bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of cancer screening practices after BRCA testing in Michigan.
Authors: Zenger Hain Julie , Mange Sarah , Bach Janice , Duquette Debra , McLosky Jennifer , Dohany Lindsay , Roberson Jacquelyn , Biro Katie , Petrucelli Nancie , Iacoboni Daniela , Ahsan Samira , Merajver Sofia , Milliron Kara J. , Everett Jessica , Zakalik Dana 
Published: March 2020

1557 Background: Women who harbor BRCA1/2 mutations are at increased risk for breast and ovarian cancer and are advised to undergo high risk surveillance and/or preventative surgery. The compliance with screening guidelines in these women is not well known. This study aims to evaluate the uptake and screening practices of women with known deleterious BRCA mutations and BRCA true negatives who received genetic counseling in the state of Michigan. Methods: A telephone survey coordinated by the Michigan Department of Community Health was conducted on pts seen at 8 genetics clinics between 10/07 to 10/09. Each center was staffed by board certified genetics professionals who provided pre and post-test genetic counseling. Pts who were found to carry a deleterious BRCA mutation, or to be negative for a known familial mutation, were queried regarding adherence to NCCN guidelines. Results: 138 of 253 (55%) pts responded to the phone survey, with an elapsed time of 1.7 to 4.6 years from post-test counseling session. Among BRCA mutation carriers over age 25 years with no cancer history or mastectomy, 11 of 21 pts (52%) adhered to MRI screening guidelines, 3 pts (14%) reported two MRIs, and 7 (33%) pts had no MRI screening in the preceding year. 18 of 21 pts (86%) reported having a screening mammogram in the preceding year and the remaining 3 had two or more. 8 of 20 (40%) pts had two clinical breast exams. Of the women who had breast cancer and no mastectomy, 5 of 9 (56%) pts did not have MRI screening. Of the BRCA true negatives with no cancer history, CA-125 or transvaginal ultrasound was performed in 7 (19%) and 8 (20%) of 37 pts, respectively. Conclusions: This study reveals sub-optional compliance with screening guidelines in women who were identified to be carriers of BRCA mutations or those who were true negatives, despite pre and post-test genetic counseling and communication of established management guidelines. Some recommended screening measures were under-utilized in BRCA mutation carriers, and some were over-utilized in the true negatives. Additional interventions are needed to improve adherence to evidence-based screening guidelines aimed at promoting early detection, with an emphasis on appropriate utilization of limited healthcare resources.
Occurrence of familial malignant tumors in the first-degree relatives of patients with differentiated (non-medullar) thyroid carcinoma.
Authors: Mindruta-Stratan Rodica , Belev Nicodim F. , Sturgis Erich M. , Xu Li 
Published: March 2020

1567 Background: Family aggregation of thyroid cancer and aggregation of a number of "associated" malignant tumors in one family indicates a possible significant genetic predisposition and an increased risk for developing cancer in blood relatives of these families. Methods: Distribution of malignant tumors in first degree relatives of 1135 patients surgically treated for thyroid tumors during 3 years period was studied. These families don’t refer to hereditary syndromes. Patients were distributed in 3 groups: I group - 453 patients with thyroid carcinoma, II group - thyroid carcinoma on adenoma background (222) and III group - thyroid gland adenoma (460 probands). Results: In the I-st group from 2868 first degree relatives 870(64, 5±1.6%) was affected by cancer. From these: 49(3.9±2.8%) had thyroid cancer (TC), 39(3.1±2.8%) - gastric cancer (GC), 36(2.8±2.7%) - colorectal cancer (CRC), 26(2.05±2, 8%) - breast cancer (BC) and 20(1.6±2.8%) - endometrial cancer (EC). Thyroid adenoma was seen in 86(6, 6%) cases. Incidence of the TC was 23, GC- 11, CRC-5, and BC- 4, EC 12 times higher, respectively in compare with general population. From 1414 relatives (II group) 445(66, 1±2.2%) first degree relatives were affected by cancer. From these: 27(4.3±3.9%) - TC, 22(3.5±4.0%) - GC, 21(3.3±3.9%) - CRC, 14(2.2±4.1%) – BC and 5(0.8%) - EC. Thyroid adenoma was seen in 45(6.9±3.7%) cases. In III group - from 2945 investigated first degree relatives 924(66.6±1.5%) relatives were affected by cancer. From these: 44(3.4±2.7%) - TC, 37(2, 8±2.7%) - GC, 27(2.1±2.8%) - CRC, 34(2.6±2.7%) – BC and 19(1.5±2.8%) - EC. Thyroid adenoma represented 116(8, 6±2.6%) cases. Differences between groups are not statistically significant (p <0,05). Conclusions: The results obtained by clinical and genetic research of non-medullar thyroid cancer patients and their first degree relatives are an important reason to direct the monitoring of these families for the risk assessment of hereditary predisposition to cancer, genetic testing, dynamic monitoring and performing of preventive interventions.
Clinical factors affecting HE4 and CA125 in women at high risk of developing ovarian cancer.
Authors: Raamanathan Archana , Holman Laura L. , Urbauer Diana L , Baggerly Keith A. , Shen Yu , Bast Robert C. , Lu Karen H. 
Published: March 2020

1569 Background: CA125 is often used to screen high-risk patients (pts) for ovarian cancer (OC), but levels are affected by many factors, especially in premenopausal pts. In prior studies of low-risk pts, HE4 is more stable than CA125. The objective of this study was to determine how clinical variables affect CA125 and HE4 in pts at high risk for ovarian cancer. Methods: Serum from 373 pts at high risk of OC was collected every 3-12 mo from 2006-2012, for a total of 1081 samples. Serum CA125 and HE4 were measured in duplicate utilizing a commercially available multiplexed sandwich immunoassay (MagPlex). Multilevel regression models were used to examine the associations of clinical factors with CA125 and HE4, while considering the inter-correlated nature of outcomes measured periodically from the same subject. Results: The mean age was 44.6 years, 51.2% were premenopausal, 72.7% were white, 9.1% were Ashkenazi Jewish, 65.2% had a history of breast cancer, and 81.5% had a BRCA mutation. Log transformed CA125 was found to be 0.32 units higher in premenopausal pts compared to postmenopausal pts (p=0.0023), and 0.27 units higher in pts with active breast cancer (BC) compared to pts with no active BC (p=0.0044). In premenopausal pts, CA125 varied throughout the menstrual cycle, with highest levels noted at menstruation (p<0.0001). Age, smoking status, and hormone use did not affect CA125 levels. Interestingly, there was no significant association between HE4 levels and any of the evaluated variables, including age, menopausal status, active BC, smoking status, hormone use, or point in menstrual cycle (all p>0.05). Conclusions: In women at high-risk for OC, HE4 levels fluctuate less with the menstrual cycle and are less likely to be elevated in BC than CA125. This finding is important as many high-risk pts that undergo screening are pre-menopausal and have a BC history. HE4 may provide a valuable addition to the current screening regimen of high-risk pts.
Adiposity post prophylactic oophorectomy in young women at high risk for breast and ovarian cancer.
Authors: Visvanathan Kala , Huynh Minh-Huy , Al-Lozi Rawan , Oidtman Jessica , May Betty J , Ouyang Pamela 
Published: March 2020

1572 Background: Bilateral prophylactic salpingo-oophorectomy (BPSO) is the current standard of care for BRCA1/2 mutation carriers and women with a strong family history of ovarian cancer. We have previously demonstrated an association between early oophorectomy, adiposity and mortality in the general population. Methods: A cross sectional study was conducted between November 2009 and January 2013 in 87 women with a family history of breast and ovarian cancer and/or BRCA1/2 mutation to identify the effect of early BPSO on multiple health outcomes. Twenty-two women who underwent BPSO within 1 to 5 years of enrollment while premenopausal and not on hormone therapy were compared to 44 premenopausal women with intact ovaries and the same age distribution and 21 postmenopausal women with intact ovaries and not on hormone therapy. Multiple anthropometric measures were taken and % body fat assessed by DEXA scan. Linear regression was used to estimate differences in these measures between the three groups. Results: The mean ages were 47, 47, and 54 years in the BPSO, premenopausal and postmenopausal groups respectively. Parity, alcohol intake, smoking and race did not significantly differ between groups. Fewer BPSO women had ever used oral contraceptives (OCP) compared to the premenopausal group (p =0.05). The BPSO group had lower mean physical activity (p = 0.05) compared to the two other groups. BMI was increased in the BPSO group but was not statistically different across groups. However, mean waist and abdominal circumference and trunk % body fat were significantly higher among women who underwent BPSO compared to both groups. In multivariate analyses adjusting for age, physical activity, and OCP use, the average waist circumference was 7.92 cm (95% CI 1.46, 14.37) higher and 8.98 cm (95% CI 0.40, 17.46) higher in the BPSO group compared to the postmenopausal and premenopausal groups, respectively. A similar pattern was seen for abdominal circumference. Association with % body fat were not statistically significant. Conclusions: This pilot study suggests that increased central adiposity, is a sequelae of BPSO in young women. Longitudinal studies are needed to confirm results and evaluate the efficacy of interventions.
The impact of family information services on genetic testing uptake among relatives in Lynch syndrome families.
Authors: Lynch Henry T. , Buxbaum Sarah G. , Snyder Carrie L. , Stacey Mark , Shaw Trudy G. , Lynch Patrick M. 
Published: March 2020

1573 Background: A mismatch repair (MMR) pathogenic mutation in an index patient provides a basis for predictive mutation testing in at-risk members of Lynch syndrome (LS) families. Mutation carriers warrant aggressive surveillance. As importantly, non-carriers can safely follow general population screening guidelines. However, penetration of predictive testing has been disappointing in first-degree relatives (FDR), and has been even more limited in second- and more distant-degree relatives, even though the benefits can be as great as in FDRs. Family Information Services (FISs), involve an in-person session in which expert providers and counselors meet with multiple family members in a convenient geographical location. Education and counseling are intended to lead to testing for the family MMR mutation, followed by appropriate surveillance. Methods: LS families with a known MMR mutation (n=97) were targeted for this study. Selection for FIS was based on family size and convenient geographic location. Twenty-eight were offered an FIS and 69 received standard care (mailed educational material and invitation for testing). Data were collected on testing rates. Results: In at-risk patients that did receive FIS, 20.4% (std dev = 11.4%, 95% CI: 16.0 to 24.8%, range: 3 to 57.5%) were DNA tested, whereas in families that did not receive FIS, 12.9% (std dev = 10.8%, 95% CI: 10.2 to 15.5%, range: 0 to 43.5%) were DNA tested. The difference in proportions tested between the FIS and non-FIS families was statistically significant (p=0.003) and was more pronounced in family members whose relationship to the proband was beyond first-degree (p<0.0001). Of those individuals that attended an FIS, 81.1% were tested. Conclusions: Genetic counseling in the FIS setting facilitates uptake of predictive mutational testing in FDRs and in more distant at-risk relatives. However, the FIS is time-consuming and labor intensive; more efficient means of disseminating LS risk information and the benefits of predictive testing in more distant relatives are needed. A cost-effectiveness analysis as well as a randomized study that controls for participation bias must be done.
HIV-associated high-risk HPV infection in Nigerian women.
Authors: Akarolo-Anthony Sally Nneoma , Ogbonna Celestine C. , Famooto Oluranti Ayotunde , Dareng Eileen O. , Al-Mujtaba Maryam , Odonye George , Olaniyan Olayinka , Offiong Richard , Lawal Ishak , Wheeler Cosette , Adebamowo Clement Adebayo 
Published: March 2020

1576 Background: The incidence of cervical cancer has remained stable in HIV+ women but the prevalence and multiplicity of high risk HPV (hrHPV) infection, a necessary cause of cervical cancer, appears different comparing HIV+ to HIV- women. Because this has not been well studied in Africa, we conducted this study to identify single and multiple hrHPV infection among HIV+ and HIV- women in Nigeria. Methods: We enrolled HIV+ and HIV- women presenting at our cervical cancer screening program in Abuja, Nigeria between April 2012 and August 2012. Using a nurse administered questionnaire, we collected information on demographic characteristics, risk factors of HPV infection and cervical exfoliated cells samples from all participants. We used Roche Linear Array HPV Genotyping Test to characterize the prevalent HPV according to manufacturer’s instruction and logistic regression models to estimate the association between HIV infection and the risk of high-risk HPV infection. Results: There were 278 participants, 40% (111) of whom were HIV negative, 54% (151) HIV positive and 6% (16) with HIV status unknown. Of these, 108 HIV+ women cases and 149 HIV- women controls were available for analysis. The mean ages (±SD) were 37.6 (±7.7) for HIV+ and 36.6 (±7.9) years for HIV- women (p-value = 0.34). Cases and controls had similar socio-demographic characteristics. Among HIV+ women, HPV35 (8.7%) and HPV56 (7.4%) were the most prevalent hrHPV, while HPV52 and HPV68 (2.8%, each) were the most prevalent among HIV- women. The age adjusted RR for prevalent hrHPV was 4.18 (95% CI 2.05 – 8.49, p-value <0.0001), comparing HIV+ to HIV- women. The multivariate RR for any HPV and multiple hrHPV was 3.75 (95% CI 2.08 – 6.73, p-value 0.01) and 6.6 (95% CI 1.49 – 29.64, p-value 0.01) respectively, comparing HIV+ to HIV- women, adjusted for age, and educational level. Conclusions: HIV infection was associated with increased risk of any HPV, hrHPV and multiple HPV infections. Oncogenic HPV types 35, 52, 56 and 68 may be more important risk factors for cervical pre-cancer and cancer among women in Africa. Polyvalent hrHPV vaccines meant for African populations should protect against HPV types other than 16 and 18.
U.S. Preventive Services Task Force (USPSTF) recommendations on breast cancer screening (BCS): Are they justified?
Authors: Pai Lori H. , Strauss Gary M. 
Published: March 2020

1584 Background: Nine randomized population trials (RPTs) on BCS with mammography have been reported. Conclusions based upon mortality (MOR) comparisons in RPTs have long led to uncertainty about whether BCS saves lives, especially in women in their 40s. In Nov 2009, USPSTF recommended against BCS in women 40-49 and biennial BCS for women >50. By 2010, BCS fell by >4% in US. Does the evidence support USPSTF recommendations? Methods: MOR quantifies the effect of intervention across an entire population. However, the key issue is whether BCS reduces MOR among those with disease. This is reflected by survival (SUR), not MOR. While SUR is considered flawed due to conventional screening biases, the confounding influence of these biases is misunderstood. In a RPT, randomization provides an opportunity to eliminate these biases, so that (SUR) may accurately reflect screening efficacy. MOR would be biased if randomization fails to produce populations at equal risk for the target disease. Results: Among 9 RPTs, significant MOR reductions were reported only in Swedish Two-County Study in women >50 and in the Gothenburg Study in women 39-49. However, problems with randomization were responsible for MOR overestimating BCS efficacy in these trials. In 7 RPTs, significant MOR reductions were not seen. However, MOR underestimated BCS efficacy in several RPTs. The Canadian National BCS Study, the most influential RPT in women <50 yrs, showed a trend toward increased BC MOR in the screened group. However, randomization failure was likely responsible for significantly more high risk BC in the screening group, which confounded MOR comparisons. Conclusions: It’s never been possible to justify BCS based on MOR comparisons in RPTs. While meta-analyses have been widely utilized, they can be biased when MOR fails to accurately reflect BCS in individual RPTs. Abundant evidence from RPTs supports that BCS leads to significant stage and SUR advantages not attributable to conventional biases, and which more accurately reflect BCS efficacy. The magnitude of benefit is similar for women in their 40s and for those >50. USPSTF recommendations are not supported by the data. If fully implemented, these guidelines can lead to increased BC MOR in US.
Androgen deprivation therapy and survival in patients with lung cancer.
Authors: Harlos Craig Henry , Pitz Marshall W. , Musto Grace 
Published: March 2020

1597 Background: The epidemiology of lung cancer differs between men and women. There exists significant evidence suggesting estrogens influence the pathophysiology of lung cancer, however the role of androgens remains unclear. This study was performed to determine if exposure to androgen deprivation therapy (ADT) has an effect on survival in male patients (pts) diagnosed with lung cancer. Methods: Using the population-based Manitoba Cancer Registry and Manitoba Health Administrative Databases, all pts diagnosed with lung cancer from January 1, 2004 to December 31, 2010 were identified. Information from the Drug Program Information Network (DPIN) and the Aria electronic record at CancerCare Manitoba were used to determine prescriptions filled for anti-androgens, 5-alpha reductase inhibitors and GnRH agonists as a measure of exposure (defined as having filled at least 2 prescriptions and/or bilateral orchiectomy). Multivariable analysis with Cox proportional hazards analysis was used to compare survival. Results: A total of 3018 men with lung cancer were identified between 2004 and 2010. Of these, 339 (10%) were identified as having used a form of ADT. The majority of pts received 5-alpha reductase inhibitors (85%), the most common being finasteride (80% of total). Multivariable analysis revealed that patients who received ADT prior to the diagnosis of lung cancer had no statistically significant difference in survival (HR: 0.97 p=0.69) compared to those who did not. Patients exposed to ADT after their diagnosis were found to have a significantly better survival than those not exposed (HR 0.36 p=0.0007). This effect was also seen in those who received ADT before and after diagnosis (HR 0.53 p<0.0001). Conclusions: In male pts diagnosed with lung cancer, exposure to ADT is associated with significantly better survival when compared with no exposure. This effect is only seen when some or all of the exposure has occurred after the diagnosis of lung cancer. This study supports the hypothesis that the androgen pathway plays a role in lung cancer pathophysiology, and that androgen deprivation may improve prognosis
NCCTG (Alliance) N0572: A phase II trial of sorafenib and temsirolimus in recurrent glioblastoma (GBM) patients who progress following prior RT/temozolomide (TMZ) and VEGF inhibitors (VEGFi).
Authors: Jaeckle Kurt A. , Schiff David , Anderson S. Keith , Galanis Evanthia , Stella Philip J. , Flynn Patrick J. , Sarkaria Jann Nagina , Giannini Caterina , Erickson Bradley J. , Buckner Jan C 
Published: March 2020

2014 Background: PFS6 is low (2.3%) and med OS brief (4 mos) for recurrent GBM pts who progress after prior RT/TMZ and bevacizumab (Bev), and then receive non-Bev containing regimens (Reardon et al, Br J Canc 2012). Following VEGFi exposure, tumor cell resistance potentially may result from activation of Ras/Raf/MEK/ERK (MAPK) and PI3K/Akt/mTOR signaling pathways. Temsirolimus (mTOR inhibitor) and sorafenib (Raf, PDGFR, VEGFR inhibitor) have previously shown limited single agent activity in GBM. Methods: Recurrent GBM pts who showed radiographic progression despite prior surgery, RT + temozolomide, and VEGFi (initially or at recurrence) received sorafenib 200 mg PO bid and temsirolimus 20 mg IV weekly (the NCCTG N0572 phase I MTD) until progression. All pts had received < 2 prior chemo regimens. A two-stage design was used, with 90% power to detect an increase in PFS6 from 8% to 23%, requiring 41 evaluable pts. The primary endpoint was PFS6; secondary endpoints included OS, TTP, and ORR. Toxicity (TOX) was assessed using CTC ver 3.0. Results: 44 evaluable pts were accrued. Four of the first 40 (10%) reached PFS6, but this did not meet the pre-study threshold for success. Median TTP was 1.8 mos. (40 events, 95% CI: 1.5 – 2.3); median OS was 5 mos. (36 events, 95% CI: 6.6 – 3.1), and no objective responses were reported. Eight pts are alive; 4 have not progressed (median F/U 3.1 mos.; max, 12.2 mos.). Grade 3+ non-heme AE were observed in 51% (23/45; fatigue-5, hypophosphatemia-7, hypercholesterolemia-5, hypertriglyceridemia-5). One grade 4 hematologic AE (thrombocytopenia) occurred. 13.3% (6/45 pts) went off due to TOX, and 71.1% (32/45) due to disease progression. Conclusions: Sorafenib plus temsirolimus was tolerable, but the primary endpoint threshold for success (PFS6) was not met in post-VEGFi recurrent GBM patients. Nevertheless, PFS6 (10%) and OS (5 mos.) compared favorably to contemporary series of Bev-refractory, recurrent GBM pts who are subsequently treated with a non-Bev containing regimen. Supported by NCI CA-25224. Clinical trial information: NCT00329719.