Objective: To investigate the effect of neoadjuvant chemotherapy combined with surgery on locally advanced breast cancer and its prognosis. Methods: One hundred and fifty-four patients with locally advanced breast cancer who were admitted to our hospital from February 2014 to April 2015 were selected as the study subjects. They were divided into an observation group and a control group according to the principle of random equalization, 77 each group. The observation group was treated with TAC scheme, neoadjuvant chemotherapy combined with modified radical resection, and continuously treated with the same scheme after operation until the end of the course of treatment. The control group was treated with modified radical resection and TAC scheme. The clinical efficacy of the two groups was observed, and the perioperative indications, prognosis and occurrence of adverse reactions were compared between the two groups. Results: The total effective rate of the observation group was 76.62%, significantly higher than that of the control group (55.84%, P<0.05). The observation group had shorter operation time and hospitalization time and less bleeding amount compared to the control group (P<0.05). The metastasis rate and recurrence rate of the observation group were significantly lower than those of the control group (P<0.05); there was a significant difference between the two groups (P<0.05). The one-year and three-year survival rates of the observation group were significantly higher than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups after operation (P>0.05). Conclusion: Preoperative neoadjuvant chemotherapy in combination with TAC scheme can reduce the difficulty of operation, improve the curative effect of patients, significantly improve the prognosis of patients and prolong the survival time, which is worth clinical application. doi: https://doi.org/10.12669/pjms.35.5.310 How to cite this:Zhao H, Zhang J, Lu Y, Jin J. Neoadjuvant chemotherapy in combination with surgery in the treatment of local advanced breast cancer. Pak J Med Sci. 2019;35(5):---------. doi: https://doi.org/10.12669/pjms.35.5.310 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective:To investigate the expression of Topo IIα and Ki67 and its clinical significance.Methods:The clinical pathological data of one hundred and sixteen invasive breast cancer patients who were admitted into our hospital from July 2013 to December 2015 and underwent radical mastectomy were retrospectively analyzed. The expression of topoisomerase (Topo) IIα and Ki67 was detected using immunohistochemical method, and the correlation between the two kinds of proteins and the general clinical pathological characteristics of the patients was analyzed.Results:The positive expression rates of Topo IIα and Ki67 in breast cancer were 58.6% and 75% respectively. The expression of Topo IIα was in no apparent correlation with the age, tumor size, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) (P>0.05), but in a correlation with the number of metastatic lymph glands (P<0.05). The expression of Ki67 was in no apparent correlation with the age, tumor size, EP and HER-2, but in a correlation with the number of metastatic lymph glands and PR (P<0.05). The multi-factor logistic regression analysis results suggested that the number of metastatic lymph glands was the independent predictive factor of Topo IIα positive expression and the number of metastatic lymph glands and PR protein expression state are the independent predictive factors of Ki67 positive expression.Conclusion:Topo IIα and Ki67 can be regarded as the indicators for reflecting the proliferation activity of tumor cells, and the detection of Topo IIα and Ki67 expression is of great significance to the prognosis evaluation of breast cancer patients and clinical treatment.

Background: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab (T), the cytotoxic agent DM1, and a stable thioether linker; it is being evaluated for the treatment (tx) of HER2-positive cancer. EMILIA is a randomized, multicenter, open-label phase 3 study assessing the efficacy and safety of T-DM1 vs capecitabine (X) and lapatinib (L) in pts with HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with T and a taxane. We report the pharmacokinetics (PK) of T-DM1 in EMILIA and compare these data with historical data of single-agent T-DM1. The effects of T-DM1 exposure on efficacy outcomes in EMILIA are also reported. Methods: In EMILIA, pts were randomized 1:1 to receive T-DM1 3.6 mg/kg q3w (n = 495) or X + L (n = 496) in 21-day cycles. At least 1 PK sample was collected from 350 pts in the T-DM1 arm; 307 of these had adequate PK profiles for the estimation of ≥1 PK parameter in cycle 1. PK parameters were estimated by noncompartmental analysis for serum T-DM1, serum total T (conjugated and unconjugated T), and plasma DM1. A logistic regression model was used to evaluate the relationship between T-DM1 exposure (ie, T-DM1 AUC and DM1 Cmax) and objective response rates (ORR). Analyses of progression-free survival (PFS) and overall survival (OS), stratified by T-DM1 exposure, were conducted. Cox regression was used to evaluate the effect of T-DM1 exposure and other potential covariates on PFS and OS. Results: The PK parameters for T-DM1, total T, and DM1 in EMILIA and other studies of single-agent T-DM1 are summarized in Table 1. The PK parameters appear similar regardless of prior tx for MBC. No significant differences in mean serum T-DM1 AUC (P = 0.091) or plasma DM1 Cmax (P = 0.812) were observed between responders and non-responders following T-DM1 tx. Furthermore, variability in T-DM1 AUC and DM1 Cmax does not appear to affect the probability of response to therapy (P = 0.23 for T-DM1 AUC and P = 0.74 for DM1 Cmax). Based on Cox proportional hazards analysis, no significant exposure-efficacy relationship was observed between T-DM1 AUC (P = 0.23 for PFS and p = 0.53 for OS) or DM1 Cmax (P = 0.96 for PFS and P = 0.34 for OS) and PFS or OS, respectively. Conclusions: T-DM1 PK data in EMILIA pts were similar to those observed in previous phase 2 studies, which include pts who have and have not received prior therapy for MBC. Variation in T-DM1 exposure among pts who received T-DM1 3.6 mg/kg q3w had no significant impact on ORR, PFS, or OS. Detailed analyses will be presented. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-11.

MDPurpose/Objective(s): In 2011, ASTRO released consensus guidelines stating that hypofractionated whole breast irradiation (HF-WBI) should be considered in women > 50 with T1-2N0 breast cancer as part of breast conserving therapy (BCT). Due to underrepresentation of high grade tumors such as TNBC, the initial ASTRO consensus guidelines did not give specific recommendations regarding HF-WBI in this cohort. We sought to identify trends over time with respect to the use of HF-WBI in TNBC women in the national cancer database (NCDB). Materials/Methods: Data from the NCDB was available from 2004-2013. As complete receptor status was largely unavailable prior to 2008, we truncated our analysis to women diagnosed between 2008-2013. Trends in the utilization of HF-WBI in T1-2N0 TNBC women undergoing BCT were evaluated. Cases were matched to luminal A women during the same period. Variables included age, race, year of diagnosis, insurance status, income quartile, receipt of neoadjuvant chemotherapy, and institution (academic vs community). Statistical analysis performed included chi-square, logistic regression, and multivariate analysis using SPSS v24. Results: A total of 53,269 TNBC women were identified. Trends in the utilization of HF-WBI steadily increased from 4.7% in 2008 to 14.0% in 2013 for women with TNBC, statistically less than for women with luminal A cancer whose utilization increased from 7.3% to 23.3% over the same time frame (p<0.001). On univariate analysis, HF-WBI was more common in older women (p<0.001), women with Medicare (pZ0.026) or private insurance (pZ0.038), higher income quartile (pZ0.003), and women treated at academic institutions (p<0.001). Receipt of neoadjuvant chemotherapy was negatively associated with use of HF-WBI (p<0.001, ORZ0.605). Race did not impact the use of HF-WBI vs CF-WBI. On multivariate analysis , age (p<0.001, ORZ1.05 per year), income quartile (pZ0.006, ORZ1.06 per increase in quartile), and women treated at an academic institution (p<0.001, ORZ1.78) were significantly more likely to undergo HF-WBI. Conclusion: Treatment at an academic center was most correlated with increased HF-WBI in T1-2N0 TNBC women in the NCDB from 2008-2013, followed by increasing age and income. While HF-WBI utilization increased annually from 2008 onward, only 14% of T1-2N0 TNBC women received HF-WBI in 2013 despite similar survival with HF-WBI vs SF-WBI. In our current healthcare climate, it is necessary to take a more value-based approach and further expand utilization of HF-WBI in TNBC. This analysis highlights the need for increased utilization amongst nonacademic centers, lower income women, and women > 50 years old per the ASTRO consensus guidelines.

Purpose: To analyse and compare the clinical effects and safety of capecitabine and tegafur/gimeracil/oteracil (S-1)