tbuckley/cabot-search huggingface dataset:
Presentation of breast cancer in young women
Authors: K. J. Ruddy, S. Gelber, R. Tamimi, L. Schapira, S. Come, S. Kereakoglow, N. U. Lin, E. P. Winer, A. H. Partridge
Journal: Journal of Clinical Oncology (2009)

6608 Background: Current guidelines for early detection of breast cancer do not adequately address diagnosis in young women. Furthermore, a lower suspicion for malignancy in this population may cause diagnostic delays. It is unknown how much the lack of routine screening and potential diagnostic delays contribute to the poorer outcomes of younger women. Methods: We surveyed women age &lt;40 with recently diagnosed breast cancer in a prospective multicenter cohort study started in late 2006. We evaluated initial sign/symptom of cancer, time to first seeking medical attention, time from seeking medical attention to diagnosis, and patient factors associated with delays of &gt;30 days in either timeframe. Chi square and Fisher's Exact tests were used to compare those with and without delays. Results: The first 222 women enrolled in the cohort are included in this analysis. Median age at diagnosis was 36 years (range 17–40). 79% of women initially identified their cancers through breast self exam. Only 6% were initially identified by clinical breast exam, 14% by breast imaging, 1% by systemic symptoms. While the median time between initial sign and seeking medical attention was 10 days (range 0–3,600), 54 women had &gt;30 days between initial sign and medical attention (median 102, range 44–3,600). Similarly, median time from seeking medical attention to diagnosis was 21 days (range 0–2,970), yet 59 women had &gt;30 days from attention to diagnosis (median 70, range 33–2,970). Preliminary comparison of women with and without delays did not reveal significant differences in age, race, education, marital status, or gravidity. Analyses will be updated and psychosocial factors, tumor subtype, and stage at diagnosis will be evaluated. Conclusions: In this large modern cohort of young women with breast cancer, nearly 80% presented with a self-detected breast abnormality, and most were diagnosed soon after they developed a sign/symptom. However, nearly 25% delayed seeking medical attention and 25% experienced a delay in diagnosis after seeking medical attention. Further research is warranted to compare delays between younger and older women, to evaluate delays in more diverse populations, to explore predictors of delays, and to assess for prognostic implications of delays in order to improve outcomes in young women. No significant financial relationships to disclose.
Thromboembolic events (TEE) in UK NCRI Adjuvant Breast Cancer (ABC) international trial –retrospective and prospective audits
Authors: A. N. Harnett, J. M. Bliss, L. Johnson, D. Lawrence, V. Raina, A. Robinson
Journal: Journal of Clinical Oncology (2004)

666 Background: In 1996, NCIC (Pritchard et al JCO 1996:14;2731) reported a high incidence of TEEs in postmenopausal breast cancer (BC) patients receiving concurrent tamoxifen (T) and chemotherapy (CT) compared with T alone (13.6% vs. 2.6%). For trials open to recruitment at that time, including the ABC Trial, this triggered a need for urgent review. Methods: The ABC trial is a pragmatic, randomised phase III trial which accrued 3854 patients between 1993 and 2000. One aspect of ABC compares CT (any type but CMF recommended) vs. none in patients with early BC. All patients were prescribed 20mg T for 5 years. In Oct '97 a retrospective audit of TEEs was carried out on UK patients randomised before 30 Sept '96 and a prospective audit initiated for all patients entered after 1 Jul '97. Time period of interest was date of surgery to 18 months. Analyses focused on TEE before BC relapse. Results: Retrospectively, 59/1222 (4.8%) patients had TEE (16 with more than 1 TEE, 51 within 12 months, 8 after BC relapse/2nd primary, 14 superficial phlebitis). A higher rate of TEEs occurred in CT patients, significant only in postmenopausal patients, (7.7% vs 1.8%; difference 5.9% (95%CI 2.0–9.8%)). 2 patients died due to PE (1 with CT). Prospectively, 46/1420 (3.2%) patients had TEE (4 with more than 1 TEE, 39 within 12 months, 4 after BC relapse/2nd primary, 8 superficial phlebitis). Again, a higher rate of TEEs occurred in CT patients, significant in both pre (5.5% vs. 0%; difference 5.5% (95%CI 0.2–10.8%)) and postmenopausal patients (7.2% vs. 0.4%; difference 6.8% (95%CI 3.5–10.2%)). 4 patients died - 3 due to PE and 1 MI (4 with CT). Rates of TEE were similar according to type of CT (CMF 5.0%, anthracycline containing 5.0%). Conclusions: Incidence of TEEs is increased by concurrent CT and T compared with T alone, but rates are lower than NCIC trial. No evidence of excess TEEs in patients treated with anthracyclines. In our opinion it is unlikely that the number of TEEs will differ following recent changes in practice to sequential chemo-endocrine therapy. No significant financial relationships to disclose.
Pleural fluid cell-free dna integrity index and mesothelin to identify cytologically negative malignant pleural effusions including mesotheliomas
Authors: K. B. Sriram, Relan, B. E. Clarke, E. E. Duhig, M. N. Windsor, K. S. Matar, R. Naidoo, L. Passmore, E. McCaul, D. Courtney, I. A. Yang, R. Bowman, K. M. Fong
Journal: Journal of Thoracic Oncology (2012)
Phase I trial of cisplatin (CDDP), docetaxel (TXT) and CPT-11 in patients (p) with advanced esophagogastric cancer: Feasibility and activity related to XPD and UGT1A1 gene polymorphisms
Authors: A. Font, J. Maurel, R. Salazar, J. L. Ramirez, M. Botia, E. Casado, R. Gallego, L. Manos, J. L. Tisaire, M. Taron
Journal: Journal of Clinical Oncology (2005)

4043 Background: The purpose of this study was to determine the maximum tolerated dose (MTD) of CDDP/TXT/CPT-11 in p with advanced esophagogastric cancer. XPD and UGT1A1 polymorphisms were also analyzed to examine their relationship with the tolerance and activity of this triplet. The XPD heterozygotes Lys751Gln and Asp312Asn have been linked to lower DNA repair capacity and better outcome with cisplatin-based regimens. UGT1A1*28 polymorphisms can determine toxicity and activity of CPT-11 by decreasing SN-38 inactivation Methods: We assessed XPD and UGT1A1 polymorphisms in blood samples of chemotherapy-naïve p with advanced esophageal and gastric cancer treated in a phase I dose-escalation study with CDDP (60 mg/m2 d1), TXT (25–30 mg/m2 d 1&8), CPT-11 (50–70 mg/m2 d1&8) every 3 weeks Results: 27 p were included: median age 59 years; 24 males; 74% Karnofsky index > 80%; esophagus: 8 p, G-E junction: 5 p, gastric: 14 p; 16 p (60%) had liver metastases. MTD was reached at level III (CDDP:60 d1, TXT 30 d1&8, CPT-11 60 d1&8). 3 of 4 p had febrile neutropenia, asthenia G3 and diarrhea G4. Recommended dose (RD) was established at level II (CDDP:60 d1, TXT 25 d1&8, CPT-11:60 d1&8). An additional cohort of 9 p was treated at the RD level. Objective response was observed in 14 of 25 patients (56%) with measurable disease (4 CR, 10 PR). Median survival is 14 months (95%C.I, 5.4–22.5). Frequencies of XPD polymorphisms: 9 Lys751Lys, 16 Lys751Gln, 2 Gln751Gln, 10 Asp312Asp, 14 Asp312Asn, 3 Asn312Asn. No differences in survival were observed according to XPD polymorphisms. Median survival was not reached in 15 p heterozygous for UGT1A1*28 genotype, compared to 9 months in 12 p with wild-type UGT1A1 (P=0.07). 8 of 15 p (53%) with UGT1A1*28 genotype had grade 3–4 toxicity, compared to 4 of 12 p (33%) with wild-type UGT1A1 (P=0.25). Conclusions: CDDP/TXT/CPT-11 is a feasible regimen with a promising activity. Patients with UGT1A1*28 genotype showed a tendency towards higher toxicity but with improved survival benefit. No significant financial relationships to disclose.
Recurrence Score and Quantitative Er Expression Predicts Late Distant Recurrence Risk in Er+ Bc After Five Years of Tamoxifen
Authors: T. Mamounas, N. Wolmark, F. Baehner, S. Butler, G. Tang, F. Jamshidian, A. Sing, S. Shak, S. Paik
Journal: Annals of Oncology (2014)
Oxaliplatin and capecitabine (XELOX) as first-line therapy for metastatic or relapsed squamous cell carcinoma of the head and neck
Authors: O. E. Silva, K. Tolba, N. Farfan, M. Karr, C. Calfa, L. E. Raez
Journal: Journal of Clinical Oncology (2007)

16524 Background: Prognosis is very poor when patients with head and neck (H/N) squamous cell carcinomas (SQCC) present with systemic metastasis or disease relapse after primary therapy. (Survival less than 6 months despite palliative therapy). Capecitabine (Xe) is a rationally designed, oral, tumor-selective fluoropyrimidine that mimics continuous 5-FU infusion. Oxaliplatin (Ox) is an alkylating agent that is not generally cross-resistant to cisplatin or carboplatin, and it was shown to be more effective that cisplatin and with increase the antitumor activity of 5-FU in tumor models. Methods: The objective of this study was to determine the safety and efficacy of this new combination (XELOX) for pts with H/N SQCC. Based in two phase I studies with solid tumors we choose the combination of Ox: 130mg/m2 IV day 1, and Xe: 850 mg/m2 PO BID day 2 to 15 every 21 days. Pts were treated until there is disease progression or received a maximum of 6 cycles. All pts had metastatic or relapsed H/N SQCC and they had not received chemotherapy yet for their metastatic or relapsed disease. Results: We have enrolled 16 pts. The enrollment was slower than predicted because several patients that were elegible were not enrolled because they were not able to swallow Xe due to the presence of feeding tubes. The median age was 61 years (range 46–78), most of them were males (10/16), smokers (13/16), whites (13/16), with ECOG PS 1 (11/16), and with Hispanic heritage (10/16). Eleven of them had metastasis to the lungs already and most of the pts had already received chemotherapy (9/16) or radiation therapy (14/16) during the initial therapy. Two pts withdraw consent and were not treated. From the 14 eligible pts to asses response we had 2 partial responses and 6 disease stabilizations. From 47 cycles administered we have seen few grade ¾ adverse (all of them less 10%) events including: leucopenia, hyponatremia, hoarseness, hyperglycemia, depression, and respiratory failure. Two pts reported grade 3 tumor pain. Conclusion: This study shows that the XELOX combination is probably safe and might be effective in the palliative therapy of patients with relapsed or metastatic SQCC of the H/N with these poor prognostic features. No significant financial relationships to disclose.
Bortezomib reinduction therapy to improve response rates in pediatric ALL in first relapse: A Children’s Oncology Group (COG) study (AALL07P1).
Authors: Terzah M. Horton, Xiaomin Lu, Maureen Megan O'Brien, Michael J. Borowitz, Meenakshi Devidas, Elizabeth A. Raetz, Patrick Andrew Brown, Hui Zeng, Hao W. Zheng, Stephen Hunger, James Whitlock
Journal: Journal of Clinical Oncology (2013)

10003 Background: Bortezomib (bortez) is a reversible inhibitor of the 26S proteasome. Promising results have been reported adding bortezomib to reinduction chemotherapy in patients (pts) with ALL in 2 nd or later relapse (Messinger, Blood 2012). Methods: This was a phase 2 study of bortez with reinduction chemotherapy in 1 st relapse pediatric ALL that enrolled pts with pre-B ALL (relapse &lt;36 months (m) from diagnosis). This report summarizes results from 61 evaluable pre-B ALL pts ≤21 yrs old, either &lt;18m (stratum 1) or 18-36m (stratum 2) from diagnosis. Therapy consisted of bortez (1.3 mg/m 2 , days 1, 4, 8, and 11) with reinduction chemotherapy (vincristine, prednisone, PEG-asparaginase, doxorubicin). Complete response (CR2) rates and minimal residual disease (MRD) were determined at the end of the first 5-week therapy block. AALL07P1 utilized a stratified 2-stage design (London 2005) with the primary objective of comparing CR2 rates at the end of block 1 of therapy to historical control CR2 rates (AALL01P2). Block 2 included cyclophosphamide, etoposide, and bortez followed by 5g/m 2 methotrexate. Biology studies included assessment of NF-κB activity. Results: 61 evaluable pre-B ALL pts were assessed. Toxicities were similar to AALL01P2, including 10 Grade 3- 4 hypotension, 4 Grade 4 hypertriglyceridemia, 3 Grade 3-4 typhlitis, and 2 Grade 3-4 enterocolitis. There were 2 deaths due to infection. Although Grade 3-4 infections were not infrequent (13 in block 1 and 7 in block 2) there were no reports of respiratory distress syndrome or Grade 4 peripheral neuropathy. 42 of the 61 patients enrolled (18/28 (64%) in Stratum 1 and 24/33 (73%) in stratum 2) attained CR2 at the end of Induction I. Based on CR2 response rate compared to historical controls, the study met its primary response objective. The number of pts in CR2 with MRD &lt;0.1% also improved from AALL01P2; among pts achieving CR2, MRD was &lt;0.1% in 41% (16/39) in AALL01P2 vs. 71% (25/35) (p= 0.073, Fisher’s exact test). Conclusions: Based on response rates in the very early and early first relapse pre-B ALL, AALL07P1 met its predefined efficacy benchmark. We conclude that bortezomib is worthy of further study in pediatric ALL. Clinical trial information: NCT00873093.
Daily concurrent preoperative chemoradiotherapy with docetaxel (D) and cisplatin (C) using new superselective intra-arterial infusion via superficial temporal artery (HFT method) for stage III, IV head and neck cancer
Authors: I. Tohnai, N. Fuwa, K. Mitsudo, T. Shigetomi, T. Fukui, N. Yamamoto, M. Ueda, S. Yanagawa, T. Ishigaki
Journal: Journal of Clinical Oncology (2005)

5567 Background: Recently, combined radiotherapy and intra-arterial chemotherapy using the Seldinger method was performed for head and neck cancers. However, chemotherapy and radiotherapy cannot be performed simultaneously on a daily basis because long-term catheterization is not possible. Therefore, we developed a new method of superselective intra-arterial infusion via the superficial temporal artery (HFT method reported by Hattori, Fuwa and Tohnai) and preoperatively performed daily concurrent radiotherapy and chemotherapy with D and C using this method for stage III, IV head and neck cancer. Methods: Forty-one patients with stage III, IV oral cancer were treated. A new catheter was prepared by modifying an angiographic catheter measuring 1.35 mm in diameter. This was inserted superselectively into the feeding artery of the tumor via the superficial temporal artery using a guide wire. Long-term catheterization is possible with this method. Radiotherapy (total dose: 40 Gy) and superselective intra-arterial infusion chemotherapy using D (total dose: 60 mg/m2) and C (total dose: 100 mg/m2) were concurrently performed daily, followed by surgery. Results: In 35 patients, intra-arterial infusion was successful, but 6 intra-arterial infusions were not successful due to arterial anomalies. Toxicities in excess of grade 3 were leukopenia of 8.6%, thrombocytopenia of 2.9%, mucositis of 20.0%, and dermatitis of 14.3%. No infection was associated with catheterization and no major complications were observed. The clinical effects were CR in 29 (82.9%) patients and PR in 6 (17.1%). Pathological effects of resected tumor after surgery were pathological CR in 31 (88.6%) patients and pathological PR in 4 (11.4%). The 5-year cumulative survival rate (overall rate) was 78.8%. This rate is higher than the rate associated with conventional therapy. Conclusions: Unlike the Seldinger method, superselective intra-arterial infusion allows for long-term catheterization and thus daily concurrent chemoradiotherapy can be performed. This method holds promise for treating stage III, IV head and neck cancer. No significant financial relationships to disclose.
Mouse prostate tumor inhibition via disruption of murine telomerase: In vivo and in vitro data for a new preclinical cancer model
Authors: T. Xu, Y. Xu, R. Lao, K. He, L. Xue, A. Goldkorn
Journal: Journal of Clinical Oncology (2009)

e14631 Background: Telomerase-interference (TI), a novel therapeutic strategy, exploits the high telomerase activity in prostate cancer by introducing a mutated telomerase RNA (MT-Ter) that encodes toxic telomeres. Until now, TI has been tested by targeting human telomerase in tumor cells xenografted into immuno-deficient mice, an inadequate model for predicting efficacy and toxicity. We designed and validated 2 new TI gene constructs that specifically target murine telomerase RNA (mTER), enabling the study of TI in preclinical mouse models that are immuno-competent and that develop endogenous prostate tumors. Methods: We designed 2 constructs and cloned them into a lentiviral delivery system: MT-mTER and siRNA against wild type mTer (α-mTer-siRNA). Using a mouse prostate cancer cell line, E4, we tested the 2 constructs for expression (RT-PCR), telomerase activity (TRAP), and biologic activity (53bp1 DNA damage staining, MTS growth assay, TUNEL and caspase apoptosis assays), as well as in vivo efficacy (NOD-SCID allografts). Results: We confirmed MT-mTER expression (∼50-fold) and showed that α-mTer-siRNA specifically depleted WT-mTER (80% reduction) but not MT-mTER when the 2 constructs are co-expressed; thus, the 2 constructs in combination effectively substituted MT-mTer for WT-mTer in the mouse prostate cancer cells. MT-mTER caused mutant telomeric repeats (TTTGGG instead of TTAGGG) to be added to the ends of telomeres, resulting in rapid telomeric uncapping marked by 53bp1 DNA damage foci (an average 7.5 foci/cell vs. 1.4 foci/cell in vector control). This, in turn, led to rapid and significant apoptosis (&gt;90% TUNEL and caspase +) and growth inhibition in vitro (90% reduction by MTS) and in vivo (75% reduction in tumor allograft size). Conclusions: We successfully designed and validated MT-mTer and α-mTer-siRNA, 2 novel gene constructs that specifically target and co-opt murine telomerase activity within mouse prostate cancer cells. These constructs offer a significant advantage, as they can be used to investigate TI in immuno-competent mice that develop prostate cancer, thereby modeling actual human disease and testing TI-based therapies in a much more informative and authentic manner. No significant financial relationships to disclose.
Effectiveness of bevacizumab (BV) beyond disease progression in metastatic colorectal cancer (mCRC): Analyses by sex in the ARIES observational cohort study (OCS).
Authors: Allen Lee Cohn, Herbert Hurwitz, Tanios S. Bekaii-Saab, Johanna C. Bendell, Mark Kozloff, Haluk Tezcan, Elizabeth Dawn Flick, Yong Mun, Susan Fish, Darshan Dalal, Axel Grothey
Journal: Journal of Clinical Oncology (2013)

514 Background: Randomized trials and OCSs have demonstrated that BV treatment in 1st-line (1L), in 2L, and across multiple lines is associated with longer survival in patients (pts) with mCRC. This analysis was aimed at comparing the effectiveness of BV after 1st disease progression (PD) between male and female mCRC pts who received 1L BV-containing therapy in a real-world setting. Methods: ARIES is a large, prospective OCS that enrolled pts who received BV and chemotherapy (CT) for 1L mCRC. Post-PD effectiveness was assessed for men and women characterizing BV use by cumulative and dichotomous approaches. The primary analysis treated BV exposure as cumulative BV doses after 1st PD and post-progression overall survival (ppOS) as the time from 1st PD to death. A time-dependent Cox regression model was fitted to assess the effect of cumulative BV exposure on ppOS, while controlling for potential confounders. A dichotomous secondary analysis characterized BV exposure as receipt of CT + BV (BBP) or CT alone (No BBP) within 2 months after PD and ppOS as time from 1st PD + 2 months to death. Results: Among the 1,550 1L mCRC pts enrolled, 1,199 (532 women) had PD. In the primary analysis, hazard ratios (HRs) for ppOS decreased, on average, by 1.2% with each additional BV dose. When stratified by sex, the average risk reduction per BV dose over 15 doses was 1.8% in women and 0.7% in men. In the secondary analysis that included 331 women (BBP, 180; No BBP, 151) and 417 men (BBP, 245, No BBP, 172) who received BV ± CT within 2 months post-PD, the HRs for ppOS with BBP treatment were 0.46 (95% CI, 0.35–0.59) in women and 0.52 (95% CI, 0.41–0.67) in men. Statistical interaction tests for differences in the effectiveness of BV between men and women were negative for primary and secondary analyses (P of 0.58 and 0.77). Protocol-specified adverse events occurred in 17.8% of women and 10.2% of men in the BBP population; this difference was largely related to rates of hypertension (8.3% vs 2.4%, respectively). Conclusions: In ARIES, the effectiveness of BV after first PD was not statistically different between women and men with mCRC. Clinical trial information: NCT00388206.
The present and the future of breast cancer burden in the Kingdom of Saudi Arabia
Authors: E. M. Ibrahim, A. M. Zeeneldin, B. Bin Sadiq
Journal: Journal of Clinical Oncology (2008)

22089 Background: Despite the low cancer incidence in the Kingdom of Saudi Arabia (KSA), the country must be ready to face the challenge of foreseeable increase in cancer burden attributed to growth and aging of population. This work designed to study female breast cancer as a model to assess future cancer burden and the impact on healthcare resources. Methods: Cancer statistics for the KSA were compared with that for the USA. The Joinpoint regression program was used to identify changes in secular trends, while the GLOBOCAN 2002 software projected future incidence and mortality. Results: In the KSA, the age-standardized cancer rate (ASR) is 61 per 100,000 population, while the median age at diagnosis is 54 and 49 years for men and women, respectively. Fitting the ASR for breast cancer did not show any significant trend over a ten-year calendar period (16.2 to 18.2 per 100,000), a pattern that was similar to that for the USA in the pre screening mammography era. Considering the growth and aging of population and using conservative estimates for the annual percent change in incidence (increase) and mortality (decrease) by 2025, incidence and mortality cases are expected to increase by about 350% and 160%, respectively. Conclusions: In developing countries, future cancer rates could demonstrate a considerable increase and enormous demands on healthcare resources. The present work may provide an impetus to study other prevalent cancer types particularly in developing countries. No significant financial relationships to disclose.