IntroductionBariatric surgeries induce well-documented weight loss and resolve obesity comorbidities. Sexual function is one of the aspects of life quality and may benefit from surgery. Few studies have revealed the impact of bariatric surgeries on sexual function in Chinese men with obesity. MethodsThis is a retrospective cohort study of patients undergoing bariatric surgery [laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB)]. Data were collected between September 2017 and February 2022. The International Index of Erectile Function (IIEF) questionnaire was used to evaluate erectile function, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. Sex hormones and other blood tests were evaluated before and at least 1 year after the surgery. ResultsFifty-nine Chinese male patients completed the IIEF questionnaire. The multivariate logistic regression analysis revealed that body mass index (BMI) was the single independent risk factor of the severity of erectile dysfunction (ED). Preoperative testosterone levels had negative correlations with BMI and waist circumference. Thirty-seven patients completed the postoperative questionnaire with a mean follow-up of 23.2 months. ConclusionBMI and waist circumference were negatively correlated with testosterone levels. BMI was an independent risk factor for the severity of ED. LSG and LRYGB led to positive and sustained improvement in sexual function of men with obesity. The two procedures had a comparable effect, more subjects being needed. Sex hormone levels also could be reversible. However, more weight loss did not predict a positive change in sexual function. A greater BMI loss might predict a greater increase in testosterone.

Current guidelines do not recommend pregnancy within 12 months after bariatric surgery; however, there is a lack of consensus and scientific evidence to support this. The study is to evaluate the influence of early pregnancy (≤ 12 months) after bariatric surgery on maternal and perinatal outcomes. PubMed, Embase, Web of Science, and the Cochrane Library were searched for all studies comparing maternal and perinatal outcomes for surgery-to-conception intervals of ≤ 12 months and > 12 months. A total of 13 studies were included. The pooled results showed that early pregnancy was associated with insufficient gestational weight gain (WMD: − 6.04, 95%CI [− 7.39, − 4.15], p < 0.01). No significant difference was found in gestational diabetes, gestational hypertension, preeclampsia, caesarean section, and postpartum hemorrhage between surgery-to-conception intervals of ≤ 12 months and > 12 months. There were also no significant differences between the two groups regarding the neonatal outcomes, including preterm birth, small for gestational age, large for gestational age, macrosomia, birth defect, neonatal intensive care unit admission, and Apgar score ≤ 7 within 5 min. Early pregnancy (≤ 12 months) after bariatric surgery seems have no significant adverse effects on maternal and perinatal outcomes, with the exception of insufficient gestational weight gain. Pregnancy after bariatric surgery should be personalized based on the individual patient. Further studies on larger cohorts are warranted.

乳腺结节是女性常见疾病，部分结节有可能是乳腺恶性肿瘤。随着中国肥胖人口比例的增加，肥胖带来的健康问题日益凸显，减重手术也越来越频繁地走进公众视野。减重手术能够持续且稳定地维持体重减轻、治愈或改善肥胖相关的代谢合并症，对于肥胖合并2型糖尿病（type 2 diabetes mellitus,T2DM）的疗效优于传统药物治疗 [1] 。我国学者经多因素分析指出，肥胖是乳腺癌发病的独立危险因素 [2] ，

肥胖及其相关并发症对健康的损害已被人们日益重视,在经济社会发展和生活方式改变的背景下,我国肥胖人群已逾8500万[1].肥胖及相关代谢紊乱引起多种疾病,涵盖了多学科内容,具体可细至分子水平.肥胖及其相关疾病在内科治疗不佳甚至无效的情况下,减重手术能有效、持久地达到减肥、并治愈或改善肥胖相关合并症.我国肥胖代谢外科经过二十余年的发展,已是相对成熟的学科,越来越多的外科医生能够熟练掌握减重手术主流术式,其学术广度和深度不断被发掘、拓展,社会对减重手术的接纳程度也逐渐增加.

Although the classic molecular subtype of breast cancer (BRCA) has been widely used in clinical diagnosis, as a highly heterogeneous malignant tumor, the classic scheme is not enough to accurately predict the prognosis of breast cancer patients. Immune cells in the tumor microenvironment (TME) are thought to play a paramount role in tumor development and driving poor prognosis. In this study, we aimed to develop a TME-associated, immune-related signature to improve prognosis prediction of BRCA. BRCA_OURS enriched transcriptomic RNA sequencing (RNA-seq) of tumor tissue was acquired from 43 breast cancer patients before any treatment. On the immune gene profiles of 43 patients from BRCA_OURS and 932 BRCA patients from The Cancer Genome Atlas (TCGA), we identified a robust immune-related signature including one positive coefficients gene (IL-10) and other 9 genes (C14orf79, C1orf168, C1orf226, CELSR2, FABP7, FGFBP1, KLRB1, PLEKHO1, and RAC2), of which the negative coefficients suggesting higher expression were correlated with better prognosis. Based on the expression of these genes, patients were grouped into the high- and low-risk group with significant overall survival (OS) (P<0.0001). The high-risk group was likely to have inferior outcomes related to several important cancer-associated pathways, including mobilizing more Golgi vesicle-mediated transport and intensive DNA double-strand breaking, which are closely related to the infiltration of immune cells and holds the key for further growing and metastasizing. Collectively, our results highlight that the immunological value within BRCA is an essential determinant of prognostic factor. Our signature may provide an effective risk stratification tool for clinical prognosis assessment of patients with BRCA.

随着经济社会的快速发展和生活方式的巨大改变,肥胖症的发病率在世界范围内越来越高,肥胖还会引起肥胖相关的代谢并发症[1].我国成年人肥胖率已超过10％,且有进一步增长的趋势[2].循证医学证据表明,对于重度肥胖患者,减重手术可以有良好的减重效果,同时还可治疗2型糖尿病,具有缓解相关代谢疾病等效果[3].根据2018年最新版国际肥胖与代谢病外科联盟全球数据注册系统数据报告[4],已有38.2％的肥胖患者接受Roux-en-Y胃旁路术(Roux-en-Y gastric bypass,RYGB),46.0％的肥胖患者接受袖状胃切除术(sleeve gastrectomy,SG).据中国肥胖代谢外科数据库统计,2019年我国减重手术已逾 11 700例,其中85.78％为 SG,11.43％为 RYGB[5].

PURPOSE:Breast cancer is a heterogeneous disease, and although advances in molecular subtyping have been achieved in recent years, most subtyping strategies target individual genes independent of one another and primarily concentrate on proliferative markers. The contributions of biological processes and immune patterns have been neglected in breast cancer subtype stratification.METHODS:We performed a gene set variation analysis to simplify the information on biological processes using hallmark terms and to decompose immune cell data using the immune cell gene terms on 985 breast invasive ductal/lobular carcinoma RNAseq samples in the TCGA database.RESULTS:The samples were gathered into three clusters following implementation of the t-SNE and DBSCAN algorithms and were categorized as 'hallmark-tsne' subtypes. Here, we identified a high-risk luminal A dominant breast cancer subtype (C3) that displayed increased motility, cancer stem cell-like features, a higher expression of hormone/luminal-related genes, a lower expression of proliferation-related genes and immune dysfunction. With regard to immune dysfunction, we observed that the motility-increased C3 subtype exhibited high granulocyte colony stimulating factor (G-CSF) expression accompanied by neutrophil aggregation. Cancer cells that produce high levels of G-CSF can stimulate neutrophils to form neutrophil extracellular traps, which promote cancer cell migration. This finding sheds light on one potential explanation for why the C3 subtype correlates with poor prognosis.CONCLUSIONS:The hallmark-tsne subtypes confirmed again that even the luminal A subtype is heterogeneous and can be further subdivided. The biological processes and immune heterogeneity of breast cancer must be understood to facilitate the improvement of clinical treatments.

Circulating tumour cell (CTC) behaviours are distinct from those of bulk tissues. Thus, treatments to eliminate CTCs differ from the regimens followed to reduce the primary tumour and its metastases. Accordingly, comprehensively deciphering the single nucleotide variant (SNV) profiles in CTCs, which partially determine CTC behaviours, is a priority. Using viable CTCs isolated with the oHSV1-hTERT-GFP virus coupled with fluorescence-activated cell sorting (FACS), the whole genome was amplified using the multiple annealing and looping-based amplification cycle (MALBAC) method. CTC behaviours were evaluated using the SNVs found to be recurrently mutated in different cells (termed CTC-shared SNVs). Analysis of the sequencing data of 11 CTCs from 8 patients demonstrated that SNVs accumulated sporadically among CTCs and their matched primary tumours (22 co-occurring mutated genes were identified in the exomes of CTCs and their matched primary tissues and metastases), and 394 SNVs were shared by at least two CTCs. Mutated APC and LRP1B genes co-occurred in CTC-shared and bulk-tissue SNVs. Additionally, the breast-originating identity of the CTC-shared SNVs was verified, and they demonstrated the following CTC behaviours: i) intravasation competency; ii) increased migration or motility; iii) enhanced cell-cell interactions; iv) variation in energy metabolism; v) an activated platelet or coagulation system; and vi) dysfunctional mitosis. These results demonstrated that it is feasible to capture and amplify the genomes of single CTCs using the described pipeline. CTC-shared SNVs are a potential signature for identifying the origin of the primary tumour in a liquid biopsy. Furthermore, CTCs demonstrated some behaviours that are unique from those of bulk tissues. Therefore, therapies to eradicate these precursors of metastasis may differ from the existing traditional regimens.

Objective To explore the correlation between axillary lymph node metastasis (ALNM) and clinicopatho-logical characteristics in patients with T1-2 breast carcinoma, in order to guide the application of sentinel lymph node biop-sy (SLNB) to avoid the postoperative complications caused by axillary lymph node dissection (ALND). Method Clini-cal data of 2108 patients with T1-2 breast cancer were retrieved from institutional database, and then the clinicopathologic parameters were analyzed. Univariate and multivariate analysis were used to identify relevant factors predictive of axil-lary lymph node metastasis. Result In the enrolled 2108 patients, 1021 (48.4%) cases were observed with lymph node metastasis. In univariate analysis, the incidence of ALNM was significantly associated with age, tumor size, pathological type, histological grade, lymph-vascular invasion (LVI), ER, PR, Ki-67 expression and molecular subtyping (all P<0.05);while HER-2 status was irrelevant. In multivariate analysis, ALNM was significantly associated with the tumor size, path-ological type, histological grade, LVI and ER receptor status (all P<0.05), and age was also a potential yet independent predictor (P=0.053). Conclusion Larger tumor size, infiltrating lobular carcinoma, higher histological grade, the pres-ence of LVI, as well as the positive expression of ER had a higher risk of developing ALNM, and a younger age (≤50) al-so may be a risk-prone factor. In all, caution is suggested when ALND is applied.

ObjectiveTo evaluate the clinicopathologic characteristics and their correlation with axillary lymph nodes invasion in a large cohort of patients with microinvasive breast cancer (MIBC).MethodAll cases of microinvasive breast cancer were retrieved from institutional database from July 2010 to June 2015. Clinicopathologic parameters were analyzed for entire cohort. Moreover, cases underwent axillary lymph node evaluation were identified. Multivariate analysis was used to identify factors predictive of lymph node involvement.Result199 cases (1.7% of operated breast cancers) were evaluated in this period. The MIBC were almost always encountered in the setting of ductal carcinoma in situ (DCIS). Patients with MIBC had a higher frequency of HER-2 overexpression, with the microinvasive component being 52.4% and the in situ component being 69.8%. 182 cases were selected for axillary staging analysis. Lymph nodes metastases were identified in 10 patients (5.5%): 8 macrometastases (4.4%) and 2 micrometastases (1.1%). The maximum involved lymph nodes were 2 (2 cases), with only 1 involved lymph nodes in the other 8 cases. Among the 10 lymph nodes positive patients, 4 underwent sentinel lymph node biopsy (SLNB) and the other 6 underwent axillary lymph node dissection (ALND). No additional positive lymph nodes were found in all SLNB cases. Tumor size≥2.5cm (P=0.044) and patients with≥2 foci of microinvasion (P=0.011) were significant predictors of lymph node metastasis by multivariable analysis.ConclusionThe higher frequency of HER-2 overexpression in MIBC and its associated in situ component implied that it might play an important role in the process of first invasion from in situ to invasive breast cancer. MIBC is associated with a low rate of lymph node metastases and therefore whether axillary lymph nodes evaluation (especially the SLNB) should be performed routinely is still in debate. Patients with≥2 foci of microinvasion and tumor size≥2.5cm are independent risk factors for lymph node metastasis.

Background Performing sentinel lymph node biopsy (SLNB) for preoperative diagnosis of carcinoma in situ (CIS) remains controversial. A common scenario:some patients are diagnosed as CIS by preoperative core needle bi-opsy (CNB) or intraoperative frozen section, yet without SLNB, whereas microinvasive breast cancer (MIBC) is the final pathologic finding after surgery, making it a difficult choice to perform reoperation for evaluating the status of axillary lymph nodes. On one hand, the risk of lymph node metastasis is unclear for MIBC;on the other hand, the sensitivity and feasibility of SLNB as reoperation is often questionable, while axillary lymph node dissection (ALND) is left to be the on-ly option generally. Objective To determine the risk factors associated with CIS and microinvasion;compare the risk of auxiliary metastasis of CIS and MIBC;determine the criteria of enrolling patients to take upfront intra and pre-operative SLNB and avoid reoperation. Method All cases with pathologically confirmed CIS (n=493) and MIBC (n=199) were in-cluded and retrospectively analyzed for clinicopathologic parameters;. comparison between the two groups were carried out with Pearson chi-square test and Fisher exact test;univariate and multivariate analysis were used to identify factors predictive of microinvasion from CIS. Result There were 4 cases of lobular carcinoma in situ (LCIS) in the CIS group, and all the others were ductal carcinoma in situ (DCIS), whereas MIBC was almost always accompanied with DCIS. Uni-variate analysis revealed that patients with MIBC had a higher frequency of tumors with microcalcification of BI-RADS≥4, tumor size>2.5 cm, high-grade DCIS, ER(-), PR(-) and HER-2(+++) overexpression (all P<0.05);perhaps including the ki-67≥20%(P=0.057). All these factors (including age) were further analyzed by Logistic regression analysis, and it was found that age>50 (P=0.034), tumor size>2.5 cm (P=0.033) and high-grade DCIS (P=0.011) were independent pre-dictors of microinvasion. Comparing to the lymph node positivity rate of 2.0%for CIS cases, the rate rose up to 5.5%for MIBC (P=0.029). Conclusion The rate of lymph node involvement was as high as 5.5%for MIBC cases. Microinvasion was associated with more extensive DCIS, higher grade and older patients (age≥50). Therefore, upfront SLNB for pa-tients with these characteristics is a reasonable and safe choice, by which can avoid the unnecessary reoperations and pave the way for further therapy.

Objective To elucidate the anatomy of lateral thoracic vessels and the possibility for preserving them during axillary lymph node dissection.Methods 126 patients were enrolled for preservation of lateral thoracic vessels when undergoing axillary node clearance for breast cancer from July to December 2015.The origin or inflow position,the orientation,as well as the distribution of the LTA and LTV were recorded.The possibility of preservation and its clinical significance were analyzed.121 patients undergoing conventional axillary dissection in the first half year of 2015 served as control.Results 65 LTA (51.6％) and 75 LTV (59.5％) were preserved in the study group.With later N stage,the preservation of LTA and LTV became more difficult (P =0.000).21 lymph nodes were dissected in the control group compared with 26 in the research group (P =0.000).Conclusions The lateral thoracic vessels can be preserved without compromising the number of resected lymph nodes.Preservation of LTA and LTV is more likely in earlier N stage patients.

BACKGROUND:Incidence rates of breast cancer continue to rise in the People's Republic of China. The purpose of this study was to describe Chinese trends in radical surgical modalities and influential imaging and demographic factors for breast malignancies.MATERIALS AND METHODS:This study was a hospital-based, multicenter, 10-year (1999-2008), retrospective study. Descriptive statistical tests were used to illustrate information regarding radical surgical trends for the treatment of breast malignancies. Chi-square tests were used to assess effect of demographic factors in addition to imaging and pathological data on the specific surgical method.RESULTS:A total of 4,211 patients were enrolled in the survey. Among them, 3,335 patients with stage 0 to stage III disease undergoing mastectomy or breast-conserving surgery (BCS) were included in the final analysis. The rate of BCS increased from 1.53% in 1999 to 11.88% in 2008. The rate of mastectomy declined over this time period, from 98.47% in 1999 to 88.12% in 2008, with increasing use of diagnostic imaging methods and pathological biopsies. A significantly greater percentage of patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy.CONCLUSION:Rates of mastectomy in China remain elevated due to diagnosis at higher stages; however, because of increased use of diagnostic imaging, improvement of biopsy methods, and patient education, rates of less invasive lumpectomy are increasing and rates of mastectomy have decreased in China.IMPLICATIONS FOR PRACTICE:In this study, 4,211 cases were collected from 1999 to 2008 through a multicenter retrospective study of varying geographic and socioeconomic areas to illustrate trends of surgeries in the People's Republic of China. The correlations between demographic and tumor characteristics and among methods of surgical treatment were explored. This study shows that the rate of breast-conserving surgery (BCS) increased and the rate of mastectomy declined over this time period with increasing use of diagnostic imaging methods and pathological biopsies. Patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy in China.

BACKGROUND AND OBJECTIVEIncidence of and mortality rates for breast cancer continue to rise in the People's Republic of China. The purpose of this study was to analyze differences in characteristics of breast malignancies between China and the U.S.METHODSData from 384,262 breast cancer patients registered in the U.S. Surveillance, Epidemiology, and End Results (SEER) program from 2000 to 2010 were compared with 4,211 Chinese breast cancer patients registered in a Chinese database from 1999 to 2008. Outcomes included age, race, histology, tumor and node staging, laterality, surgical treatment method, and reconstruction. The Pearson chi-square and Fisher's exact tests were used to compare rates.RESULTSInfiltrating ductal carcinoma was the most common type of malignancy in the U.S. and China. The mean number of positive lymph nodes was higher in China (2.59 vs. 1.31, p < .001). Stage at diagnosis was higher in China (stage IIA vs. I, p < .001). Mean size of tumor at diagnosis was higher in China (32.63 vs. 21.57 mm). Mean age at diagnosis was lower in China (48.28 vs. 61.29 years, p < .001). Moreover, 2.0% of U.S. women underwent radical mastectomy compared with 12.5% in China, and 0.02% in China underwent reconstructive surgery.CONCLUSIONChinese women were diagnosed at younger ages with higher stage and larger tumors and underwent more aggressive surgical treatment. Prospective trials should be conducted to address screening, surgical, and tumor discrepancies between China and the U.S.IMPLICATIONS FOR PRACTICEBreast cancer patients in China are diagnosed at later stages than those in America, which might contribute to different clinical management and lower 5-year survival rate. This phenomenon suggests that an earlier detection and treatment program should be widely implemented in China. By comparing the characteristics of Chinese and Chinese-American patients, we found significant differences in tumor size, lymph nodes metastasis, and age at diagnosis. These consequences indicated that patients with similar genetic backgrounds may have different prognoses due to the influence of environment and social economic determinates.

浸润性乳腺癌由临床表现、影像学特点、病理特征及生物学潜能等方面均不同的一组异质性病变所组成。因此，正确的浸润性乳腺癌分类是判别病变范围、制定最佳治疗计划、评估疗效、判断预后及科研协作交流的重要条件和标准。目前，应用最广泛的分类方法为WHO乳腺肿瘤分类法，该方法建立在肿瘤的组织学类型、分级、病变侵及范围、激素受体状态等基础上。近年来，以基因表达谱和基因芯片为基础提出的乳腺癌基因分型发展迅速，初步研究已表明其能更精确地反应肿瘤的生物学行为及判断预后，并有利于选择和研究更具针对性的个性化治疗方法。

Objective To evaluate the clinical characteristics, treatment modalities and prognosis for primary squamous cell carcinoma of the breast. Method Twelve patients of primary squamous cell carcinoma of the breast were retrospectively analyzed. Result Squamous cell carcinoma of the breast accounted for 0.058% (12/20750) of all breast cancer in our hospital from 1999 to 2014. The age of the 12 cases ranged from 31 to 73 years, with a me-dian age of 52 years old. Two patients were in stage I, 6 in stage IIA, 1 in stage IIB and 3 in stage IIIA. Nine pa-tients underwent the modified radical mastectomy, 2 accepted breast-conserving surgery. Four patients received post-operative radiotherapy, 9 were administered with adjuvant chemotherapy and 3 had endocrine therapy. Eight patients had the whole follow-up data, in which 1 patient survived 4 years with stable disease after treated by trastuzumab plus toremifene for multiple metastases after operation. One patient underwent salvage mastectomy for the local re-lapse after breast-conserving surgery and was still alive without disease for 6 years. Two patients died of lung metas-tases, and survived 11 and 36 months after more courses of chemotherapy, respectively. The other four patients were alive without diseases. The follow-up ended at July 2014. The disease-free survival ranged from 7 to 157 months. Conclusion The incidence of primary squamous cell carcinoma of the breast is rare. Combination of mastectomy and adjuvant therapy are needed.

BACKGROUND Intraductal administration of cytotoxic agents has been shown to inhibit the development of breast cancer in animal models. The object of this study was to demonstrate the safety of intraductal delivery cytotoxic agents in patients prior to mastectomy. This method is hopeful to be developed as a chemoprevention approach in patients with pre-malignant or non-invasive ductal lesions to prevent breast cancer which will be further developed. METHODS TWO DRUGS, PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) AND CARBOPLATIN WERE ADMINISTERED AT THREE DOSE LEVELS (PLD: 10, 20, 50 mg and carboplatin 60, 120, 300 mg). There were five subjects in each group with 15 subjects treated with each drug once. Venous blood samples were obtained for pharmacokinetic analysis. The breast was removed surgically 2-5 days post administration and the treated ducts were marked to enable identification on pathological evaluation. RESULTS Intraductal administration was generally well-tolerated with mild, transient breast discomfort. In the carboplatin arm, three women at the 300 mg dose experienced mild nausea and vomiting. In the PLD arm most women had mild erythema and swelling of the breast over the 72 hours following the drug administration. Patients receiving the 50 mg dose experienced local erythema until the time of surgery. Pharmacokinetic analysis showed that carboplatin rapidly entered systemic circulation with an early peak time (Tmax ~30 min) with a corresponding plasma ultrafiltrate area under the curve (AUC) consistent with the Calvert Formula using estimated glomerular filtration rate (GFR). Total plasma doxorubicin had delayed peak concentration times (Tmax >48 hours) with a linear dose response and peak concentrations substantially lower than expected from equivalent intravenous injection dosing. No doxorubicinol metabolite was detected in the plasma. CONCLUSIONS This study demonstrates that cytotoxic drugs can be safely administered into breast ducts with minimal toxicity.

Objective To analyze the clinical characteristics, treatment and prognosis for bilateral synchronous breast cancer(BSBC) Method We retrospectively analyzed the 114 cases of bilateral synchronous breast cancer reg-istered in our hospital since 1999 to 2013 in terms of clinical and pathological features, treatment and prognosis. Re-sult Invasive ductal cancer was the most common pathologic type in the first and second lesions. BSBC patients re-ceived mostly mastectomy and axillary lymph node dissection. The positive rate of hormone receptor was up to 70%. The rate of negative HER2 is higher than the positive one. The size of first lesion, the lymph node stage of first lesion and TNM stage of first and second lesion were the independent prognostic factors. Conclusion The inci-dence of bilateral synchronous breast cancer is very rare. Modified radical mastectomy was the most common opera-tion method according to past literatures. The size and lymph node stage of first lesion could influence the prognosis of patients. Early TNM stage of BSBC patients will have a better prognosis.

Preclinical data have shown the potential of the intraductal administration of chemotherapy for breast cancer prevention. Direct translation of this work has been stymied by the anatomical differences between rodents (one duct per teat) and women (5–9 ductal systems per breast). The objective of this phase I study was to show the safety and feasibility of intraductal administration of chemotherapy drugs into multiple ducts within one breast in women awaiting mastectomy for treatment of invasive cancer. Thirty subjects were enrolled in this dose escalation study conducted at a single center in Beijing, China. Under local anesthetic, one of two chemotherapy drugs, carboplatin or pegylated liposomal doxorubicin (PLD), was administered into five to eight ducts at three dose levels. Pharmacokinetic analysis has shown that carboplatin was rapidly absorbed into the bloodstream, whereas PLD, though more erratic, was absorbed after a delay. Pathologic analysis showed marked effects on breast duct epithelium in ducts treated with either drug compared with untreated ducts. The study investigators had no difficulty in identifying or cannulating ducts except in one case with a central cancer with subareolar involvement. This study shows the safety and feasibility of intraductal administration of chemotherapy into multiple ducts for the purpose of breast cancer prevention. This is an important step toward implementation of this strategy as a “chemical mastectomy”, where the potential for carcinogenesis in the ductal epithelium is eliminated pharmacologically, locally, and without the need for surgery. Cancer Prev Res; 6(1); 51–58;. ©2012 AACR.

BACKGROUND:Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.METHODS:One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.RESULTS:Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.CONCLUSION:GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.