bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does radiation therapy increase late cardiac death in patients with left breast cancer?
Authors: Lin Chi , Denniston Kyle A. , Charlton Mary E. 
Published: March 2020

1127 Background: The objective of this study was to evaluate the effect of external beam radiation therapy (RT) on late cardiac death (CD) in patients with left breast cancer. Methods: A total of 529,246 patients who were diagnosed with adenocarcinoma of the breast between 1983 and 2004 and survived ≥ 5 years were identified from the SEER database. After excluding patients who were male, had right breast cancer, received brachytherapy or had missing data, 163,894 patients remained. Examined risk factors for CD include age (≤49/50-59/60-69/70-100), race (white/non-white), stage (In situ/local/regional/distant), breast subsite (nipple and areola/inner quadrant/outer quadrant), diagnosis year (1983-1993/1994-2004), surgery status (none/less than mastectomy/mastectomy) and RT. Time to CD was evaluated using the Kaplan-Meier method. A multivariate logistic regression model was used to evaluate factors associated with the use of RT and the Cox Proportional Hazards model was used to evaluate risk factors for CD. Results: A multivariate logistic regression model revealed that patients who received RT tended to be younger, white, more recently diagnosed, have inner quadrant and more advanced disease and undergo less than mastectomy. Median overall survival for patients with RT was significantly longer than those without RT (263 vs. 226 months, Log-Rank p < .0001). RT group had a lower risk of CD than no-RT group (Log-Rank p < .0001). Median time to CD was not reached in either group. The probability of CD was increased with increasing age and stage, and decreased with more recent diagnosis year and after mastectomy. Cox model found RT to be associated with lower probability of CD (HR 0.66, 95% CI 0.62-0.70), after adjusting for age, stage, surgery status and diagnosis year. Race and breast subsite were not associated with CD. Conclusions: Patients with left breast cancer who survived ≥ 5 years and received RT had a lower risk of cardiac death than those who did not. The cause of this difference is unclear but suggests influence from an uninvestigated factor, potentially the increased use of cardiotoxic chemotherapy or other cardiovascular comorbidity in those patients not receiving RT. Continued study, accounting for such factors, is warranted.
Clinicopathologic analysis of a large series of microinvasive breast cancer.
Authors: Leach Joseph W. , Lillemoe Tamera , Krueger Janet 
Published: March 2020

1129 Background: Microinvasive breast cancer (Tmic) is defined by the AJCC as extension of cancer cells beyond the basement membrane with no single focus larger than 1 mm. The clinical behavior of this entity is unclear. Most series suggest that prognosis is similar to non-invasive cancer although the literature is mixed. Surgical management typically reflects invasive breast cancer including lymph node sampling. Published incidence of nodal involvement is also variable with some small series reporting incidence as high as 20%. We present a clinicopathologic review of a large series from a community practice setting. Methods: Using the AJCC definition of Tmic, we retrospectively identified all cases treated within Allina Health System from 2001-2011. Inclusion criteria included no prior history of breast cancer and available follow-up data. Data collected included ER/PR and HER2 status (when available), margin status and surgical and adjuvant therapy. Results: 118 eligible cases were identified with a mean follow-up of 3.65 years and mean age of 56.8 years (34-88). 39 were triple negative and 29 were HER2+. ER/PR data was available on all cases, HER2 on 60. 72 were treated with mastectomy. All patients underwent axillary staging. Lymph node metastasis was identified in 2 cases (one triple negative, one HER2+). In one case the metastasis measured 0.25 mm, in the other 0.4 mm. Complete axillary dissection performed on both cases demonstrated no additional lymph node involvement. Isolated tumor cells were also identified in 9 cases. 2 cases developed local recurrence following lumpectomy and radiation, both in the ipsilateral breast. One recurred with microinvasive disease, the second with DCIS only. There were no cases of metastatic recurrence and no breast cancer associated deaths. Conclusions: The clinical behavior of microinvasive breast cancer in this series is similar to DCIS. The incidence of lymph node metastasis was low (1.7%) and there were no cases of distant metastasis. Our data supports management of microinvasive breast cancer as a subset of DCIS and suggests that the benefit of routine lymph node sampling is questionable.
Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative prospective cohort study.
Authors: Wang Ange , Kubo Jessica , Luo Juhua , Desai Manisha , Henderson Michael T , Chlebowski Rowan T. , Tindle Hilary , Chen Chu , Manson JoAnn E , Schwartz Ann G. , Cote Michele L , Wactawski-Wende Jean , Gomez Scarlett Lin , Patel Manali I. , Stefanick Marcia L , Wakelee Heather A. 
Published: March 2020

1504 Background: The relationship between both active and passive smoking and lung cancer incidence in post-menopausal women was examined in theWomen’s Health Initiative Observational Study (WHI-OS). Methods: The WHI-OS, a prospective cohort study conducted at 40 U.S. centers, enrolled women ages 50-79 from 1993-1998.Among 93,676 participants, 76,304 women with complete smoking and covariate data comprised the analytic cohort, in which the association of lung cancer incidence with active and passive (childhood, adult home, and work) smoking exposure was studied. Results: Over 10.5 meanyears of follow-up with 901 lung cancer cases, lung cancer incidence was higher in current smokers (HR 13.44, 95% CI 10.80-16.75) and former smokers (HR 4.20, 95% CI 3.48-5.08), compared to never smokers. This relationship was dose-dependent for both current and former smokers. Risk of all lung cancer subtypes, particularly small cell lung cancer (SCLC) and squamous cell carcinoma (SqCC), was higher in smokers. Among never smokers, any passive smoking exposure (HR 0.88, 95% CI 0.52-1.49) and most passive smoking categories did not significantly increase lung cancer risk, compared to no passive exposure; however, passive exposure as an adult at home for >=30 years was associated with increased risk, of borderline significance (HR 1.61, 95% CI 1.00-2.58). Current smokers had an annualized lung cancer incidence rate of 472.9 cases/100,000 person-years, compared to 158.1 for former smokers and 36.2 for never smokers (112.3 overall). Conclusions: To our knowledge, this is the first study to examine both active and passive smoking in relation to lung cancer incidence in a complete prospective cohort of U.S. women. Active smoking is associated with significant increases in incidence of all lung cancer subtypes in post-menopausal women, particularly SCLC and SqCC. Smoking cessation decreases lung cancer risk. Prolonged exposure as an adult at home may be the strongest passive smoking contributor to lung cancer risk in this cohort. The findings support continued need for investment in smoking prevention and cessation, research on passive smoking, and understanding of lung cancer risk factors other than smoking.
MRI volumetric analysis of fibroglandular tissue to assess risk of the spared nipple in BRCA 1/2 patients who are considering prophylactic nipple-sparing mastectomy.
Authors: Baltzer Heather , Alonzo Olivier , Yaffe Martin , Narod Steven , Metcalfe Kelly A. , Warner Ellen , Semple John 
Published: March 2020

1507 Background: Prophylactic nipple sparing mastectomy (NSM) in BRCA 1/2 mutation carriers is an option for risk reduction but is controversial over concern that residual fibroglandular tissue (FGT) with malignant potential remains in the spared nipple. Since the volume of FGT in the nipple has not been formally evaluated, the objective of this study is to measure the residual volume of FGT in the spared nipple at a standard retroareolar margin (5mm) and identify sources of variability, including a greater margin and patient factors. Methods: A segmentation protocol was applied to breast MRIs from 105 consecutive BRCA 1/2patients. The MRI segmentation quantified volumes for total breast and nipple FGT. The nipple FGT volume was determined by setting the retroareolar margin (depth on MRI). The proportion of FGT in the nipple with 5mm retroareolar margin relative to the breast was calculated as the primary outcome and compared to 10mm margins. Associations between the proportion of FGT in the nipple (5mm) and patient characteristics were examined using uni- and multivariable analyses. Effect size was measured where appropriate. Results: At 5mm and 10mm retroareolar thickness, residual FGT comprised 0.24% (0.02-0.9%) and 0.42% (0.0.2-01.2%), respectively, of the total breast FGT (p < 0.001, Cohen d = 0.03). Smaller breast volume, lower BMI and parity (p < 0.001, p < 0.009, p < 0.009 respectively) were predictive of greater proportion of residual FGT on univariate analysis, while breast volume and parity were predictive with multivariate (R2 = 0.28, F = 16.5, p < 0.0005). Conclusions: The proportion of FGT remaining in the spared nipple with a 5mm margin is extremely small, suggesting very little added risk over a skin sparing mastectomy. This proportion may be influenced by breast volume and childbearing. Doubling the retroareolar margin statistically increases the proportion, yet this likely does not translate into a clinically meaningful increase and may support a slightly thicker retroareolar margin. Overall, our findings support safety of the current trend toward increased rates of prophylactic NSM performed in the BRCA 1/2 patient population.
Time-related changes in yield and harms of screening breast MRI.
Authors: Pederson Holly Jane , O'Rourke Colin , Bolden Lauren D , Khan Sobia , Yadav Manisha , Lyons Joanne , Shepardson Laura , Rim Alice , Crowe Joseph P. , Grobmyer Stephen R. 
Published: March 2020

1508 Background: MRI has been accepted as a useful adjunct to screening mammography in high-risk women. Concerns remain over false positive findings, however, and little is known about harms and yield over time. Such information will help women decide about enhanced surveillance. Methods: Of 350 high risk patients offered MRI screening, 320 underwent 757 screens with a 1.5 Tesla magnet from 2008 to 2012 alternating (q 6 mo.) with digital mammography. Data collected included patient characteristics, mammographic density, estimated lifetime risk, and need for additional imaging and/or biopsy. Harms were defined as second look ultrasounds, US or MRI guided core biopsies, surgical biopsies or recommendation for short interval follow up. Estimates of harms over time were modeled by logistic regression. A significance level of 0.05 was used for all testing. Results: Compliance with MRI screening as recommended was 91% with the first MRI, and was not associated with age, race or level of risk. Harms were highest with the first MRI and decreased significantly with subsequent MRIs. Of 59 biopsies, 7 were malignant. Two were found in MRI 1, 3 in MRI 3 and 2 in MRI 4. Women with biopsies resulting from false positive findings were significantly younger (median age 44.5 as compared with 48; p=0.049) and were more likely to have extremely dense breast tissue (36% vs 17%; p=0.028.) Conclusions: This study of highly compliant high risk patients supports the use of MRI as an adjunct to mammography for early detection. The rate of harmful events decreased over time, yet cancer detection did not. This information is critical in counseling women who are considering annual screening breast MRI, particularly younger women and those with dense tissue. [Table: see text]
Chemoprevention of cancer with metformin: A meta-analysis.
Authors: Gandini Sara , Heckman-Stoddard Brandy M. , Puntoni Matteo , Dunn Barbara k , Ford Leslie , Bonanni Bernardo , Szabo Eva , De Censi Andrea 
Published: March 2020

1516 Background: Previous meta-analyses have shown that the anti-diabetic agent metformin is associated with reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models and recent epidemiological studies. Here we update the meta-analyses of observational studies with a focus on confounders and biases. Methods: We identified 47 articles published between 1966 to August 2012 that were related to metformin and cancer incidence or mortality. Study characteristics and outcomes were abstracted for each study that met inclusion criteria. Results: The analysis is based on a total of 32,647 cancer events and 1,198 cancer deaths. Cancer incidence was reduced by 34% (SRR=0.66, 95%CI: 0.42-1.03) in subjects taking metformin compared with other antidiabetic medications. Cancer mortality was reduced by 49% (SRR=0.51, 95%CI: 0.30-0.86). The SRR estimates for liver (SRR=0.40, 95%CI: 0.20-0.80) and lung cancer incidence (SRR=0.87, 95%CI: 0.83-0.93) were significant. Adjustment for BMI and exclusion of studies with time-related biases showed a significant reduction in cancer incidence of 26% (95%CI: 1% to 45%) or 10% (95%CI: 9% to 11%), respectively (Table). Breast cancer was significantly reduced by 24% (95%CI: 7% to 38%) in BMI-adjusted studies and the reduction remains significant in prospective studies and in studies without time-related biases. Conclusions: Metformin is a promising agent for cancer prevention, although it may not benefit all populations equally. Clinical trials are needed to determine if the observations seen in diabetic populations apply to pre-diabetic or non-diabetic populations and to optimize the benefit/risk ratio. [Table: see text]
Second malignant neoplasms (SMN) in Cowden syndrome patients with underlying germline PTEN mutations.
Authors: Ngeow Joanne YY , Mester Jessica , Mahdi Haider , Yehia Lamis , Barnholtz-Sloan Jill , Eng Charis 
Published: March 2020

1527 Background: Cowden syndrome (CS) patients with underlying germline PTEN mutations are at significantly increased risks of breast, thyroid, endometrial and renal cancers. Current estimates of lifetime cancer risks do not provide the majority of patients who present after their first cancer a meaningful gauge of their risk of a SMN. Quantification of the risk of a SMN will allow patients to be better informed and provide clinicians a much needed guide to finally address patients’ question of “how likely am I to have a second cancer and will it likely be the same primary?” Methods: We conducted a 5-year, multi-center prospective study of CS and CS-like patients, all of whom had comprehensive PTEN analysis done. Patients’ records were reviewed for prior history of invasive cancers. Invasive SMNs were confirmed by pathology reports or physician reports where possible. All metastatic disease, synchronous primary cancer at the same site and non-melanoma skin cancers were excluded. Incidences of SMNs were compared between patients with pathogenic PTEN mutations (PTENmut+) and wildtype PTEN (PTENwt). Standardized incidence ratios (SIR), cumulative incidences and excess absolute risks for SMNs were calculated comparing against SEER-derived data. Results: Of 2,792 CS/CS-like patients who present with 1 or more cancers, there were 100 (4%) PTENmut+patients. Compared with PTENwt CS/CS-like patients with SMNs (223/2039; 11%), PTENmut+cases (42/100; 42%) were more likely to develop SMNs (p<0.0001). PTENmut+ cases were also younger at median age of SMN diagnosis (48yrs vs 54 yrs; p=0.30). PTENmut+ patients were 56-fold more likely to develop any SMN compared with the general population (95%CI 41-55); corresponding to an excess absolute risk of 731/10000 person years. Breast cancer was the most common SMN encountered in PTENmut+CS/CS-like patients (SIR 73; 95%CI 45-122) followed by endometrial (SIR 44; 95% CI 18-92), renal (SIR 47; 95% CI 15-113) and thyroid cancers (SIR 222; 95% CI 37-734). Conclusions: Our study shows that PTENmut+CS/CS-like patients are significantly more likely to present with a SMN compared to PTENwt CS/CS-like patients and the general population, and should be advised and surveillanced accordingly.
Effect of smoking on survival from non-small cell lung cancer.
Authors: Bhatt Vijaya Raj , Loberiza Fausto R. , Ganti Apar Kishor 
Published: March 2020

1570 Background: Although a well-established risk factor for lung cancer, the impact of smoking on the survival of non-small cell lung cancer (NSCLC) is not well-known. This study evaluated the effects of tobacco exposure on outcomes from NSCLC. Methods: We performed a retrospective analysis of Veteran’s Affairs Comprehensive Cancer Registry of NSCLC patients diagnosed between 1995 and 2009. Data abstracted included age, gender, family history, stage at diagnosis, histology, tumor grade, smoking history, other exposures, treatment received and overall survival (OS). Smoking status was categorized as never-smoker, past-smoker and current-smoker based on the self-reported history at diagnosis. Multivariate analysis was performed using SAS version 10.2. Results: The study population (n=61,440) comprised predominantly of males (98%), of which Caucasians (81%) formed the majority. The median age at diagnosis within this cohort was 68 years (range: 22-108 years) and median follow-up was 6 months (range: <1 – 161 months). Squamous cell carcinoma (35%) and adenocarcinoma (30%) were the most common histologies. The majority (71%) presented with stage III or IV disease. Positive family history was identified in one-third. Current smokers were diagnosed with NSCLC at a younger age (65 yrs) compared to never-smokers (71 yrs) and past-smokers (72 yrs) (p<0.001). After adjusting for age at diagnosis, grade, histology, family history and treatment, current-smokers (n=34613) [Hazard ratio (HR) 1.059; 95% CI, 1.012-1.108], but not past-smokers (n=23864) (HR 1.008; 95% CI, 0.962-1.056), had worse OS for Stage III and IV NSCLC, compared to never-smokers (n=2963). Smoking status was not prognostic in stage I and II NSCLC. Conclusions: Current smokers were 6 years younger than never-smokers at diagnosis of NSCLC. Although current smoking was associated with worse prognosis, especially in stages III and IV, the impact of smoking status on OS was modest, at least in males. Therefore, primary prevention of smoking cessation is more likely to be meaningful than efforts on smoking cessation after the diagnosis of NSCLC.
The impact of body mass index on survival in stage 3 and 4 lung cancer.
Authors: Wong Kit Man , Cuffe Sinead , Coate Linda E. , Espin-Garcia Osvaldo , Boyd Kevin , Feld Ronald , Leighl Natasha B. , Shepherd Frances A. , Xu Wei , Liu Geoffrey 
Published: March 2020

1579 Background: Obesity is an adverse prognostic factor in several cancers, including colorectal, breast, endometrial and prostate. Studies on body mass index (BMI) and lung cancer outcomes are lacking. Understanding the clinical impact of body weight is important given the high prevalence of obesity globally. We retrospectively evaluated the BMI at diagnosis and its effects on survival in stage 3/4 lung cancer patients. Methods: 1,121 patients with stage 3/4 lung cancer were analyzed. Clinicopathologic data were collected retrospectively. Adjusted hazard ratios (aHR) for overall survival (OS) were generated by Cox regression for each BMI (kg/m2) category (underweight: <18.5, normal: 18.5-24.9, overweight: 25.0-29.9, obese: ≥30), after adjusting for age, gender, Charlson Comorbidity Index, performance status (PS), clinical stage and treatment regimen. Results: In this cohort (n=1,121), the frequencies of stage 3A, 3B and 4 lung cancers were 35%, 32% and 33%, respectively. There were 633 (57%) adenocarcinomas, 238 (21%) squamous cell carcinomas, 38 (3%) small cell lung cancers, and 210 (19%) other histologies. Patients had variable BMI: 82 (7%) underweight, 550 (49%) normal weight, 333 (30%) overweight, 156 (14%) obese. Being overweight/obese was associated with older age (p=0.002) and stage 3A disease (p=0.001); underweight patients were more likely current smokers (p<0.001). OS was significantly decreased with age ≥65, males, PS 2-3, stage 4, and lack of systemic therapy (p<0.001). Median OS in underweight, normal weight, overweight and obese patients were 14, 23, 24 and 26 months, respectively. Compared with BMI≥18.5, being underweight was associated with poorer OS (aHR 1.33, 95% CI 1.01-1.77, p=0.045), but not progression-free survival (aHR 1.12, 95% CI 0.86-1.46, p=0.414). The magnitude of this association was greatest in those aged <65 (aHR 1.57, 95% CI 1.11-2.22, p=0.011). Conclusions: Underweight patients with stage 3/4 lung cancer, especially if aged <65, have significantly poorer OS. Lower BMI was mostly observed in current smokers, while above normal BMI was seen in stage 3A. Unlike other cancers, obesity does not increase mortality in this population. The inverse BMI-survival relationship in lung cancer requires further study.
Comparison of adenocarcinoma (ACA) and squamous cell carcinoma (SCC) of the uterine cervix: A population-based epidemiologic study of 60,000 women in Brazil.
Authors: Rodrigues Angelica Noguelra , Thuler Luiz Claudio Santos , Bergmann Anke , Aguiar Suzana Sales de , Ferreira Carlos Gil Moreira 
Published: March 2020

1587 Background: Most cancers of the uterine cervix are SCC, but the relative and absolute incidence of ACA has risen in recent years, particularly in younger patients, and ACA now accounts for about 20% of invasive cervical cancers in screened populations worldwide. However, the developing world, with sub-optimally screened women, accounts for more than 80% of incident cervical cancers. Our objective was to compare epidemiological, clinical characteristics, and treatment outcome of ACA with those of SCC of the cervix, with respect to ethnic group, age and stage at diagnosis, and pattern of response to first treatment in a sub-optimally screened population. Methods: Data of cervical cancer patients with SCC and ACA (adenosquamous + adenocarcinoma) treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer Register databases. Summary odds ratios and chi-square tests were estimated. Results: A total of 60,883 patients were analyzed: 54,425 (89.4%) cases of SCC, and 6,458 (10.6%) of ACA. Compared to ACA, the SCC cohort were younger (49.37 x 51.83 years, p<0.001), more frequently black (58.1% x 49.2%, p<0.001), presented higher degree of illiteracy (22.7 x 16.1%, p<0.001), and alcohol (13 x 9.8%, p<0.001) and tobacco dependence (41.5 x 31%, p<0.001). Tumor stage at the time of diagnosis was also significantly different (p<0.01). Considering prognostic factors, in both subtypes, more than 60% of the patients were stage II or inferior and ACA was associated with a significantly increased risk of inadequate response after the first course of treatment (crude OR=1.14 CI95%=1.07-1.21; adjusted OR=0.94 CI95%=0.87-1.01) and of death (crude OR=1.26 CI95%=1.15-1.38; adjusted OR=1.1 CI95%=1.00-1.23). Conclusions: Differences between ACA and SCC were found in age at diagnosis, extent of disease and ethnic distribution. In spite of these differences, the inadequate response to treatment seems to be mainly the result of more advanced stage, rather than cell type. Screening strategies with higher sensitivity are necessary, and irrespectively of histological subtype, quality of treatment must be improved in developing countries.