bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of bone marrow micrometastasis (BMM) in breast cancer patients predicts a poor-prognosis pattern of first distant metastasis: Results from the pooled analysis
Authors: Braun S. , Vogl F. D. , Pantel K. 
Published: March 2020

567 Background: As a putative surrogate marker of ubiquitous distant metastasis, which is assessable both at initial diagnosis of breast cancer and during adjuvant therapy, BMM would be a valuable end-point marker for adjuvant clinical trials. Methods: Based on individual pt data of 4,686 breast cancer pts with a 10-year follow-up (median, 62 months), we analyzed distant disease-free survival (DDFS) of BMM+/BMM− pts, and looked specifically into sites of first metastatic relapse, expressed as bone metastasis-free (BFS), visceral metastasis-free (VFS), and multiple metastasis-free survival (MFS; i.e., simultaneous diagnosis of bone and visceral metastases). We performed Kaplan-Meier analysis and computed incidence rates (IR)/ incidence rate ratios (IRR) for the occurrence of metastasis at different sites. Results: BMM were detected in 1,432 (30.6%) of pts overall and significantly more often in pts with subsequent diagnosis of distant metastasis as compared to those who survived without metastases (48.5% vs. 26.0%, P<0.001). BMM+ pts had a significantly shorter DDFS than BMM- pts (IRR 2.36; 95%CI, 2.07–2.69; P<0.001). This was also true when we analyzed either bone (IRR 2.73; 95%CI, 2.27–3.29; P<0.001) or visceral metastases only (IRR, 2.48; 95%CI, 2.11–2.91; P<0.001). Among 952 pts with occurrence of distant metastasis, IR of such an event was 1.28-fold (95%CI, 1.12–1.46; P<0.001) higher in BMM+ pts than in BMM- pts. Among 462 BMM+ pts (but not among those 490 BMM- pts), IRs for MFS were significantly increased as compared to both VFS (IRR 1.72; 95%CI, 1.36–2.18; P<0.001) and BFS (IRR 1.85; 95%CI 1.21–2.06; P=0.001). IR for BFS of BMM+ patients (1.08; 95%CI 0.87–1.34) was not significantly increased over VFS. Conclusion: Our data provide conclusive evidence that presence of BMM predicts an early onset and a poor prognosis pattern of overt distant metastasis. With the similar likelihood of the occurrence of subsequent metastasis in bone and at visceral sites, BMM appears to be a marker of generalized tumor cell spread. No significant financial relationships to disclose.
Autoimmune hypothyroidism protects against breast cancer development in the elderly
Authors: Sandhu M. , Zagorski B. , Sykora K. , Booth G. , Brezden-Masley C. 
Published: March 2020

588 Background: An association between breast cancer and autoimmune hypothyroidism has been suggested. While a biological role for thyroid hormone in breast tumorigenesis has been demonstrated in vitro, epidemiological evidence is lacking. Methods: A retrospective, population-based cohort study was conducted to examine the risk of postmenopausal breast cancer (BRCA) in women with or without autoimmune hypothyroidism, identified on the basis of prescriptions for levothyroxine (LT4). Administrative health records were used to capture information on all women aged 66 and older living in Ontario, Canada at baseline (April 1, 1993 to March 31, 1996) and during a 10-year follow up. Propensity scores were used to create a matched cohort of LT4 and non-LT4 users. Cox proportional hazards modeling was used to evaluate the impact of LT4 use on the 5-year incidence of BRCA and benign breast disease, and on all-cause mortality rates among women diagnosed with breast cancer during follow-up. Results: LT4 users (N=89,093) and non-LT4 users (N=89,093) were well-matched with respect to baseline sociodemographics, estrogen use, comorbidity, and health care utilization, including the likelihood of receiving mammography or a breast biopsy. The 5-year incidence of BRCA was 0.86% in LT4 users compared to 0.97% in non-LT4 users (p=0.002). Adjustment for baseline characteristics did not alter these results (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.77–0.95; p= 0.004). Among women who developed BRCA, all cause mortality was significantly lower in LT4 users than in non-users (43.9% vs. 56.1%; adjusted HR 0.82; 95% CI 0.70–0.96; p= 0.01). The incidence of benign breast disease did not vary between groups. Conclusions: Elderly women with autoimmune hypothyroidism appeared to have a protective advantage in the incidence of BRCA and in mortality following a breast cancer diagnosis. These results suggest a biological role for thyroid hormone in the development of breast cancer, with a modulating effect of treated autoimmune hypothyroidism in promoting a less aggressive disease course. Further studies exploring the effect of thyroid hormone in breast cancer development are needed and may uncover novel therapeutic targets in the management of breast cancer in the future. No significant financial relationships to disclose.
The impact of an exercise intervention on body composition, fat distribution, and weight in breast cancer survivors
Authors: Ligibel J. A. , Chen W. , Keshaviah A. , Adloff K. , Partridge A. , Salinardi T. , Winer E. P. 
Published: March 2020

590 Background: Recent research has demonstrated that obesity increases a woman’s risk of breast cancer recurrence. Although the mechanism is not well understood, it is known that obese women have higher levels of insulin and other hormones related to energy balance. In this study, we sought to explore the impact of an exercise intervention on body composition, fat distribution, weight, and insulin levels in a population of breast cancer survivors. Methods: Inactive women with early stage breast cancer who had completed adjuvant chemotherapy and/or radiation were randomized to a 16-week exercise intervention or a normal care control group. The exercise intervention consisted of supervised strength training and unsupervised cardiovascular exercise, with a goal of 2 strength training sessions and 90 minutes of cardiovascular exercise each week. Measurement of weight, body composition, and circumference at the waist and hip, were collected at baseline and after 16 weeks in both groups. Fasting blood samples were also collected at these two time points for insulin and glucose levels, so that changes in these levels between the intervention and control groups could be compared. Results: Eighty-five women have been randomized; complete anthropometric data are presently available for 51. Women in the exercise group experienced a nonsignificant decrease in body weight, body fat, and circumference at the waist and hip, as compared to control patients. Participants completed a median of 84% of scheduled strength training sessions and 80% of recommended cardiovascular sessions. Strength increased by an average of 40% during the exercise intervention. Prior studies have demonstrated significant inter-assay variability in biomarker testing, thus insulin and glucose testing will be performed when all patients have completed the protocol. Conclusions: Compliance with the exercise intervention was good. Women in the exercise group experienced non-significant changes in anthropometric measures, and increased strength during the 16-week intervention. Final strength and anthropometric data from the entire cohort will be available for presentation. This project was supported by an ASCO Career Development Award and funding from the Lance Armstrong Foundation. No significant financial relationships to disclose.
Use of statins and breast carcinoma: A case-control study
Authors: Dumasia L. , Lobocki C. , Couturier A. , Lebeis C. , Drelichman A. 
Published: March 2020

592 Background: Statin drugs, which enzymatically inhibit HMG CoA reductase, are used in the treatment of hypercholesterolemia. In vitro, statins have been shown to induce apoptosis and inhibit growth in breast cancer cell lines. Although controversial, recent clinical data has indicated that statins may have a chemopreventive effect against breast cancer. Our objective was to determine whether the long-term intake of statins (at least four years) demonstrates a protective effect against breast cancer as a primary endpoint. Methods: We conducted a retrospective, case-control study of female patients from a community-based hospital and medical center located in southeastern Michigan. Cases included patients diagnosed with invasive breast carcinoma between 1995–2005, as identified through the tumor registry. Controls were family practice patients (age > 35 years) randomly selected from a database generated for this same time-period. Patients completed a mailed questionnaire with information pertaining to their use of statins and other medications, as well as other breast cancer risk factors. Subjects (N = 521) and controls (N = 521) were case matched by age, race, and body mass index (BMI). Results: The mean age of patients was 62.9 (range 35–101 yrs.) with an average BMI of 27.5. Reported usage of statins for four or more years prior to diagnosis was 5.5% in breast cancer subjects and 6.9% in case-matched controls. Compared to nonusers, women who had been on statin therapy for four or more years prior to diagnosis were not found to have a decreased risk of breast cancer (odds ratio 0.78: 95% CI 0.47 - 1.31). Similarly, there was no difference in risk for nonusers versus those taking statins for <1 yr., 1–4 yrs., or ≥ 4 yrs. However, nulliparity, positive family history, report of any benign breast biopsy, and ≥ 5-year use of oral contraceptives (before age 30) were significantly associated with the occurrence of breast cancer (p < 0.002, Chi-square test). Conclusion: Although statins have been shown to inhibit growth in breast cancer cell lines in vitro, its effect in vivo has remained inconclusive. Our study did not demonstrate a significant protective effect against breast carcinoma in women who had ever taken statins, or those who had taken the drug for a minimum of four years. No significant financial relationships to disclose.
Measuring quality of care in the treatment of colorectal cancer: The Moffitt Network Initiative on Practice Quality (MNIPQ)
Authors: Jacobsen P. B. , Shibata D. , Siegel E. , Lee J. , Druta M. , Marshburn J. , Levine R. , Gondi A. , Defelice J. , Malafa M. 
Published: March 2020

6001 Background: As the first step in a larger effort to improve quality of care among its member institutions, the MNIPQ sought to develop and implement methods to assess quality of care in the treatment of colorectal cancer. The current report focuses on our initial experience conducting quality assessments at 4 of 20 member institutions. Methods: Medical chart reviews were conducted of all patients diagnosed with colon or rectal cancer in 2004 and seen by a medical oncologist at the Moffitt Cancer Center or at any of three affiliate institutions. Abstractors, who were trained and periodically monitored, conducted the reviews using a web-based abstraction tool. Abstraction focused on assessing adherence to quality indicators consistent with evidence-, consensus-, and regulatory-based guidelines. Variability in adherence across sites was evaluated by conducting Fisher’s exact tests. The 186 patients whose charts were reviewed were predominantly female (57%) and diagnosed with colon cancer (74%). Results: Adherence was consistently (p values>.05) high across all four study sites for: presence of a pathology report confirming malignancy (91–100%); evidence of staging based on established criteria (88–94%); documentation of discussion or referral for chemotherapy in cases of lymph node (colon and rectal cancer) or rectal wall (rectal cancer) involvement (89–100%); and presence of chemotherapy flow sheets (92–100%). Adherence was consistently (p values>.05) lower across sites for: performance of complete colon evaluation within 12 months of surgery (24–47%) and performance of CEA test before (48–74%) or in the 6 months after (56–82%) surgery or chemotherapy. Adherence varied significantly (p < .001) across sites only for documentation of consent for patients treated with chemotherapy (41–100%). Discussion: Findings identified several areas where efforts should be made to improve the quality of colorectal cancer care at one or more member institutions. In addition, the methods developed have laid the groundwork for future efforts to measure and improve quality of care for other cancers and among a larger number of member institutions. No significant financial relationships to disclose.
The relative influence of clinical information, financial incentives, and other factors on physician’s choice of chemotherapy
Authors: Johnson S. J. , Bilenker J. H. , Epstein A. J. 
Published: March 2020

6002 Background: Understanding the effect of financial incentives for specialty pharmaceuticals on physician choice has been a priority for policy makers. This research seeks to identify the extent to which published clinical information and financial incentives affect a physician’s choice of chemotherapy along with other factors. Methods: SEER-Medicare and Medispan pricing data were formed into a panel of 4,503 patients who were diagnosed with metastatic breast cancer and treated with chemotherapy from 1991 to 2002. A conditional logit discrete choice model was employed to analyze the effects of product attributes, including financial margin, volume of randomized controlled trial citations, FDA labeled indications, years since launch, generic status, and other covariates, on odds of choice of chemotherapy. A chemotherapy-level fixed effects specification was used to analyze choices of drug in patients’ first and subsequent drug administrations. Results: The natural log of clinical information was positive and significant (β = 1.270; p < 0.001); a one unit increase in log of citations increased odds of choice by 27 percent, all else constant. Physicians avoided generics (β = 0.703; p < 0.01), preferred on- to off-label drugs (β = 0.468; p < 0.01), and preferred older drugs to newer ones. Financial incentives for the first chemotherapy administration were positive and significant influences on choice of drug (β = 1.001; p < 0.001). A $100 increase in reimbursement per day increased the odds of choosing a drug by 10 percent. Preference for financial incentives, more clinical information, and on-label drugs declined in subsequent administrations. Conclusions: This research provides evidence that financial incentives have a positive but modest effect on the average physician’s choice of chemotherapy when treating metastatic breast cancer. New clinical information about a drug also had a positive effect on choice. [Table: see text]
Patients involved in clinical research are more concerned about intrinsic and traditional research (“publish or perish”) conflicts of interests (COI) than potential financial conflicts: Results of interviews with advanced cancer patients enrolling in phase I trials
Authors: Daugherty C. K. , Hlubocky F. J. , Gray S. , Ratain M. J. 
Published: March 2020

6008 Background: Concerns exist about the potential for financial COI to bias the design, conduct, analysis, and reporting of clinical trials. However, information is lacking about the perceptions of these COI among actual research subjects—both in general and relative to more intrinsic and traditional research COI. Methods: Using a standardized survey, cancer patients (pts) were asked closed-ended and semi-qualitative questions regarding their concerns about extrinsic, e.g., financial, and intrinsic, e.g. career advancement, COI. Results: To date, 120 pts either enrolled, or being evaluated for participation, in phase I trials have been approached for an interview with 96 completing the interview (80% response rate). Median age of respondents is 61 y (33–82); 55% male; 83% Ca, 10% AA, 2% AsA or HA; 38% college educated. 91%, 100%, and 94% thought that the involved investigators (MDs), drug companies, and hospitals benefited from a clinical trial respectively. The benefits cited for MDs was improvement in knowledge/ability to treat pts. The benefits cited for the hospital and drug company were described as prestige and financial. 38% would be concerned if an MD involved in a clinical trial receives financial benefit from the research, e.g., being a paid consultant or owning stock in company involved in a trial, and 43% thought that they should be informed of these potential benefits. 64% thought they should be concerned if an MD receives career advancement benefits from trial participation, and 69% thought they should be informed of this benefit. 45% thought that investigators might feel institutional pressure to enroll pts. Qualitative data revealed that pts’ lack of concern about financial COI related to their assumption that MDs already receive financial benefits-believing this to be acceptable-with some even encouraging it. Conclusions: Cancer pts were more concerned about intrinsic and traditional research COI than potential financial COI. As well, many assume that MDs receive financial benefits from research. These results may be helpful when considering COI management policies. No significant financial relationships to disclose.
Factors influencing accrual to ACOSOG Z0011, a randomized phase III trial of axillary dissection vs. observation for sentinel node positive breast cancer
Authors: Leitch A. M. , McCall L. , Beitsch P. , Whitworth P. , Reintgen D. , Blumencranz P. , Saha S. , Bauer T. , Hunt K. K. , Giuliano A. 
Published: March 2020

601 Background: The American College of Surgeons Oncology Group opened a phase III randomized trial to assess the value of axillary node dissection (ALND) after positive sentinel node biopsy (SNB). After 5.5 years, the trial closed due to poor accrual with only 891 patients of the planned 1900 accrued. The purpose of the current analysis is to assess factors impacting accrual to Z0011. Methods: Women having SNB for T1 or T2 breast cancer were eligible for participation in the Z0010 trial to assess the significance of micrometastases identified by immunohistochemistry. If the SN was positive for metastasis by H&E, the patient was eligible for randomization on Z0011 trial. Intraoperative (IOR) and postoperative randomization were allowed. Patients having SNB outside of the Z0010 trial were eligible. Results: 1003 patients from the Z0010 trial were eligible for randomization on Z0011. Of these, only 37% were entered in Z0011. Z0010 participants accounted for 42% of patients in Z0011. 16% of patients not randomized refused ALND. 69% of those not randomized had ALND. 67% of these had no additional positive nodes. Only 14% had ≥ 4 positive nodes. Enrollment of eligible Z0010 patients varied by type of institution: 25% at academic sites, 42% at teaching affiliated and 53% at community (p < 0.0001). By geographic region, sites in the South entered 42% of eligible patients compared with 24–36% in other geographic regions (p=0.0027). Only 32% of patients were consented for IOR based on frozen section of the SN. Sites in the South and West were less likely to use IOR (25% and 28%) compared to Northeast and Midwest (45% and 46%) (p < 0.0001). 110 sites participated in Z0011, yet 48% of patients were enrolled by 10% of sites. Conclusions: Failure of this important trial to accrue as planned is likely related to the clinical bias of physicians and patients to standard ALND. Yet, 2/3 of patients had no additional positive nodes and extensive nodal disease was infrequent. While it was thought that IOR might improve accrual to Z0011, the most successful sites were less likely to use this approach. Community surgeons were most successful in randomizing patients. [Table: see text]
Preferences for and expectations about experimental therapy among participants in randomized trials
Authors: Joffe S. , Stumacher M. , Clark J. W. , Weeks J. C. 
Published: March 2020

6013 Background: Equipoise is often viewed as the ethical precondition for randomized controlled trials (RCTs). Equipoise is usually defined as a state of uncertainty or disagreement among expert clinicians, but some ethicists argue instead that individual participants should be indifferent between the study arms. The degree to which cancer RCT participants have preferences for either arm is not known. Methods: Adults who had enrolled in a 2-arm RCT at a Dana-Farber/Harvard Cancer Center institution within 21 days were eligible. A mailed questionnaire asked about treatment assignment, treatment preference, and expectations about the relative efficacy and toxicity of the 2 arms. The primary analysis was a goodness-of-fit chi-square test of the null hypothesis that equal proportions of respondents would prefer the standard vs. investigational arm. Results: 82 of 126 RCT participants (65%) responded. 31 (38%) were assigned to the standard arm, 26 (32%) were assigned to the experimental arm, and 25 (30%) were enrolled in blinded trials. Respondents tended to prefer assignment to the experimental rather than the standard arm (p = 0.006), and expected the investigational arm to be more effective than the standard arm (p = 0.0004). Respondents did not consistently expect that either arm would be more toxic ( Table ). Conclusions: Cancer RCT participants tend to prefer the experimental arm. Thus either the design of cancer RCTs must be altered to accommodate participant preference, or individual-participant equipoise must be abandoned. [Table: see text] No significant financial relationships to disclose.
Do post-approval phase III trials for accelerated approved cancer drugs violate equipoise?
Authors: Lurie A. J. , Djulbegovic B. , Nebeker J. R. , Angelotta C. , Gordon L. I. , Raisch D. W. , Yarnold P. R. , Carson K. R. , McKoy J. M. , Bennett C. L. 
Published: March 2020

6026 Background: Since 1992, the Food and Drug Administration (FDA) has allowed accelerated approval of novel cancer drugs based on improvements in surrogate outcomes, provided that subsequent phase III trials, in compliance with subpart H, show evidence of clinical benefits. However, drugs that receive accelerated approval must already show promise, making it difficult to recruit for randomized studies in which patients might get other drugs which are likely to be inferior. We evaluated whether drugs granted accelerated approval were just as likely to be superior as inferior to standard therapy during phase III clinical trials, a necessary condition known as equipoise, which is used as the ethical basis for recruitment. Methods: Descriptions of marketing approval decisions and subpart H commitments for all drugs that received accelerated approval for oncology indications between 1992 and 2005 were obtained from the FDA website, transcripts of the Oncologic Drug Advisory Committee of the FDA, and PubMed searches. Results: Accelerated approval has been granted for 25 drugs and 29 indications. These approvals have been based on phase II clinical trials (23 indications) or phase III trials (6 indications). 14 approvals were for novel cancer therapeutic drugs. Post-approval phase III clinical trials, outlined in subpart H commitments, have been reported for 9 indications associated with common cancers of the colon, lung, or breast, and 1 indication associated with multiple myeloma, a less common cancer, for which 9 studies identified improved clinical outcomes with the accelerated approved drug. Of 15 drugs that received accelerated approval prior to 2003 for cancers that affect small numbers of patients, 13 are years behind planned recruitment milestones for post-approval phase III trials. Conclusion: While the equipoise theory would predict that 50% of the completed phase III trials would support the novel therapy, empirical data have identified that 90% of the studies required by subpart H commitments support the novel therapy. Therefore, it is likely to hinder recruitment to ongoing phase III trials evaluating other accelerated approved cancer drugs. No significant financial relationships to disclose.