To explore the clinicopathological characteristics of breast cancer patients with bone metastasis, and analyze their prognosis and related influencing factors.

According to the inclusion and exclusion criteria, totally 5 815 patients with metastatic breast cancer from January 1975 to December 2016 were screened out from the Surveillance, Epidemiology and Results (SEER) database of the U. S. National Cancer Institute for a retrospective analysis. The clinicopathological characteristics, treatment methods and prognosis of patients were evaluated. Among them, there were 3 146 patients with bone metastasis and 2 669 without. According to their prognosis, 3 146 patients with bone metastasis were divided into two subgroups: 1 669 patients in the death group and 1 477 patients in the survivor group. The χ² test and Mann-Whitney U test were used to compare the clinicopathological characteristics between bone metastasis group and non-bone metastasis group, binary Logistic regression was used to analyze the influencing factors of bone metastasis in breast cancer, the Kaplan-Meier method was used for survival analysis. The univariate log-rank test was used to analyze clinicopathological characteristics between the dead cases and survivors in 3 146 patients with bone metastasis, and the multivariate Cox proportional hazards regression model was used to find risk factors affecting the survival of patients.

There were significant differences in T stage, N stage, pathological grade, race, ER, PR, HER-2, molecular subtyping and prognosis between the bone metastasis group and non-bone metastasis group (Z=-5.71, -2.39, -13.87, χ²=14.55, 305.74, 245.56, 69.34, 335.36, 79.15, all P<0.050), while patient age, gender and position of primary tumor presented no significant difference (χ²=0.57, 2.71, 0.45, all P>0.050). The result of Logistic regression analysis showed that ER positive, PR positive, advanced T stage and advanced N stage were independent risk factors of bone metastasis in breast cancer patients(OR=1.775, 95%CI: 1.258-2.505, P=0.001; OR=1.425, 95%CI: 1.236-1.643, P<0.001; OR=1.095, 95%CI: 1.043-1.149, P<0.001; OR=1.396, 95%CI: 1.246-1.564, P<0.001), while advanced pathological stage indicated lower risk of bone metastasis (OR=0.815, 95%CI: 0.733-0.907, P<0.001). The overall survival showed a significant difference between the bone metastasis group and non-bone metastasis group (χ²=133.53, P<0.001). In patients with bone metastasis, there were significant differences in T stage, N stage, pathological grade, patient age, ER, PR, HER-2, molecular subtyping, primary tumor surgery, chemotherapy and radiation therapy between death group and survivor group (Z=-7.75, -3.22, -8.14, χ²=39.80, 69.81, 87.45, 51.87, 132.47, 36.24, 6.05, 36.24, all P<0.050). The multivariate analysis of Cox proportional hazards model showed that patient age, T stage, N stage, PR, HER-2, molecular subtyping, pathological grade, chemotherapy, radiotherapy and primary tumor surgery were independent factors affecting the prognosis of breast cancer patients with bone metastasis(HR =1.349, 95%CI: 1.195-1.523, P<0.001; HR=1.151, 95%CI: 1.101-1.203, P<0.001; HR=1.077, 95%CI: 1.033-1.123, P<0.001; HR= 0.715, 95%CI: 0.626-0.817, P<0.001; HR=0.695, 95%CI: 0.627-0.770, P<0.001; HR=1.349, 95%CI: 1.260-1.414, P<0.001; HR=1.371, 95%CI: 1.261-1.489, P<0.001; HR=0.626, 95%CI: 0.562-0.697, P<0.001; HR=0.874, 95%CI: 0.791-0.966, P=0.008; HR=0.663, 95%CI: 0.561-0.784, P<0.001).

The prognosis of breast cancer patients with bone metastasis is superior to that of the patients with non-bone metastasis, related to patient age, T stage, N stage, PR, HER-2, molecular subtyping and pathological grade. Primary tumor surgery, radiotherapy and chemotherapy can significantly improve the prognosis of patients with bone metastasis.

To investigate the potential role of activated pregane X receptor (PXR) in the regulation of programmed cell death proteins(PDCDs) in MCF-7 cells and explore the mechanism involved.

MCF-7 cells were treated with PXR agonist rifampicin (10 μmol/L) for 24 h as rifampicin group, and the cells treated with DMSO served as the control group (DMSO control group). Meanwhile, to rule out the nonspecific effect of the PXR agonist, MCF-7 cells were infected with continuously activated PXR adenovirus for 36 h (VP-PXR group), which served as VP-PXR group, and the cells infected with Mock adenovirus served as the control group (Mock control group). The mRNA expressions of PDCD2, PDCD4, PDCD5, PDCD6 and the PXR target genes (CYP3A4 and MDR1) in aforementioned groups were detected by real-time fluorescent quantitative reverse transcriptase PCR (qRT-PCR). The protein level of PDCD4 was assessed by Western blot. The expression of microRNA (miRNA) 21 (the negative regulatory factor of PDCD4) was determined by qRT-PCR, and protein level of PTEN (a target gene of miRNA21) was detected by Western blot. The data of normal distribution were expressed as ±s and the data of skewed distribution were expressed as M(P₂₅-P₇₅). The t test of two independent samples or nonparametric rank sum test of two independent samples were used to compare the parameters between two groups.

(1)The qRT-PCR result demonstrated that mRNA expressions of PDCD4 and PDCD6 in rifampicin group were significantly lower than those in DMSO control group (0.896±0.069 vs 1.262±0.103, t=-2.961, P=0.012; 0.708±0.085 vs 0.963±0.029, t=-2.829, P=0.029); the mRNA expressions of PDCD2 and PDCD5 showed no significant difference (0.834±0.148 vs 1.040±0.086, t=-1.210, P=0.254; 0.896±0.142 vs 0.946±0.110, t=-0.281, P=0.786). Meanwhile, mRNA expressions of CYP3A4 and MDR1, the known PXR target genes, were significantly increased in rifampicin group compared with DMSO control group (2.192±0.418 vs 1.000±0.071, t=2.809, P=0.045; 2.112±0.397 vs 1.000±0.071, t=2.758, P=0.048). The mRNA expressions of PDCD2 and PDCD4 in VP-PXR group were significantly reduced compared with Mock control group (0.721±0.085 vs 0.975±0.035, t=-2.767, P=0.033; 0.766±0.131 vs 1.635±0.284, t=-2.775, P=0.017), and the mRNA expressions of PDCD6 and CYP3A4 showed no significant difference [2.053(0.932-2.653) vs 1.000(0.796-2.091), Z=0.314, P=0.753; 1.844±0.397 vs 1.000±0.071, t=2.097, P=0.100], while the MDR1 mRNA expression in rifampicin group was significantly increased (3.323±0.600 vs 1.000±0.071, t=3.846, P=0.017). (2) Western blot analysis demonstrated that the protein expression of PDCD4 in rifampicin group was significantly decreased compared with DMSO control group (0.865±0.062 vs 1.080±0.060, t=-2.490, P=0.026), and PDCD4 protein expression in VP-PXR group was significantly lower compared with Mock control group (0.901±0.065 vs 1.130±0.045, t=-2.921, P=0.019). (3) miRNA21 expression in rifampicin group was significantly higher than that in DMSO control group (1.641±0.227 vs 1.029±0.070, t=2.576, P=0.032), and miRNA21 in VP-PXR group was significantly higher than that in Mock control group (1.920±0.251 vs 1.274±0.161, t=2.657, P=0.028). In addition, the protein expression of PTEN in the rifampicin or VP-PXR group was significantly lower than that in DMSO or Mock control group (0.694±0.057 vs 0.875±0.038, t=-2.630, P=0.030; 0.713±0.0353 vs 0.859±0.020, t=-3.661, P=0.006).

PXR can inhibit the expression of PDCD4 via miRNA21 in MCF-7 cells, thus promoting the drug resistance of breast cancer cells.

To investigate the safety and cosmetic effect of mastectomy combined with primary implant breast reconstruction for breast cancer patients.

The clinical data of 59 breast cancer patients who underwent mastectomy combined with primary implant breast reconstruction in the General Hospital of PLA from Janurary 2008 to December 2016 were retrospectively analyzed. All patients were divided into two groups: skin-sparing mastectomy (SSM) group and nipple-sparing mastectomy (NSM) group (sparing the nipple-areola complex) or according to the different methods of breast reconstruction, they were divided into one-step reconstruction group and two-step reconstruction group. The rank sum test or Fisher exact test was used to compare the complications and cosmetic effect between SSM group and NSM group, or between one-step reconstruction group and two-step reconstruction group. The Kaplan-Meier method was used for survival analysis.

In all cases, 33.9% (20/59) of the patients underwent SSM and 66.1% (39/59) underwent NSM; 44.1% (26/59) underwent one-step breast reconstruction and 55.9% (33/59) underwent two-step breast reconstruction. Totally 30.5% (18/59) of cases underwent contralateral prophylactic mastectomy plus implant reconstruction at the same time. The median follow-up was 71 months (range: 27-133 months), and 12 cases were missing in the follow-up. The incidence of postoperative prosthesis displacement was 10.6% (5/47), and the incidence of capsular contracture and prosthesis rupture were both 4.3% (2/47). The implants were removed in 21.3% of the patients (10/47). The complication rate and incidence of implant removal presented no significant difference between SSM group and NSM group (P=0.697, 0.716), or between one-step reconstruction group and two-step reconstruction (P= 0.449, 1.000). The proportion of patients with excellent and good cosmetic scores was 73.3% (33/45), indicating no significant difference between SSM group and NSM group, or between one-step reconstruction group and two-step reconstruction (P=0.296, 1.000). There was no significant difference in the cosmetic scores between patients with contralateral prophylactic mastectomy plus implant reconstruction and patients without (P=0.571). The OS of all patients was 95.7% (45/47), and the DFS was 89.4% (42/47).

The mastectomy combined with primary implant breast reconstruction yeilds excellent overall survival, low incidences of adverse events or complications and good cosmetic effect in breast cancer patients whether they receive SSM or NSM, one-step or two-step breast reconstruction.

To investigate the effect of preoperative fibrinogen to albumin ratio(FAR)on prognosis of operable breast cancer patients.

According to the inclusion and exclusion criteria, 520 patients with stage Ⅰ to Ⅲ operable breast cancer in the Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from January to December 2013 were involved in this retrospective study. Serum levels of fibrinogen and albumin were measured before operation. FAR was defined as the concentration ratio of fibrinogen and albumin multiplied by 100. Subjects were divided into two groups according to the cutoff value determined by the receiver operating characteristic curve: high FAR group(FAR>6.99)(147 patients)and low FAR group(FAR≤6.99)(343 patients). DFS and OS in two groups were assessed using the Kaplan-Meier method and log-rank test. Cox proportional hazard regression model was used to identify the influencing factors of DFS and OS.

The log-rank test showed that high FAR group had significantly lower DFS and OS compared with low FAR group (χ²=32.885, 16.320, both P<0.001). The univariate and multivariate analyses showed that high FAR was an independent risk factor of DFS (HR=4.092, 95%CI: 2.425-6.903, P<0.001; HR=4.226, 95%CI: 2.476-7.212, P<0.001)and OS (HR=3.907, 95%CI: 1.913-7.978, P<0.001; HR=4.320, 95%CI: 2.087-8.942, P<0.001).

The patients with preoperative high FAR are prone to short progression-free survival and low OS rate, so preoperative FAR is a potential prognostic factor of breast cancer.

To explore the application of the single-port endoscopic breast-conserving surgery in the treatment of early breast cancer.

The clinical data of 102 patients with stage I and II breast cancer who underwent breast-conserving surgery in the Beijing Friendship Hospital, Capital Medical University from May 2017 to November 2018 were retrospectively analyzed. Among them, 48 patients underwent single-port endoscopic breast-conserving surgery (endoscopic surgery group) and 54 patients received open breast-conserving surgery (open surgery group). The operative time, cosmetic effect, complications and recurrence were assessed. The t test of two independent samples was used to compare the operation time and cosmetic effect between the two groups.

All 102 patients had successfully completed the surgery. The operative time in the endoscopic surgery group was (184.2 ±76.2) min, significantly longer than (127.8 ±68.4) min in the open surgery group (t=3.923, P<0.001). The cosmetic evaluation at postoperative two months showed that the score of cosmetic effect in the endoscopic surgery group was significantly higher than that in the open surgery group (11.2±0.8 vs 9.1±0.9, t=6.407, P<0.001). There was no skin necrosis, active bleeding and infection in both groups. The median follow-up was 11.2 months. There was no local recurrence or distant metastasis in both groups.

The single-port endoscopic breast-conserving surgery can guarantee the radical resection of early breast cancer, and obtain better cosmetic effect compared with open breast-conserving surgery.

To investigate the expression differences of molecular markers ER, PR, HER-2, Ki67 and p53 between primary lesions and recurrent/metastatic lesions and molecular subtype transformation in breast cancer patients in Xinjiang region.

This study was a two-way cohort study. The female breast cancer patients with first local recurrence or distant metastasis in the Affiliated Cancer Hospital of Xinjiang Medical University from May 2017 to May 2019 was enrolled in this study. The expression of ER, PR, HER-2, Ki67, and p53 in recurrent/metastatic lesions was detected with the samples obtained by surgery or aspiration biopsy. Meanwhile the clinical data of patients before recurrence or metastasis was retrospectively analyzed to extract the expression of ER, PR, HER-2, Ki67, and p53 in primary lesions. The paired χ² test was used to compare the expressions of ER, PR, HER-2, Ki67, and p53 between recurrent/metastatic lesions and primary lesions.

Totally 103 patients were enrolled. In primary lesions, the positive rates of ER, PR, HER-2 and p53 were 63.1%(65/103), 55.3%(57/103), 31.1%(32/103)and 68.9%(71/103), and the high expression of Ki67 (>14%) accounted for 68.93%(71/103)of the total. In recurrent/metastatic lesions, the positive rates of RR, PR, HER-2 and p53 in recurrent/metastatic lesions were 56.3%(58/103), 42.7%(44/103), 30.1%(31/103)and 77.7%(80/103), and the high expression of Ki67 accounted for 68.9%(71/103)of total. The rates of expression change of ER, PR, HER-2, Ki67 and p53 were 8.7%(9/103), 16.5%(17/103), 6.8%(7/103), 29.1%(30/103)and 14.6%(15/103). There was no significant difference in the expression of HER-2 and Ki67 between recurrent/metastatic lesions and primary lesions (P=1.000, 1.000), while the expression of ER, PR and p53 presented a significant difference (P=0.039, 0.002, 0.035). In 103 patients, luminal A, luminal B, HER-2 overexpression and triple negative subtypes in primary lesions and recurrent/metastatic lesions accounted for 8.7% (9/103) and 10.7% (11/103), 54.3% (56/103) and 53.4% (55/103), 18.4% (19/103) and 14.6% (15/103), 18.4% (19/103) and 21.4% (22/103), respectively. After recurrence and metastasis, the proportion of luminal A and triple-negative subtypes increased, and the proportion of other molecular subtypes decreased. Then 6/9, 30.4% (17/56), 7/19, 3/19 of luminal A, luminal B, HER-2 overexpression, and triple-negative subtypes in primary lesions were transformed into other subtypes after recurrence and metastasis.

Gene expression often changes after recurrence and metastasis of breast cancer, and the molecular subtype transformation is common. Through the molecular expression and molecular subtype of recurrent and metastatic lesions, we can develop more accurate treatment schemes to improve the therapeutic effect.