Tomoko Higuchi

Prognostic value of FDG-PET and DWI in breast cancer

ObjectiveTo investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer.MethodsA total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADCmean) and minimum ADC (ADCmin)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods.ResultsAfter a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUVmax (≥ 3.60), MTV (≥ 3.15), and TLG (≥ 16.0) had a significantly lower DFS rate than those with a low SUVmax (< 3.60), MTV (< 3.15), and TLG (< 16.0), respectively (p = 0.0054, p = 0.0054, and p < 0.0001, respectively). SUVmean, ADCmean, and ADCmin were not significantly associated with recurrence. Univariate analysis showed that SUVmax (p = 0.0054), MTV (p = 0.0054), TLG (p < 0.0001), tumor size (p = 0.0083), estrogen receptor negativity (p = 0.046), progesterone receptor negativity (p = 0.0023), human epidermal growth factor receptor 2 positivity (p = 0.043), and the presence of axillary lymph node metastasis (p = 0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor.ConclusionsThe preoperative SUVmax, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.

High levels of serum CA15-3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy: FUJIMOTO et al.

To identify surrogate markers for prognosis of breast cancer patients with non‐pathological complete response (non‐pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on the serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15‐3) as well as clinicopathological factors both before and after NAC.

Significant Association Between Low Baseline Neutrophil-to-Lymphocyte Ratio and Improved Progression-free Survival of Patients With Locally Advanced or Metastatic Breast Cancer Treated With Eribulin But Not With Nab-Paclitaxel

Introduction Although eribulin and nab‐paclitaxel are chemotherapy agents widely used for locally advanced or metastatic breast cancer (MBC), their predictive factors remain unknown. Because the absolute neutrophil‐to‐lymphocyte ratio (NLR) is a significant prognostic factor for early‐stage breast cancer, we investigated its usefulness in terms of the eribulin or nab‐paclitaxel treatment efficacy for MBC. Patients and Methods A total of 85 patients with MBC treated with eribulin (n = 59) or nab‐paclitaxel (n = 26) were recruited. NLR values were collected at baseline, after 1 cycle, after 2 cycles, and at the end of treatment. The NLR cutoff value was set at 3. Results The progression‐free survival (PFS) of patients with an NLR < 3 at baseline (median, 242 days; n = 24) was significantly better than that of patients with an NLR of ≥ 3 (median, 98 days; n = 35; hazard ratio, 0.37, 95% confidence interval, 0.18‐0.71; P = .0032). Similarly, the overall survival was marginally significantly better in patients with an NLR < 3 who were treated with eribulin (P = .058). However, the NLR was not significantly associated with PFS or overall survival for patients treated with nab‐paclitaxel. No significant association was found between the NLR during treatment and PFS in the eribulin group. The significance of the NLR for the efficacy of eribulin was consistent, irrespective of estrogen receptor status, previous anthracycline or endocrine use, and the number of previous chemotherapy regimens. Conclusion A low NLR at baseline was significantly associated with improved PFS in patients treated with eribulin but not in those treated with nab‐paclitaxel. Therefore, the baseline NLR might be clinically useful for selecting patients who would benefit from eribulin. Micro‐Abstract Both eribulin and nab‐paclitaxel are widely used and effective chemotherapy agents for metastatic breast cancer; however, their predictive factors remain unknown. The usefulness of the neutrophil‐to‐lymphocyte ratio (NLR) in terms of treatment efficacy was investigated. We observed that a low NLR at baseline might be a significant indicator of improved outcomes for patients treated with eribulin but not with nab‐paclitaxel.

Abstract P2-05-27: Baseline serum CA15-3 levels are associated with prognosis for breast cancer patients with non-complete pathological response to neoadjuvant chemotherapy

Background: It has been well demonstrated that patients who achieved pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) had a favorable prognosis compared with patients who did not (non-pCR). Even though pCR was not attained, reduction in tumor volume after chemotherapy may be associated with improved prognosis for a certain number of patients. However, the association between residual tumor volume and prognosis is not necessarily consistent. In order to identify substitute markers for breast cancer patients with non-pCR after NAC, we investigated the impact of serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) at baseline as well as post-NAC. Patients and Methods: Ninety-six breast cancer patients treated with NAC and operated on at the Hyogo College of Medicine were recruited for this study. Serum CEA and CA15-3 were measured prior to chemotherapy as well as at completion of pre-operative treatment. The optimal cutoff points for CEA (1.55ng/m, normal range: Results: pCR and non-pCR was attained by 21 and 75 patients, respectively. For the non-pCR patients, serum CEA levels at baseline were classified into high (n=35) and low (n=38) and serum CA15-3 levels at baseline into high (n=31) and low (n=43). RFS of non-pCR patients with high serum CA15-3 levels was significantly worse than of those with low levels (3-year RFS: 0.47 vs 0.93; p=0.0009). RFS for patients with high and low serum levels of CA15-3 after NAC was also significantly different (p=0.037). As for CEA, no significant association with RFS was observed either at baseline or post-NAC. Univariate analysis demonstrated that tumor size and baseline CA15-3 were significant prognostic factors for RFS. Multivariate analysis showed that both tumor size (hazard ratio (HR): 3.88, 95% confidence interval (CI): 1.21-12.35, p=0.023) and baseline CA15-3 (HR: 13.51, 95% CI: 1.74-105.08, p=0.013) were significant and independent risk factors for relapse. As for lymph node metastasis, tumor grade, residual tumor size and pre- and post-NAC Ki67 expression levels of patients with non-pCR showed no significant association with RFS. Conclusion and discussion: High levels of serum CA15-3 at baseline constituted a significantly worse prognosis for breast cancer patients with non-pCR. Tumor size at baseline but not residual size and baseline CA15-3 seems to suitable as a substitute for prediction of outcome for patients with non-pCR. Our findings suggest that these markers may be useful for identifying patients with poor prognosis who may be candidates for additional adjuvant treatment. Citation Format: Fujimoto Y, Imamura M, Higuchi T, Nishimukai A, Yanai A, Miyagawa Y, Murase K, Takatsuka Y, Miyoshi Y. Baseline serum CA15-3 levels are associated with prognosis for breast cancer patients with non-complete pathological response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-27.

Abstract P2-08-24: High levels of serum C-terminal crosslinking telopeptide of type 1 collagen at baseline are associated with poor prognosis for breast cancer patients

Background: It has been demonstrated that adjuvant treatment using bisphosphonate may reduce recurrence among breast cancer patients. However, these improved prognoses of patients are reportedly limited to breast cancers of estrogen receptor (ER)-positive and postmenopausal women. Although the mechanisms of the effects of bisphosphonate remain unknown, this finding seems to represent support for the hypothesis that suppression of bone resorption by bisphosphonate results in favorable prognoses at least for patients in this subset. In order to determine the prognostic significance of bone resorption in breast cancer patients, we investigated these markers c-terminal crosslinking telopeptide of type I collagen (1CTP) and N-telopeptide of type I collagen (NTX). Patients and Methods: 469 breast cancer patients were recruited who were operated on Hyogo College of Medicine and histologically confirmed to have invasive carcinoma. Serum 1CTP and NTX were measured preoperatively with the two-antibody radioimmunoassay and enzyme-linked immunosorbent assay methods, respectively, and blood samples were obtained before treatment from patients who were treated with neoadjuvant chemotherapy or endocrine therapy. The area under receiver operating characteristic curves were applied and optimal cutoff values were set at 3.6ng/ml for 1CTP, and 10.55nmolBCE/L premenopausal and 14.05nmolBCE/L postmenopausal for NTX. The relationships between these bone turnover markers and various clinicopathological characteristics were evaluated with the chi square or Fisher9s exact test. The log-rank test was used to compare relapse-free survival (RFS) in Kaplan-Meier plots. Associations of RFS were assessed with a Cox proportional-hazards model based on the results of univariate and multivariate analyses. Differences were considered statistically significant if p Results: There were significantly more 1CTP-high patients among postmenopausal women and RFS of 1CTP-high patients was significantly worse than that of 1CTP-low patients (5-year RFS: 0.65 vs 0.86; p=0.0002). Similarly, NTX-high patients were significantly associated with postmenopausal status, but there was no significant association between NTX-high worse RFS (p=0.0976). Multivariate analysis of tumor size, lymph node metastasis and nuclear grade identified 1CTP (hazard ratio: 2.04, 95% confidence interval: 1.13-3.68; p=0.018) as a significant independent prognostic factor. Subset analyses of 1CTP showed that prognosis was consistently worse recognized for postmenopausal (p=0.0002), but not premenopausal (p=0.37) patients. Furthermore, prognosis for 1CTP-high patients was worse for the estrogen receptor (ER)-positive subset (p=0.0005) but not for the ER-negative subset (p=0.22). Conclusion and discussion: High levels of serum bone resorption markers at baseline were identified as significant unfavorable prognostic factors for breast cancer patients. The prognostic significance of 1CTP seems to be prominent for postmenopausal patients with ER-positive breast cancers. These findings suggest the use of bone-modifying agents as an adjuvant therapy may be beneficial for breast cancer patients, especially for patients with high serum levels of 1CTP. Citation Format: Imamura M, Nishimikai A, Yanai A, Miyagawa Y, Higuchi T, Ozawa H, Murase K, Takatsuka Y, Miyoshi Y. High levels of serum C-terminal crosslinking telopeptide of type 1 collagen at baseline are associated with poor prognosis for breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-24.

Abstract P6-16-01: Differences in patterns of change of bone turnover markers during treatment with bone-modifying agents of breast cancer patients with bone metastases

Background: Bone-modifying agents have demonstrated their efficacy for treatment by suppressing osteoclast function. The activity of bone-modifying agents can be monitored by means of bone resorption markers such as c-terminal crosslinking telopeptide of type I collagen (1CTP) and N-telopeptide of type I collagen (NTX) as well as bone forming marker bone-specific alkaline phosphatase (BAP). In contrast to these markers which indirectly indicate bone turnover, tartrate-resistant acid phosphatase-5b (Tracp-5b) has been established as a direct marker showing osteoclast number and activity. The aim of this study was to identify the relative significance of these bone turnover markers as indicators of treatment efficacy induced by bone-modifying agents for breast cancer patients with bone metastases. Patients and Methods: For this study, 52 breast cancer patients with bone metastases treated with bone-modifying agents were recruited. Zoledronic acid and denosumab were administered as bone-modifying agents to 36 and 22 patients, respectively (for 6 patients, denosumab was used after zoledronic acid). Serum Tracp-5b, 1CTP, NTX and BAP were measured with, respectively, the EIA (enzyme immunoassay), RIA (two-antibody radioimmunoassay), ELISA (enzyme-linked immunosorbent assay) and CLEIA (chemiluminescent enzyme immunoassay) method. Blood samples were obtained pretreatment and 1, 3 and 6 months after treatment. Changes in these bone turnover markers were statistically analyzed with Friedman9s test, and correlation between serum markers and clinicopathological factors was calculated with Mann-Whitney9s test. Results: Serum tracp-5b decreased significantly after treatment (p Conclusion and discussion: Although baseline values of the bone turnover markers Tracp-5b, NTX and BAP decreased significantly after treatment with bone-modifying agents, the pattern of reduction for these three markers varied. Tracp-5b appears to reflect efficacy of bone-modifying agents most quickly and sensitively, possibly due to its direct link to the number and activity of osteoclasts. These findings may prove usefulness of Tracp-5b when considering the efficacy of various bone-modifying agents in clinical practice. Citation Format: Higuchi T, Nishimukai A, Yanai A, Miyagawa Y, Murase K, Imamura M, Ozawa H, Takatsuka Y, Miyoshi Y. Differences in patterns of change of bone turnover markers during treatment with bone-modifying agents of breast cancer patients with bone metastases. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-16-01.