Weight Gain during Neoadjuvant Chemotherapy is Associated with Worse Outcome among the Patients with Operable Breast Cancer

Qiong Fang,Jiahui Huang,Lu Gan,Kunwei Shen,Xiaosong Chen,Beiwen Wu 한국유방암학회 2019 Journal of breast cancer Vol.22 No.3

Purpose: This study was aimed at identifying the influence of initial weight and weight change during neoadjuvant chemotherapy (NAC) on pathologic complete response (pCR) and long-term survival in Chinese patients with operable breast cancer. Methods: We conducted a retrospective study using data from 409 female patients who received NAC for stage II or III breast cancer and had complete record of body mass index (BMI) before and after NAC. BMI of < 25 kg/m2 was categorized as normal weight/underweight (NW/UW); 25.0–29.9 kg/m2 was categorized as overweight (OW); ≥30 kg/m2 was categorized as obese (OB). BMI change was defined as the difference in BMI between day 1 of the first cycle of NAC and the day before surgery. A BMI gain or loss of > 2 kg/m2 following NAC was considered to be significant, else was considered stable. The study end points included pCR rates, disease-free survival (DFS), and overall survival (OS). Results: The median follow-up time was 43.2 (8.9–93.6) months. The average BMI was 23.40 ± 3.04 kg/m2 before NAC and 23.66 ± 3.02 kg/m2 after NAC (t = −3.604, p < 0.001). The pCR rate was 25.3% in the NW/UW group and 24.1% in the OW/OB group (p = 0.811), and was similar between the BMI-gain (23.3%) and the BMI-stable/loss (25.1%) groups (p = 0.787). Initial BMI was an independent prognostic factor for DFS (hazard ratio, 1.69; 95% confidence interval [CI], 1.13–2.53; p = 0.011) but not for OS, while BMI-gain was an independent prognostic factor for both DFS (hazard ratio, 2.09; 95% CI, 1.28–3.42; p = 0.003) and OS (hazard ratio, 1.97; 95% CI, 1.04–3.74; p = 0.039). Conclusion: BMI increased after NAC in Chinese breast cancer patients. Initial BMI and BMI change during NAC were not associated with pCR but were reversely associated with survival.

Impact of Prior Cancer History on the Clinical Outcomes in Advanced Breast Cancer: A Propensity Score–Adjusted, Population-Based Study

Caijin Lin,Jiayi Wu,Shuning Ding,Chihwan Goh,Lisa Andriani,Kunwei Shen,Li Zhu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose Despite the rapid growing of cancer survivors, prior cancer history is a commonly adopted exclusion criterion. Whether prior cancer will impact the survival of patients with advanced breast cancer (ABC) remains uncertain. Materials and Methods Patients with ABC diagnosed between 2004 and 2010 were identified using Surveillance, Epidemiology, and End Results (SEER) database. Timing, stage, and type were used to characterize prior cancer. Multivariable analyses using propensity score–adjusted Cox regression and competing risk regression were conducted to evaluate the prognostic effect of prior cancer on overall survival (OS) and breast cancer-specific survival (BCSS). Results A total of 14,176 ABC patients were identified, of whom 10.5% carried a prior cancer history. The most common type of prior cancer was female genital cancer (32.4%); more than half (51.7%) were diagnosed at localized stage; most were diagnosed more than 5 years (42.9%) or less than 1 year (28.3%) prior to the index cancer. In multivariate analyses, patients with prior cancer presented a slightly worse OS (hazard ratio, 1.18; 95% confidence interval [CI], 1.07 to 1.30; p=0.001) but a better BCSS (subdistribution hazard ratio, 0.64; 95% CI, 0.56 to 0.74; p < 0.001). In subset analyses, no survival detriment was observed in patients with prior malignancy from head and neck or endocrine system, at in situ or localized stage, or diagnosed more than 4 years. Conclusion Prior cancer provides an inferior OS but a superior BCSS for patients with ABC. It does not affect the survival adversely in some subgroups and these patients should not be excluded from clinical trials.

Long Noncoding RNA Signature and Disease Outcome in Estrogen Receptor- Positive Breast Cancer Patients Treated with Tamoxifen

Gen Wang,Xiaosong Chen,Yue Liang,Wei Wang,Yan Fang,Kunwei Shen 한국유방암학회 2018 Journal of breast cancer Vol.21 No.3

Purpose: Recent data have shown that the expression levels of long noncoding RNAs (lncRNAs) are associated with tamoxifen sensitivity in estrogen receptor (ER)-positive breast cancer. Herein, we constructed an lncRNA-based model to predict disease outcomes of ER-positive breast cancer patients treated with tamoxifen. Methods: LncRNA expression information was acquired from Gene Expression Omnibus by re-mapping pre-existing microarrays of patients with ER-positive breast cancer treated with tamoxifen. The distant metastasis-free survival (DMFS) predictive signature was subsequently built based on a Cox proportional hazard regression model in discover cohort patients, which was further evaluated in another independent validation dataset. Results: Six lncRNAs were found to be associated with DMFS in the discover cohort, which were used to construct a tamoxifen efficacy-related lncRNA signature (TLS). There were 133 and 362 patients with TLS high- and low-risk signatures in the discover cohort. Both univariate and multivariate analysis demonstrated that TLS was associated with DMFS. TLS high-risk patients had worse outcomes than low-risk patients, with a hazard ratio of 4.04 (95% confidence interval, 2.83–5.77; p<0.001). Both subgroup analysis and receiver operating characteristic analysis indicated that TLS performed better in lymph node-negative, luminal B, 21-gene recurrence score high-risk, and 70-gene prognosis signature high-risk patients. Moreover, in a comparison of the 21-gene recurrence score and 70-gene prognosis signature, TLS showed a similar area under receiver operating characteristic curve in all patients. Gene Set Enrichment Analysis indicated that TLS high-risk patients showed different gene expression patterns related to the cell cycle and nucleotide metabolism from those of low-risk patients. Conclusion: This six-lncRNA signature was associated with disease outcome in ER-positive breast cancer patients treated with tamoxifen, which is comparable to previous messenger RNA signatures and requires further clinical evaluation.

Changes of Tumor Infiltrating Lymphocytes after Core Needle Biopsy and the Prognostic Implications in Early Stage Breast Cancer: A Retrospective Study

Jiahui Huang,Xiaosong Chen,Xiaochun Fei,Ou Huang,Jiayi Wu,Li Zhu,Jianrong He,Weiguo Chen,Yafen Li,Kunwei Shen 대한암학회 2019 Cancer Research and Treatment Vol.51 No.4

Purpose The purpose of this study was to investigate the changes of tumor infiltrating lymphocytes (TILs) between core needle biopsy (CNB) and surgery removed sample (SRS) in early stage breast cancer patients and to identify the correlating factors and prognostic significance of TILs changes. Materials and Methods A retrospective study was carried out on 255 patients who received CNB and underwent surgical resection for invasive breast cancer. Stromal TILs levels of CNB and SRS were evaluated respectively. Tumors with  50% stromal TILs were defined as lymphocyte-predominant breast cancer (LPBC). Clinicopathological variables were analyzed to determine whether there were factors associated with TILs changes. Log-rank tests and Cox proportional hazards models were used to analyze the influences of TILs and TILs changes on survival. Results SRS-TILs (median, 10.0%) were significant higher than CNB-TILs (median, 5.0%; p < 0.001). Younger age (< 60 years, p=0.016) and long surgery time interval (STI,  4 days; p=0.003) were independent factors correlating with higher TILs changes. CNB-LPBC patients showed better breast cancer-free interval (BCFI, p=0.021) than CNB-non-LPBC (CNB-nLPBC) patients. Patients were categorized into four groups according to the LPBC change pattern from CNB to SRS: LPBCLPBC, LPBCnLPBC, nLPBCLPBC, and nLPBCnLPBC, with estimated 5-year BCFI 100%, 100%, 69.7%, and 86.0% (p=0.016). nLPBCLPBC pattern was an independent prognostic factor of worse BCFI (hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.53; p=0.035) compared with other patterns. Conclusion TILs were significantly higher in SRS than in CNB. Higher TILs changes were associated with younger age and long STI. Changing from nLPBC to LPBC after CNB indicated a worse BCFI, which needs further validation.

Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study

Jiayi Wu,Shuning Ding,Linling Yin,Xiaochun Fei,Caijin Lin,Lisa Andriani,Chihwan Goh,Jiahui Huang,Jin Hong,Weiqi Gao,Siji Zhu,Hui Wang,Ou Huang,Xiaosong Chen,Jianrong He,Yafen Li,Kunwei Shen,Weiguo Che 대한암학회 2020 Cancer Research and Treatment Vol.52 No.3

Purpose This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). Materials and Methods Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). Conclusion RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.