Assessing the discordance rate between local and central HER2 testing in women with locally determined HER2-negative breast cancer.

BackgroundThe importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in invasive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options.MethodsBreast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared.ResultsOf the 552 unique patient samples centrally retested with local HER2-negative results recorded, tumor samples from 22 (4.0%) patients were determined to be HER2-positive (95% confidence interval [CI] = 2.5%-5.7%). Of these, 18 had been tested locally by only one testing methodology; 15 of 18 were HER2-positive after the central retesting, based on the testing methodology not performed locally. Compared with the 530 patients with centrally confirmed HER2-negative tumors, the 22 patients with centrally determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years) and more likely to have ER/PR-negative tumors (27.3% versus 22.3%). These patients also had shorter median progression-free survival (6.4 months [95% CI = 3.8-15.9 months] versus 9.1 months [95% CI = 8.3-10.3 months]) and overall survival (25.9 months [95% CI = 13.8-not estimable] versus 27.9 months [95% CI = 25.0-32.9 months]).ConclusionsThis study highlights the limitations of employing just one HER2 testing methodology in current clinical practice. It identifies a cohort of patients who did not receive potentially efficacious therapy because their tumor HER2-positivity was not determined by the test initially used. Because of inherent limitations in testing methodologies, it is inadvisable to rely on a single test to rule out potential benefit from HER2-targeted therapy

Quality indicators for systemic anticancer therapy services: a systematic review of metrics used to compare quality across healthcare facilities.

PURPOSE: The number of systemic anticancer therapy (SACT) regimens has expanded rapidly over the last decade. There is a need to ensure quality of SACT delivery across cancer services and systems in different resource settings to reduce morbidity, mortality, and detrimental economic impact at individual and systems level. Existing literature on SACT focuses on treatment efficacy with few studies on quality or how SACT is delivered within routine care in comparison to radiation and surgical oncology. METHODS: Systematic review was conducted following PRISMA guidelines. EMBASE and MEDLINE were searched and handsearching was undertaken to identify literature on existing quality indicators (QIs) that detect meaningful variations in the quality of SACT delivery across different healthcare facilities, regions, or countries. Data extraction was undertaken by two independent reviewers. RESULTS: This review identified 63 distinct QIs from 15 papers. The majority were process QIs (n = 55, 87.3%) relating to appropriateness of treatment and guideline adherence (n = 28, 44.4%). There were few outcome QIs (n = 7, 11.1%) and only one structural QI (n = 1, 1.6%). Included studies solely focused on breast, colorectal, lung, and skin cancer. All but one studies were conducted in high-income countries. CONCLUSIONS: The results of this review highlight a significant lack of research on SACT QIs particularly those appropriate for resource-constrained settings in low- and middle-income countries. This review should form the basis for future work in transforming performance measurement of SACT provision, through context-specific QI SACT development, validation, and implementation

Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer

BACKGROUND We previously reported prolonged progression-free survival and marginally prolonged overall survival among postmenopausal patients with hormone receptor-positive metastatic breast cancer who had been randomly assigned to receive the aromatase inhibitor anastrozole plus the selective estrogen-receptor down-regulator fulvestrant, as compared with anastrozole alone, as first-line therapy. We now report final survival outcomes. METHODS We randomly assigned patients to receive either anastrozole or fulvestrant plus anastrozole. Randomization was stratified according to adjuvant tamoxifen use. Analysis of survival was performed by means of two-sided stratified log-rank tests and Cox regression. Efficacy and safety were compared between the two groups, both overall and in subgroups. RESULTS Of 707 patients who had undergone randomization, 694 had data available for analysis. The combination-therapy group had 247 deaths among 349 women (71%) and a median overall survival of 49.8 months, as compared with 261 deaths among 345 women (76%) and a median overall survival of 42.0 months in the anastrozole-alone group, a significant difference (hazard ratio for death, 0.82; 95% confidence interval (CIS, 0.69 to 0.98; P=0.03 by the log-rank test). In a subgroup analysis of the two strata, overall survival among women who had not received tamoxifen previously was longer with the combination therapy than with anastrozole alone (median, 52.2 months and 40.3 months, respectively; hazard ratio, 0.73; 95% CI, 0.58 to 0.92); among women who had received tamoxifen previously, overall survival was similar in the two groups (median, 48.2 months and 43.5 months, respectively; hazard ratio, 0.97; 95% CI, 0.74 to 1.27) (P=0.09 for interaction). The incidence of long-term toxic effects of grade 3 to 5 was similar in the two groups. Approximately 45% of the patients in the anastrozole-alone group crossed over to receive fulvestrant. CONCLUSIONS The addition of fulvestrant to anastrozole was associated with increased long-term survival as compared with anastrozole alone, despite substantial crossover to fulvestrant after progression during therapy with anastrozole alone. The results suggest that the benefit was particularly notable in patients without previous exposure to adjuvant endocrine therapy.National Cancer Institute; AstraZeneca6 month embargo; published 28 March 2019.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Phase II Trial of Simple Oral Therapy with Capecitabine and Cyclophosphamide in Patients with Metastatic Breast Cancer: SWOG S0430

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139899/1/onco0179.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139899/2/onco0179-sup-0001.pd

The challenge of measuring intra-individual change in fatigue during cancer treatment

Evaluate how well three different patient-reported outcomes (PROs) measure individual change

Expedition Inspiration Fund for Breast Cancer Research Meeting 2003

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44216/1/10549_2004_Article_5139058.pd

Links Between Communication and Relationship Satisfaction Among Patients With Cancer and Their Spouses: Results of a Fourteen-Day Smartphone-Based Ecological Momentary Assessment Study

Cancer treatment poses significant challenges not just for those diagnosed with the disease but also for their intimate partners. Evidence suggests that couples' communication plays a major role in the adjustment of both individuals and in the quality of their relationship. Most descriptive studies linking communication to adjustment have relied on traditional questionnaire methodologies and cross-sectional designs, limiting external validity and discernment of temporal patterns. Using the systemic-transactional model of dyadic coping as a framework, we examined intra- and inter-personal associations between communication (both enacted and perceived) and relationship satisfaction (RS) among patients with stage II–IV breast or colorectal cancer and their spouses (N = 107 couples). Participants (mean age = 51, 64.5% female patients, and 37.4% female spouses) independently completed twice-daily ecological momentary assessments (EMA) via smartphone for 14 consecutive days. Items assessed RS and communication (expression of feelings, holding back from expression, support and criticism of partner, and parallel ratings of partner behavior). Linear mixed models employing an Actor Partner Interdependence Model were used to examine concurrent, time-lagged, and cross-lagged associations between communication and RS. Expressing one's feelings was unassociated with RS. Holding back from doing so, in contrast, was associated with lower RS for both patients and spouses in concurrent models. These effects were both intrapersonal and interpersonal, meaning that when individuals held back from expressing their feelings, they reported lower RS and so too did their partner. Giving and receiving support were associated with one's own higher RS for both patients and spouses in concurrent models, and for patients in lagged models. Conversely, criticizing one's partner and feeling criticized were maladaptive, associated with lower RS (own and in some cases, partner's). Cross-lagged analyses (evening RS to next-day afternoon communication) yielded virtually no effects, suggesting that communication may have a stronger influence on short-term RS than the reverse. Findings underscore the importance of responsive communication, more so than expression per se, in explaining both concurrent and later relationship adjustment. In addition, a focus on holding back from expressing feelings may enhance the understanding of RS for couples coping with cancer

Couple Communication in Cancer: Protocol for a Multi-Method Examination

Cancer and its treatment pose challenges that affect not only patients but also their significant others, including intimate partners. Accumulating evidence suggests that couples’ ability to communicate effectively plays a major role in the psychological adjustment of both individuals and the quality of their relationship. Two key conceptual models have been proposed to account for how couple communication impacts psychological and relationship adjustment: the social-cognitive processing (SCP) model and the relationship intimacy (RI) model. These models posit different mechanisms and outcomes, and thus have different implications for intervention. The purpose of this project is to test and compare the utility of these models using comprehensive and methodologically rigorous methods. Aims are: (1) to examine the overall fit of the SCP and RI models in explaining patient and partner psychological and relationship adjustment as they occur on a day-to-day basis and over the course of 1 year; (2) to examine the fit of the models for different subgroups (males vs. females, and patients vs. partners); and (3) to examine the utility of various methods of assessing communication by examining the degree to which baseline indices from different measurement strategies predict self-reported adjustment at 1-year follow up. The study employs a longitudinal, multi-method approach to examining communication processes including: standard self-report questionnaires assessing process and outcome variables collected quarterly over the course of 1 year; smartphone-based ecological momentary assessments to sample participant reports in real time; and laboratory-based couple conversations from which we derive observational measures of communicative behavior and affective expression, as well as vocal indices of emotional arousal. Participants are patients with stage II-IV breast, colon, rectal, or lung cancer and their spouses/partners, recruited from two NCI-designated comprehensive cancer centers. Results will be published in scientific journals, presented at scientific conferences, and conveyed to a larger audience through infographics and social media outlets. Findings will inform theory, measurement, and the design and implementation of efficacious interventions aimed at optimizing both patient and partner well-being

Goserelin for Ovarian Protection During Breast-Cancer Adjuvant Chemotherapy

Premature ovarian failure is a devastating long-term toxic effect of chemotherapy for premenopausal women. The survival benefit of adjuvant chemotherapy in young women with operable hormone receptor–negative breast cancer is well known, but concern over becoming infertile may influence the choice of treatment for many women. A number of trials have investigated the combined use of a gonadotropin-releasing hormone (GnRH) agonist and adjuvant chemotherapy in an attempt to protect ovarian function in premenopausal women. Results of such studies were mixed, and there were few data on pregnancy outcomes. The aim of this randomized trial was to determine whether administration of the GnRH agonist goserelin with chemotherapy would reduce the rate of ovarian failure after adjuvant or neoadjuvant treatment of hormone-receptor–negative early-stage breast cancer. A total of 257 premenopausal women with operable hormone receptor–negative breast cancer were randomized to receive standard chemotherapy with goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The rate of ovarian failure at 2 years was the primary study end point. Ovarian failure was defined as the absence of menses for the preceding 6 months and follicle-stimulating hormone levels in the postmenopausal range at 2 years. Conditional logistic regression was used to compare rates. Secondary end points evaluated included pregnancy outcomes and disease-free and overall survival. Of the 257 patients, 218 were eligible and could be evaluated: 113 in the chemotherapy-alone group and 105 in the goserelin group. Complete primary end-point data were available for 135 of the 218 patients who could be evaluated. Among these, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group; the odds ratio was 0.30, with a 95% confidence interval of 0.09 to 0.97; 2-sided P = 0.04. To determine the effect of the missing primary end-point data on the main study findings, sensitivity analyses were performed. The results of these analyses showed that the missing data had no significant effect on the association between treatment and stratification variables (age and planned chemotherapy regimen). Among the 218 patients who could be evaluated, more women became pregnant in the goserelin group than in the chemotherapy-alone group (21% vs 11%, P = 0.03). Kaplan-Meier curves showed that more women in the goserelin group had improved disease-free survival (P = 0.04) and overall survival (P = 0.05). Consistent with the findings of previous randomized trials, these data suggest that administration of a GnRH agonist with chemotherapy protects ovarian function, reducing the risk of early menopause and improving prospects for fertility. Although missing primary-end-point data weaken interpretation of the findings, there is no evidence that the missing data influenced the relative comparison between randomized groups

Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer

Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older