)
5 (5.0%)
 
HG
1
54 (28.3%)
18 (19.9%)
36 (36.0%)
0.15
 
2
89 (46.6%)
47 (51.6%)
42 (42.0%)
 
 
3
23 (12.0%)
14 (15.3%)
9 (9.0%)
 
 
Unknown
25 (13.1%)
12 (13.2%)
13 (13.0%)
 
Subtype
Lunimal
107 (56.0%)
51 (56.0%)
56 (56.0%)
0.79
 
Luninal HER2
37 (19.4%)
19 (20.9%)
18 (18.0%)
 
 
HER2 enriched
24 (12.6%)
12 (13.2%)
12 (12.0%)
 
 
TNBC
23 (12.0%)
9 (9.9%)
14 (14.0%)
 
Regimens of NAC
AC
11 (5.8%)
10 (11.0%)
1 (1.0%)
0.02
 
AC → PTX and/or HER
91 (47.6%)
52 (57.2%)
39 (39.0%)
 
 
AC → DOC and/or HER
89 (46.6%)
29 (31.8%)
60 (60.0%)
 
Operation procedures
Bt,Ax
128 (67.1%)
59 (64.8%)
69 (69.0%)
0.65
 
Bp,Ax
63 (32.9%)
32 (35.2%)
31 (31.0%)
 
Pathological response to NAC
non-pCR
154 (80.6%)
78 (85.7%)
76 (76.0%)
0.10
 
pCR
37 (19.4%)
13 (14.3%)
24 (24.0%)
 
Pre-NAC PNI
 
52.6 ± 3.8
50.9 ± 3.7
54.1 ± 3.6
< 0.01
Post-NAC PNI
 
46.5 ± 4.5
48.8 ± 3.9
44.5 ± 4.0
< 0.01
Recurrence
 
38 (19.9%)
13 (14.3%)
25 (25.0%)
0.06
NAC Neoadjuvant chemotherapy, HG Histological grade, IDC Invasive ductal carcinoma, ILC Invasive lobular carcinoma, AC Antracycline, PTX paclitaxel, DOC docetaxel, HER Trastuzumab, Bt Mastectomy, Bp Partial resection of breast, Ax Axillary dissection, NAC neoadjuvant chemotherapy, PNI prognostic nutritional index
The mean PNI (pre: 52.6 ± 3.8 vs post: 46.5 ± 4.5; p < 0.01) and Alb (pre: 4.41 ± 0.30 vs post: 4.11 ± 0.36; p < 0.01) were significantly decreased after NAC, whereas NLR was significantly increased after NAC (pre: 2.50 ± 1.4 vs post: 2.96 ± 1.6; p < 0.01). Meanwhile, there was no significant difference in BMI before and after NAC (pre: 22.5 ± 3.9 vs post: 22.3 ± 3.9; p = 0.63) (Fig. 1, Additional file 1: Figure S1, Table 2). Among these four factors, PNI was the most commonly decreased (181/191; 94.7%) (Additional file 2: Table S1).
Table 2
Comparison of nutritional factors before and after NAC (mean ± standard deviation)
Variables
Pre-NAC
Post-NAC
p value
PNI
52.6 ± 3.8
46.5 ± 4.5
< 0.01
Serum albumin level (g/dl)
4.41 ± 0.30
4.11 ± 0.36
< 0.01
NLR
2.50 ± 1.4
2.96 ± 1.6
< 0.01
BMI
22.5 ± 3.9
22.3 ± 3.9
0.63
NAC Neoadjuvant chemotherapy, PNI Prognostic nutritional index, NLR Neutrophil/lymphocyte ratio, BMI Body mass index

Association between nutritional parameters and disease-free survival

Disease-free survival in the high and low groups of each nutritional parameter was analyzed to examine the correlation between nutritional status and patient outcome. The optimal cutoff values of PNI, Alb, NLR, and BMI for disease-free survival as identified using the ROC curves were 53.1, 4.36, 2.32, and 21.7 for pre-NAC, respectively, and 45.4, 4.04, 2.57 and 21.5, respectively, for post-NAC (Additional file 3: TableS2). In pre-NAC, there were no significant differences in disease-free survival between the high and low groups for each nutritional parameter (p = 0.89 for PNI, p = 0.65 for Alb, p = 0.25 for NLR, and p = 0.76 for BMI) (Fig. 2a, Additional file 4: Figure S2). Similar findings were found on post-NAC (p = 0.21 for PNI, p = 0.78 for Alb, p = 0.58 for NLR, and p = 0.58 for BMI) (Fig. 2b, Additional file 5: Figure S3). As well as disease-free survival, disease-specific survival was not different between the high and low groups for each nutritional parameter (Pre-NAC: p = 0.21 for PNI, p = 0.65 for Alb, p = 0.068 for NLR, and p = 0.43 for BMI, Post-NAC: p = 0.98 for PNI, p = 0.14 for Alb, p = 0.57 for NLR, and p = 0.80 for BMI) (Additional file 6: Figure S4).

Association between changes of nutrition parameters during NAC and disease-free survival

Next, we focused on the association between changes in nutrition parameters during NAC and disease-free survival. The optimal cutoff value determined via the ROC curve for disease-free survival was 5.26 for ΔPNI, 0.34 for ΔAlb, − 0.17 for ΔNLR, and − 0.26 for ΔBMI (Additional file 3: TableS2). Interestingly, the high ΔPNI group had significantly poorer disease-free survival than the low ΔPNI group (p = 0.015) (Fig. 3). Additionally, a trend for lower disease-specific survival was found in the high ΔPNI group than in the low ΔPNI group, although no statistical difference was observed (p = 0.14) (Additional file 7: Figure S5). Meanwhile, there were no significant differences in either disease-free survival or disease-specific survival between the high and low groups according to ΔAlb (p = 0.053 for disease-free survival, p = 0.14 for disease-specific survival), ΔNLR (p = 0.65 for disease-free survival, p = 0.20 for disease-specific survival), and ΔBMI (p = 0.66 for disease-free survival, p = 0.66 for disease-specific survival) (Additional file 8: Figure S6, Additional file 9: Figure S7).
The clinicopathological characteristics of the high and low ΔPNI groups are shown in Table 1. The median follow-up period after surgery was 64 (3–151) months for the high ΔPNI group and 43 (1–151) for the low ΔPNI group. The mean age, clinical stage, histological type, HG, subtype, operation procedure, and pathological response to NAC were not significantly different between the two groups. Meanwhile, NAC regimens differed significantly, with a higher rate of patients who underwent NAC with DOC in the high ΔPNI group (p = 0.02). Recurrence was more frequent in the high ΔPNI group with marginal significance (p = 0.06). In the high ΔPNI group, pre-NAC PNI was significantly higher than that in the low ΔPNI group (p < 0.01). Furthermore, the mean ΔPNI was significantly higher in the patients with high pre-NAC PNI than in those with low pre-NAC PNI (Additional file 10: Figure S8), indicating that a large PNI change may be likely to occur in patients with high PNI at baseline.
The higher proportion of patients treated with DOC in the high ΔPNI group prompted us to examine whether NAC regimens affected disease-free survival. However, we found no significant difference in disease-free survival among the three NAC regimens (AC, AC followed by PTX and/or trastuzumab, or AC followed by DOC and/or trastuzumab) (Additional file 11: Figure S9). These data suggest that the difference in disease-free survival by ΔPNI is independent of NAC regimens.
Next, we examined if tumor burden at time of the diagnosis could influence the pre-NAC PNI, post-NAC PNI, or ΔPNI. When we divided the patients into stage I, II and stage III, pre-NAC PNI, post-NAC PNI, or ΔPNI were not different (p = 0.87, p = 0.73, and p = 0.85, respectively), indicating that the volume of disease did not affect either the PNI value or the change in PNI (Additional file 12: Figure S10).

Association between disease-free survival and ΔPNI based on tumor characteristics

To investigate whether the effect of ΔPNI on disease-free survival depends on tumor characteristics, we divided the patients according to ER and HER2 expression on tumors. In the ER-positive population, the high ΔPNI group had significantly poorer disease-free survival than the low ΔPNI group (p = 0.030) (Fig. 4a). Meanwhile, as for HER2 status, the high ΔPNI group presented significantly poorer disease-free survival than the low ΔPNI group among HER2-negative cases (p = 0.029) (Fig. 4b). Disease-free survival was not significantly associated with ER negative (p = 0.32) and HER2 positive (p = 0.48) status, but the high ΔPNI group tended to have poorer disease-free survival than the low ΔPNI group in both the ER-negative and HER2-positive cohorts (Fig. 4a,b).
On division into four subtypes (luminal; ER+ and/or PgR+ / HER2-, luminal HER2: ER+ and/or PgR+ / HER2+, HER2 enriched: ER- and PgR- / HER2+, and TNBC: ER- and PgR−/HER-), the high ΔPNI group showed a trend of poorer disease-free survival than the low ΔPNI group, although the differences were not significant because of the small number of patients with each subtype (p = 0.091 for luminal, p = 0.098 for luminal HER2, p = 0.67 for HER2 enriched, and p = 0.18 for TNBC) (Additional file 13: Figure S11).
Regarding clinical stage, the high ΔPNI group showed significantly poorer disease-free survival than the low ΔPNI group among patients with stage III breast cancer (p = 0.0064). In patients with stage I or II breast cancer, the high ΔPNI group tended to show poorer disease-free survival than the low ΔPNI group, although the difference was not significant (p = 0.39). As for HG, the high ΔPNI group consistently showed poorer disease-free survival with respect to each HG with marginal or significant differences (p = 0.048 for HG1, p = 0.072 for HG2, p = 0.069 for HG3) (Additional file 14: Figure S12).

Prognostic factors of disease-free survival

To confirm the significance of ΔPNI in disease-free survival, univariate and multivariate analyses were performed. Univariate analysis revealed that ΔPNI was a significant predictor of disease-free survival (HR: 2.2, 95% CI: 1.14–4.41, p = 0.018). Other factors associated with disease-free survival were pre-NAC clinical stage (HR: 3.1, 95% CI: 1.58–5.81, p < 0.01) and HER2 status (HR: 0.3, 95% CI: 0.11–0.77, p = 0.012). On multivariate analysis using Cox hazard model, ΔPNI was an independent risk factor for disease-free survival (HR: 2.17, 95% CI: 1.08–4.76, p = 0.042) (Table 3).
Table 3
Univariate and multivariate Cox proportional hazards regression analyses of the clinicopathological parameters
 
Univariate
  
Multivariate
  
p value
HR
95% CI
p value
HR
95% CI
Age, years (≥50 vs. < 50)
0.73
0.89
0.47–1.68
   
Pre-NAC clinical stage (stage I and II vs. stage III)
< 0.01
3.1
1.58–5.81
< 0.01
2.17
1.57–7.27
ER (positive vs. negative)
0.97
1.1
0.48–2.14
   
HER2 (positive vs. negative)
0.012
0.3
0.11–0.77
0.016
0.28
0.10–0.79
ΔPNI (high vs. low)
0.018
2.2
1.14–4.41
0.042
2.17
1.08–4.76
ΔAlb (high vs. low)
0.058
1.9
0.97–3.52
   
ΔBMI (high vs. low)
0.66
0.87
0.45–1.63
   
ΔNLR (high vs. low)
0.66
1.2
0.61–2.18
   
Histological type (IDC vs. ILC or special type)
0.23
2.4
0.58–10.03
   
Pathological response to NAC (non-pCR vs. pCR)
0.19
0.64
0.32–1.25
   
ER Estrogen receptor, HER-2 Human epidermal growth factor receptor type 2, BMI Body mass index, NLR Neutrophil/lymphocyte ratio, PNI Prognostic nutritional index, IDC Invasive ductal carcinoma, ILC Invasive lobular carcinoma, NAC Neoadjuvant chemotherapy, pCR Pathological complete response

Discussion

The present study demonstrates that high ΔPNI is significantly associated with poor disease-free survival and is an independent predictor of disease-free survival. To the best of our knowledge, this is the first report to demonstrate that high ΔPNI is a reliable prognostic factor of disease-free survival in patients with breast cancer who underwent NAC.
Several parameters, including PNI [3], serum albumin level [19], or NLR [20], are used to evaluate nutritional status. Increasing evidence suggests that high preoperative PNI is a predictor of better postoperative complications and patients outcomes in various types of malignancy [410]. Meanwhile, both high serum albumin level and low preoperative NLR also have been reported to be associated with better postoperative outcomes in several cancers [1927]. BMI is also a well-known prognostic factor in breast cancers [2830], and body weight is also associated with the patients’ nutritional condition [31]. These four factors (i.e., PNI, serum albumin level, NLR, and BMI) are easily calculated or obtained from clinical records or physical examinations. Therefore, we used these four factors as nutritional parameters in the present study.
We found no association between pre-NAC PNI, serum albumin level, NLR, or BMI and disease-free survival. Furthermore, post-NAC PNI, serum albumin level, NLR, or BMI also did not show any correlation with disease-free survival, although the low post-NAC PNI group tended to present poorer disease-free survival than the high post-NAC PNI group. These data indicated that the nutritional index itself did not predict the prognosis either before or after NAC. In general, chemotherapy worsen patients’ nutritional condition due to its adverse gastrointestinal effects [15]. Although some studies have demonstrated significant decreases of various nutritional parameters such as albumin, pre-albumin, and transferrin due to preoperative chemotherapy in cancers of the digestive tract [16, 32], the influence of NAC on the nutritional status of patients with breast cancer has remained unclear. In the present study, we observed significant decreases in PNI and serum albumin level and increases in NLR after NAC. Particularly, PNI was decreased in 181 patients of 191 (94.7%) after NAC. These results suggest that NAC has a negative effect on the nutritional status of patients with breast cancer, and that among the four commonly used parameters, PNI may be the most sensitive parameter to evaluate the nutritional status in patients with breast cancer. Therefore, we consequently focused on changes in the value of these nutritional parameters and found that a decreased PNI after NAC predicts poorer disease-free survival in patients with breast cancer. Significant differences in disease-specific survival were not observed in the present study. However, a trend of poorer disease-specific survival was observed in patients with a high decrease in PNI. A larger-scale study or longer follow-up periods will be able to reveal the differences in disease-specific survival.
In the comparison of clinicopathological characteristics between the high ΔPNI group and the low ΔPNI group, there was a higher percentage of patients who received DOC-containing regimens in the high ΔPNI group than the low ΔPNI group. However, there was no significant difference in disease-free survival among the three NAC regimens (AC only, AC followed by PTX and/or trastuzumab, and AC followed by DOC and/or trastuzumab), indicating that the significant difference in disease-free survival according to ΔPNI does not depend on the type of chemotherapy regimen. One explanation for the higher number of patients who underwent DOC-containing regimens in the high ΔPNI group may simply be due to the stronger gastrointestinal adverse effects of DOC compared with PTX [33, 34]. On the other hand, patients treated with DOC are likely to develop peripheral edema [33, 35], which is associated with hypoalbuminemia. This can be another explanation for the increase of DOC-treated patients in the high ΔPNI group.
The biology of breast cancer is known to depend largely on its intrinsic subtype, which is determined mainly according to ER and HER2 status. Further, it is globally accepted that the prognosis is different between each subtype, and thus the therapeutic strategy depends on the subtype [36]. However, the nutritional status of patients with breast cancer may largely depend on patient factors, and not of the tumor. Consistent with this notion, the present study demonstrated that the influence of ΔPNI on disease-free survival may be similar across all breast cancer subtypes, particularly in patients with ER-positive or HER2-negative breast cancer; however, this should be interpreted cautiously as there was no statistical significance in the number of patients with different subtypes owing to the small number of patients enrolled in this study. Particularly, patients with HER2-positive breast cancer had markedly good disease-free survival to evaluate the statistical difference between those with high and low ΔPNI. This may be due to the administration of trastuzumab that contributed to improved prognosis in patients with HER2-positive breast cancer [37]. As well as intrinsic subtype, clinical stage and HG are also universally accepted as prognostic factors of breast cancer [38, 39]. This study showed that the influence of ΔPNI on disease-free survival is stronger in the advanced stage, although the pre NAC-PNI, post NAC-PNI, and ΔPNI values itself were not dependent on clinical stage. In addition, high ΔPNI is consistently associated with poorer disease-free survival, independent from HG. Although further large-scale studies are required for determining the importance of nutritional change in patient outcomes according to the cancer subtype or the tumor burden, the results of the present study suggest that the association between changes in nutritional status during NAC and patient outcome mainly depends on the patient’s nutritional status, especially in the advanced stage, but not on tumor characteristics.
From the point of view of immunity, better immunological condition has been considered to lead to improved survival in cancer. Malnutrition has been shown to be related to cancer progression due to its association with weak immune response [40, 41]. Accordingly, immune response has also been shown to correlate with better outcomes during various antitumor therapies in breast cancer [42]. Collectively, the result of the present and previous studies supports that maintaining the PNI during NAC may be beneficial to prevent worse prognosis in patients with breast cancer. Several studies have demonstrated that nutritional support such as supplemental immunonutrition containing n-3 polyunsaturated fatty acids enabled improved the nutritional condition of patients who underwent chemotherapy [4345]. Individual nutritional counseling has also been demonstrated to be important in maintaining the nutritional status [46]. In line with our findings, providing these nutritional support strategies during NAC may result in better patient outcome by maintaining the nutritional condition. Indeed, several clinical trials are ongoing to test whether nutrition interventions could improve the treatment outcome of metastatic breast cancer patients (NCT03045289, NCT03045289). In line with the results of this study, the concept of nutrition intervention should be further broadened to the neo-adjuvant setting.
Several limitations of the present study need to be considered. First, it was a retrospective analysis with a small study population in a single institution. In addition to the heterogeneous nature of breast cancer, the limited number of patients may reduce the statistical power. Second, the NAC regimens varied between patients because the study period spanned several years when treatment regimens changed. Further investigations are therefore needed to validate our results.

Conclusions

The findings of the present study indicate that a decrease of PNI can be a marker to predict poor prognosis after NAC in patients with breast cancer. Our results imply the importance of monitoring the nutritional status during NAC.

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12885-020-6647-4.

Acknowledgements

We would like to thank Editage (www.​editage.​com) for English language editing.
This study was approved by the Medical Ethics Committee on Clinical Investigation of Shinshu University (no. 4077). Patients were provided the opportunity to opt out of participation in this study via notifications displayed in the outpatient ward and the institution’s website. Unless patients reject the enrollment in this study, the requirement for written informed consent was waived by the Medical Ethics Committee on Clinical Investigation of Shinshu University.
Not applicable.

Competing interests

The authors declare that they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

Publisher’s Note

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

Supplementary information

Literatur
1.
2.
Zurück zum Zitat Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62:243–74.PubMedCrossRef Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62:243–74.PubMedCrossRef
3.
Zurück zum Zitat Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi. 1984;85:1001–5.PubMed Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi. 1984;85:1001–5.PubMed
4.
Zurück zum Zitat Yang Y, Gao P, Song Y, Sun J, Chen X, Zhao J, et al. The prognostic nutritional index is a predictive indicator of prognosis and postoperative complications in gastric cancer: a meta-analysis. Eur J Surg Oncol. 2016;42:1176–82.PubMedCrossRef Yang Y, Gao P, Song Y, Sun J, Chen X, Zhao J, et al. The prognostic nutritional index is a predictive indicator of prognosis and postoperative complications in gastric cancer: a meta-analysis. Eur J Surg Oncol. 2016;42:1176–82.PubMedCrossRef
5.
Zurück zum Zitat Yang Y, Gao P, Chen X, Song Y, Shi J, Zhao J, et al. Prognostic significance of preoperative prognostic nutritional index in colorectal cancer: results from a retrospective cohort study and a meta-analysis. Oncotarget. 2016;7:58543–52.PubMedPubMedCentral Yang Y, Gao P, Chen X, Song Y, Shi J, Zhao J, et al. Prognostic significance of preoperative prognostic nutritional index in colorectal cancer: results from a retrospective cohort study and a meta-analysis. Oncotarget. 2016;7:58543–52.PubMedPubMedCentral
6.
Zurück zum Zitat Shoji F, Morodomi Y, Akamine T, Takamori S, Katsura M, Takada K, et al. Predictive impact for postoperative recurrence using the preoperative prognostic nutritional index in pathological stage I non-small cell lung cancer. Lung Cancer. 2016;98:15–21.PubMedCrossRef Shoji F, Morodomi Y, Akamine T, Takamori S, Katsura M, Takada K, et al. Predictive impact for postoperative recurrence using the preoperative prognostic nutritional index in pathological stage I non-small cell lung cancer. Lung Cancer. 2016;98:15–21.PubMedCrossRef
7.
Zurück zum Zitat Qiu C, Qu X, Shen H, Zheng C, Zhu L, Meng L, et al. Evaluation of prognostic nutritional index in patients undergoing radical surgery with nonsmall cell lung Cancer. Nutr Cancer. 2015;67:741–7.PubMedCrossRef Qiu C, Qu X, Shen H, Zheng C, Zhu L, Meng L, et al. Evaluation of prognostic nutritional index in patients undergoing radical surgery with nonsmall cell lung Cancer. Nutr Cancer. 2015;67:741–7.PubMedCrossRef
8.
Zurück zum Zitat Mori S, Usami N, Fukumoto K, Mizuno T, Kuroda H, Sakakura N, et al. The significance of the prognostic nutritional index in patients with completely resected non-small cell lung Cancer. PLoS One. 2015;10:e0136897.PubMedPubMedCentralCrossRef Mori S, Usami N, Fukumoto K, Mizuno T, Kuroda H, Sakakura N, et al. The significance of the prognostic nutritional index in patients with completely resected non-small cell lung Cancer. PLoS One. 2015;10:e0136897.PubMedPubMedCentralCrossRef
9.
Zurück zum Zitat Kanda M, Fujii T, Kodera Y, Nagai S, Takeda S, Nakao A. Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg. 2011;98:268–74.PubMedCrossRef Kanda M, Fujii T, Kodera Y, Nagai S, Takeda S, Nakao A. Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg. 2011;98:268–74.PubMedCrossRef
10.
Zurück zum Zitat Broggi MS, Patil D, Baum Y, Nieh PT, Alemozaffar M, Pattaras JG, et al. Onodera's prognostic nutritional index as an independent prognostic factor in clear cell renal cell carcinoma. Urology. 2016;96:99–105.PubMedCrossRef Broggi MS, Patil D, Baum Y, Nieh PT, Alemozaffar M, Pattaras JG, et al. Onodera's prognostic nutritional index as an independent prognostic factor in clear cell renal cell carcinoma. Urology. 2016;96:99–105.PubMedCrossRef
11.
Zurück zum Zitat Mohri T, Mohri Y, Shigemori T, Takeuchi K, Itoh Y, Kato T. Impact of prognostic nutritional index on long-term outcomes in patients with breast cancer. World J Surg Oncol. 2016;14:170.PubMedPubMedCentralCrossRef Mohri T, Mohri Y, Shigemori T, Takeuchi K, Itoh Y, Kato T. Impact of prognostic nutritional index on long-term outcomes in patients with breast cancer. World J Surg Oncol. 2016;14:170.PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Yang Z, Zhang B, Hou L, Xie Y, Cao X. Pre-operative prognostic nutritional index predicts the outcomes for triple-negative breast cancer. Tumour Biol. 2014;35:12165–71.PubMedCrossRef Yang Z, Zhang B, Hou L, Xie Y, Cao X. Pre-operative prognostic nutritional index predicts the outcomes for triple-negative breast cancer. Tumour Biol. 2014;35:12165–71.PubMedCrossRef
13.
Zurück zum Zitat Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.CrossRef Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.CrossRef
14.
Zurück zum Zitat von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef
15.
Zurück zum Zitat Hiura Y, Takiguchi S, Yamamoto K, Takahashi T, Kurokawa Y, Yamasaki M, et al. Effects of ghrelin administration during chemotherapy with advanced esophageal cancer patients: a prospective, randomized, placebo-controlled phase 2 study. Cancer. 2012;118:4785–94.PubMedCrossRef Hiura Y, Takiguchi S, Yamamoto K, Takahashi T, Kurokawa Y, Yamasaki M, et al. Effects of ghrelin administration during chemotherapy with advanced esophageal cancer patients: a prospective, randomized, placebo-controlled phase 2 study. Cancer. 2012;118:4785–94.PubMedCrossRef
16.
Zurück zum Zitat Migita K, Matsumoto S, Wakatsuki K, Ito M, Kunishige T, Nakade H, et al. A decrease in the prognostic nutritional index is associated with a worse long-term outcome in gastric cancer patients undergoing neoadjuvant chemotherapy. Surg Today. 2017;47:1018–26.PubMedCrossRef Migita K, Matsumoto S, Wakatsuki K, Ito M, Kunishige T, Nakade H, et al. A decrease in the prognostic nutritional index is associated with a worse long-term outcome in gastric cancer patients undergoing neoadjuvant chemotherapy. Surg Today. 2017;47:1018–26.PubMedCrossRef
17.
Zurück zum Zitat Tomita M, Shimizu T, Ayabe T, Yonei A, Onitsuka T. Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res. 2011;31:2995–8.PubMed Tomita M, Shimizu T, Ayabe T, Yonei A, Onitsuka T. Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res. 2011;31:2995–8.PubMed
18.
Zurück zum Zitat Shimizu K, Okita R, Saisho S, Maeda A, Nojima Y, Nakata M. Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer. World J Surg Oncol. 2015;13:291.PubMedPubMedCentralCrossRef Shimizu K, Okita R, Saisho S, Maeda A, Nojima Y, Nakata M. Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer. World J Surg Oncol. 2015;13:291.PubMedPubMedCentralCrossRef
19.
Zurück zum Zitat Miura K, Hamanaka K, Koizumi T, Kitaguchi Y, Terada Y, Nakamura D, et al. Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: comparative study of normal lung, emphysema, and pulmonary fibrosis. Lung Cancer. 2017;111:88–95.PubMedCrossRef Miura K, Hamanaka K, Koizumi T, Kitaguchi Y, Terada Y, Nakamura D, et al. Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: comparative study of normal lung, emphysema, and pulmonary fibrosis. Lung Cancer. 2017;111:88–95.PubMedCrossRef
20.
Zurück zum Zitat Ethier JL, Desautels D, Templeton A, Shah PS, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res. 2017;19:2.PubMedPubMedCentralCrossRef Ethier JL, Desautels D, Templeton A, Shah PS, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res. 2017;19:2.PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124.PubMedCrossRef Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124.PubMedCrossRef
22.
Zurück zum Zitat Song Y, Yang Y, Gao P, Chen X, Yu D, Xu Y, et al. The preoperative neutrophil to lymphocyte ratio is a superior indicator of prognosis compared with other inflammatory biomarkers in resectable colorectal cancer. BMC Cancer. 2017;17:744.PubMedPubMedCentralCrossRef Song Y, Yang Y, Gao P, Chen X, Yu D, Xu Y, et al. The preoperative neutrophil to lymphocyte ratio is a superior indicator of prognosis compared with other inflammatory biomarkers in resectable colorectal cancer. BMC Cancer. 2017;17:744.PubMedPubMedCentralCrossRef
23.
Zurück zum Zitat Sharaiha RZ, Halazun KJ, Mirza F, Port JL, Lee PC, Neugut AI, et al. Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol. 2011;18:3362–9.PubMedPubMedCentralCrossRef Sharaiha RZ, Halazun KJ, Mirza F, Port JL, Lee PC, Neugut AI, et al. Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol. 2011;18:3362–9.PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Marin Hernandez C, Pinero Madrona A, Gil Vazquez PJ, Galindo Fernandez PJ, Ruiz Merino G, Alonso Romero JL, et al. Usefulness of lymphocyte-to-monocyte, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios as prognostic markers in breast cancer patients treated with neoadjuvant chemotherapy. Clin Transl Oncol. 2018;20:476–83.PubMedCrossRef Marin Hernandez C, Pinero Madrona A, Gil Vazquez PJ, Galindo Fernandez PJ, Ruiz Merino G, Alonso Romero JL, et al. Usefulness of lymphocyte-to-monocyte, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios as prognostic markers in breast cancer patients treated with neoadjuvant chemotherapy. Clin Transl Oncol. 2018;20:476–83.PubMedCrossRef
25.
Zurück zum Zitat Ma J, Kuzman J, Ray A, Lawson BO, Khong B, Xuan S, et al. Neutrophil-to-lymphocyte ratio (NLR) as a predictor for recurrence in patients with stage III melanoma. Sci Rep. 2018;8:4044.PubMedPubMedCentralCrossRef Ma J, Kuzman J, Ray A, Lawson BO, Khong B, Xuan S, et al. Neutrophil-to-lymphocyte ratio (NLR) as a predictor for recurrence in patients with stage III melanoma. Sci Rep. 2018;8:4044.PubMedPubMedCentralCrossRef
26.
Zurück zum Zitat Iwase T, Sangai T, Sakakibara M, Sakakibara J, Ishigami E, Hayama S, et al. An increased neutrophil-to-lymphocyte ratio predicts poorer survival following recurrence for patients with breast cancer. Mol Clin Oncol. 2017;6:266–70.PubMedCrossRef Iwase T, Sangai T, Sakakibara M, Sakakibara J, Ishigami E, Hayama S, et al. An increased neutrophil-to-lymphocyte ratio predicts poorer survival following recurrence for patients with breast cancer. Mol Clin Oncol. 2017;6:266–70.PubMedCrossRef
27.
Zurück zum Zitat Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol. 2012;19:217–24.PubMedCrossRef Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol. 2012;19:217–24.PubMedCrossRef
28.
Zurück zum Zitat Ryu SY, Kim CB, Nam CM, Park JK, Kim KS, Park J, et al. Is body mass index the prognostic factor in breast cancer?: a meta-analysis. J Korean Med Sci. 2001;16:610–4.PubMedPubMedCentralCrossRef Ryu SY, Kim CB, Nam CM, Park JK, Kim KS, Park J, et al. Is body mass index the prognostic factor in breast cancer?: a meta-analysis. J Korean Med Sci. 2001;16:610–4.PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123:627–35.PubMedCrossRef Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123:627–35.PubMedCrossRef
30.
Zurück zum Zitat Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J Clin Oncol. 2002;20:1128–43.PubMedCrossRef Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J Clin Oncol. 2002;20:1128–43.PubMedCrossRef
31.
Zurück zum Zitat Chlebowski RT. Nutrition and physical activity influence on breast cancer incidence and outcome. Breast. 2013;22(Suppl 2):S30–7.PubMedCrossRef Chlebowski RT. Nutrition and physical activity influence on breast cancer incidence and outcome. Breast. 2013;22(Suppl 2):S30–7.PubMedCrossRef
32.
Zurück zum Zitat Yoshida N, Watanabe M, Baba Y, Ishimoto T, Iwagami S, Sakamoto Y, et al. Influence of preoperative docetaxel, cisplatin, and 5-fluorouracil on the incidence of complications after esophagectomy for resectable advanced esophageal cancer. Dis Esophagus. 2014;27:374–9.PubMedCrossRef Yoshida N, Watanabe M, Baba Y, Ishimoto T, Iwagami S, Sakamoto Y, et al. Influence of preoperative docetaxel, cisplatin, and 5-fluorouracil on the incidence of complications after esophagectomy for resectable advanced esophageal cancer. Dis Esophagus. 2014;27:374–9.PubMedCrossRef
33.
Zurück zum Zitat Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005;23:5542–51.PubMedCrossRef Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005;23:5542–51.PubMedCrossRef
34.
Zurück zum Zitat Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008;358:1663–71.PubMedPubMedCentralCrossRef Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008;358:1663–71.PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, et al. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006;24:4963–70.PubMedCrossRef Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, et al. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006;24:4963–70.PubMedCrossRef
36.
Zurück zum Zitat Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies-improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast Cancer 2015. Ann Oncol. 2015;26:1533–46.PubMedPubMedCentralCrossRef Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies-improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast Cancer 2015. Ann Oncol. 2015;26:1533–46.PubMedPubMedCentralCrossRef
37.
Zurück zum Zitat Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375:377–84.PubMedCrossRef Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375:377–84.PubMedCrossRef
38.
Zurück zum Zitat DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67:439–48.PubMedCrossRef DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67:439–48.PubMedCrossRef
39.
Zurück zum Zitat Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010;12:207.PubMedPubMedCentralCrossRef Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010;12:207.PubMedPubMedCentralCrossRef
40.
Zurück zum Zitat Zitvogel L, Pietrocola F, Kroemer G. Nutrition, inflammation and cancer. Nat Immunol. 2017;18:843–50.PubMedCrossRef Zitvogel L, Pietrocola F, Kroemer G. Nutrition, inflammation and cancer. Nat Immunol. 2017;18:843–50.PubMedCrossRef
41.
Zurück zum Zitat Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010;9:69.PubMedPubMedCentralCrossRef Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010;9:69.PubMedPubMedCentralCrossRef
42.
Zurück zum Zitat Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29:1949–55.PubMedCrossRef Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29:1949–55.PubMedCrossRef
43.
Zurück zum Zitat Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011;117:3774–80.PubMedCrossRef Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011;117:3774–80.PubMedCrossRef
44.
Zurück zum Zitat Xue H, Sawyer MB, Field CJ, Dieleman LA, Baracos VE. Nutritional modulation of antitumor efficacy and diarrhea toxicity related to irinotecan chemotherapy in rats bearing the ward colon tumor. Clin Cancer Res. 2007;13:7146–54.PubMedCrossRef Xue H, Sawyer MB, Field CJ, Dieleman LA, Baracos VE. Nutritional modulation of antitumor efficacy and diarrhea toxicity related to irinotecan chemotherapy in rats bearing the ward colon tumor. Clin Cancer Res. 2007;13:7146–54.PubMedCrossRef
45.
Zurück zum Zitat Kiss NK, Krishnasamy M, Isenring EA. The effect of nutrition intervention in lung cancer patients undergoing chemotherapy and/or radiotherapy: a systematic review. Nutr Cancer. 2014;66:47–56.PubMedCrossRef Kiss NK, Krishnasamy M, Isenring EA. The effect of nutrition intervention in lung cancer patients undergoing chemotherapy and/or radiotherapy: a systematic review. Nutr Cancer. 2014;66:47–56.PubMedCrossRef
46.
Zurück zum Zitat Ravasco P, Monteiro-Grillo I, Camilo M. Individualized nutrition intervention is of major benefit to colorectal cancer patients: long-term follow-up of a randomized controlled trial of nutritional therapy. Am J Clin Nutr. 2012;96:1346–53.PubMedCrossRef Ravasco P, Monteiro-Grillo I, Camilo M. Individualized nutrition intervention is of major benefit to colorectal cancer patients: long-term follow-up of a randomized controlled trial of nutritional therapy. Am J Clin Nutr. 2012;96:1346–53.PubMedCrossRef
Metadaten
Titel
Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer
verfasst von
Takaaki Oba
Kazuma Maeno
Daiya Takekoshi
Mayu Ono
Tokiko Ito
Toshiharu Kanai
Ken-ichi Ito
Publikationsdatum
01.12.2020
Verlag
BioMed Central
Erschienen in
BMC Cancer / Ausgabe 1/2020
Elektronische ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-020-6647-4

Weitere Artikel der Ausgabe 1/2020

BMC Cancer 1/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.