Nomogram for predicting the risk of bone metastasis in breast cancer: a SEER population-based study.

BACKGROUND: Bone is the most common metastasis site of breast cancer. The prognosis of bone metastasis is better than other distant metastases, but patients with skeletal related events (SREs) have a poor quality of life, high healthcare costs and low survival rates. This study aimed to establish an effective nomogram for predicting risk of bone metastasis of breast cancer. METHODS: The nomogram was built on 4,895 adult/female/primary invasive breast cancer patients with complete clinicopathologic information, captured by the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Five biological factors (age, grade, histologic type, surgery of breast lesions and subtypes) were assessed with logistic regression to predict the risk of bone metastases. The predictive accuracy and discriminative ability of the nomogram were determined by the Receiver Operating Characteristic (ROC) curves and the calibration plot. Results were validated on a separate 2,093 cohort using bootstrap resampling from 2010 to 2015 as an internal group and a retrospective study on 120 patients in the First Affiliated Hospital of China Medical University from 2010 to 2014 at the same situation as an external group. RESULTS: On multivariate logistic regression of the primary cohort, independent factors for bone metastases were age, grade, histologic type, surgery of breast lesions and subtypes, which were all selected into the nomogram. The calibration plot for probability of incidence showed good agreement between prediction by nomogram and two observations. The ROC curves presented a good statistical model for risk of bone metastasis, and the corresponding AUC value of the development group, internal validation group and external validation group were 0.678, 0.689 and 0.704 respectively. CONCLUSIONS: The proposed nomogram resulted in more-accurate prognostic prediction for breast cancer patients with bone metastases.

[Analysis of the factors affecting pathologic complete response to neoadjuvant chemotherapy in breast cancer patients].

OBJECTIVE: To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed. RESULTS: Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences. CONCLUSIONS: The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

[Analysis of intraoperative molecular assessment of sentinel lymph nodes in breast carcinoma].

OBJECTIVE: To evaluate the reliability and application of GeneSearch(TM) breast lymph node assay (Genesearch), a real-time fluorescence quatitative PCR method, in intraoperative assay of metastasis in sentinel lymph nodes (SLNs) from breast cancer patients. METHODS: Totally 140 SLNs from 80 patients with breast carcinoma were prospectively studied from May 2010 to August 2010. The 80 patients included 78 women and 2 men who ranged in age from 29 to 85 years, and the median age is 49 years. The expression of CK19 and mammaglobulin in all 140 SLNs were detected by Genesearch, and the results were compared with that of histological evaluation of both frozen and paraffin-embedded sections. RESULTS: Among SLNs, by histological analyses, there were 121 without metastasis, 17 with macrometastasis, 2 with micrometastasis, and none of isolated tumor cell. By Genesearch, there were 119 without metastasis and 21 with metastasis. Genesearch showed sensitivity of 89.4%, positive predictive value of 81.0%, negative predictive value of 98.3% and specificity of 96.7% by comparing to histological analyses. The concordance between Genesearch and histological analysis was 95.7%. The sensitivity of Genesearch was 15/17 for macrometastasis and 2/2 for micrometastasis. CONCLUSIONS: Genesearch detection presents high sensitivity and specificity in evaluating metastasis of sentinel lymph nodes in breast cancer, but strict performance technically is necessary to avoid false positive and false negative results. Inability of further subtyping for the positive cases might be the key limitations for wide application of this method.

[Feasibility of sentinel lymph node biopsy peri-neoadjuvant chemotherapy in breast cancer].

OBJECTIVE: To explore the feasibility of sentinel lymph node biopsy in peri-neoadjuvant chemotherapy for breast cancer patients. METHODS: A total of 252 breast cancer patients underwent sentinel lymph node biopsy and axillary lymph node dissection from January 2005 to November 2011, including 150 patients in pre-neoadjuvant chemotherapy group and 102 in post-neoadjuvant chemotherapy group. The feasibility of sentinel lymph node biopsy under different clinical states of axillary lymph node was compared. RESULTS: No significant difference was found in the detection rate (98.5% vs 92.8%), false negative rate (6.7% vs 7.9%), accuracy (98.4% vs 91.9%) and negative sensitivity (97.9% vs 88.0%) of sentinel lymph node biopsy before neoadjuvant chemotherapy whether the axillary lymph node was negative or positive. However, the transfer rate of sentinel lymph node in the positive group was significantly higher than the negative group (28.8% vs 67.5%, P = 0.000). False negative rate of sentinel lymph node in biopsy was significantly higher in the post-neoadjuvant chemotherapy group than the pre-neoadjuvant chemotherapy group (7.5% vs 23.9%, P = 0.024) and the accuracy/negative sensitivity decreased significantly (95.1% vs 83.5%, P = 0.005/94.4% vs 75.0%, P = 0.003). No statistical difference existed in the detection rate, false negative rate, accuracy, negative sensitivity of sentinel lymph node in biopsy before and after neoadjuvant chemotherapy in patients with negative axillary lymph node for a preliminary diagnosis. The accuracy of sentinel lymph node decreased significantly in biopsy after neoadjuvant chemotherapy in patients with positive axillary lymph node confirmed pathologically for a preliminary diagnosis compared with before (98.4/83.7%, P = 0.010), the transfer rate of sentinel lymph node increased significantly (28.8/53.7%, P = 0.005) and negative sensitivity reduced significantly (97.9/68.0%, P = 0.007); Compared with pre-neoadjuvant chemotherapy, the negative sensitivity decreased significantly in patients with axillary lymph node positive confirmed pathologically and then turned negative (94.4% vs 57.1%, P = 0.005) while the transfer rate of sentinel lymph node increased significantly (28.8%/65.0%, P = 0.003). CONCLUSIONS: Sentinel lymph node before neoadjuvant chemotherapy may accurately predict axillary lymph node metastasis. The detection rate, false negative rate, accuracy, negative sensitivity of sentinel lymph node in biopsy after neoadjuvant chemotherapy in patients with negative axillary lymph node for preliminary diagnosis are the same before neoadjuvant chemotherapy. Patients with positive axillary lymph node for a preliminary diagnosis are unsuitable for sentinel lymph node biopsy whether axillary lymph node turns negative or not after neoadjuvant chemotherapy.

A case-control study on risk factors of breast cancer in China.

INTRODUCTION: To screen the risk factors associated with breast cancer among Chinese women in order to evaluate the individual risk of developing breast cancer among women in China. MATERIAL AND METHODS: A case-control study on 416 breast cancer patients and 1156 matched controls was conducted in 14 hospitals in 8 provinces of China in 2008. Controls were age- and region-matched to the cases. Clinicians conducted in-person interviews with the subjects to collect information on demographics and suspected risk factors for breast cancer that are known worldwide. Conditional logistic regression was used to derive odds ratios (OR) and 95% confidence intervals (CI) for the associations between risk factors and breast cancer. RESULTS: Compared with matched controls, women with breast cancer were significantly more likely to have higher body mass index (BMI, OR = 4.07, 95% CI: 2.98-5.55), history of benign breast disease (BBD) biopsy (OR = 1.68, 95% CI: 1.19-2.38), older age of menarche (AOM) (OR = 1.41, 95% CI: 1.07-1.87), stress anticipation (SA), for grade 1-4, OR = 2.15, 95% CI: 1.26-3.66; for grade 5-9, OR = 3.48, 95% CI: 2.03-5.95) and menopause (OR = 2.22, 95% CI: 1.50-3.282) at the level of p < 0.05. Family history of breast cancer (FHBC) in first-degree relatives (OR = 1.66, 95% CI: 0.77-3.59) and use of oral contraceptives (OC) (OR = 1.59, 95% CI: 0.83-3.05) were associated with an increased risk of breast cancer at the level of p < 0.20. CONCLUSIONS: Our results showed that BMI, history of BBD biopsy, older AOM, SA and menopause were associated with increased risk of breast cancer among Chinese women. The findings derived from the study provided some suggestions for population-based prevention and control of breast cancer in China.

Mesenchymal stem cells from primary breast cancer tissue promote cancer proliferation and enhance mammosphere formation partially via EGF/EGFR/Akt pathway.

Mesenchymal stem cells (MSCs) play a critical role in promoting cancer progression. However, it is not clear whether MSCs are located in breast cancer tissues and correlated with tumor proliferation. The aim of this study was to investigate the presence of MSCs in breast cancer tissues and evaluate their interactions with cancer cells. We successfully isolated and identified MSCs from primary breast cancer tissues. Breast cancer-associated MSCs (BC-MSCs) showed homogenous immunophenotype, and possessed tri-lineage differentiation potential (osteoblast, adipocyte, and chondrocyte). When co-transplanted with cancer cells in a xenograft model in vivo, BC-MSCs significantly increased the volume and weight of tumors. We observed that BC-MSCs stimulated mammosphere formation in the transwell co-culture system in vitro. This effect was significantly suppressed by the EGF receptor inhibitor. We verified that BC-MSCs could secrete EGF and activate cancer cell's EGF receptors. Furthermore, our data showed that EGF derived from BC-MSCs could promote mammosphere formation via the PI3K/Akt signaling pathway. Our results confirmed the presence of MSC in primary breast cancer tissues, and they could provide a favorable microenvironment for tumor cell growth in vivo, partially enhance mammosphere formation via the EGF/EGFR/Akt pathway.

[Multicenter cross-sectional study of anemia in patients with gastric and colorectal cancer before and after the operation].

OBJECTIVES: To determine the prevalence of cancer-related anemia and iron deficiency anemia (IDA) in patients with gastric and colorectal cancer in North of China. METHODS: A cross-sectional study of 262 inpatients diagnosed with gastric or colorectal cancer admitted to eight general hospitals in Beijing from August 2009 to December 2009 was performed. The blood samples were took on the day after admission and the seventh day after operation for the tests of hemoglobin, serum iron and ferritin. The morbidity of cancer-related anemia and IDA before and after the surgery was also compared respectively. RESULTS: The preoperative morbidity of cancer-related anemia was 36.6% in 131 patients with gastric cancer, and the morbidity of IDA was 52.1%. The mean age of the anemic patients was higher than that in cases without anemia [(62 ± 11) yrs vs. (57 ± 12) yrs, P < 0.05]; the postoperative morbidity of IDA increased to 72.6% (P < 0.05). In the 131 cases with colorectal cancer, the preoperative incidence of cancer-related anemia and IDA was 37.4% and 61.2%, respectively. About 45% of the cases with anemia had a tumor in the right colon. Postoperative incidence of IDA was significantly higher than that before the surgery (76.7%, P < 0.05). Only 10.3% of the anemic patients were treated with chalybeate therapy before surgical procedures, and the proportion was 22.7% after the operation. More than 50% of anemic patient received blood transfusion. CONCLUSIONS: Cancer-related anemia is a common clinical manifestation in patients with gastrointestinal cancer, and anemia occurs more frequently in elder and patients with right colon tumor. The treatment to cancer-related anemia is insufficient and a systematic therapy is needed to be established.

[Comparison of response evaluation methods of neoadjuvant chemotherapy in breast cancer patients].

OBJECTIVE: To compare the efficiency of response evaluation by clinical examination, ultrasonograghy and mammography in neoadjuvant chemotherapy (NAC) for breast cancer. METHODS: A retrospective cohort study was conducted to analyze the data of 141 patients treated with neoadjuvant chemotherapy. Response evaluation was performed by clinical palpation, ultrasound and mammography. RESULTS: Only 12 (8.5%) among the 141 patients presented with a stage I tumor. The tumor size determined by palpation was often larger than that by ultrasound before therapy (P < 0.01). Among patients with suspicions axillary nodes checked by ultrasound, 88.3% (53/60) of them had positive nodes by pathology before NAC, and 34.5% (10/29) of patients with negative nodes determined by ultrasound had positive nodes by pathology. In all the 141 patients, 21(14.9%) showed pathological complete remission in both the primary tumor and lymph node. For response evaluation, the false complete remission rate judged by clinical examination was 46.8% (22/47), and the false tumor residual rate by ultrasound was 84.0% (21/25). In 53.5% (23/43) of patients the response could not be assessed by mammography due to that the tumors were undistinguishable in size. The range of microcalcification was not reduced in 5 patients with a partial response of the tumor. 25 patients experienced needle puncture during therapy. Among them, in the 9 pathologically negative patients, only 3 achieved pCR, and the other 16 positive patients didn't achieve pCR. CONCLUSION: Using the puncture or sentinel lymph node biopsy, clinicians should pay enough emphasis on the pathological determination of the node status before chemotherapy. Clinicians will make a quite of false judgment of the tumor by clinical examination, ultrasound or mammography. They may use needle puncture during therapy to evaluate the response of neoadjuvant chemotherapy, and the result should be analyzed synthetically.

[Differentiation of bone marrow derived Thy-1+ beta2M- cells into liver cells in AA induced liver injury micro-environment].

OBJECTIVE: To investigate the differentiation of bone marrow derived Thy-1+ beta2M- cells (BDTCs) into liver cells in allyl alcohol (AA) induced liver injury micro-environment. METHODS: BDTCs of male F344 rats were isolated by two-step magnetic separation system (MACS) technique, and infused intraportally into female recipients after labeling with PKH26. Thirty recipients were divided randomly into 3 groups: (1) AA-injured liver + BDTCs infusion, (2) normal liver + BDTCs infusion and (3) AA-injured liver + NS infusion (control). Blood biochemical examination, fluorescence labeled cellular localization, Y-chromosome sry gene in-situ hybridization and immunohistochemistry were carried out to evaluate BDTCs distribution, differentiation and proliferation in recipients's livers after different intervals. RESULTS: Fluoromicroscopy and in situ hybridization suggested that BDTCs of donors were interspersed in pieces and cords among the necro-periportals induced by AA; immunohistochemistry indicated that those implanted cells expressed OV-6, AFP, CK19 and albumin successively, while positive cells were hardly seen in the normal liver + BDTCs infusion group. Compared with the controls, the blood biochemical restitution was more rapid in group (1), (9.8 d +/- 3.1 d vs. 13.7 d +/- 4.2 d). CONCLUSION: The injury micro-environment induced by AA facilitates BDTCs integration with hepatic cell plates and differentiation into mature liver cells. BDTCs differentiation into liver cells might accelerate endogenous liver cell regeneration and reparation.

[Anergy, apoptosis and decreased MHC class I molecule expression of C57BL/6J mouse CD4+ T cells induced by SEB].

AIM: To study the mechanism of peripheral T cell tolerance induced by superantigen Staphylococus aureus enterotoxin B (SAgSEB). METHODS: Splenocytes from C57BL/6J (B6) mice were stimulated with SEB in-vitro. The proliferation of lymphocytes was determined by MTT colorimetry. The apoptosis of anergic T cells, the cells being in the S and G(0)-G(1) phase and MHC-I (H-2K(b)) expression of T cells were analyzed by flow cytometry (FCM). Apoptosis of anergic T cells was also demonstrated by DNA electrophoresis ladder. RESULTS: SEB could induce strong proliferation of CD4+ T cells and the maximal percentage of CD4+ T cells in S phase appeared on 3rd day after SEB stimulation and then decreased, but the changes of percentage of CD4+ T cells in G(0)-G(1) phase was opposite to that in S phase. CD4+ T cells became anergy on 3rd day and apoptosis of anergic CD4+ T cells appeared on 5th day. Percentage of apoptosis cells increased gradually and could not be reversed by addition of anti-CD3 Ab and ConA. Expression of MHC-I (H-2K(b)) was marginally declined accompanied by CD4+ T cell anergy after SEB exposure. CONCLUSION: SEB-induced tolerance may have relation to anergy and apoptosis of CD4+ T cells, and down-regulation of MHC-I molecules.