Mutation Analysis in the BRCA1 Gene in Chinese Breast Cancer Families

Objective: To study the mutation of BRCA1 gene in Chinese breast cancer families. Methods:Fifteen families were selected, involving 41 members, consisting of 23 breast cancer patients. Using poly-merase chain reaction and single stranded conformation polymorphism (PCR-SSCP), and subsequent DNA sequencing, the mutation of BRCA1 genes were analyzed. Results: Four mutations were found in all fam-ilies, and the proportion of mutation was 26.7% (4/15) in breast cancer families. One of the 4 mutations was 2228 insC, resulting in chain termination at codon 711. The remaining 3 mutations were 1884A→T and 3232A→G, resulting in single amino acid change respectively. Conclusion: BRCA1 is a breast cancer susceptibility gene. The relatively low proportion and frequency of BRCA1 mutations in our study hints additional BRCA genes existed.     

Clinical Analysis of 276 Cases of Non-Palpable TO Breast Cancer

OBJECTIVE Discussion of diagnosis, treatment and prognosis of nonpalpable TO breast cancer.METHODS Between 1978 and 1997, 9,980 female patients with operable breast cancer were treated surgically, of which 276 were determined to have TO breast cancer. Most TO breast cancers could be detected promptly with careful examination of presenting symptoms, such as nipple discharge, local thickening of the breast, nipple erosion, nipple retraction and postmenopausal mastalgia, while 12 cases were detected by routine mammography of the contralateral breast.RESULTS All patients were treated surgically and their tissue subjected to histopathological examination. Most cases (73.0%) were noninvasive or early invasive carcinoma. Axillary lymph nodes metastases were found in 7.69% of 234 mastectomy cases.CONCLUSION The survival rate was significantly increased if the tumor was in an early stage. The 5-, 10-, 15-years survival rates were 98.1%,94.6% and 90.3%, respectively.     

Screening for Breast Cancer - is There an Alternative to Mammography?

Given the continuing increase in mammary cancer incidence and in many cases also mortality across the world, ‍as well as the difficulty with primary prevention, the question of whether screening for early detection is effective is ‍of prime importance. If there is a real benefit in terms of reduced mortality then attention should clearly be focused ‍on the modality which should be recommended in different resource settings. In the developed world where ‍mammography is generally available the results are less than conclusive. It seems possible that there is a segment of ‍breast cancer benefited both by screening and by treatment, and that far from these effects being additive, they ‍affect the same spectrum of cases, so that as treatment improves, the benefit we can expect to see from screening ‍falls. In the Asian Pacific setting, randomized trials on the basis of the cost and benefit should be a high priority. ‍However, the lesson from all programmes of breast screening, is that for success, attention has to be paid to all ‍aspects of the programme, compliance with screening, high quality screening tests, quality in the referral, diagnosis ‍and treatment process, as well as adequate follow-up.     

Operable Breast Cancer： a Clinical Analysis of 6,263 Cases

OBJECTIVE In Europe and America breast cancer commonly occurs in women of middle and old age, with a median age of about 57 years. Modified radical mastectomy now called standard radical mastectomy, has taken the place of traditional radical mastectomy. Patients with breast cancer at an early stage commonly receive BCT (breast conservative therapy). The TNM stage (especially the lymph node status) affects the prognosis, and adjuvant therapy can improve survival. In China, only a few reports have been pubIished studying large numbers of breast cancer patients. This study was designed to analyze the clinical features, surgical pattern and treatment outcome of resectable breast cancer, as well as to explore the prognostic factors and the effect of adjuvant therapy, with a goal to improve the level of diagnosis and treatment.METHODS Records of the 6,263 patients with resectable breast cancer who had been admitted into our hospital from June 1964 to June 2003 were analyzed retrospectively.RESULTS Of the 6,263 cases, 98.8% were female. Breast cancer occurred most frequently in patients of ages 40～49 years (41.0%), especially in patients 45～49 years old (25.2%). A breast lump, which occurred in 96.2% of the patients, was the main clinical manifestation. The overall 5- and 10-year survival rates were 75.16% and 40.44%. Of the patients in TNM stages 0-1,Ⅱ, and Ⅲ, the 5-year survival rates were 96.8%, 73.7% and 46.4% respectively and the 10-year survival rates were 78.7%, 64.6% and 33.5% respectively. The 5-, and 10-year survival rates were higher in the lymph node negative group than in the lymph node positive group (80.3% vs. 55.6%, and 59.2% vs. 31.9%, P＜0.01). Since the 1980s there was no significant difference in survival rates of patients who received a radical mastectomy compared to a modified radical mastectomy(P＞0.05). Of the 73 patients who underwent breast conservative therapy, no local recurrence or metastasis occurred during a maximal follow-up of 17 years. Of the patients in stage T2T4, the 5-, and 10-year survival rates were significantly higher in the group treated with adjuvant chemotherapy compared to the non-chemotherapy group (78.2% vs. 60.1%, and 48.9% vs. 30.7%, P＜0.01).CONCLUSION According to our data, breast cancer most frequently occurred in patients of ages 45～49 years. The TNM stage (especially the lymph node status) relates to breast cancer prognosis. The prognosis was worse in patients with positive lymph nodes compared to the patients with negative lymph nodes. The efficacy of a modified radical mastectomy is equal to that of a radical mastectomy, and breast conservative therapy can be applied to patients in an early stage. Adjuvant chemotherapy and endocrine therapy can improve the survival of resectable breast cancer patients.     

Advanced Breast MRI Techniques: Helpful for Screening Breast Cancer?

Breast magnetic resonance imaging (MRI) is increasingly used in conjunction with mammography as a screening tool to detect breast cancers in asymptomatic high-risk women. Conventional dynamic contrast-enhanced (DCE) breast MRI has a high sensitivity but only moderate specificity for the detection of breast cancer. The primary goal of developing and applying advanced breast MRI techniques that can assess tissue biology is to improve lesion specificity. This review provides a summary of the advances in DCE-MRI techniques and the use of diffusion-weighted imaging and magnetic resonance spectroscopy for breast cancer detection. Publications on the use of these advanced MRI techniques are largely single-institution studies with small numbers of patients, which limits the generalization of this data to a wider screening population. In their current forms, these adjunctive techniques require further research, incorporating an expanded patient population, to validate their utility for breast cancer screening.     

Breast Conserving Surgery for BRCA Mutation Carriers—A Systematic Review

Similar to mastectomy, breast conserving surgery (BCS) is currently the reference standard of surgical treatment of sporadic breast cancer in patients. However, its oncologic safety for BRCA mutation carriers has remained controversial. Thus, we conducted a systematic review to critically evaluate the best evidence from reported studies. A comprehensive search was performed of the Medline, EMBASE, CINAHL, and Cochrane databases using a predefined strategy. The retrieved studies were independently screened and rated for relevance. Data were extracted for qualitative synthesis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol for systematic reviews. No randomized controlled trial has directly compared BCS and mastectomy for BRCA mutation carriers. Of the 18 studies included in our review, the pooled analysis of overall survival at 5, 10, and 15 years were comparable between BCS and mastectomy (88.7%, 89.0% and 83.6% with BCS and 83%, 86.0%, and 83.2% with mastectomy, respectively). However, the pooled ipsilateral breast cancer recurrence rates at 5, 10, and 15 years were higher in the BCS group (8.2%, 15.5%, and 23%, respectively) than in the mastectomy group (3.4%, 4.9%, and 6.4%, respectively). BCS was associated with a greater rate of ipsilateral breast cancer recurrence in BRCA mutation carriers. However, it was not associated with adverse short- and long-term survival outcomes. BCS should be offered as an option to BRCA mutation carriers with proper preoperative counseling.     

Is Height of Prognostic Significance in Breast Cancer Cases?

Objective: The objective of this study was to investigate the correlation of height with prognosis and other prognostic factors in Turkish breast cancer cases. Materials and Methods: We retrospectively reviewed a total of 393 women aged between 26 and 88 years, diagnosed with stage 1-3 invasive ductal breast cancer, treated and followed-up in Kayseri Education and Research Hospital. Findings: The mean age at admission was 55.7 years; 77.6% were aged under 65, 56.7% were postmenopausal, 97.4% had undergone modified radical mastectomy, 47.3% were AJCC stage II, 36.8% N0, 46.0% grade II, 95.4% had received chemotherapy, 81.1% radiotherapy and 71.5% hormonotherapy. Height was under 151 cm in 20.8 %, 151-160 cm in 57.3 % and over 161 in 21.9 %. Follow-up duration differed between 0.3 and 195.3 months. Mean overal survival (OS) was 125.0 (65.6-184.3) months and progression free survival was 91.5 (37.7-145.2) months, with a tendency for better survival in taller individuals but no signficant variation between height groups. The 5 and 10-year OS rates were 74.5% and 56.4%, and PFS rates were 64.5% and 49.2%. Regarding association of height with other prognostic factors, a significant correlation was found between height and AJCC stage (p= 0.011) and estrogen status (ER) (p= 0.043). Conclusion: In conclusion, overal survival was found to be longer in patients with a height between 151 and 160 cm than those under 151 cm and over 161 cm. The reason for not obtaining significant results might be a relatively small number of patients and lack of the evaluation of clinical and pathologic characteristics together with anthropometric measurements in the patient population. Further studies are warranted to clarify any association.     

Are We Overtreating Patients With T1a HER2+ Breast Cancer? An Analysis of the National Cancer Database

IntroductionThe potential benefit of systemic therapy in patients with T1a HER2+ cancers is not well understood, and no consensus guidelines exist. We sought to investigate practice patterns of chemotherapy use in this population.MethodsFrom the National Cancer Database (2013-2018), we identified female patients with HER2+ cancers staged as cT1aN0 or pT1aN0 and stratified by receipt of chemotherapy. Using univariate and multivariable analyses we assessed the clinicopathologic features associated with the receipt of chemotherapy. We also compared rates of overall survival (OS).ResultsOf 5176 women with cT1aN0 HER2+ cancers, 88 (2%) received neoadjuvant chemotherapy. Younger age and hormone-receptor (HR) negative tumors were factors independently associated with receipt of neoadjuvant chemotherapy (all P < .001). Of 11,688 women with pT1aN0 HER2+ cancers, 5,588 (48%) received adjuvant chemotherapy. Rates of use increased over the analysis period from 39% in 2013 to 53% in 2018 (P < .001). Factors independently associated with receipt of adjuvant chemotherapy included younger age, having a poorly differentiated tumor, exhibiting lymphovascular invasion, undergoing adjuvant radiation (all P < .001). There were no differences in OS when comparing those who did and did not receive chemotherapy in either group.ConclusionsThe use of chemotherapy in patients with HER2+ T1a cancers is increasing over time and is, as expected, more common among patients with unfavorable clinicopathologic features. Since no prognostic algorithm currently exists, more prospective data is needed to understand which of these patients may derive benefit from systemic therapy and which may safely avoid the morbidity of chemotherapy.     

Role Playing for Improving Women’s Knowledge of Breast Cancer Screening and Performance of Breast Self-Examination

Background: To enhance knowledge and performance of screening as a strategy to control breast cancer, use of effective teaching methods is necessary. The objective of this study was to determine the effect of role-playing on knowledge of breast cancer screening and performance of breast self-examination (BSE). Methods: A quasi experimental design was used. Women enrolled in community cultural centers (n=314) were randomly divided into two educational groups: role playing (intervention) and lecture (control). Data were collected using a structured questionnaire before and after intervention. Reliability of the questionnaire was determined as 0.80 by Cronbach’s alpha. The women were followed up regarding performance of BSE one month later. Results: Of the 314 women, 113 (36%) and 132 (42%) had low and medium levels of knowledge, respectively. More than a third (38.2%) reported that TV and radio were the most important information sources for breast cancer and screening. There were significant differences between mean scores of knowledge before and after the intervention in both groups, but change was greater with role playing (31.3±1.9 as compared to 23.5±1.3) (P=0.001). After a month of educational intervention, 75.7% and 69.8% of those in role playing and control groups had undergone BSE. Conclusion: It appears that application of a role playing method by providers improves women’s knowledge and behavior with respect to breast cancer screening.     

Molecular Structure of BRCA1-estrogen Receptor Alpha-estrogen Complex: Relevance to Breast Cancer?

Recent studies indicate that BRCA1, the first breast cancer susceptibility gene to be identified and cloned, interacts ‍with and regulates the activity of estrogen receptor alpha. The availability of genetic tests for BRCA gene mutations ‍has prompted cancer geneticists to generate information about genetic risk and inform women with a personal or ‍family history of breast or ovarian cancer of preventive measures. However, knowledge on the human BRCA1- ‍estrogen receptor alpha-estrogen complex is limited. Here, the author focuses on its 3D molecular structure and ‍properties.     

Predictors of Breast Cancer Screening Among Korean American Women: Is Having an Annual Checkup Critical?

Objective: Korean American (KA) immigrant women underutilize breast cancer screening. This study examinedfactors predicting breast cancer screening behavior among KA women in the United States. Methods: 233 KA womenaged 19 to 85 were recruited in the metro area of Atlanta, Georgia. Andersen’s behavioral model theoretically guidedthe study. Result: Of the predisposing factors, age (OR=1.043, p<.01, 95% CI [1.017, 1.069]) and marital status(OR=2.154, p<.05, 95% CI [1.022, 4.539]) were significantly associated with clinical breast exam (CBE), while income(OR=2.289, p<.05, 95% CI [1.060, 4.945]) and annual checkup (OR=2.725, p<.01, 95% CI [1.342, 5.533]) werelinked to CBE as enabling factors. For the receipt of mammographic screening, annual checkup was only significantlyassociated among enabling factors (OR=4.509, p<.05, 95% CI [1.263, 16.102]), while family cancer history wasidentified as the only significant need factor (OR=.112, p<.01, 95% CI [.023, .552]). Conclusion: Differing factorsexplained the receipt of CBEs and mammographic use among KA women. Specifically, the findings shed light on theimportance of having an annual checkup for the uptake of both CBEs and mammographic use. Intervention strategiesshould focus on promoting health accessibility for KA women to adhere to recommended breast cancer screening.     

A Germline Mutation in the BRCA1 3’UTR Variant Predicts Susceptibility to Breast Cancer in a Saudi Arabian Population

Purpose: The impact of the BRCA1-3’UTR-variant on BRCA1 gene expression and altered responses to externalstimuli was previously tested in vitro using a luciferase reporter assay. Its ability to predict breast cancer risk in womenwas also assessed but the conclusions were inconsistent. The present study concerns the relationship between theBRCA1-3’UTR germline variant rs8176318G>T and susceptibility to Breast cancer in an ethnic population of SaudiArabia. Methodology: The study included 100 breast cancer patients and 100 sex matched healthy controls fromthe northwestern region (Tabuk) and Dammam of Saudi Arabia were investigated for the BRCA1-3’UTR germlinevariant rs8176318G>T using an allele specific PCR technique. Genotype distributions were then compared. Results:The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian patients were 26%, 8% and 66% andin healthy controls were 45%, 5% and 50%, respectively (p=0.03). Risk of developing breast cancer was found to besignificantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47, 1.11-1.93; P=0.007), GT+TT (OR, 2.32,1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and the T allele (OR 1.62 , 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). Therewere 2.76 and 2.28 fold increase risks of developing breast cancer associated with the TT and GT genotypes in ourcases. A significant correlation was also found between the BRCA1 3’UTR variants with the stage of the disease anddistant metastasis but not with age, grade, and ER, PR and her2/neu status. Conclusion : The rs8176318G/T in the3’untranslated region (UTR) of the BRCA1 gene was found to be associatedwith increased susceptibility to breastcancer in our study population, increased risk being noted with the GT and TT genotypes. Further association studiesare needed to confirm this finding in other regions of Saudi Arabia.     

The National Cancer Screening Program for Breast Cancerin the Republic of Korea: Is it Cost-Effective?

This goal of this research was to evaluate the cost-effectiveness of the National Cancer ScreeningProgram (NCSP) for breast cancer in the Republic of Korea from a government expenditure perspective. In2002-2003 (baseline), a total of 8,724,860 women aged 40 years or over were invited to attend breast cancerscreening by the NCSP. Those who attended were identified using the NCSP database, and women weredivided into two groups, women who attended screening at baseline (screened group) and those who did not(non-screened group). Breast cancer diagnosis in both groups at baseline, and during 5-year follow-up wasidentified using the Korean Central Cancer Registry. The effectiveness of the NCSP for breast cancer wasestimated by comparing 5-year survival and life years saved (LYS) between the screened and the unscreenedgroups, measured using mortality data from the Korean National Health Insurance Corporation and theNational Health Statistical Office. Direct screening costs, indirect screening costs, and productivity costs wereconsidered in different combinations in the model. When all three of these costs were considered together,the incremental cost to save one life year of a breast cancer patient was 42,305,000 Korean Won (KW)(1 USD=1,088 KW) for the screened group compared to the non-screened group. In sensitivity analyses,reducing the false-positive rate of the screening program by half was the most cost-effective (incrementalcost-effectiveness ratio, ICER=30,110,852 KW/LYS) strategy. When the upper age limit for screening wasset at 70 years, it became more cost-effective (ICER=39,641,823 KW/LYS) than when no upper age limitwas set. The NCSP for breast cancer in Korea seems to be accepted as cost-effective as ICER estimates werearound the Gross Domestic Product. However, cost-effectiveness could be further improved by increasingthe sensitivity of breast cancer screening and by setting appropriate age limits.     

Incidence of Brain Metastases in Nonmetastatic and Metastatic Breast Cancer: Is There a Role for Screening?

BackgroundCurrent National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines recommend against screening breast cancer patients for asymptomatic brain metastases. Because brain metastases are a major cause of morbidity and mortality from breast cancer, we undertook a literature review to ascertain whether there might be a role for brain metastases screening in high-risk patient subgroups.Materials and MethodsA literature search was conducted on the OvidSP platform in the MedLine database, using MeSH terms and subject headings related to breast cancer, brain metastases, and incidence. The search was conducted without language or publication restrictions, and included articles indexed from January 1, 2006 to June 10, 2018. Experimental and observational studies that reported the incidence of brain metastases in patients with nonmetastatic or metastatic breast cancer were included.ResultsOne hundred seventy studies were identified, with 33 included in the final analysis. Among nonmetastatic breast cancer patients, incidence of brain metastases as site of first recurrence per year of median follow-up ranged from 0.1% to 3.2%. Although incidence of brain metastases was much higher among the metastatic breast cancer population overall, it was particularly high among metastatic HER2-overexpressing (HER2⁺) and triple-negative populations, ranging between 22% and 36% for the former, and 15%-37% for the latter in the absence of screening.ConclusionIn patients with nonmetastatic breast cancer, screening for asymptomatic brain metastases cannot currently be justified. However, due to the high incidence of brain metastases among patients with metastatic HER2⁺ and triple-negative breast cancer, studies to determine the value of screening for brain metastases should be undertaken in these subgroups.     

Thermal Ablation as an Alternative for Surgical Resection of Small (≤ 2 cm) Breast Cancers: A Meta-Analysis

Women with early-stage breast cancer have an excellent prognosis with current therapy, but could presumably be treated less invasively, without the need for surgery. The primary goal of this meta-analysis was to examine whether thermal ablation is an effective method to treat early-stage breast cancer.Studies reporting on complete ablation rate after thermal ablation as a treatment of small breast cancers (≤ 2 cm) were included. Methodologic quality of included studies was assessed using MINORS criteria. Complete ablation rates are given as proportions, and meta-regression and subgroup analyses were performed.The overall complete ablation rate in 1266 patients was 86% and was highest after radiofrequency ablation (RFA) (92%). Local recurrence rates varied from 0% to 3%, with a median follow-up of 15 to 61 months. Overall, complication rates were low (5%-18% across techniques) and were highest after high-intensity focused ultrasound ablation and lowest after cryoablation. Cosmetic outcome was good to excellent in at least 85% of patients but was reported infrequently and long-term results of cosmetic outcome after thermal ablation and radiotherapy are still lacking.Thermal ablation techniques treating early-stage breast cancer (≤ 2 cm) are safe and effective based on complete ablation rate and short-term local recurrence rates. Especially, RFA, microwave ablation, and cryoablation are promising techniques as an alternative to surgical resection without jeopardizing current treatment effectiveness or safety. Owing to great heterogeneity in the included studies, a formal recommendation on the best technique is not possible. These findings warrant the design of large randomized controlled trials comparing thermal ablation and breast-conserving surgery in the treatment of T1 breast cancer.     

Analysis of Predictors of Breast Cancer Screening among Japanese Women using Nationally Representative Survey Data, 2001–2013

Objective: Predictors of participation in breast cancer screening in recent years or the trend of participation rate by predictors over the years has not been investigated in Japan. In this study, we investigated predictors for participation in breast cancer screening and analyzed the trend of participation rate depending on the predictors using nationally representative survey data in Japan. Methods: The data of “Comprehensive Survey of Living Conditions” in Japan from 2001 to 2013 were used. Participation in breast cancer screening was used as an outcome. Next, as explanatory variables, we used age group, marital status, living arrangements, educational level, household income, employment status, smoking status, regular outpatient visit status, and self-rated health status. Then, the participation rate for breast cancer screening was calculated for each of the factors over the years. In addition, multivariate logistic regression analysis was conducted to analyze the association between each factor and the participation rate using data from 2010 and 2013. Results: We found that non-married women, women with lower educational level, women with low household income, self-employed or unemployed women, smokers, and women with low self-rated health status were significantly less likely to participate in breast cancer screening. Conversely, the participation rate increased for all predictor groups from 2001 to 2013, and the increase in the participation rate for never-married women was particularly evident compared with the other marital statuses. However, significant differences in the participation rate for breast cancer screening existed depending on marital status, household income, employment status, and smoking status throughout the analyzed years. Conclusion: Our findings suggest that further recommendations for breast cancer screening are particularly needed among women of low socioeconomic status and those who are self-employed or unemployed to increase the participation rate in Japan.