Fu Ou-Yang

STAT3 ser727 phosphorylation and its association with negative estrogen receptor status in breast infiltrating ductal carcinoma.

Although it is known that STAT3 transcriptional activity is modulated by phosphorylation at serine residue 727, the role of STAT3 serine phosphorylation in breast cancer remains mostly unexplored. In this study, we examined the expression patterns of serine residue 727‐phosphorylated STAT3 (p‐ser727‐STAT3) in breast infiltrating ductal carcinoma tissues and nearby noncancer tissues by using immunoblotting techniques, and correlated the expression profiles with clinicopathological characteristics. A significantly elevated p‐ser727‐STAT3 expression was observed in 61.8% (42/68) of breast cancer tissues as compared to corresponding noncancer tissues (p < 0.001). Further, immunohistochemical analysis also showed an increased nuclear p‐ser727‐STAT3 staining in cancer lesions. The increased p‐ser727‐STAT3 expression in breast infiltrating ductal carcinoma tissues correlated significantly with negative estrogen receptor (ER) status, increased stage of cancer and increased tumor size (p = 0.001, 0.024 and 0.014, individually). Intriguingly, we noticed that the expression levels of p‐ser727‐STAT3 in ER‐negative breast cancer cell lines were higher than those in ER‐positive breast cancer cell lines. In ER‐positive MCF7 cells, treatment with ERα‐specific siRNA increased, whereas treatment with anticancer drug tamoxifen decreased the expression of p‐ser727‐STAT3, phenomena not observed in ER‐negative MDA‐MB‐231 cells. In conclusion, our results suggest that p‐ser727‐STAT3 may be involved in the pathogenesis of breast cancer in an ER‐dependent manner.

The clinical significance between activation of nuclear factor kappa B transcription factor and overexpression of HER-2/neu oncoprotein in Taiwanese patients with breast cancer.

BACKGROUND This study investigated the role of nuclear factor-kappa B (NF-kappaB) activity in human breast cancer with overexpression of HER-2/neu oncoprotein, as well as its role on expression of different histological grades of cancer cells taken from Taiwanese breast cancer patients. MATERIALS AND METHODS Specimens were collected from 82 female breast cancer patients. The HER-2/neu oncoprotein was measured by immunohistochemistry. NF-kappaB activity expression was assessed by the electrophoretic mobility shift assay, and confirmed by the supershift technique using anti-P65 antibody in both breast cancer tissue and the adjacent normal tissue. The histological grades were measured by Modified Bloom-Richardson Grading Scheme. RESULTS Of the 82 cancer specimens, 81 (98.7%) showed higher or equal expressions of NF-kappaB activity when compared to the adjacent normal tissue. Fifty-five cases (67.1%) had higher levels of NF-kappaB activity in the cancerous tissue than in the adjacent normal tissue (p<0.005). With regard to tumor size, steroid receptors, stages, histological types, and node status, there were no statistically significant differences in NF-kappaB activity between cancerous tissues and adjacent normal tissues. However, significantly higher expressions of NF-kappaB activity were seen in those cases with positive HER2/neu oncoprotein, poorly differentiated histological grades, high nuclear pleomorphisms, and high mitotic counts (p<0.05). Positive HER-2/neu overexpression of oncoprotein had higher NF-kappaB activity (86%) than negative overexpression (60%) (p<0.05). It has been shown that the NF-kappaB activity increases in the HER-2/neu oncoprotein overexpression in human breast cancer. CONCLUSION Overexpression of HER-2/neu gene could induce NF-kappaB activity in human breast cancer cells, as has been confirmed in other research on cell lines.

Intensity modulated radiotherapy with simultaneous integrated boost vs. conventional radiotherapy with sequential boost for breast cancer – A preliminary result

PURPOSE This study was aimed to assess the acute dermatological adverse effect from two distinct RT techniques for breast cancer patients. We compared intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and conventional radiotherapy followed by sequential boost (CRT-SB). METHODS The study population was composed of 126 consecutive female breast cancer patients treated with breast conserving surgery. Sixty-six patients received IMRT-SIB to 2 dose levels simultaneously. They received 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Sixty patients in the CRT-SB group received 50 Gy in 25 fractions to the whole breast followed by a boost irradiation to tumor bed in 5-7 fractions to a total dose of 60-64 Gy. Acute skin toxicities were documented in agreement with the Common Terminology Criteria for Adverse Events version 3 (CTCAE v.3.0). RESULTS Ninety-eight patients had grade 1 radiation dermatitis while 14 patients had grade 2. Among those with grade 2, there were 3 patients in IMRT-SIB group (4.5%) while 11 in CRT-SB group (18.3%). (P = 0.048) There was no patient with higher than grade 2 toxicity. Three year local control was 99.2%, 3-year disease free survival was 97.5% and 3-year overall survival was 99.2%. CONCLUSIONS A significant reduction in the severity of acute radiation dermatitis from IMRT-SIB comparing with CRT-SB is demonstrated.

Comparison between sonography and mammography for breast cancer diagnosis in oriental women after augmentation mammaplasty

Augmentation mammaplasty has become more popular in Taiwan. Therefore, clinical imaging is necessary to evaluate those patients who develop breast cancers. The purpose of this study was to evaluate the detection of breast diseases after augmentation mammaplasty by means of mammography and sonography. A retrospective follow-up study and analysis of diagnostic methods including mammography, sonography, physical examination, and aspiration cytology was conducted on 105 patients who underwent augmentation mammaplasty at Kaohsiung Medical University Hospital between 1989 and 2001. A total of 105 patients were identified in this study, and mean follow-up was 4 years. Two tumors from 8 cancer patients were visible on standard mammograms, and seven tumors were diagnosed as cancer by sonography. One of 15 benign breast tumors was interpreted as a suspected cancer, and 7 tumors were interpreted as normal findings on mammograms. Fourteen of 15 benign breast tumors were diagnosed correctly except for one suspicious case examined by sonography. Sonography showed the highest rate of diagnostic accuracy (91.3%) and mammograms had the lowest rate (73.9%). The accuracy rate of physical examination was 73.9%, and aspiration cytology was 90.0% accurate. This study affirms that sonography is a more useful diagnostic tool than mammography in Taiwanese women who have undergone augmentation mammaplasty.

Immediate transverse rectus abdominis musculocutaneous flap reconstruction is associated with improved cancer-specific survival in locally advanced breast cancer.

BackgroundThis study of stage III (locally advanced) breast cancer patients evaluated the survival improvement conferred by immediate breast reconstruction by transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction after modified radical mastectomy (MRM) in comparison with MRM alone. MethodsThis retrospective study analyzed data for all women who had received TRAM immediately after unilateral modified radical mastectomy for locally advanced breast cancer at a single institution from January 2002 to December 2009. The analysis included 192 patients divided into 2 groups: patients who had received MRM immediately followed by TRAM flap reconstruction (MRM-TRAM group, n = 52) and patients who had received MRM alone (MRM group, n = 140). Data collection included demographic characteristics, underlying comorbidities, and cancer characteristics. Postoperative adjuvant therapies, oncologic outcomes, and survival were compared between the 2 groups. Kaplan-Meier plots, univariate log-rank test, multivariate Cox proportional hazards regression models, and t-test were used to evaluate potential predictors of cancer recurrence and patient survival. ResultsIn comparison with the MRM group, significant differences in the MRM-TRAM group included a younger mean age, a better overall health status, and a higher education level (all P < 0.001). Severity of breast cancer disease did not significantly differ in terms of cancer characteristics. Additionally, there were no significant differences in local recurrence (P = 0.326) and distant metastasis (P = 0.338). Immediate breast reconstruction was not associated with delays in detection of local recurrence and initiation of adjuvant therapiesThe 5-year breast cancer-specific survival rate was significantly higher in the MRM-TRAM group (84.6%) compared with the MRM group (61.2%) (P = 0.003). Multivariate analysis showed that TRAM flap reconstruction is an independent predictor of survival in breast cancer patients. The MRM-TRAM group had a significantly lower hazard of death (HR, 0.235; 95% CI, 0.070–0.788; P = 0.019) compared with the MRM group. ConclusionsImmediate TRAM flap reconstruction is oncologically safe and is unassociated with delayed adjuvant therapies or delayed detection of local recurrence. Patients with locally advanced breast cancer can be considered appropriate candidates for TRAM flap reconstruction because the procedure is an independent predictor of breast cancer survival and is associated with a 76.5% decrease (HR, 0.235) in the risk of cancer death.

P53 codon 72 polymorphism in Taiwanese breast cancer patients.

There are clear discrepancies between ethnicity and geographic area regarding the peak age incidence and mortality of breast cancer. Underlying variances include genetic, environmental, and socioeconomic factors. The wild‐type p53 codon has two common polymorphic variants from a single‐base‐pair substitution at codon 72, where either C‐C‐C encodes proline (p53‐p72) or C‐G‐C encodes arginine (p53‐R72). We aim to study the p53 codon 72 genotypes of patients with breast cancer in Taiwan and make a comparison with the published data to ascertain whether any difference exists between Taiwanese and Western patients with breast cancer. We also evaluated the effect of the p53 codon 72 polymorphism on clinicopathologic features. We examined blood from 170 Taiwanese women with breast cancer with polymerase chain reaction–restriction fragment length polymorphism for the genotypes of p53 codon 72. For the p53 codon 72 polymorphism, there were 31 p53‐P/P72 (18.2%), 93 p53‐R/P72 (54.7%), and 46 p53‐R/R72 (27.1%) with the allele frequencies 0.54 for the p53‐R72 and 0.46 for p53‐P72, respectively. Our results indicate that there was more p53‐P72 (40.6% in Asians vs. 26.4% in Caucasians) and twice the incidence of p53‐P/P72 homozygotes (18% in Asians vs. 8% in Caucasians) among the Asian population. Patients with the p53‐R/R72 variant were more likely to have a t1 tumor size status (55.2%) compared with patients with the P53‐P/R72 (30.9%) or P53‐P/P72 variant (36%). Our results support the hypothesis that genetic factors may contribute to the difference between Taiwanese or Asian breast cancer and Western breast cancer patient populations.

Multi-center study on patient selection for and the oncologic safety of intraoperative radiotherapy (IORT) with the Xoft Axxent® eBx® System for the management of early stage breast cancer in Taiwan

Background In this multi-center study, we report the patient selection criteria for and preliminary oncologic outcomes associated with intraoperative radiotherapy (IORT) delivered by the Xoft Axxent® eBx® system for early-stage breast cancer in Taiwan. Methods Patients with early breast cancer in Taiwan received breast conserving surgery and received IORT with Xoft Axxent® eBx® System during 2013–2015 was search from database of Taiwan IORT study cooperative group (T-IORTSCG). Patients’ clinicopathologic characteristics and early post-operative results were collected and reported. Results During the study period, 26 hospitals in Taiwan performed a total of 261 Xoft IORT procedures for breast cancer. The mean age of them was 52.9 ± 9.8 years (37–72), and tumor size was 1.5 ± 0.8 cm (0.1–4.2 cm) for invasive cancer and 1.2 ± 0.8 cm (range, 0.2–3.0 cm) for ductal carcinoma in situ (DCIS) lesions. Lymph node metastasis was found in 6 (2.3%) patients. The patients received IORT in Taiwan differed markedly from those used in the ELIOT and TARGIT-A studies. Specifically, patients selected for IORT in Taiwan tended to be younger, their tumors tended to be larger and the prevalence of lymph node metastasis tended to be lower. Among these 261 patients, 8 (3.1%) patients required whole breast radiotherapy. During a mean follow up of 15.6 months, locoregional recurrence was observed in 2 (0.8%) patients. Conclusion In real world experience, patients received IORT differed quite significantly with criteria formulated by trials. The preliminary results of IORT in Taiwan showed it is well acceptable by patients and clinicians.

Comparison of Long-Term Outcomes of Postmastectomy Radiotherapy between Breast Cancer Patients with and without Immediate Flap Reconstruction

Purpose To compare the long-term clinical outcomes of postmastectomy radiotherapy (PMRT) between breast cancer patients with and without immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction. Methods The study included 492 patients with stage II or III breast cancer who underwent modified radical mastectomy (MRM) and chemotherapy followed by PMRT between 1997 and 2011. Cox regression model and Kaplan-Meier curves were calculated, and the log-rank test was used to evaluate the differences between overall and disease-free survival rates in the 2 groups. Results Among 492 patients, 213 patients had immediate TRAM flap reconstruction. The mean follow-up was 7.2 years (range, 11–191 months). The 5-year and 10-year disease free survival rates were 81% and 76% for the TRAM flap group and 78% and 73% for the non-flap group. The 5-year and 10-year overall survival rates were 89% and 73% for the TRAM flap group and 83% and 74% for the non-flap group. Conclusions There exists no statistically significant difference in the rates of local recurrence, distant metastasis, disease-free and overall survival when comparing immediate TRAM flap reconstruction with no reconstruction. Our results suggest that immediate TRAM flap reconstruction does not compromise long term clinical outcomes in breast cancer patients requiring PMRT.

The Combinational Polymorphisms of ORAI1 Gene Are Associated with Preventive Models of Breast Cancer in the Taiwanese.

The ORAI calcium release-activated calcium modulator 1 (ORAI1) has been proven to be an important gene for breast cancer progression and metastasis. However, the protective association model between the single nucleotide polymorphisms (SNPs) of ORAI1 gene was not investigated. Based on a published data set of 345 female breast cancer patients and 290 female controls, we used a particle swarm optimization (PSO) algorithm to identify the possible protective models of breast cancer association in terms of the SNPs of ORAI1 gene. Results showed that the PSO-generated models of 2-SNP (rs12320939-TT/rs12313273-CC), 3-SNP (rs12320939-TT/rs12313273-CC/rs712853-(TT/TC)), 4-SNP (rs12320939-TT/rs12313273-CC/rs7135617-(GG/GT)/rs712853-(TT/TC)), and 5-SNP (rs12320939-TT/rs12313273-CC/rs7135617-(GG/GT)/rs6486795-CC/rs712853-(TT/TC)) displayed low values of odds ratios (0.409–0.425) for breast cancer association. Taken together, these results suggested that our proposed PSO strategy is powerful to identify the combinational SNPs of rs12320939, rs12313273, rs7135617, rs6486795, and rs712853 of ORAI1 gene with a strongly protective association in breast cancer.

Breast cancer quality of care in Taiwan in relation to hospital volume: a population‐based cohort study

To evaluate, compare and improve quality of care for patients with breast cancer at the institution and population level requires a standard set of core measures. We performed a population‐based cohort study to examine the association between hospital volume and breast cancer core measures compliance in Taiwan.