Concurrent neoadjuvant chemotherapy and estrogen deprivation in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (CBCSG-036): A randomized, controlled, multicenter trial.

BACKGROUND: The current randomized, controlled, multicenter clinical trial was conducted to investigate the efficacy of concurrent neoadjuvant chemotherapy (NCT) and estrogen deprivation in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: Eligible patients with AJCC stage IIB to stage IIIC, ER-positive, HER2-negative breast cancer were enrolled and randomly assigned to receive NCT with or without estrogen deprivation. The primary endpoint was the objective response rate (ORR). RESULTS: A total of 249 patients were assigned to either neoadjuvant chemoendocrine therapy (NCET) (125 patients) or the NCT group (124 patients). In the intention-to-treat analysis, the ORR was found to be significantly higher in the NCET group compared with the NCT group (84.8% vs 72.6%; odds ratio, 2.11 [95% CI, 1.13-3.95; P = .02). The efficacy of NCET was more prominent in tumors with a higher Ki-67 index (>20%), with an ORR of 91.2% reported in the NCET group versus 68.7% in the NCT group (P = .001). The pathologic complete response and pathological response rates did not differ significantly between the 2 groups. Although there was no significant difference with regard to progression-free survival (PFS) between the 2 groups (P = .188), patients with a higher baseline Ki-67 index appeared to derive a greater PFS benefit from NCET (2-year PFS rate of 91.5% in the NCET group vs 76.5% in the NCT group; P = .058). Adding endocrine agents to NCT did not result in significant differences in adverse events (grade 3 or 4; graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) between the 2 groups. CONCLUSIONS: The addition of estrogen deprivation to NCT appears to improve the clinical response in patients with ER-positive, HER2-negative breast cancer, especially for those individuals with a higher Ki-67 index. Patients with a higher Ki-67 index might derive more PFS benefit from concurrent neoadjuvant treatment.

Correction to: Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer.

After the publication of this work [1] an error in Fig. 1c was brought to our attention: the Western blots for PRDX6 and ß-actin were similar to those shown in lanes 5-6 of Fig. 4g. To verify these findings, we have repeated this experiment and the results are shown in a new Fig. 1c below. The repeated experimental results are consistent with the previously reported findings in the original study [1] and the functional role for PRDX6 in malignant progression of human cancer including breast cancer has been widely documented and recognized in numerous other studies [2]. We apologize for the error. However, this correction does not affect the conclusions of the article.

The association between China's Great famine and risk of breast cancer according to hormone receptor status: a hospital-based study.

PURPOSE: The Great Chinese Famine afflicted almost all Chinese people between 1959 and 1961. No study has explicitly assessed the association between an exposure to Chinese Famine and risk of overall breast cancer and tumor subtype. We evaluated the unique historical environmental influences of famine exposure on breast cancer subtypes. METHODS: 16,469 Chinese women who were diagnosed with invasive breast cancer in the Fudan University Shanghai Cancer Center (FUSCC) from 1999 to 2014 were analyzed. Four tumor subtypes were defined by both estrogen-receptor (ER) and progesterone-receptor (PR) status. Multinomial logistic regression models were used to estimate the odds ratios (ORs) of ER-PR-, ER+PR-, and ER-PR+ relative to ER+PR+ breast cancer for exposure to famine and age at the exposure. RESULTS: Compared with cases not exposed to the Famine, exposed cases were more likely to be diagnosed with ER-PR- (OR 1.60, 95 % CI 1.43-1.81), ER-PR+ (OR 4.85, 95 % CI 3.80-6.19), and ER+PR- (OR 1.99, 95 % CI 1.67-2.37) than ER+PR+ breast cancer after controlling for established breast cancer risk factors. Women exposed to Famine after first birth had a higher risk of EP-PR- (OR 1.66, 95 % CI 1.28-2.15), ER-PR+ (OR 9.75, 95 % CI 5.85-16.25), and ER+PR- (OR 2.35, 95 % CI 1.69-3.26) compared to those with ER+PR+ breast cancer. CONCLUSIONS: Women exposed to the Famine, particularly those exposed after first birth, were more likely to be diagnosed with ER-PR-, ER-PR+, and ER+PR- breast cancer. This retrospective analysis suggests that famine, malnutrition, or the associated lack of fruit and vegetable consumption in adulthood may be related to epidemiological heterogeneity within breast cancer subtypes.

Predicting Non-sentinel Lymph Node Metastasis in a Chinese Breast Cancer Population with 1-2 Positive Sentinel Nodes: Development and Assessment of a New Predictive Nomogram.

BACKGROUND: We have developed a new nomogram to predict the probability of a patient with 1-2 metastatic sentinel lymph nodes (SLNs) to present further axillary disease. METHODS: Data were collected from 480 patients who were diagnosed with 1-2 positive lymph nodes and thus underwent axillary lymph node dissection between March 2005 and June 2011. Clinical and pathological features of the patients were assessed with multivariable logistic regression. The Shanghai Cancer Center Non-SLN nomogram (SCC-NSLN) was created from the logistic regression model. This new model was subsequently applied to 481 patients from July 2011 to December 2013. The predictive accuracy of the SCC-NSLN nomogram was measured by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: Based on the results of the univariate analysis, the variables that were significantly associated with the incidence of non-SLN metastasis in an SLN-positive patient included lymphovascular invasion, neural invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis (P < 0.05). Using multivariate analysis, lymphovascular invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis were identified as independent predictors of non-SLN metastasis. The SCC-NSLN nomogram was then developed using these four variables. The new model was accurate and discriminating on both the modeling and validation groups (AUC: 0.7788 vs 0.7953). The false-negative rates of the SCC-NSLN nomogram were 3.54 and 9.29 % for the predicted probability cut-off points of 10 and 15 % when applied to patients who have 1-2 positive SLNs. CONCLUSION: The SCC-NSLN nomogram could serve as an acceptable clinical tool in clinical discussions with patients. The omission of ALND might be possible if the probability of non-SLN involvement is <10 and <15 % in accordance with the acceptable risk determined by medical staff and patients.

Weekly paclitaxel/carboplatin/trastuzumab therapy improves pathologic complete remission in aggressive HER2-positive breast cancers, especially in luminal-B subtype, compared with a once-every-3-weeks schedule.

BACKGROUND: The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB-IIIC) breast cancers were evaluated in this phase II trial. METHODS: Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla. To detect an assumed 35% pCR absolute difference between the two schedules, a minimum of 26 assessable patients in each group was required (two-sided α = 0.05, ß = 0.2). RESULTS: A total of 56 patients were enrolled (weekly group, n = 29; every-3-weeks group, n = 27). In the intent-to-treat analysis, pCR in the breast/axilla were found in 31 patients (55%; 95% confidence interval [CI]: 41%-69%). Compared with the every-3-weeks schedule, the weekly administration achieved higher pCR (41% vs. 69%; p = .03). After adjustment for clinical and pathological factors, the weekly administration was more effective than the every-3-weeks schedule, with hazard ratio of 0.3 (95% CI: 0.1-0.9; p = .03). Interestingly, weekly administration resulted in high pCR rates in both luminal-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas luminal-B (HER2-positive) tumors benefited less from the every-3-weeks schedule compared with the ERBB2+ tumors (21% vs. 62%, p = .03). These results remain after multivariate adjustment, showing weekly administration was more effective in the luminal-B (HER2-positive) subgroup (p = .02) but not in the ERBB2+ subgroup (p = .50). CONCLUSION: A more frequent administration might improve the possibility of eradicating invasive cancer in the breast and axilla, especially in the luminal-B (HER2-positive) subtype. Further studies to validate our findings are warranted.

Association of HER-2 copy number and HER-2/CEP-17 ratio with neoadjuvant taxane-containing chemotherapy sensitivity in locally advanced breast cancer.

PURPOSE: Aneusomy 17 causes inconsistency in fluorescence in situ hybridization (FISH)-based human epidermal growth factor receptor (HER)-2 status assessment using different algorithms (copy number or the HER-2/centromere enumerator probe 17 [CEP-17] ratio). We investigated the effects of FISH-based HER-2 status assessment and aneusomy 17 on responsiveness to neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: This prospective study recruited 152 patients with locally advanced breast cancer who underwent four-cycle weekly paclitaxel plus carboplatin without trastuzumab. RESULTS: The pathologic complete remission (pCR) rate in the breast and axilla was 24.3% (95% confidence interval [CI], 17.7%-32.0%). Although HER-2 status, assessed by either HER-2/CEP-17 ratio-based FISH or copy number-based FISH, was a predictor of NAC sensitivity, ratio-assessed HER-2 status had a poorer performance in determining patients' responsiveness to NAC (p = .029). Patients who were not HER-2 amplified when assessed using the HER-2/CEP-17 ratio but were HER-2 amplified when assessed using copy number (~5%) were eventually proven to be responsive to NAC, with a pCR rate of 57% (95% CI, 18.4%-90.1%). In contrast, patients who were HER-2 amplified when assessed by the ratio but not HER-2 amplified when assessed using copy number (~3%) were completely irresponsive. Higher HER-2 copy numbers represented increasing chances of a pCR (adjusted odds ratio, 3.09; 95% CI, 1.35-7.08), with an apparent gene-dose effect (p for trend < .001). CONCLUSION: It is likely that HER-2 copy number but not the HER-2/CEP-17 ratio determines NAC sensitivity. Additional studies to validate our findings are warranted.

RAD50 and NBS1 are not likely to be susceptibility genes in Chinese non-BRCA1/2 hereditary breast cancer.

Deleterious mutations in several genes that are involved in repair of damage to DNA have been associated with an increased risk of breast cancer. Recent studies have shown sequence variants in two such genes, RAD50 and NBS1, which can be predisposed to breast cancer. The aim of this study is to elucidate the contribution of RAD50 and NBS1 germline mutations to the etiology of non-BRCA1/2 hereditary breast cancer in China. We conducted a mutational analysis of RAD50 and NBS1 in genomic DNA from 384 Chinese women with early-onset breast cancer and/or affected relatives. All the coding exons and adjacent intronic splice junction rejoins of RAD50 and NBS1 were screened using PCR-DHPLC and DNA sequencing analysis. Among all cases, no obviously deleterious mutations were observed in RAD50; one synonymous change c.102G>A at codon 34 and one single nucleotide polymorphism IVS9 + 19C>T were identified in NBS1. Furthermore, there was no remarkable difference in the allele frequency of NBS1 c.553G>C (E185Q) between cases (172/384) and controls (182/420). Our results exclude the possible role of RAD50 and NBS1 in familial breast cancer predisposition in Chinese women, and there is no evidence for the recommendation of RAD50 and NBS1 for genetic testing in China.

Expression of CXCL14 and its anticancer role in breast cancer.

CXCL14, also known as breast and kidney-expressed chemokine, was initially identified as a chemokine highly expressed in the kidney and breast. The exact function of CXCL14 in human breast cancer is still unclear, although it has been testified to play an anti-tumor role in other tumors, including head and neck squamous cell carcinoma, lung cancer, prostate cancer, and so on. In this study, we tried to demonstrate the relationship between CXCL14 and breast cancer. CXCL14 expressions were detected by reverse transcription-PCR and western blot in 2 normal breast epithelial cell lines and 6 breast cancer cell lines. The effects of CXCL14 on the proliferation and invasion in vitro were tested using the CXCL14-overexpressing cells (MDA-MB-231HM-CXCL14) which were established by stable transfection. We established an orthotropic xenograft tumor model in SCID mice using the MDA-MB-231HM-CXCL14 cells and explored the influence of CXCL14 overexpression on tumor growth and metastasis in vivo. Furthermore, we detected the protein level of CXCL14 in 208 breast cancer patients by immunohistochemistry and discussed the correlation between CXCL14 and the prognosis of breast cancer. CXCL14 mRNA expression is lower in breast cancer cell lines, and MDA-MB-231HM express the lowest levels of CXCL14 mRNA. Overexpression of CXCL14 inhibited cell proliferation and invasion in vitro and attenuated xenograft tumor growth and lung metastasis in vivo. CXCL14 protein level is positively correlated to the overall survival of all patients as well as the patients with lymph node metastasis, and it has a negative correlation with the lymph node metastasis. Our study showed for the first time that CXCL14 is a negative regulator of growth and metastasis in breast cancer. The re-expression or up-regulation of this gene may provide a novel strategy in breast cancer therapy in the future.

The chemokine receptor CCR4 promotes tumor growth and lung metastasis in breast cancer.

Increasing evidence has shown that chemokines and chemokine receptors are associated with tumor growth and metastasis. CCR4, an important chemokine receptor for regulating immune homeostasis, is thought to be involved in hematologic malignancies and has also recently implicated in some solid tumors, such as gastric cancer. The possible role of CCR4 in breast cancer has not been well elucidated. In this study, we show that CCR4 is differentially expressed in human breast cancer cell lines. Specifically, we find that CCR4 is overexpressed in breast cancer cell lines with high metastatic potential. More importantly, we used a combination of overexpression and RNA interference to demonstrate that CCR4 promotes breast tumor growth and lung metastasis in mice. Furthermore, we find that microvessel density is significantly increased in tumors formed by CCR4-overexpressing cells and decreased in those formed by CCR4-knockdown cells. We find that overexpression of CCR4 can enhance the chemotactic response of breast cancer cells to CCL17. However, the expression of CCR4 does not affect the proliferation of breast cancer cells in vitro. Furthermore, we show that CCR4 expression is positively correlated with HER2 expression, tumor recurrence and lymph node, lung and bone metastasis (P < 0.05). Multivariate analysis showed that CCR4 expression is a significant independent prognostic factor for overall survival (P = 0.036) but not for disease-free survival in patients with breast cancer (P = 0.071). Survival analysis indicated a strong association between CCR4 expression and lower overall survival (P = 0.0001) and disease-free survival (P = 0.016) in breast cancer.

Predicting sentinel lymph node metastasis in a Chinese breast cancer population: assessment of an existing nomogram and a new predictive nomogram.

We assessed the MSKCC nomogram performance in predicting SLN metastases in a Chinese breast cancer population. A new model (the SCH nomogram) was developed with clinically relevant variables and possible advantages. Data were collected from 1,545 patients who had a successful SLN biopsy between March 2005 and November 2011. We validated the MSKCC nomogram in the modeling and validation group. Clinical and pathologic features of SLN biopsy in modeling group of 1,000 patients were assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The SCH nomogram was created from the logistic regression model and subsequently applied to 545 consecutive SLN biopsies. By multivariate analysis, age, tumor size, tumor location, tumor type, and lymphovascular invasion were identified as independent predictors of SLN metastasis. The SCH nomogram was then developed using the five variables. The new model was accurate and discriminating (with an AUC of 0.7649 in the modeling group) compared to the MSKCC nomogram (with an AUC of 0.7105 in the modeling group). The area under the ROC curve for the SCH nomogram in the validation population is 0.7587. The actual probability trends for the various deciles were comparable to the predicted probabilities. The false-negative rates of the SCH nomogram were 1.67, 3.54, and 8.20 % for the predicted probability cut-off points of 5, 10, and 15 %, respectively. Compared with the MSKCC nomogram, the SCH nomogram has a better AUC with fewer variables and has lower false-negative rates for the low-probability subgroups. The SCH nomogram could serve as a more acceptable clinical tool in preoperative discussions with patients, especially very-low-risk patients. When applied to these patients, the SCH nomogram could be used to safely avoid a SLN procedure. The nomogram should be validated in various patient populations to demonstrate its reproducibility.

A prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving patients' persistence to adjuvant aromatase inhibitor medication for postmenopausal, early stage breast cancer.

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients' beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients' persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8% for the standard treatment group and the standard treatment plus patient support program group, respectively (P=0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P=0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P=0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio=3.9; 95% CI, 1.1-13.7; P=0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients' persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.

Outcome of pure mucinous breast carcinoma compared to infiltrating ductal carcinoma: a population-based study from China.

PURPOSE: Pure mucinous breast carcinoma (PMBC) is a rare pathologic finding. Few studies have addressed the biologic features of PMBC and prognostic factors among patients with this disease. We performed a study to compare PMBC and invasive ductal carcinoma (IDC) by means of a large database to reliably assess the biologic phenotype and clinical behavior of PMBC. METHODS: A total of 2,511 patients who met the inclusion criteria were identified from 1999 to 2010; 2,202 patients had pure IDC and 309 had PMBC. Clinical and biologic features, overall survival, and recurrence/metastasis-free survival (RFS) were compared for both groups. RESULTS: PMBC had favorable characteristics including smaller size, lower rates of lymph node positivity, lower stage, higher expression of hormone receptors, and less HER2 overexpression. Patients with PMBC had better 10-year RFS (71 %) than patients with IDC (64 %). Multivariate analysis revealed that node status and tumor, node, metastasis system (TNM) stage were statistically significant prognostic factors for survival. RFS curves stratified for node status revealed a highly significant difference between node negative and node positive patients. Additionally, patients with PMBC underwent breast-conserving surgery (BCS) more frequently than patients with IDC, and the 5-year overall survival rate of the BCS group was not significantly different from the total mastectomy group. CONCLUSIONS: PMBC in Chinese women showed less aggressive behavior and had a better prognosis than IDC, and this favorable outcome was maintained after 10 years. Node status and TNM stage appeared to be the most significant predictors of worse prognosis. BCS should be preferred over mastectomy in the treatment of early-stage PMBC.

Tumor characteristics and the clinical outcome of invasive lobular carcinoma compared to infiltrating ductal carcinoma in a Chinese population.

BACKGROUND: We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between ILC and infiltrating ductal carcinoma (IDC) using a large database. METHODS: Clinicopathologic features, overall survival (OS), and recurrence/metastasis-free survival (RFS) were compared between 2,202 patients with IDC and 215 patients with ILC. RESULTS: ILC was significantly more likely to be associated with a favorable phenotype, but the incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (8.4% vs. 3.9%; P=0.001). The frequencies of recurrence/metastasis (P = 0.980) and death (P = 0.064) were similar among patients with IDC and patients with ILC after adjustment for tumor size and nodal status. The median follow-up was 42.8 months. CONCLUSIONS: Chinese women with ILCs do not have better clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.

[Chinese HER2 positive early breast cancer trastuzumab adjuvant therapy: preliminary outcomes].

OBJECTIVE: To evaluate the efficacy and safety of 1-year adjuvant trastuzumab (herceptin) versus 1-year non-trastuzumab observation in Chinese patients with HER2-positive early breast cancer during a median follow-up of 1 year. METHODS: The HERA trial was an international, multicenter, randomized, open-label, phase III trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard adjuvant chemotherapy, radiotherapy or both in patients with HER2-positive node-positive or high-risk node-negative early breast cancer. The primary endpoint was disease-free survival. Secondary end points included recurrence-free survival, distant disease-free survival, overall survival and cardiac safety. The first planned interim analysis comparing the efficacy and safety of treatment with trastuzumab for 1 year versus observation were completed in April 2005. Only the outcomes of recruited Chinese patients were reported. RESULTS: A total of 122 Chinese patients from 8 participating centers were included for planned interim analysis. And they were divided into trastuzumab (n = 68) and observation (n = 54) groups. Three and eight disease-free survival events were observed in the trastuzumab and observation groups respectively. Two-year disease-free survival rates were 92.9% and 81.4% respectively (P = 0.0489); 2-year recurrence-free survival and distant disease-free survivals were 98.1% vs 81.4% (P = 0.0064) and 98.1% vs 83.3% (P = 0.0117) respectively. Trastuzumab was generally well-tolerated with a decent safety profile. Severe cardiotoxicity was not observed. CONCLUSION: One-year treatment with adjuvant trastuzumab improves disease-free survival, recurrence-free survival and distant disease-free survival in Chinese patients with HER2-positive early breast cancer.

Functional polymorphisms, altered gene expression and genetic association link NRH:quinone oxidoreductase 2 to breast cancer with wild-type p53.

We hypothesized that NRH:quinone oxidoreductase 2 (NQO2) is a candidate susceptibility gene for breast cancer because of its known enzymatic activity on estrogen-derived quinones and its ability to stabilize p53. We performed case-control studies to investigate the contributions of genetic variants/haplotypes of the NQO2 gene to breast cancer risk. In the first hospital-based study (n = 1604), we observed significant associations between the incidence of breast cancer and a 29 bp-insertion/deletion polymorphism (29 bp-I/D) and the rs2071002 (+237A>C) polymorphism, both of which are located within the NQO2 promoter region. Decreased risk was associated with the D-allele of 29 bp-I/D [odds ratio (OR), 0.76; P = 0.0027] and the +237C-allele of rs2071002 (OR, 0.80; P = 0.0031). Specifically, the susceptibility variants within NQO2 were notably associated with breast carcinomas with wild-type p53 (the most significant P-value: 3.3 x 10(-6)). The associations were successfully replicated in an independent population set (familial/early-onset breast cancer cases and community-based controls, n = 1442). The combined P-values of the two studies (n = 3046) are 3.8 x 10(-7) for 29 bp-I/D and 2.3 x 10(-6) for rs2071002. Furthermore, we revealed potential mechanisms of pathogenesis of the two susceptibility polymorphisms. Previous work has demonstrated that the risk-allele I-29 of 29 bp-I/D introduces transcriptional-repressor Sp3 binding sites. Using promoter reporter-gene assays and electrophoretic-mobility-shift assays, our present work demonstrated that the other risk-allele, +237A-allele of rs2071002, abolishes a transcriptional-activator Sp1 binding site. Furthermore, an ex vivo study showed that normal breast tissues harboring protective genotypes expressed significantly higher levels of NQO2 mRNA than those in normal breast tissues harboring risk genotypes. Taken together, the data presented here strongly suggest that NQO2 is a susceptibility gene for breast carcinogenesis.

Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes.

Some evidence suggests that atypical chemokine binders (ACBs) including DARC, D6, and CCX-CKR play an important role in inhibiting invasion and metastasis of cancer cells; however, their expression in breast cancer has not been well characterized. The purpose of this study was to determine the predictive value of ACBs for relapse-free survival and overall survival in breast cancer. The expressions of the three molecules were analyzed immunohistochemically in a total of 558 consecutive breast specimens comprising 12 normal breast tissues, 29 noninvasive (carcinoma in situ), and 517 invasive breast carcinoma and their relationships to clinicopathological features and survival were investigated in invasive breast cancer. Coexpression of ACBs in invasive breast carcinoma (55.9%) was much lower that of noninvasive breast carcinoma (93.1%) and normal breast tissue (100.0%), P = 0.0004, 0.0096, respectively. Their separate stainings in invasive cancer were significantly conversely correlated with lymph node status and tumor stage. In univariate analysis, the three proteins and their coexpression were significantly associated with higher relapse-free survival and overall survival. In multivariate analysis, each of these molecules was favorable for relapse-free survival, but not overall survival. Surprisingly, their coexpression was not only independently prognostic factor for relapse-free survival (RR = 0.182, 95% CI: 0.101-0.327, P < 0.001), but also for overall survival (RR = 0.271, 95% CI: 0.081-0.910, P = 0.035). These findings highlight that the multiple loss of ACBs may occur during the development of tumorigenesis and their coexpression in breast cancer is predictive of favorable outcomes.

Different distribution of breast cancer subtypes in breast ductal carcinoma in situ (DCIS), DCIS with microinvasion, and DCIS with invasion component.

BACKGROUND: Breast ductal carcinoma in situ with microinvasion (DCIS-Mi) is considered to be the interim stage in the progression from DCIS to invasive breast cancer (IDC). Cases that exceed DCIS-Mi but still do not fulfill the diagnostic criteria of IDC often are observed. We define those cases as DCIS with invasion component (DCIS-I), and attempt to study the differences of clinicopathological features and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and DCIS-I. METHODS: In this retrospective study, 550 consecutive DCIS patients were recruited, 271 (49.3%) cases were diagnosed as pure-DCIS, 67 as DCIS-Mi, and 212 as DCIS-I. They were categorized into four groups: luminal-A (ER+ and/or PR+, HER2-), luminal-B (ER+ and/or PR+, HER2+), ERBB2+ (ER-, PR-, HER2+), and basal-like (ER-, PR-, HER2-). RESULTS: DCIS-Mi and DCIS-I patients tended to have larger tumors with highly graded nuclear (P = 0.011 for size; P < 0.0001 for nuclear grade). The proportion of luminal-like tumors decreased, whereas ERBB2+ and basal-like tumors increased in DCIS-I/DCIS-Mi compared with pure-DCIS (P = 0.039). Although the HER2-positive tumors displayed a stable proportion among DCIS subgroups, the essences of them were varying. In pure-DCIS, luminal-B was the major subtype of HER2-positive tumors (luminal-B vs. ERBB2+, 19% vs. 14.6%), whereas in DCIS-I, the proportion of luminal-B decreased vastly (luminal-B vs. ERBB2+, 12.8% vs. 23.5%). DCIS-I had a worse relapse-free survival outcome compared with pure-DCIS. CONCLUSIONS: Different distribution of subtypes and distinctive characteristics among DCIS, DCIS-Mi, and DCIS-I indicate that they are distinct entities. Further studies with larger sample size are needed to replicate our observations.

Adjuvant therapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and 5-fluorouracil.

We performed a retrospective study of 856 breast cancer patients in our hospital, to compare the therapeutic effect of pirarubicin with cyclophosphamide and 5-fluorouracil (CPF) with the standard epirubicin-based regimen (CEF) in adjuvant treatment of breast cancer. Patients were given cyclophosphamide and 5-fluorouracil 500 mg/m(2) each, and either pirarubicin 40 mg/m(2) or epirubicin 75-100 mg/m(2) , every 3 weeks, six cycles. A total of 233 patients used CPF and 623 patients used CEF regimen. The clinical and pathologic characteristics were well balanced between the two groups. The median follow-up time was 41 months, relapse-free survival (RFS) and overall survival (OS) were similar in both groups, p = 0.561 and p = 0.783, respectively. No treatment-related congestive heart failure or death was observed in either group. Regardless of chemotherapy regimens, only tumor size, lymph node status, and ER status were predictive factors in multivariate survival analysis. In stratified analysis, the total hazard ratio estimate for RFS was 0.876 (95% CI 0.561-1.369; p = 0.562), not in favor of either regimen, and no significant difference was observed in any subgroups between the two treatment arms. Our study verified that 3 weekly CPF gives the same efficacy and safety as the standard CEF; both CPF and CEF are the effective regimens that can be used in adjuvant chemotherapy of breast cancer.

Unfavourable clinicopathologic features and low response rate to systemic adjuvant therapy: results with regard to poor survival in young Chinese breast cancer patients.

The prognostic factors of young breast cancer patients (BCPs) are still controversial. This study is aimed at evaluating the prognosis of young BCPs by characteristics and treatment response. We analysed the data on 2,593 operable BCPs age 0.05). Higher TNM stage and chemotherapy, but not HER2/neu over-expression, were predictive factors for young Chinese BCPs. The characteristics of breast cancer are more aggressive in young Chinese BCPs. Their prognostic factors are obviously different from those of the elder group. Current therapy was not as effective for them.

Five common single nucleotide polymorphisms in the PALB2 gene and susceptibility to breast cancer in eastern Chinese population.

Certain rare germline mutations in the PALB2 gene have been confirmed to increase susceptibility to breast cancer in diverse populations, but it has not been very clear that whether some common polymorphic variants in PALB2 also increase breast cancer risk. We conducted a case-control study to validate the association of common variations in the PALB2 gene and breast cancer in eastern Chinese population. A total of six common single nucleotide polymorphisms (rs8053188, rs16940342, rs249954, rs447529, rs249935, and rs3096145), which tagged the known common variants (minor allele frequency >0.1) of PALB2, were genotyped among 660 cases and 756 cancer-free controls by SNPstream assay. Except rs3096145, other five SNPs passed the quality assessment criteria with genotyping call rate >95%. Genotype and allele frequencies were statistically different between cases and controls for PALB2 rs447529 and rs249935. PALB2 rs249935 G allele was related to a 1.21-fold (95% confidence interval = 1.02-1.43) increase in risk for each 'A' allele carried (P = 0.029). Based on the dominant inheritance model tests, we found that compared with rs447529 CC homozygotes, the variant homozygote GG and heterozygote GC carriers had a 0.43-fold decreased risk of breast cancer (95% confidence interval = 0.24-0.78, P = 0.005). Combined with the results of the former study, our findings further verified that some common PALB2 polymorphisms may contribute to the etiology of breast cancer in Chinese women, so other large studies are warranted to confirm these observations in different ethnic populations.