[Evaluation of menopause and treatment choice of breast cancer patients before endocrine therapy].

Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study.

Objective The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Patients from the Hanyang BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE. Results Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01-1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03-2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24-0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85-1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03-9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12-28.96, p < 0.01). Conclusion Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.

[Diagnosis and treatment of osteoblastic metastasis in patients with breast cancer].

Osteoblastic metastasis of breast cancer is relatively rare, but there are cases of misdiagnosis and mistreatment in clinical treatment. They can only be diagnosed by X ray or CT bone scan and must be identified from bone repair after effective treatment in patients with osteolytic or mixed bone metastases. Bone metastasis is often seen in the disease-free condition of breast cancer, and very few can occur in stage Ⅳ lesions prior to surgery. Based on the analysis of clinical phenomena, we questioned the evaluation criteria of the therapeutic effect on bone metastasis of breast cancer created by the World Health Organization and the MD Anderson Cancer Center and concluded the formation mechanism of bone metastasis. For patients with simple osteoblastic bone metastasis, we broke through the recommendations of the National Comprehensive Cancer Network guideline and advocated the concept of "noninterference" . Patients with positive hormone receptor can be treated with traditional endocrine therapy. Hormone receptor negative and/or human epidermal growth factor receptor 2 positive patients can be observed first, followed by chemotherapy and/or targeted therapy when there is osteolytic bone metastasis or visceral metastasis. Furthermore, bisphosphonates are not required since osteoblastic bone metastasis is generally not associated with the risk of bone related events. The active treatment of primary lesion should be taken into account in stage Ⅳ patient before operation.

[Evaluation and classification of drug therapy for breast cancer with bone-only metastasis].

Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

[A study on the correlation between Neo-Bioscoresystem and disease-free survival of breast cancer patients with neoadjuvant chemotherapy].

Obiective: To explorethe correlation between Neo-Bioscore and disease-free survival (DFS) after neoadjuvant therapy in patients with breast cancer in China. Methods: The clinical and pathological data of 429 patients with early or locally advanced breast cancer who received neoadjuvant therapy at the No.307 Hospital of PLA from January 1, 2005 to December 31, 2015 were analyzed and we followed up their DFS. Results: Neo-Bioscore were closely related to DFS (χ(2)=47.662, P<0.001). When the groups were divided by Neo-Bioscore 3, they weremore relevantto DFS (HR=5.093 vs HR=2.044), equivalent tothe role of traditional recurrence risk grouping in guiding the choice of adjuvantendocrine regimen for hormone receptor (HR) positive patients who were premenopausalafter neoadjuvant chemotherapy, andmore relevantto DFS than whetherthe pathologic complete response (pCR)grouping in the same molecular pathology subgroup of HR positive/human epidermal growth factor receptor 2 (HER-2)negative (P<0.001 vs P=0.166), HER-2 positive (P<0.001 vs P=0.166), HRnegative/HER-2 negative (P<0.001 vs P=0.166). Conclusions: Neo-Bioscore could be used as an early indicator of predicting DFS for breast cancer patients after neoadjuvant therapy.When the groups were divided by Neo-Bioscore 3, they were more relevant to DFS, equivalent to the role of traditional recurrence risk grouping in guiding the choice of adjuvantendocrine regimen for premenopausal HR positive patients, andmore relevantto DFS than whetherthe pCRgrouping in the same molecular pathology subgroup.

[Predictive values of pathologic complete response for patient outcome in different molecular subtypes of breast cancer].

Objective: To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes. Methods: Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of Military Medical Science Academy of the PLA were enrolled.The clinical and pathological characteristics of patients were collected. The primary endpoint was pCR rate and the secondary endpoint was disease free survival (DFS). We analyzed the predict values of pCR rate for patient outcome, and the predict factors for DFS by univariate and multivariate Analysis. Results: A total of 416 BC patients confirmed by pathology were enrolled and received treatment and assessment in this study. The overall pCR rate was 23.1% (96/416). The pCR rate was 6.9% (14/204) in patients of HR+ /HER2- Subtype, 41.5% (27/65) in HR-/HER2+ Subtype, 30.9% (17/55) in HR+ /HER2+ Subtype, and 41.1% (37/91) in HR-/HER2- Subtype. The correlation of the pathological status and the patient outcome was analyzed in all patients. Compared with no pCR group, pCR group had significant higher DFS rates. In HER2+ Subtype and HR-/HER2- Subtype, DFS rates of patients who achieved pCR was higher than that of who didn't achieved pCR. In HR+ /HER2- Subtype, DFS rates of patients who achieved pCR was higher than that of who didn't achievced pCR, but without statistics difference. The Cox proportional hazards regression analysis revealed that ER status, T stage, pCR affected the patient outcome of BC. Conclusion: So far, pCR was an established prognostic factor: reaching a pCR could predicte improved survival in HER2-enriched BC and triple-negative breast cancer (TNBC) subgroup, while data remain controversial for the luminal subtypes. Our results do not support the use of pCR as a surrogate end point of treatment efficacy in unselected patients with BC submitted to neoadjuvant systemic therapy.

Clinical manifestations and radiological features may contribute to the early diagnosis of radiation-induced sarcoma after breast cancer.

AIM: To describe the clinical manifestations and radiological features contributing to the early diagnosis of radiation-induced sarcoma (RIS) after radiotherapy for breast cancer. MATERIALS AND METHODS: This retrospective analysis included four typical cases of RIS diagnosed at Affiliated Hospital of Academy of Military Medical Sciences between 1980 and 2013. Patient and imaging characteristics, treatment modalities, and outcomes were extracted from patients' medical records. Two pathologists reviewed all histological slides. RESULTS: All four cases were misdiagnosed and treated for several months as cases of breast cancer relapse. CT using the bone-window setting and three-dimensional reconstructions clearly displayed bone tumours of RIS in three cases. Skin alterations were observed in all cases. At the time of RIS diagnosis, three patients were free of breast cancer. In one patient with bilateral breast cancer and lung metastasis, chemotherapy resulted in complete remission of the metastasis, but RIS progression. No RIS in this series responded to chemotherapy or endocrine therapy. CONCLUSIONS: Abnormalities appearing in the radiation field long after RT should alert clinicians to the potential development of RIS. Careful physical examination and follow-up imaging studies are necessary. The presence of skin alterations, bone tumours at CT or radiography, and poor response to anti-cancer drugs may contribute to the early detection of RIS. Biopsy should be performed immediately when RIS is suspected.

Cobrotoxin-containing analgesic compound to treat chronic moderate to severe cancer pain: results from a randomized, double-blind, cross-over study and from an open-label study.

Cobrotoxin produces intense analgesia but it has an onset of response of 1-3 h which hampers its clinical use in cancer pain. Recently, a compound analgesic formulation combining cobrotoxin, tramadol hydrochloride and ibuprofen (Compound Keluoqu, CKLQ) has become available in China. The aim of this study was to evaluate the clinical efficacy of CKLQ for moderate to severe cancer pain. A consecutive series of patients with chronic moderate to severe cancer pain was enrolled into two multicenter trials. Of the 230 eligible patients, 119 were assigned to a randomized, double-blind, cross-over study, while 111 entered an open-label study. They were all of Han-China nationality and had a mean age of 52.0 and 55.4 years and a mean body weight of 55.6 and 52.9 kg, respectively. A total of 11 patients discontinued the study, 6 (54.5%) because of insufficient pain relief and 5 due to the occurrence of adverse events. In the cross-over study, 59 patients were randomized to receive a CKLQ package with 2 CKLQ tablets (each containing 0.16 mg cobrotoxin, 25 mg tramadol hydrochloride and 50 mg ibuprofen) and 2 placebo capsules, a placebo package with 2 placebo tablets and 2 placebo capsules, and an active control package with 2 tramadol hydrochloride capsules (each containing 50 mg tramadol hydrochloride) and 2 placebo tablets (arm A), and 60 to receive a tramadol hydrochloride package, a placebo package and a CKLQ package (arm B), sequentially and only once. Patients in the open-label study only received CKLQ and were given the option to continue for up to 7 days as long as they had satisfactory pain relief. Pain response was classified as CR, PR and NC. CR was defined as 100% pain relief, with a pain score of 0 on a 0-10 VAS. PR was defined as decreased to mild pain, with a pain score of no more than 4 on a 0-10 VAS. NC was defined as pain that either remained unchanged or that was reduced from severe to moderate at baseline, with a VAS pain score of more than 4 after treatment. One hundred and eight patients completed the cross-over study with all the three drug units. The overall rate of pain relief was 93/111 (83.7%) for CKLQ, 75/110 (68.2%) for tramadol hydrochloride (P=0.011) and 39/111 (35.1%) for placebo (P<0.001). The mean duration of pain relief with CKLQ was significantly longer than that of the other two agents (P<0.001). Of the 35 patients who did not respond to tramadol hydrochloride, 27 (77.1%) responded to CKLQ, while of the 18 who did not respond to CKLQ, 8 (55.6%) achieved satisfactory pain control with tramadol hydrochloride. In the open-label study, the overall relief rate of a single-dose of CKLQ was 99/111 (89.2%). A reduction in the percentage of complete relief, an increase in that of PR and a significant decrease in duration of relief were observed after continuous treatment with at least 10 doses of CKLQ. The frequency of adverse events for CKLQ was similar to that of tramadol hydrochloride. The results of the randomized, double-blind, cross-over study and the open-label study of CKLQ in cancer patients with chronic moderate to severe cancer pain suggest that the CKLQ may be valuable for the treatment of chronic moderate to severe cancer pain. However, the tolerance of CKLQ remains to be further defined.

A novel evaluation system of metastatic potential of oral squamous cell carcinoma according to the histopathological and histochemical grading.

We established a new evaluation system for metastatic potential of oral squamous cell carcinoma (SCC), utilizing a combined examination of histopathological grades of the carcinomas based on cell differentiation and invasive mode according to Yamamoto's criteria, and the cellular expressions of CD44, E-cadherin (E-cad), heparan sulfate glycosaminoglycan (HS-GAG) and Phaseolus vulgaris leukoagglutinin (L-PHA)-binding oligosaccharides on the carcinomas. Histochemical patterns of expression of these markers were classified into positive (+2), weakly positive (+), and negative (-). The histopathological grades and the histochemical patterns of the SCC were estimated on a 0-2 point scale, i.e. point 2 for poorly differentiated, mode 4D, CD44++, E-cad-, HS-GAG++, or L-PHA++; point 1 for moderately differentiated, mode 4C, CD44+, E-cad+, HS-GAG+, or L-PHA+; and point 0 for well differentiated, mode 1, mode 2, mode 3, CD44-, E-cad++, HS-GAG-, or L-PHA-. As a result, incidence of metastasis in the cases with a total score of more than 6 (62.8%) was significantly higher than that with a total score of less than 5 (9.3%). This evaluation system will yield useful information concerning the prognosis of patients with oral SCC.

Neoadjuvant chemotherapy in inoperable, locally advanced, and inflammatory breast carcinoma: a pilot study of MTT assay in vitro and outcome analysis of 10 patients.

Patients with inoperable, locally advanced, and inflammatory breast carcinoma (LAIBC), whether with supraclavicular lymph nodes (SLN) or not (stage IIIB and IV), usually carry an overall poor prognosis. The current treatment for these patients is by means of combined modality, including preoperative chemotherapy. This strategy has led to a substantial improvement in clinical response, making some patients operable, and even making breast conservative surgery possible. However, the long-term results still are not promising. The aim of this pilot study was to determine the efficacy of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro in directing chemotherapy (including preoperative adjuvant chemotherapy and postoperative adjuvant chemotherapy) for these patients. Between June 1994 and March 1997, 10 patients with inoperable LAIBC, whether with SLN or not, were enrolled. During the period of the combined therapy modalities, the neoadjuvant chemotherapy was adopted for three cycles according to the results of chemosensitivity in vitro by MTT assay. Then a modified radical or radical mastectomy was performed, which was followed by radiotherapy and further postoperative adjuvant chemotherapy with the same regimen as that of neoadjuvant chemotherapy. All patients had been followed up from the beginning of neoadjuvant chemotherapy to the end of October 1999. Two patients had clinical complete response (CRs), with one having pathologic CR in both breast tumor and axillary lymph node, and the other having pathologic CR in axillary lymph node. The other eight patients had partial response. By the time of analysis, six patients had been dead of relapse or progression. Among the four patients who were still alive, one had local relapse, one had distant metastatic disease, and the other two had no evident disease. By retrieving from MEDLINE before 1999, the authors learned that this is the first pilot study of neoadjuvant chemotherapy for inoperable LAIBC using MTT assay to predict the chemosensitivity in vitro. Compared with conventional chemotherapy, the clinical response and long-term results seem to be more encouraging.

[Association of HLA with breast cancer and its ER status].

Results of comparative study of HLA-A, -B typing in 73 patients with breast cancer (BC) who had different ER status and 50 healthy individuals in north China are reported. Of these 73 patients, HLA-C, -DR typing were also studied in 58 patients. The results showed that HLA-Bw61 (40) were negatively associated with BC but -Cw7 and -DRw6 were positively associated with BC. Moreover, -DRw6 was more closely associated with ER(+) status, with a RR value of 8.621. In the ER (-) group, there were no specific related antigens. In the light of the difference in pathology, prognosis and effect of endocrine therapy between ER (+) and ER (-), the authors believe that the two kinds of breast cancer may be a heterogeneous disease.

[The influence and significance of obtaining, storing and assay on estrogen receptor (ER) content in breast cancer tissue].

Estrogen receptor (ER) was measured in 275 samples from 170 patients with breast cancer by DCC assay. The results showed that the ER status and content of cytosol separated by ultracentrifuge (105,000 X G) or orthocentrifuge (1,200 X G) confirmed well (P greater than 0.5). Therefore, the ordinary centrifuge is suitable. But there was a poor correlation between the ER level measured by DCC method and that by Lee's cytochemical method (P greater than 0.05). The store time of the sample in liquid nitrogen did not seem to effect much on the ER positive rate (chi 2 = 0.7686). The ER status in samples obtained from the primary or metastatic lesion or at different intervals were generally similar in the same patient (P greater than 0.2). It is suggested that the ER status be an inherent property of patients with breast cancer. The authors propose that more samples be taken in order to render the determination more reliable.

[Clinical and pathological characteristics of estrogen receptor-positive breast cancer].

Estrogen receptor (ER) was measured in 275 samples from 170 patients with breast cancer by dextran-coated charcoal assay. The results showed that the ER positive rate was 51.2%. The ER status of female patients was not related to age or menopause. The positive rate was lowest in AB blood type. The distribution of positive patients in all types was similar to that reported by Japanese authors. The DNA levels of ER positive cancers were relatively lower than those of negative ones. Pathological examination of cancer tissue indicated that ER positive cancer is well differentiated. The 3 year disease-free rate and 4 year survival rate are both high in ER positive patients than that in the negative patients. Knowledge of ER status is helpful in planning the treatment of breast cancer.

[Detoxifying effect of lisheng-se on cisplatin and its relation to metallothionein induction].

The effects of Lisheng-Se (Seleninized wheat germ) on metallothionein (MT) induction, lethal systemic toxicity, nephrotoxicity, hemotoxicity and anticancer activity of cisplatin (CDDP), were investigated in mice. The systemic toxicity of CDDP was significantly reduced by preadministration of Lisheng-Se (P < 0.05 or P < 0.01). The protective effects were better than its inorganic form (Na2SeO3) and Bi (BSN), (0.05 < P < 0.1). The MT level in the liver, kidney, heart and tumor tissues of mice treated with one of those compounds was determined. The results show that the levels of MT induced by Lisheng-Se were significantly increased in liver and kidney (P < 0.01 and P < 0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with Lisheng-Se. These results suggest that increased MT synthesis in the liver and kidney may be involved in the protective effects of Lisheng-Se tested on the lethal toxicity, nephrotoxicity and hemotoxicity produced by CDDP. The experiments also show that Lisheng-Se did not affect the anticancer activity of CDDP in vitro and in vivo, while the MT level was not increased in cancer (P < 0.05), so Lisheng-Se might not only improve the therapeutic index of CDDP, but also did not cause drug-resistance of cancer cells.

[Clinical studies on serum glutathione S-transferase level in human breast cancer patients].

The level of serum Glutathioe S-transferase (GSTs) was first measured in 224 female patients with breast cancer and 17 patients with benign breast tumor and 96 normal female subjects. The relationship between serum GSTs and biological characteristics of breast cancer was studied. The mean serum GSTs in patients with breast cancer was 1.22 +/- 1.44 ng/ml. The positive rate was 51.8%. The level of serum GSTs in the patients with breast cancer was significantly higher than in normal subjects and patients with benign breast tumor. No correlation was found with regard to the level of serum GSTs, the size of the breast cancer, stage, lymphatic metastasis and estrogen receptor status. Serum GSTs level is thus of little value in the evaluation of response and prognosis of breast cancer.

[The protective effects of two hydration protocols against cisplatin nephrotoxicity].

A comparative study was performed in 37 patients with breast cancer who received high doses of cisplatin (100 mg/m2, I.V. drip) accompanied by two different hydration protocols. The new hydration protocol is based on the study of relationship between the pharmacokinetic parameters of plasma and urinary platinum concentration and the cisplatin-induced nephrotoxicity. In the new hydration protocol the diuretic drugs were given twice- amid and twelve hours after the cisplatin infusion instead of giving once--immediately after the cisplatin infusion, and 1,000ml drinking water was given by p.o. before taking cisplatin. Because of the increase in urinary volume the peak levels of urinary platinum were decreased from 47.34 micrograms/ml to 13.49 micrograms/ml, so that the rate of the nephrotoxicity was reduced from 36.8% (7/19) to 5.6% (1/18). The results suggest that the new hydration protocol is more effective than that previously used to protect against cisplatin nephrotoxicity.

[The effect of zinc glycyrrhizate on toxicity and anticancer activity of cisplatin in mice].

The preventive effects of Zn Glycyrrhizate (Gly-Zn) on lethal toxicity, nephrotoxicity, hemotoxicity, testicular toxicity and anticancer activity of cisplatin (CDDP) were investigated in mice. The toxicity of CDDP evaluated by the above criterion was significantly reduced by preadministration of Gly-Zn 400 mg.kg-1.d-1 x 5 (P < 0.05 or P < 0.01). The protective effects were better than bismuth subnitrate (BSN) which has been studied previously (0.05 < P < 0.1). The metallothionein (MT) level in the liver, kidney, heart and cancer of mice treated with one of these compounds were determined. The results showed that the levels of MT induced by Gly-Zn were significantly increased in liver and kidney (P < 0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with preadministration of Gly-Zn. These results suggest that increased MT synthesis in the liver and kidney may be involved in the protective effect of Gly-Zn on the toxicities produced by CDDP. The experiments also showed that Gly-Zn did not affect the anticancer effect of CDDP in vitro and in vivo, while the MT level was not increased in cancer (P < 0.05), so Gly-Zn might improve the therapeutic index of CDDP.

[Inhibition of 5-fluorouracil-cisplatin-induced stomatitis by oral cryotherapy: use of an ice-bar containing fibrinolysin and deoxyribonuclease combine (Elase)].

Stomatitis caused by a combined chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP) is a serious problem in the course of treatment for patients with oral carcinoma. In the present study, we proposed a form of cryotherapy using an ice-bar containing fibrinolysin and deoxyribonuclease (Elase) to inhibit the stomatitis. The therapeutic effect of the ice-bar cryotherapy was evaluated in 20 patients with oral squamous cell carcinoma who were undergoing 5-FU-CDDP chemotherapy. Nine of the 20 patients were given the ice-bar cryotherapy while the remaining patients were not. As a result, although there was no significant difference between the incidence of stomatitis in the groups with and without the ice-bar cryotherapy, the incidence of severe stomatitis with ulcers and/or eating disturbance in the 11 cases without the ice-bar cryotherapy (90%) was significantly higher than that in the 9 cases with the cryotherapy (44%) (p < 0.05). However, no significant difference in the clinical response rate of the 5-FU-CDDP chemotherapy was observed between the two groups.