bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin and breast cancer risk: A meta-analysis and critical literature review.
Authors: Col Nananda , Ochs Leslie , Springmann Vicky , Aragaki Aaron K , Chlebowski Rowan T. 
Published: February 2017

25 Background: Observational studies have suggested that metformin, commonly used for diabetes treatment that increases insulin sensitivity and improves glycemic control, decreases the incidence of several common cancers. However, findings regarding metformin and breast cancer incidence have been mixed. To explore this issue, a systematic literature review and meta-analysis were performed with a focus on potential biases. Methods: We conducted a comprehensive literature search for all pertinent studies addressing metformin use and breast cancer risk by searching Pub Med, Cochrane Library, Scopus (which includes Embase, ISI Web of Science) using the Mesh terms: "metformin" or "biguanides" or "diabetes mellitus, type 2/therapy" and "cancer" or "neoplasms". When multiple hazard ratios (HR) or odds ratio (OR) were reported, the most adjusted estimate was used in the base-case analysis. We pooled the adjusted HR using and performed sensitivity analyses on duration of metformin use (> or < 3 years use), study quality (assessed using the GRADE system), and initial observation year of the cohort (before vs after 1997). Results: From a total of 421 citations, 13 full-text articles were considered, and 7 independent studies were included. All were observational (4 cohort and 3 case control). Our combined OR for metformin association with invasive breast cancer of all 7 studies was 0.83 (95% CI, 0.71-0.97). Funnel plot analyses did not suggest publication bias. Stronger associations were found when analyses were limited to studies estimating the impact of longer metformin duration (OR = 0.75. 95% CI, 0.62-0.91) or among studies that began observing their cohort before 1997 (OR=0.68. 95% CI, 0.55-0.84). Stratification according to study quality did not affect the combined OR but higher quality studies had smaller CI and achieved statistical significance. Interpretation is limited by the observational nature of reports and different comparison groups. Conclusions: Our analyses support a protective effect of metformin on invasive breast cancer incidence among postmenopausal women with diabetes. Clinical trials are needed to determine whether metformin reduces breast cancer risk.
Screening mammography in southeastern Kentucky: Is it a predictor of ongoing health disparities?
Authors: Elsoueidi Raymond , Hanna Elias , Dignan Mark 
Published: February 2017

28 Background: Studies have shown that women living in rural areas have a significantly lower rate of screening mammography than women living in urban areas. Despite the dramatic improvement in the use of screening mammography in the United States, disparities are still present. Southeastern Kentucky is a rural area with a low income population and barriers such as distance and lack of public transportation to access health care. We reviewed the use of screening mammography in this population. Methods: Data for women age 50 and older who did not have a screening mammography within the past 2 years were obtained from the behavioral risk factor surveillance system for the years 2000 through 2008. Results: The rates of screening mammography in the state of Kentucky for women age 50 and older ranged from 77% in 2000 to77.6% in 2008. The rates for urban areas in Kentucky ranged from 79.5% in 2000 to 79.4% in 2008 and those for the rural southeastern part of the state ranged from 62.6 % in 2000 to 63.7 in 2008. On average, the rates of screening mammography in southeastern Kentucky were 23% lower than state rates from 2000-2008, a difference that is statistically significant (p<.05). Additionally, from 2000 to 2008 there was no statistically significant improvement in the rates of screening mammography in southeastern Kentucky. Conclusions: The results of this study showed that the rates of participation in screening mammography are substantially lower in rural southeastern Kentucky. Continued efforts are needed to improve understanding the factors that contribute to these low rates and to help develop interventions to overcome the obstacles for obtaining screening mammography in rural populations.
Does lobular carcinoma in situ (LCIS) affect biology of future breast cancer? Surveillance Epidemiology and End Results (SEER) database review.
Authors: Tesfaye Anteneh A. , Mozayen Mohammad , Morariu Ioana , Eilender David S. 
Published: February 2017

37 Background: Lobular carcinoma in situ (LCIS) is a recognized risk factor of breast cancer. Data evaluating the behavior of breast cancer arising after LCIS is lacking. Our study compared the characteristics of breast cancer arising after LCIS with the breast cancer arising de novo. Methods: From the 1973-2009 SEER database, women with breast cancer who were diagnosed and treated between 1990 and 2009 were abstracted. Patients were divided to group A: breast cancer after LCIS, group B: de novo breast cancer. Age, ethnicity, staging, tumor size, grade and hormone receptor status were reviewed. Data were analyzed using chi square, Kaplan-Meier, Life table, and Cox proportional hazard model. Results: Patients with LCIS were 7,258 with 547 (7.5%) developing breast cancer subsequently. The mean (SD) time to develop breast cancer after LCIS was 68 (2.14) months. Of the total 557,309 patients with breast cancer, group A had 547 patients and group B had 556,762 patients. The median tumor size was 1.3 and 1.8 cm in groups A and B respectively (p<0.0001). Grade 1 and 2 tumors were 78.5% and 60.8% in groups A and B respectively (p<0.0001). Local disease alone was seen in 70% and 61% of groups A and B respectively (p<0.0001). ER-PR negative tumor was seen in 14.9% and 24.5 % in groups A and B (p<0.0001). On univariate analysis, 5 year cancer specific survival was 91% and 85% in groups A and B respectively (p< 0.0001). Unlike grade, hormone receptor status and stage, prior history of LCIS was not an independent predictor of survival on multivariate analysis (see Table). Conclusions: Breast cancer diagnosed after prior LCIS has favorable features like smaller tumor, lower grade, earlier stage and less ER-PR negativity. Some of these might be a result of more diligent subsequent screening. A history of LCIS per se is not an independent prognostic factor in breast cancer. [Table: see text]
Impact of breast cancer and BRCA mutations on thoughts and feelings of future pregnancies.
Authors: Woodson Ashley Henriksen , Muse Kimberly I. , Jackson Michelle , Arun Banu , Litton Jennifer Keating 
Published: February 2017

38 Background: Many women diagnosed with premenopausal breast cancer are concerned with treatment-related infertility. Identifying a BRCA mutation associated with hereditary breast and ovarian cancer may affect attitudes regarding future childbearing. We evaluated attitudes regarding the impact of cancer or potentially being a BRCA mutation carrier on future childbearing. Methods: Women with childbearing potential were invited to participate in an IRB-approved questionnaire study administered prior to genetic counseling and after results disclosure, if applicable. Women were provided a series of 15 statements and asked to rate how often they thought about the impact of cancer or of having a BRCA mutation on the ability to conceive or carry a pregnancy on a 4-point scale ranging from not at all to often. Descriptive statistics were used. Results: We received 148 pre-questionnaires and 114 post-questionnaires. Thirteen women tested positive for a BRCA 1 mutation and 5 with a BRCA 2 mutation. The mean age was 35 (range 20-45) with 71% having breast cancer. The majority (62%) had at least 1 biological child prior to diagnosis and 45% desired a future child. Across 15 statements, 57% of women did not have any thoughts or feelings about the impact of cancer or a BRCA mutation on a future pregnancy at initial visit. Across the same 15 statements, 52% of women who tested positive for a BRCA mutation changed their answer from the pre-questionnaire to post-questionnaire. Of these women, 70% thought about the impact more often than they reported initially. When compared to women who tested negative for a BRCA mutation (n=78), only 40% of women changed their answer choice, with 54% thinking about the impact less often. Conclusions: Women testing positive for a BRCA mutation were more likely to have an increase in thoughts and feelings regarding the impact of cancer or of being a BRCA mutation carrier on the ability to have a future pregnancy, while women who tested negative showed a decrease. Therefore, women with a BRCA mutation may be influenced in their decisions regarding future childbearing.
Radiation therapy after breast-conserving surgery: When are we missing the mark?
Authors: Nassif Mohammed , Trabulsi Nora , Reidel Kristen , Meterissian Sarkis H. , Tamblyn Robyn , Mayo Nancy , Meguerditchian Ari-Nareg 
Published: February 2017

43 Background: Postoperative radiotherapy (RT) after breast conserving surgery (BCS) represents the standard of care for local control of breast cancer (BC). Despite wide dissemination of clinical guidelines, variations in practice persist. Our objective was to identify patient, disease, and physician characteristics that predict lack of consideration for RT after BCS. Methods: Cancer registry data and administrative claims for all BCs diagnosed in Quebec from 1998 to 2005 were collected. Receipt of a consultation for RT in women with non-metastatic BC treated with BCS was measured. Multivariate logistic regression was used to assess the association between patient, disease, and physician characteristics and having an RT consult. Results: 27,483 women were included. Mean age was 59 years, 76.5% had no comorbidities, and 27.6% had stage III BC. Overall, 90.1% of women were considered for RT within 1 year of diagnosis. Patients at age extremes were less likely to be considered as compared to women 50-69: those 30-49, 70-79 and 80+ had odds ratios (OR) of 0.82 (CI 0.73-0.93), 0.54 (CI 0.48-0.61) & 0.11 (CI 0.09-0.12), respectively. Women with any ER visit and women with a hospitalization (unrelated to BC) had 15% and 17% lower odds of having an RT consult, respectively. In patients with advanced disease, receiving a consultation for chemotherapy within 4 months of BCS increased the likelihood of also being considered for RT within 1 year (OR 1.54, CI 1.19-2.00). Increases in physician BCS volume in the year prior to patient diagnosis increased the chance of their patient receiving an RT consult by 7% for every additional 10 BCS performed. Conclusions: Patient age, use of non- BC-related health services and physician volume of BCS predicts use of RT. Guideline deviations in chemotherapy administration also predicts variation in RT use.
Papillary lesions of the breast: Can larger core needle biopsy samples identify patients who may avoid surgical excision?
Authors: Chung Alice P. , Huynh Kelly T. , Shamonki Jaime , Sim Myung-Shin , Lawrence Camelia , Kinnaird Michelle , Giuliano Armando E. 
Published: February 2017

44 Background: Papillary lesions of the breast are frequently diagnosed on core needle biopsy (CNB). The ability to distinguish benign from atypical/malignant papillary lesions is limited by the representative nature of the biopsy method; thus follow-up excision is usually recommended. We aimed to determine if larger CNB samples can more reliably predict the true benign nature of a papillary lesion, thereby sparing certain patients a formal surgical excision. Methods: We reviewed medical records of 53 female patients diagnosed with histologically benign papillary lesions on CNB from 2000 to 2010, who subsequently underwent surgical excision. Pathology slides of the CNB were reviewed to document the benign histologic features of the papilloma, the number of cores sampled and the area of tissue biopsied (mm2). Statistical analysis was performed to identify the characteristics of the CNB that were associated with retention of benign histology on excision. Results: Atypical ductal hyperplasia (ADH) and carcinoma were identified in 6% (3/53) and 8% (4/53) of papillary lesions, respectively, when excised. Clinical and radiographic characteristics did not distinguish the ADH/malignant lesions from benign papillomas. The CNB needle sizes ranged from 9- to 18-gauge (median 14). The number of cores sampled ranged from 3-16 (mean 4.5). Patients with benign excisions had a significantly larger area of tissue sampled by CNB than those found to have ADH/malignant lesions on excision (mean ± SD: 95.6 ± 101.2 vs. 41.7 ± 21.9, respectively, p=0.003). By logistic regression, CNB tissue samples consisting of ≥7 cores, or measuring >96 mm2 in aggregate, had a negative predictive value for ADH/malignancy of 100% (AUC of 0.69 and 0.68, respectively). Conclusions: Although no clinical or radiologic features distinguished benign from pathologically significant papillary lesions, larger sample sizes significantly improved the predictive value of benign histology on CNB. A papilloma sampled by ≥ 7 cores or > 96 mm2 showing benign histology at CNB, retained benign features upon excision. Close surveillance may be a reasonable option for patients whose benign papillomas are generously sampled at the time of CNB.
Molecular differences between normal breast epithelia, pure DCIS, and DCIS adjacent to invasion.
Authors: Guvakova Marina 
Published: February 2017

50 Background: With the use of screening mammography, the diagnosis of breast ductal carcinoma in situ (DCIS) is increasing worldwide. Currently there are no applied molecular markers to aid in predicting risk of DCIS progression to invasive breast cancer (IBC). Studies predicted that the transition from DCIS to invasive disease was associated with quantitative rather than qualitative differences in gene and protein expression. Methods: We developed monochrome imaging-based method to measure protein expression as a continuous variable in fixed tissue (Furstenau et al. BREA 2010). The insulin-like growth factor I receptor (IGF-IR), Ras oncogene –like protein 1 (Rap1), and a Rho GTPase guanine nucleotide exchange factor Vav2 implicated in the regulation of invasion in preclinical models have been chosen for protein analysis in tissue. In pilot study, we performed quantitative protein profiling on 90 samples of the breast: 17 histologically normal tissues, 16 benign lesions; 15 CIS, and 42 IBC. In addition, we analyzed 24 DCIS: 12 pure and 12 associated with IBC. Results: The expression of the IGF-IR and Rap1 was increased in pure CIS; significantly (P ≤ 0.001) increased in CIS adjacent to IBC as well as in IBC compared with non-cancerous tissue. In the majority of pure DCIS the levels of Vav2 were similar to that in normal epithelia; however, the Vav2 levels were significantly (P<0.01) higher in DCIS adjacent to invasion and in IBC. Moreover, IGF-IR, Rap1 and Vav2 significantly discriminated invasive from non-invasive tissues, with receiver operating characteristic (ROC) area under curve, AUC=0.8. Interestingly, younger women (< 50 years of age) were more likely to develop IBC with increased expression of the Vav2 protein (OR= 2.05; 95% CI 1.08-3.86). No significant correlation was found between IGF-IR, Rap1 expression levels and patient’s age. Conclusions: We conclude that our assessment of protein expression in breast tissue revealed previously unidentified quantitative differences in the IGF-IR, Rap1, and Vav2 protein expression in breast cancer progression series. These findings open door for studies on molecular-based prediction of individualized risk for developing invasion in early diagnosed DCIS.
Estimation of additional MRI resources needed in British Columbia for screening high-risk women for breast cancer.
Authors: Rajapakshe Rasika , Bitgood Christabelle , McAvoy Steven , Araujo Cynthia , Gordon Paula , Coldman Andy 
Published: February 2017

51 Background: Screening women at high risk with MRI has been shown to detect breast cancer at an early stage. Therefore, MRI screening has been recommended in the UK and USA for women who are at a high risk of developing breast cancer. However, there is no information available in the province of British Columbia (BC) about the number of women who have a high risk of developing breast cancer. Therefore, we carried out a study to estimate the breast cancer risk distribution in three sample populations in BC using Tyrer-Cuzick (TC) risk prediction model so that additional resource requirement for MRI breast screening can be calculated. Methods: A survey questionnaire was designed based on the TC model, which includes family history, hormonal factors, and benign breast disease. Additional questions also include factors that are used in other models (Gail, Claus, and BCRAPRO) as well as factors that may be included in the future. Women were recruited by staff and volunteers at three screening mammography clinics: Kelowna, Victoria General Hospital, and BC Women’s Health Centre in Vancouver. The survey was available to women to complete on the web, by phone, or on paper. An online database was constructed to store and query the data. The 10-year risk of developing breast cancer for each woman was calculated using the Tyrer-Cuzick IBIS Risk Evaluator software and the risk distribution of the survey population was analyzed. Results: Data from 3,200 women recruited from three sites, gives a risk distribution showing 2.6% are at high risk of developing breast cancer, 31.2% are at moderate risk, and 66.2% are at low risk. Based on NICE guidelines (UK), high risk is defined as having a 10-year risk of greater than 8%, moderate risk as 3-8%, and low risk as less than 3%. Extrapolating this to the approximately 500,000 women who are eligible to attend for screening mammography in BC, 13,000 women are considered at high risk. Conclusions: Our results indicate that 2.6% of women ages 40-79 attending screening mammography in BC may have a very high risk of developing breast cancer based on personal and family history. Based on a 14-hour work day, three additional MRI scanners would be required to implement MRI screening for these high-risk women in BC.
Does breast density affect the ability of MRI to detect mammographically occult cancers?
Authors: Freedman Beth Cutler , Luongo Jocelyn , Gillego Alyssa , Fulop Tamara , Boolbol Susan K. 
Published: February 2017

54 Background: In breast cancer patients, the use of preoperative MRI is increasing. A change in the operative plan due to MRI findings occurs in 8%-20% of cases. Preoperative MRI is used routinely by many surgeons and radiologists, but debate persists with regard to its indications. We evaluated whether mammographic breast density affected MRI findings. We also examined whether the number of MRI detected synchronous cancers were affected by breast density. Methods: A retrospective chart review was performed of newly diagnosed breast cancer patients who underwent preoperative MRI from 2008-2011. There were three categories of breast density: fat-replaced, scattered fibroglandular densities, and dense. We determined the number of patients in each group who underwent biopsies based on MRI findings, and evaluated the number of occult cancers diagnosed as a result of these biopsies. Results: 301 patients were included. Overall, 64 patients (21%) who underwent an image guided biopsy based on pre-operative breast MRI were diagnosed with an additional focus of cancer. Of the 17 patients with fat-replaced breasts, 4 underwent additional biopsy, and carcinoma was identified in all patients. 149 patients had scattered fibroglandular densities; 53 (36%) underwent additional biopsies. New cancers were diagnosed in 28 patients (19%). Of 135 patients with dense breasts, 61 patients (45%) had additional biopsies, and new cancers were diagnosed in 24 % of these patients. Conclusions: MRI detected additional cancer in 21% of patients in this study. MRI is sensitive and specific in patients with fat-replaced breasts (100%), but due to the small number of patients in this group, additional studies must be done to evaluate the usefulness in this group of patients. We conclude that MRI is useful for detecting additional cancers in patients of all breast densities, and may change the surgical options of the patient when multicentric or contralateral disease is diagnosed.[Table: see text]
Breast cancer detection among Irish BRCA1 and BRCA2 mutation carriers.
Authors: Walsh Elaine , Farrell Michael P. , Gallagher Fergal , Clarke Roisin , Nolan Carmel , Kennedy M. John , Daly Peter , McCaffrey John , Connolly Elizabeth M. , Boyle Terence , Kell Malcolm R. , Gallagher David J 
Published: February 2017

59 Background: High-risk breast cancer screening for BRCA1/2 mutations carriers with clinical breast exam, mammography and MRI have sensitivities approaching 100%. Even with intensive screening BRCA mutation carriers can present with self-detected interval cancers. We investigate screening practices and presentation among a cohort of Irish BRCA1/2 mutation carriers. Methods: Females with breast cancer belonging to kindreds now known to harbour BRCA1/2 mutations were retrospectively identified. Records were reviewed for BRCA mutation, demographics, breast cancer diagnosis, stage, histology and screening. We assessed screening modalities and whether breast cancers were diagnosed at screening or as interval cancers. Results: 53 cases of breast cancer were diagnosed from 1968-2010 among 53 Irish hereditary breast ovarian cancer kindreds. BRCA mutation status was unknown at time of diagnosis but subsequently confirmed. Detection method was identified in 50% of patients: 84% by clinical breast exam (CBE), 4% mammography, 4% MRI and 8% by a combination of CBE and mammography. Fifteen women (28%) developed second breast cancer; 9(60%) were undergoing screening, 2 were not and 27% were unknown. 22% were detected by CBE alone; 34% mammography; 22% a combination of mammography and CBE and 22% by MRI. In 41%, histology changed between first and second diagnosis. Two women developed a third breast cancer. In one, her second was an interval cancer despite being in a screening programme. Her third was radiologically detected. Conclusions: In this cohort of Irish BRCA1/2 mutation carriers almost 25% of second breast cancers were not detected by screening. 4% of cases were phenocopies and in 41% histology changed between first and second diagnosis. [Table: see text]