Patterns of participation and successful patient recruitment to American College of Surgeons Oncology Group Z0010, a phase II trial for patients with early-stage breast cancer

BACKGROUND: Historically, fewer than 5% of cancer patients enroll in clinical trials and lack of physician participation is a contributing factor. In 1999, the American College of Surgeons Oncology Group (ACOSOG) conducted a multicenter breast cancer trial evaluating the prognostic value of sentinel lymph node (SLN) and bone marrow micrometastases. This report elucidates factors influencing patient accrual. METHODS: Demographics of investigators (N = 198) and their success in accruing patients (N = 5327) were reviewed. ACOSOG Breast Committee members (N = 1136) were surveyed to identify factors influencing participation. RESULTS: Surgeons from 126 institutions participated in Z0010 (academic [48%], teaching-affiliated [20%], and community [29%] practices), and 28% of surgeons accrued 75% of the subjects. Twenty-four percent of surgeons accrued 75% of minority patients. Female surgeons accrued 24% of patients and accounted for 30% of investigators. On survey, 16% of respondents reported no prior experience with clinical trials and a number of factors were identified that influenced participation. CONCLUSIONS: ACOSOG successfully accrued 5327 patients to a SLN trial with surgeon participation from all practice settings. However, significant barriers to participation remain.     

Breast cancer treatment beliefs and influences among surgeons in areas of scientific uncertainty

Background

Breast cancer treatment beliefs in areas of scientific uncertainty may contribute to widely variable practices. We sought to better describe surgeons' beliefs and to identify the relative importance of different information sources on surgeons' decision-making.

Methods

A total of 2,188 American College of Surgeons (ACoS) members were surveyed on their treatment beliefs in 4 controversial areas and on the perceived influence of various information sources on their decision-making. Responses were analyzed by sex, practice type, oncology training, professional society membership, and breast cancer patient volume.

Results

Nine hundred twenty-three responses were received, with 459 eligible for analysis. Responses diverged most regarding significance of positive sentinel lymph node biopsy (SNLB) and role of post-lumpectomy radiation for low-risk ductal carcinoma-in-situ (DCIS). Overall, expert opinion ranked as the most influential information source.

Conclusions

Axillary dissection after positive SLNB and post-lumpectomy radiation in low-risk DCIS denoted areas of greater uncertainty. Breast cancer opinion leaders have substantial influence when standard practice is uncertain.     

Evaluation of eligibility and recruitment in breast cancer clinical trials

Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial.     

Measurement of factors influencing the participation of patients with prostate cancer in clinical trials: a Canadian perspective

OBJECTIVE

To identify factors that patients with prostate cancer believe to be important determinants in their decisions about future enrolment in clinical trials.

PATIENTS AND METHODS

In all, 122 patients (within 5 years of a diagnosis of prostate cancer) who had never been asked to participate in a clinical trial were asked to complete a 30‐item measure of ‘Factors Influencing Participation’ in clinical trials.

RESULTS

Factor analysis showed that variables influencing participation can be grouped into three areas: acceptability (e.g. recruitment process and altruistic beliefs); awareness (e.g. impact on quality of life, survivorship and randomization process); and accessibility (e.g. costs to patient, influence of family, age, time and need for extra tests). Awareness items were rated significantly more important by patients with T1 or T2 disease (P = 0.002). Patients who had not made a treatment decision also rated awareness (P = 0.05) and acceptability (P = 0.04) items higher. Patients with less than a university education identified access items as more important (P = 0.03). Helping future patients with prostate cancer, the impact of the study protocol on survival, being fully informed about the study, relationship with specialists, and impact of study on quality of life were identified as the five variables having the most influence on future enrolment.

CONCLUSIONS

Men rated items related to awareness and acceptability as being the most important determinants to future enrolment in a clinical trial. Knowledge about what these men believe is important for their future participation in a clinical trial will help researchers to design protocols that address the needs of targeted patient groups.     

Decision-making from multidisciplinary team meetings to the bedside: Factors influencing the recruitment of breast cancer patients into clinical trials

Aim of the studyOur aim was to determine factors influencing physicians and breast cancer patients to respectively propose or accept participation in a clinical trial following proposals made during a multidisciplinary team meeting (MTM) in a Comprehensive Cancer Centre.Patients and methodsConsecutive patients considered eligible for a clinical trial by a breast cancer-specific MTM were included. A detailed analysis of factors predictive of the physician proposing the trial and the patient's acceptance and final inclusion was conducted.ResultsMTM proposed 547 inclusions in 25 clinical trials for 397 patients between March and September 2011. The physician proposed the scheduled clinical trial in only 39% of the cases. The patients accepted the proposal in 74% of the cases, and finally 29% were included. The main reason for non-inclusion was the physician's failure to propose the trial in 45–81%, depending on the type of study. The only factor predictive of both the physician proposing the trial and final inclusion was the type of study (both p < 0.001). Diagnostic/prognostic studies were the most frequently proposed trials. The professional status (of the subject) was predictive of acceptance (p = 0.03) with higher rates among retired patients and executives (84 and 76% respectively).ConclusionThe major reason for non-inclusion in clinical trials was the physician's failure to propose the trial, while the patient's professional status and the type of study influenced both physicians and patients. Educative measures mostly directed at physicians could be implemented to overcome such poor compliance.     

Feasibility of tailored follow-up for patients with early breast cancer

As the number of breast cancer survivors increases, this study prospectively examined whether tailored follow-up with differentiated number of visits per risk group, based on a prognostic index for local recurrence, is feasible and acceptable for patients and professionals.Between March 2007 and March 2010, 180 breast cancer patients (pT1-2N0-2cM0) were included. Primary endpoint was feasibility of tailored follow-up, based on the number of follow-up visits, patient satisfaction, anxiety and attitude towards follow-up. Secondary endpoints were reasons for visits, incidence, time to detection of local recurrences and the use of alternative care.In the second and third year of follow-up, the results show a 22% reduction in visits per patient in the low-risk group compared to the intermediate-risk group; 2.8 versus 3.6 visits. The majority of interval visits in both groups was initiated by the professional. No significant differences were found in attitude towards follow-up, patient satisfaction, anxiety and depression, alternative health care use or local recurrences between the risk groups.In conclusion, implementation of a tailored follow-up programme with decreased number of visits for low-risk patients is feasible and acceptable to patients. Appointing one coordinating professional, possibly a nurse practitioner, could further reduce the number of follow-up visits.     

Defining social support systems for women with breast cancer

BACKGROUND: Providers often assume that a patient relies on the same person for primary support (PS), as emergency contact, and as health care proxy. We questioned how often this is not the case in women with breast cancer. METHODS: We questioned women who were in treatment or follow-up evaluation after a cancer diagnosis who they would name as primary support, emergency contact, and health care proxy. RESULTS: One hundred thirty-five women with breast cancer participated and 75% were married or partnered. More than 40% of women did not name the same person to these distinct roles. Even for women in relationships, almost 50% did not name their partner to all 3 support roles. CONCLUSIONS: A large proportion of breast cancer patients named different persons to these distinct support roles. By further defining the roles that social support networks play, we can identify strategies for including these support providers in the care models for women living with cancer.     

Patterns of seeking medical care among Egyptian breast cancer patients: relationship to late-stage presentation

Breast cancer is the most common cancer among Egyptian women, accounting for 37.6% of female tumors, and is often diagnosed at later stages. The objective of this study was to investigate breast cancer patient navigation through the health care system in the Nile Delta. Interviews were conducted with 163 newly diagnosed breast cancer patients at the Tanta Cancer Center (TCC), the major cancer center of the region. Patients described their medical care pathway from the initial symptom experienced until their arrival at TCC. Patients whose initial contact was with a general surgeon (OR: 7.6, 95% CI: 2.1, 27.6), primary care provider (OR: 12.2, 95% CI: 2.9, 51.0), or gynecologist (OR: 8.6, 95% CI: 1.4, 53.4) were significantly more likely to experience a delay in reaching the TCC as compared to those visiting a surgical oncologist. Overcoming health care system and patient navigation barriers in developing countries may reduce the time for breast cancer patients to reach a cancer center for early management.     

Importance of patient reported outcome measures versus clinical outcomes for breast cancer patients evaluation on quality of care

IntroductionGiven increasing numbers of breast cancer survivors, there is an increased focus on quality of life and quality of care. This study aims to investigate whether clinical or patient reported outcomes are most important for perceived quality of care by breast cancer patients.MethodsOverall, 606 patients aged 18 years or older, who underwent breast cancer surgery 9–18 months ago in five hospitals in the Netherlands, were invited to complete an internet-based questionnaire. Patients were asked to judge a random selection of 24 patient profiles and choose which of 2 presented patients had received the best quality of care, using conjoint analysis. The individual relative importance (RI) for each outcome was estimated using Hierarchical Bayes Estimation, and averaged over all patients to assess which outcomes were most important.ResultsComplete data were available for 350 patients (58%). Avoiding severe breast symptoms was most important for good quality of care according to patients (RI 23.22 [95% Confidence Interval (95% CI) 22.32–24.12]), followed by a 2 year longer disease free survival (18.30 [17.38–19.22]). However, the importance differed by age: younger patients (<50 years) assigned higher importance to longer disease free survival (21.99 [19.52–24.46]) than older patients (65 + years) (15.03 [13.88–16.18]).ConclusionAvoiding severe breast symptoms rather than 2 year longer disease free survival is considered most important in our population of breast cancer patients for evaluation of quality of care. These data should thus be included in both information provision prior to treatment choices and post treatment quality of care evaluation.     

Facilitating decision-making in women undergoing genetic testing for hereditary breast cancer: BRECONDA randomized controlled trial results

BackgroundDecision-making concerning risk-reducing mastectomy for women at hereditary risk of breast cancer entails complex personal choices. Deciding whether and how to restore breast shape after risk-reducing mastectomy is a key part of this process. We developed a web-based decision aid, BRECONDA (Breast Reconstruction Decision Aid), to assist women in decision-making regarding breast reconstruction.MethodThis study assessed the efficacy of BRECONDA to assist women at increased risk of breast cancer in making decisions regarding risk-reducing mastectomy in terms of decisional conflict, knowledge, and satisfaction with information. Women at hereditary risk of breast cancer (N = 64) were recruited into this randomized controlled trial from four Australian hereditary cancer clinics. Participants initially provided online consent and completed baseline questionnaires assessing decisional conflict, knowledge, and satisfaction with information. They were then randomly assigned to either: 1) Intervention – unlimited access to BRECONDA, with usual care; or, 2) Control – usual care. At 2-months follow-up (N = 60) the outcomes were re-assessed. Intervention participants also completed user acceptability ratings for the intervention overall and specific key modules.ResultsMANCOVA analyses indicated that Intervention participants reported lower decisional conflict (P = 0.027), and greater knowledge (P = 0.019) and satisfaction with information (P < 0.0005) at 2-months follow-up compared with Controls. Intervention participants reported high user acceptability and satisfaction with the intervention.ConclusionBRECONDA benefits women considering risk-reducing mastectomy by reducing decisional conflict, and improving knowledge and satisfaction with information. These benefits, coupled with high user acceptability, demonstrate the feasibility of implementing BRECONDA in the hereditary cancer risk context.     

Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer: Results of the Dutch national breast cancer audit

ObjectivesNeoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care.Materials and methodsAll patients aged 18–70 years who received surgery for stage III BC from January 2011 to September 2015 were selected from the national multidisciplinary NABON Breast Cancer Audit. Multivariable logistic regression was used to assess independent predictors of NAC use, focussing on hospital factors.ResultsA total of 1230 out of 1556 patients with stage III BC (79%) received NAC prior to surgery. The use of NAC did not change over time. We observed a large variation of NAC use between hospitals (0–100%). Age <50 years, breast MRI, large tumour size, advanced nodal disease, negative hormone receptor status and hospital participation in neoadjuvant clinical studies were significant independent predictors of NAC use (all P < 0.001). NAC use in stage III BC was not influenced by hospital type and hospital surgical volume. After adjustment for all independent predictors, variation in NAC use between hospitals remained (0% to 97%).ConclusionNAC was used in 79% of patients with stage III BC, which represent a high quality of care in the NL. Patient, tumour, clinical management and hospital factors could not explain considerable variation in its use between hospitals. Hospital participation in neoadjuvant studies did show to improve the use of NAC in daily practice.     

Contraception counseling for young breast cancer patients: A practical needs assessment and a survey among medical oncologists

Background/methodsWe analyzed an unselected, consecutive cohort of young breast cancer (BC) patients (≤40 years, n = 100) with regard to the contraceptive methods used at the time of diagnosis. Based on this data, we assessed the individual need for contraceptive counseling before cancer therapy. Secondly, in a study-specific self-report questionnaire, we surveyed 101 medical oncologists with the aim of evaluating attitudes towards contraception and how young patients are being counseled in the practical clinical setting.ResultsIn 62% of our cohort of young BC patients, we identified situations in which contraceptive counseling was necessary at the time of BC diagnosis. The patients did not use contraception or used an ineffective method (TIER III/IV, 42%), or were using hormonal methods (12%) or IUDs (8%).Almost all respondents of the survey (99%) stated that contraception is an important aspect in the surveillance of young BC patients and the vast majority (90%) discussed this item before starting therapy. Only 20% of the respondents reported that they a) inform the patients that reliable contraception is necessary before starting therapy, b) ask whether contraceptive methods are used during ongoing therapy, and c) regularly refer their patients to specialist counseling by a gynecologist.ConclusionsA large proportion of young women require contraceptive counseling after newly diagnosed BC. Oncologists should be aware that the use of reliable contraceptive methods should not only be discussed before starting therapy, but also during ongoing therapy. Oncologists should consider actively referring their young patients to gynecologists to ensure proper contraceptive counseling.     

Predictive role of the overexpression for CXCR4, C-Met,and VEGF-C among breast cancer patients: A meta-analysis

BackgroundThe overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients.MethodsPubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided.ResultsA total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34–4.91, P = 0.005; and HR = 1.63 95% CI = 1.20–2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52–4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69–1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64–1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43–1.33, P = 0.333].ConclusionsOur meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.     

A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting

PurposeDespite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV).MethodsThis multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1–4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events.Results218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0–5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1–46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2–32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001).ConclusionIn patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.     

Long-term patient reported outcomes and hematologic toxicity among patients who received Granulocyte-Colony Stimulating Factors during chemotherapy for early breast cancer

We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast cancer patients in CANTO (NCT01993498).Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use [95%CI]: +1.27 [-0.33 to +2.87] and −1.01 [-1.98 to −0.04], respectively). PROs were slightly worse at year-4 among patients receiving G-CSF, although differences were of trivial clinical significance. No major differences were observed in leukocyte or platelet count over time.     

Clinical interpretation of quality-of-life outcomes: an investigation of data from the randomized trial of gemcitabine plus paclitaxel compared with paclitaxel alone for advanced breast cancer

Abstract:  Quality-of-Life (QL) data are increasingly relevant to trial results, but are often difficult to interpret and apply clinically; methods to address this problem are needed. Exploratory analyses were conducted using QL data from a recent phase III trial comparing front line gemcitabine plus paclitaxel (GT) versus paclitaxel (T) alone in patients with advanced breast cancer. The most troublesome symptom and toxicity items were identified. For each QL domain, associations and change over time were analyzed using clinically relevant data. The impact of tumor response and duration of therapy on QL outcomes was assessed using pooled data from both treatment arms. Baseline QL data were available from 336 patients, out of 266 patients enrolled on the GT arm and 263 patients enrolled on the T arm. The prevalence of disease-related symptoms was low; 7 of the 10 most troublesome items were psychological. Clinical levels of psychological distress were significantly associated with global QL and reduced significantly over time in both arms. Improved QL was significantly associated with reduced functional impairment, tumor response and completing more cycles of therapy. In this patient population, QL may be closely associated with the clinical efficacy of chemotherapy, functional status and psychological well-being, rather than outcomes such as symptom palliation and toxicity.     

Validation of clinical prediction rules for a low probability of nonsentinel and extensive lymph node involvement in breast cancer patients

BACKGROUND: Two recently developed clinical prediction rules aim to anticipate the lack of nonsentinel lymph node metastases and the involvement of less than 4 lymph nodes in breast cancer patients with positive sentinel lymph nodes (SLNs). METHODS: The University of Louisville Breast SLN Study clinical prediction rules were validated on an independent set of SLN-positive patients with tumors < or = 15 mm. RESULTS: The data on 475 and 473 patients, respectively, were used for the validation. The areas under the receiver operating characteristic curves were similar to the originals for both predictive tools (.70 and .76). The lowest score of 1 identified 5 of 7 patients with disease limited to the SLNs and 161 of 165 as having less than 4 involved lymph nodes. CONCLUSIONS: A subset of patients with SLN-only involvement and less than 4 metastatic lymph nodes can probably be identified by means of the Louisville clinical prediction rules, but prediction of the lack of non-SLN metastasis seems less reliable.     

Clinical application of axillary reverse mapping in patients with breast cancer: A systematic review and meta-analysis

BackgroundThe axillary reverse mapping (ARM) technique, identify and preserve arm nodes during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), was developed to prevent breast-cancer related lymphedema (BCRL) remains controversial.MethodsA comprehensive search of Medline Ovid, Pubmed, Web of Science and the Cochrane CENTRAL databases was conducted from the inception till January 2020. The key word including “breast cancer”, “axillary reverse mapping”, and “lymphedema”. Stata 15.1 software was used for the meta-analysis.ResultsAs a result, twenty-nine related studies involving 4954 patients met our inclusion criteria. The pooled overall estimate lymphedema incidence was 7% (95% CI 4%–11%, I² = 90.35%, P < 0.05), with SLNB showed a relatively lower pooled incidence of lymphedema (2%, 95% CI 1%–3%), I² = 26.06%, P = 0.23) than that of ALND (14%, 95% CI 5%–26%, I² = 93.28%, P < 0.05) or SLNB and ALND combined (11%, 95% CI 1%–30%). The ARM preservation during ALND procedure could significantly reduce upper extremity lymphedema in contrast with ARM resection (OR = 0.27, 95% CI 0.20–0.36, I² = 31%, P = 0.161). Intriguingly, the result favored ALND-ARM over standard-ALND in preventing lymphedema occurrence (OR = 0.21, 95% CI 0.14–0.31, I² = 43%, P = 0.153). The risk of metastases in the ARM-nodes was not significantly lower in the patients who had received neoadjuvant chemotherapy, as compared to those without neoadjuvant treatment (OR = 1.20, 95% CI 0.74–1.94, I² = 49.4%, P = 0.095).ConclusionsARM was found to significantly reduce the incidence of BCRL. The selection of patients for this procedure should be based on their axillary nodal status. Preoperative neoadjuvant chemotherapy has no significant impact on the ARM lymph node metastasis rate.     

Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy

BackgroundLow muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT).Patients and methodsA skeletal muscle index (SMI) in cm²/m² and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI <41 cm²/m²), sarcopenic obesity (LMM and BMI ≥30 kg/m²) and low muscle attenuation (MA <41 HU and BMI <25 kg/m2 or MA <33 HU and BMI ≥25 kg/m2) were related to OS and TNT.ResultsThe prevalence of LMM, sarcopenic obesity and LMA were 66.9%, 7.2% and 59.6% respectively. LMM and sarcopenic obesity showed no significant association with OS and TNT, whereas LMA was associated with both lower OS (HR 2.04, 95% CI 1.34–3.12, p = 0.001) and shorter TNT (HR 1.72, 95% CI 1.14–2.62, p = 0.010). Patients with LMA had a median OS and TNT of 15 and 8 months respectively, compared to 23 and 10 months in patients with normal MA.ConclusionLMA is a prognostic factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice.