Breast Density of Mammography is Correlated with Reproductive Risk Factors Regardless of Menopausal Status: A Cross-Sectional Study of the Korean National Screening Program

Objective: To clarify the limitations of mammography screening for women with dense breasts, we examined breast density and its effects on screening results. Patients and Methods: We performed a cross-sectional, observational study on women who underwent mammography. Data from the National Cancer Screening Program(NCSP) from 2009 to 2013 were used. The study population consisted of participants with high breast density. We used a logistic regression analysis to evaluate the relationships between breast density and reproductive factors and screening results according to menopause status. Results: High breast density was reported for 57.5% of all participants (3,417,319 participants). Screening results indicated breast density of <25%, 25-50%, 51-75%, and ≥76% for 16.4%, 26.3%, 37.8%, and 19.5%, respectively, of participants. According to the screening results, high breast density was correlated with high deferment and recall rates. Reproductive factors, especially parity, breastfeeding, and use of oral contraceptives, had consistent effects on screening results of premenopausal and postmenopausal women. Regardless of menopausal status, age, early onset of menarche (15 years or younger), fewer live births (≤1 birth), and previous benign breast disease were correlated with increased breast density. In postmenopausal women, early-onset menopause and longer-term hormone replacement therapy (≥2 years) also independently increased breast density. Conclusion: Breast density influenced screening results, which could increase the rate of recall. Breast density was also influenced by reproductive factors, with patterns similar to those of breast cancer risk, regardless of menopausal status. We need to identify high-risk women with high density who would probably benefit from supplemental breast cancer screening.     

Patient-reported Upper Limb Function After Sentinel Lymph Node Biopsy for Breast Cancer: A Prospective Observational Study

IntroductionSentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in breast cancer. There is a lack of consistency in studies reporting on upper limb morbidity after SLNB. We present a prospective study evaluating upper limb function after SLNB using the validated quickDASH questionnaire.Materials and MethodsConsecutive patients who underwent wide local excision and SLNB were included in the study. Arm function was assessed using the quickDASH questionnaire at 3 time points – prior to surgery and 2 weeks and 3 months after SLNB. The scores obtained were labeled as A, B, and C respectively. The mean and median scores were compared using the paired t test and Wilcoxon signed rank test.ResultsNinety-nine patients met all inclusion criteria and were included in the final analysis. The mean A, B, and C scores were 8.46, 16.05, and 13.36. The median A, B, and C scores were 2.27, 7.5, and 4.54. There was a statistically significant difference between mean and median A and B scores, B and C scores, and A and C scores. A similar trend was observed in patients with better preoperative upper limb function. Patients with a higher body mass index had significantly worse B and C scores.ConclusionThere is a significant deterioration in upper limb function following SLNB. This improves at 3 months but does not reach baseline levels. Larger studies with long-term follow-up are required to establish the extent of upper limb functional morbidity and natural course of functional recovery after SLNB.     

Capecitabine-Based Chemoendocrine Combination as First-Line Treatment for Metastatic Hormone-Positive Metastatic Breast Cancer: Phase 2 Study

BackgroundPreclinical studies have suggested a synergistic effect of tamoxifen and capecitabine in estrogen receptor–positive cell lines. We evaluated the safety and efficacy of first-line chemoendocrine treatment in patients with metastatic breast cancer. Biochemical assessment was performed of serum levels of thymidine phosphorylase enzyme (TP), serum tamoxifen, hydroxytamoxifen, and 5-fluorouracil in relationship to efficacy.Patients and MethodsThis prospective phase 2 interventional study studied patients with estrogen receptor-positive, HER2⁻ metastatic breast cancer who received either tamoxifen/capecitabine or letrozole/capecitabine as first-line treatment. The dose of capecitabine provided at 2000 mg per day continuously as a fixed dose.ResultsForty women with a median age of 49.3 years were enrolled. For the whole study group, median progression-free survival (PFS) was 10 months and median overall survival (OS) was 23.3 months. The overall response rate was 60% and the clinical benefit rate 82.5%. Progesterone receptor positivity was associated with significantly longer PFS (12 vs. 7 months, P = .021). The most frequent adverse events were palmar–plantar erythrodysesthesia (62.5%), fatigue (62.5%), diarrhea (30%), abdominal pain (12.5%), and constipation (10%). Changes in serum level of TP were not correlated to response to treatment, PFS, or OS. Higher serum levels of tamoxifen and hydroxytamoxifen were correlated with higher response rates and longer PFS but not OS.ConclusionChemoendocrine treatment is well tolerated, with no evidence of contradictory effects between the combination components. However, the efficacy data need more validation.     

Breast reconstruction after therapeutic or prophylactic mastectomy for breast cancer: A comparison of guideline recommendations

BackgroundThe purpose of this article is to illuminate differences in published clinical practice guideline recommendations for breast reconstruction after prophylactic and therapeutic mastectomy.MethodsTen guidelines were identified through a systematic search of websites and databases of reputable oncology guideline developers, and key differences and gaps in recommendations were noted. Quality assessment of the guidelines was conducted by three reviewers using the AGREE II tool, focusing on breast reconstruction specific documents rather than the general breast cancer guidelines.ResultsThe most comprehensive guidelines were published by Alberta Health Services, Cancer Care Ontario, the American Society of Plastic Surgeons, and the Association of Breast Surgery/British Association of Plastic Reconstructive and Aesthetic Surgeons. AGREE II scores in the domains of “Scope and Purpose” and “Clarity and Presentation” were ranked relatively high for all four guidelines while “Applicability” and “Editorial Independence” were ranked relatively low. The Alberta and Ontario guidelines were the overall highest ranked guidelines across all domains.ConclusionOverall, these guidelines provide consistent recommendations on who should receive breast reconstruction education, who is a candidate for postmastectomy breast reconstruction, and the appropriate timing of reconstruction and extent of mastectomy. Future updates from all should focus on expanding to include alloplastic and autologous forms of reconstruction and should include a broad scope of relevant questions.     

乳腺癌超声特征与腋窝淋巴结转移相关性的研究进展

腋窝淋巴结状态影响着乳腺癌患者的治疗与预后,因此腋窝淋巴结的术前评估尤为重要。近年来许多研究发现,乳腺癌的常规超声、弹性成像及超声造影特征能够间接反映腋窝淋巴结的转移情况,可用于术前早期评估,避免不必要的前哨淋巴结活检。本文就乳腺癌超声特征与腋窝淋巴结转移间的相关性进行综述。     

早期皮肤接触对剖宫产产妇心理状态及母乳喂养的影响:前瞻性随机对照试验

目的探讨母婴早期皮肤接触(skin-to-skin contact,SSC)对剖宫产产妇心理状态及母乳喂养的影响。方法前瞻性选取2017年8月1日至12月31日在深圳市南山区妇幼保健院行择期足月剖宫产的产妇221例,随机分为早接触组和对照组。对照组产后常规护理;早接触组实施母婴早期SSC,即新生儿娩出后1 h内赤裸全身俯卧于母亲裸露的乳房之间,持续1~2 h。观察指标包括:(1)泌乳启动时间以及首次母乳喂养测量工具评分;(2)产后72 h和42 d的纯母乳喂养率、母乳喂养自我效能量表评分和爱丁堡产后抑郁量表评分。采用两独立样本t检验、χ2检验和二分类logistic回归进行统计学分析。结果最终210例产妇纳入分析,早接触组和对照组各105例。42 d随访时早接触组失访20例,对照组失访17例。与对照组比较,早接触组首次母乳喂养成功率[77.1%(81/105)与59.1%(62/105),χ2=7.913]、首次母乳喂养测量工具评分[(9.5±1.7)与(8.6±1.4)分,t=4.115]、泌乳启动时间≤24 h的比例[41.0%(43/105)与12.4%(13/105),χ2=23.205]、产后72 h和42 d的纯母乳喂养率[36.2%(38/105)与22.9%(24/105);76.5%(65/85)与60.2%(63/88);χ2值分别为4.486和5.261]以及产后72 h和42 d母乳喂养自我效能量表评分[(117.5±12.0)与(111.8±22.3)分;(124.3±11.6)与(113.1±19.0)分;t值分别为2.100和4.710]均提高,差异均有统计学意义(P值均<0.05)。但早接触组产后72 h和42 d的爱丁堡产后抑郁量表评分与对照组差异无统计学意义[(5.4±3.5)与(5.9±4.0)分,t=0.937,P=0.350;(7.0±3.7)与(8.1±4.0)分,t=0.905,P=0.058]。二分类logistic回归分析显示,早期SSC是产后42 d纯母乳喂养成功的保护因素(OR=2.359,95%CI:1.173~4.743,P=0.016)。结论早期SSC可以提高剖宫产产妇母乳喂养自信心,促进泌乳启动,提高首次母乳喂养的成功率和产褥期纯母乳喂养率,是一种值得推广的临床实践。     

Inhibitory effects of everolimus in combination with paclitaxel on adriamycin-resistant breast cancer cell line MDA-MB-231

ObjectiveWe aimed to evaluate the therapeutic effects of paclitaxel in combination with mTOR inhibitor everolimus on adriamycin-resistant breast cancer cell line MDA-MB-231 (MDA-MB-231/ADR).Materials and methodsMDA-MB-231/ADR cells were treated with different concentrations of paclitaxel and everolimus. The IC₅₀ values after 48 h of treatment were measured by the MTT assay. The apoptosis rate and cell cycle were detected by flow cytometry. The protein expressions of Akt, PI3K, mTOR, p-pI3K, p-AKT and p-mTOR were detected by Western blot.ResultsWhen paclitaxel at ≥1.56 μg/ml was used, the growth of MDA-MB-231/ADR cells was inhibited more significantly than that of control group (P < 0.05). After treatment with ≥6.25 μg/ml everolimus, the cell growth was also suppressed more significantly (P < 0.05). The IC₅₀ values of everolimus and paclitaxel were 32.50 μg/ml and 7.80 μg/ml, respectively. The inhibition rate of paclitaxel plus everolimus was significantly enhanced with increasing paclitaxel concentration (P < 0.001). After treatment with 7.80 μg/ml paclitaxel, the two drugs had best synergistic inhibitory effects on proliferation. Compared with drugs alone, the combination significantly promoted apoptosis (P < 0.001). The paclitaxel + everolimus group had significantly more cells in the G0-G1 phase than those of control and individual drug groups (P < 0.001). Everolimus significantly decreased mTOR and p-mTOR expressions compared with those of control group (P < 0.001). Compared with everolimus alone, the combination reduced the expressions more significantly (P < 0.05). Paclitaxel decreased the expression levels of PI3K, p-PI3K and p-AKT. Compared with paclitaxel alone, the combination significantly promoted the reduction of PI3K, p-PI3K and p-AKT expressions (P < 0.05).ConclusionEverolimus can enhance the effect of paclitaxel on MDA-MB-231/ADR cells, inhibit cell proliferation, induce apoptosis and arrest cell cycle in the G1 phase mainly by down-regulating the expressions of key proteins in the mTOR signaling pathway.     

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. It is a cancer that originates from the mammary ducts and involves mutations in multiple genes. Recently, the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness, which gives rise to therapeutic resistance. Epidemiological, population-based, and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are the main allyl sulfur compounds present in garlic, and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation, tumor metastasis, and angiogenesis. The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer. This review discusses the potential anticancer activities of DADS and DATS, with emphasis on drug resistance in triple-negative breast cancer (TNBC). Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC, especially in clinical studies.     

miR-451a suppresses the development of breast cancer via targeted inhibition of CCND2

Extensive research has indicated that miRNAs are crucial for the occurrence and progression of cancers. miR-451a, involved in breast cancer (BC), is one of the miRNAs. This study focused on the mechanism by which miR-451a regulates BC. The levels of miR-451a in BC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan‒Meier analysis showed that this was intimately related to the patient's overall survival rate. Functional experiments revealed the negative effects of miR-451a on the abilities of BC cells to multiply (tested by Cell Counting Kit-8), migrate (tested by wound healing assay), and invade (tested by Transwell assay) and its positive effects on apoptosis (tested by flow cytometry). Western blotting indicated that the expression of tumor-related proteins was affected by miR-451a. Moreover, in vivo experiments suggested that tumor growth was clearly restrained by an miR-451a agonist in a xenograft tumor model. Bioinformatic analysis indicated that miR-451a directly targeted Cyclin D2 (CCND2), as demonstrated by the luciferase reporter assay. An opposite change in the level of CCND2 and miR-451a in BC was indicated by qRT-PCR, western blotting, and immunohistochemistry. Subsequently, functional experiments and western blotting analysis confirmed that CCND2 accelerated BC progression, which was regulated by miR-451a. Cumulatively, research on miR-451a may be valuable for BC treatment.