Bridging the age gap in breast cancer: evaluation of decision support interventions for older women with operable breast cancer: protocol for a cluster randomised controlled trial.
ABSTRACT: INTRODUCTION:While breast cancer outcomes are improving steadily in younger women due to advances in screening and improved therapies, there has been little change in outcomes among the older age group. It is inevitable that comorbidities/frailty rates are higher, which may increase the risks of some breast cancer treatments such as surgery and chemotherapy, many older women are healthy and may benefit from their use. Adjusting treatment regimens appropriately for age/comorbidity/frailty is variable and largely non-evidence based, specifically with regard to rates of surgery for operable oestrogen receptor-positive disease and rates of chemotherapy for high-risk disease. METHODS AND ANALYSIS:This multicentre, parallel group, pragmatic cluster randomised controlled trial (RCT) (2015-18) reported here is nested within a larger ongoing 'Age Gap Cohort Study' (2012-18RP-PG-1209-10071), aims to evaluate the effectiveness of a complex intervention of decision support interventions to assist in the treatment decision making for early breast cancer in older women. The interventions include two patient decision aids (primary endocrine therapy vs surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical treatment outcomes algorithm for clinicians. ETHICS AND DISSEMINATION:National and local ethics committee approval was obtained for all UK participating sites. Results from the trial will be submitted for publication in international peer-reviewed scientific journals. IRAS REFERENCE:115550. TRIAL REGISTRATION NUMBER:European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015-004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching Hospitals STH17086. ISRCTN 32447*.
Project description:PURPOSE:Breast cancer patients aged 65+ ("older") vary in frailty status. We tested whether a deficits accumulation frailty index predicted long-term mortality. METHODS:Older patients (n = 1280) with non-metastatic, invasive breast cancer were recruited from 78 Alliance sites from 2004 to 2011, with follow-up to 2015. Frailty categories (robust, pre-frail, and frail) were based on 35 baseline illness and function items. Cox proportional hazards and competing risk models were used to calculate all-cause and breast cancer-specific mortality for up to 7 years, respectively. Potential covariates included demographic, psychosocial, and clinical factors, diagnosis year, and care setting. RESULTS:Patients were 65-91 years old. Most (76.6%) were robust; 18.3% were pre-frail, and 5.1% frail. Robust patients tended to receive more chemotherapy ± hormonal therapy (vs. hormonal) than pre-frail or frail patients (45% vs. 37 and 36%, p = 0.06), and had the highest adherence to hormonal therapy. The adjusted hazard ratios for all-cause mortality (n = 209 deaths) were 1.7 (95% CI 1.2-2.4) and 2.4 (95% CI 1.5-4.0) for pre-frail and frail versus robust women, respectively, with an absolute mortality difference of 23.5%. The adjusted hazard of breast cancer death (n-99) was 3.1 (95% CI 1.6-5.8) times higher for frail versus robust patients (absolute difference of 14%). Treatment differences did not account for the relationships between frailty and mortality. CONCLUSIONS:Most older breast cancer patients are robust and could consider chemotherapy where otherwise indicated. Patients who are frail or pre-frail have elevated long-term all-cause and breast cancer mortality. Frailty indices could be useful for treatment decision-making and care planning with older patients.
Project description:<h4>Background</h4>Age-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET.<h4>Methods</h4>Multicentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ?70 with breast cancer. Data on fitness, frailty, cancer stage, grade, biotype, treatment and quality of life were collected. Propensity-matching (based on age, health status and cancer stage) adjusted for allocation bias when comparing S+ET with PET.<h4>Findings</h4>A total of 3416 women (median age 77, range 69-102) were recruited from 56 breast units-2854 (88%) had ER+ breast cancer: 2354 had S+ET and 500 PET. Median follow-up was 52 months. Patients treated with PET were older and frailer than patients treated with S+ET. Unmatched overall survival was inferior in the PET group (hazard ratio, (HR) 0.27, 95% confidence interval (CI) 0.23-0.33, P < 0.001). Unmatched breast cancer-specific survival (BCSS) was also inferior in patients treated with PET (HR: 0.41, CI: 0.29-0.58, P < 0.001 for BCSS). In the matched analysis, PET was still associated with an inferior overall survival (HR = 0.72, 95% CI: 0.53-0.98, P = 0.04) but not BCSS (HR = 0.74, 95% CI: 0.40-1.37, P = 0.34) although at 4-5 years subtle divergence of the curves commenced in favor of surgery. Global health status diverged at certain time points between groups but over 24 months was similar when adjusted for baseline variance.<h4>Interpretation</h4>For the majority of older women with early ER+ breast cancer, surgery is oncologically superior to PET. In less fit, older women, with characteristics similar to the matched cohort of this study (median age 81 with higher comorbidity and functional impairment burdens, the BCSS survival differential disappears at least out to 4-5 year follow-up, suggesting that for those with less than 5-year predicted life-expectancy (>90 years or >85 with comorbidities or frailty) individualised decision making regarding PET versus S+ET may be appropriate and safe to offer. The Age Gap online decision tool may support this decision-making process (https://agegap.shef.ac.uk/).<h4>Trial registration number</h4>ISRCTN: 46099296.
Project description:OBJECTIVES:Studies that use national datasets to evaluate the management of older women with breast cancer are often constrained by a lack of information on patient fitness. This study constructed a frailty index for use with secondary care administrative records and evaluated its ability to improve models of treatment patterns and overall survival in women with breast cancer. DESIGN:Retrospective cohort study. PARTICIPANTS:Women aged ?50 years with oestrogen receptor (ER) positive early invasive breast cancer diagnosed between 2014 and 2017 in England. METHODS:The secondary care administrative records frailty (SCARF) index was based on the cumulative deficit model of frailty, using International Statistical Classification of Diseases, Injuries and Causes of Death, 10th revision codes to define a set of deficits. The index was applied to administrative records that were linked to national cancer registry datasets. The ability of the SCARF index to improve the performance of regression models to explain observed variation in the rate of surgery and overall survival was evaluated using Harrell's c-statistic and decision curve analysis. External validation was performed on a dataset of similar women diagnosed in Wales. RESULTS:The SCARF index captured 32 deficits that cover functional impairment, geriatric syndromes, problems with nutrition, cognition and mood, and medical comorbidities. In the English dataset (n=67 925), the prevalence of frailty in women aged 50-69, 70-79 and ?80 years was 15%, 28% and 47%, respectively. Adding a frailty measure to regression models containing age, tumour characteristics and comorbidity improved their ability to: (1) discriminate between whether a woman was likely to have surgery and (2) predict overall survival. Similar results were obtained when the models were applied to the Welsh cohort (n=4 230). CONCLUSION:The SCARF index provides a simple and consistent method to identify frailty in population level data and could help describe differences in breast cancer treatments and outcomes.
Project description:Importance:Clinicians should understand the prevalence of depression and decision regret in patients with head and neck cancer and whether these factors differ with age or frailty. Objectives:To assess whether age and frailty are associated with preoperative and/or worsening postoperative depression and postoperative decision regret in patients undergoing major head and neck surgery and to identify additional factors associated with depression and decision regret. Design, Setting, and Participants:This prospective cohort study was conducted at a single institution, with patients aged 50 years or older undergoing major head and neck surgery recruited from December 1, 2011, to April 30, 2014. Statistical analysis was performed from July 1, 2018, to June 30, 2019. Main Outcomes and Measures:Frailty, functional, and geriatric depression assessments were completed before surgery and 3, 6, and 12 months after surgery. Decision regret assessment was completed 6 months after surgery. The prevalence of depression and decision regret was determined by age group. Change in depression over time was compared between age groups using a linear-effects model. Variables potentially associated with moderate to severe depression and decision regret were analyzed using a logistic regression model. Results:The study included 274 patients (68 women and 206 men; mean [SD] age, 67.8 [9.5] years). Of these, 105 (38.3%) were 50 to 64 years of age and 169 (61.7%) were 65 years or older. The rate of preoperative moderate to severe depression was 9.6% (21 of 219), with no difference between younger and older adult cohorts. For both age groups, depression scores increased in the postoperative period from baseline to 6 months. At 12 months, there was a difference in depression scores between the younger and older adult cohort (4.8 [4.6] vs 3.1 [3.6]). A higher preoperative Fried Frailty Index score (odds ratio, 2.58 [95% CI, 1.63-4.06]) was associated with preoperative moderate to severe depression. For all patients, the mean Decision Regret Scale score was 18.2 (range, 0-95), and 26.7% of patients (48 of 180) had moderate to severe regret. There was no difference in Decision Regret Scale scores between younger and older patients. Preoperative depression but not frailty is associated with postoperative moderate to severe decision regret (odds ratio, 1.17 [95% CI, 1.06-1.28]). Conclusions and Relevance:In this cohort study, there was no difference based on age in the prevalence of moderate to severe depression or decision regret. A higher preoperative frailty score was associated with depression but not decision regret. Preoperative depression was the only factor associated with moderate to severe decision regret on multivariate analysis. Understanding the prevalence of and factors associated with moderate to severe depression and decision regret may aid in identifying patients who would benefit from more extensive preoperative counseling and preoperative and postoperative multispecialty assessment and treatment.
Project description:PURPOSE Physician and patient decision styles may influence breast cancer care for patients ? 65 years ("older") because there is uncertainty about chemotherapy benefits in this group. We evaluate associations between decision-making styles and actual treatment. METHODS Data were collected from women treated outside of clinical trials for newly diagnosed stage I to III breast cancer (83% response) from January 2004 through April 2011 in 75 cooperative group sites. Physicians completed a one-time mailed survey (91% response), and clinical data were abstracted from charts. Patient decision style was measured on a five-point scale. Oncologists' preference for prescribing chemotherapy was based on standardized vignettes. Regression and multiple imputation were used to assess associations between chemotherapy and other variables. Results There were 1,174 women seen by 212 oncologists; 43% of women received chemotherapy. One-third of women preferred to make their own treatment decision. Patient and physician decision styles were independently associated with chemotherapy. Women who preferred less physician input had lower odds of chemotherapy than women who preferred more input (odds ratio [OR] = 0.79 per 1-point change; 95% CI, 0.65 to 0.97; P = .02) after considering covariates. Patients whose oncologists had a high chemotherapy preference had higher odds of receiving chemotherapy (OR = 2.65; 95% CI, 1.80 to 3.89; P < .001) than those who saw oncologists with a low preference. CONCLUSION Physicians' and older patients' decision styles are each associated with breast cancer chemotherapy use. It will be important to re-evaluate the impact of decision styles when there is greater empirical evidence about the benefits and risks of chemotherapy in older patients.
Project description:BACKGROUND AND OBJECTIVE:Elderly and/or frail women with ovarian cancer are often undertreated. The aim of the study is to compare the effects of age and frailty on surgical approaches, postoperative complications, and prognosis in elderly women with ovarian cancer. METHODS:A retrospective multicenter study of women ?70 years were treated for ovarian cancer at seven French university hospitals between 2007 and 2015. RESULTS:Of the 1119 women treated for ovarian cancer during the study period, 147 were ?70 years and had complete data. Of these women, 65 were aged 70-74 years, and 82 were aged ?75 years. Overall, 77% of the younger women (49/65) received optimal treatment compared with 51% (40/82) of the older women (p = 0.018). Women ?75 years underwent fewer bowel resections (32% vs. 67%, p < 0.001) and experienced fewer postoperative complications (22.6% vs. 38.9%, p < 0.001); 53.2% of the women in this age group were treated by primary surgery or surgery only. These women also received more chemotherapy with platinum only (15% [9/56] vs. 2% [1/57], p = 0.007) and less bevacizumab (9% [5/56] vs. 32% [18/57], p = 0.003). Patients with greater frailty (a modified Charlson Comorbidity Index [mCCI] score >3) had a five-year survival rate of 30% versus 62% for those with a score ?3 (p < 0.001). CONCLUSIONS:Surgeons modify their approach to treating ovarian cancer in women ?75 years probably to reduce immediate postoperative complications. The prognosis is significantly worse in patients with greater frailty. Improvements to the sequence of treatments administered, with priority given to neoadjuvant chemotherapy in patients with greater frailty, could help increase the number of women who receive optimal treatment and improve their prognosis.
Project description:<h4>Purpose</h4>Although comorbidities, frailty, and functional impairment are common in older adults (OA) with cancer, little is known about how these factors are considered during the treatment decision-making process by OAs, their families, and health care providers. Our aim was to better understand the treatment decision process from all these perspectives.<h4>Methods</h4>A mixed methods multi-perspective longitudinal study using semi-structured interviews and surveys with 29 OAs aged ?70 years with advanced prostate, breast, colorectal, or lung cancer, 24 of their family members,13 oncologists, and 15 family physicians was conducted. The sample was stratified on age (70-79 and 80+). All interviews were analyzed using thematic analysis.<h4>Results</h4>There was no difference in the treatment decision-making experience based on age. Most OAs felt that they should have the final say in the treatment decision, but strongly valued their oncologists' opinion. "Trust in my oncologist" and "chemotherapy as the last resort to prolong life" were the most important reasons to accept treatment. Families indicated a need to improve communication between them, the patient and the specialist, particularly around goals of treatment. Comorbidity and potential side-effects did not play a major role in the treatment decision-making for patients, families, or oncologists. Family physicians reported no involvement in decisions but desired to be more involved.<h4>Conclusion</h4>This first study using multiple perspectives showed neither frailty nor comorbidity played a role in the treatment decision-making process. Efforts to improve communication were identified as an opportunity that may enhance quality of care. In a mixed methods study multiple perspective study with older adults with cancer, their family members, their oncologist and their family physician we explored the treatment decision making process and found that most older adults were satisfied with their decision. Comorbidity, functional status and frailty did not impact the older adult's or their family members' decision.
Project description:There are inconsistent and limited data regarding the risk of myeloid neoplasms (MN) among breast cancer survivors who received radiotherapy (RT) in the absence of chemotherapy. Concern about subsequent MN might influence the decision to use adjuvant RT for women with localized disease. As patients with therapy-related MN have generally poor outcomes, the presumption of subsequent MN being therapy-related could affect treatment recommendations.We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to study older women with in-situ or stage 1-3 breast cancer diagnosed 2001-2009 who received surgery. Chemotherapy and RT were ascertained using Medicare claims, and new MN diagnoses were captured using both SEER registry and Medicare claims. We excluded women who received chemotherapy for initial treatment, and censored at receipt of subsequent chemotherapy. Competing-risk survival analysis was used to assess the association between RT and risk of subsequent MN adjusting for relevant characteristics.Median follow-up for 60,426 eligible patients was 68 months (interquartile range, 46 to 92 months), with 47.6% receiving RT. In total, 316 patients (0.52%) were diagnosed with MN; the cumulative incidence per 10,000 person-years was 10.6 vs 9.0 among RT-treated vs non-RT-treated women, respectively (p = .004); the increased risk of subsequent MN persisted in the adjusted analysis (hazard ratio = 1.36, 95% confidence interval: 1.03-1.80). The results were consistent in multiple sensitivity analyses.Our data suggest that RT is associated with a significant risk of subsequent MN among older breast cancer survivors, though the absolute risk increase is very small. These findings suggest the benefits of RT outweigh the risks of development of subsequent MN.
Project description:BACKGROUND:Satisfaction with medical decisions among patients with cancer is associated not only with the results of decisions they make but also with how they make those decisions. To elucidate the decision-making process among Japanese women with breast cancer, we explored the correlates of regret with patients' treatment decision-making. METHODS:An Internet-based cross-sectional survey was utilized. Japanese women (N = 467) who self-reported that they had been diagnosed with stage 0-II breast cancer participated. Data regarding their decisional role (active, collaborative, or passive) in treatment decision-making, their most regrettable experience regarding their decision-making, the importance of various factors related to decision-making at the time, and clinical and sociodemographic factors were obtained. A forced-entry logistic regression analysis was performed on the likelihood that patients would have some regrets regarding the decision-making process. RESULTS:About half the women expressed some regret (51.4%). Women who had a mastectomy were significantly more likely to have regret than women who had breast conserving surgery. Correlates of regret differed by surgical type. For women who had a mastectomy, those who were aged ≥50 years when diagnosed, or who made their decisions collaboratively with their doctors were significantly less likely to have regret with the decision-making. For women who had breast conserving surgery, those who worked on a contract or part-time basis or whose decision-making roles matched their preferred role were significantly less likely to have regret. Among women who reported some regret, 23.8% expressed that their most regrettable experience concerned gathering information, while 21.3% regretted not consulting with others. For women who were diagnosed at a younger age, the influence on their sex life and pregnancy and childbirth was more important when making their treatment decisions than for women diagnosed an older age. CONCLUSIONS:Approximately half of the Japanese women with breast cancer in this study reported some regret in the treatment decision-making process. Effective participation in decision-making differed by surgical types. Additionally, women who are diagnosed with breast cancer at a relatively younger age, as compared to those who are older, may need additional information and support regarding their sex life and fertility after cancer treatment.
Project description:Adjuvant antioestrogen therapy with tamoxifen is recommended for all women following breast-conserving surgery for ductal carcinoma in situ (DCIS) to reduce local recurrence, despite 50% of lesions being oestrogen receptor (OR) negative. We have investigated the response to hormone manipulation in DCIS by studying changes in epithelial proliferation and progesterone receptor (PR) expression as surrogate molecular markers of treatment effects in DCIS of known OR status. Women were identified who had undergone diagnostic core biopsy followed by surgery for DCIS 14-41 days later. Ki67 (a measure of epithelial cell proliferation) and PR expression were determined by immunohistochemistry on paired paraffin sections of the core biopsy and operative specimens for each patient, with OR and HER-2 measured on the operative specimen. Women were divided into three groups according to whether they had changed hormone therapy (stopped hormone replacement therapy (HRT), group 1), continued taking HRT (group 2) or were not taking HRT (group 3) between core biopsy and surgery. In OR-positive (but not in OR-negative) DCIS after oestrogen withdrawal (group 1), a fall in the mean cell proliferation (P&<0.01) was observed. A fall in PR expression between core biopsy and surgery was also seen in this group (P=0.02). No change in either mean cell proliferation or PR expression was seen in the other two groups in OR-positive or -negative DCIS. The fall in proliferation and PR expression occurred regardless of HER-2 status. In conclusion, a biological response to hormone manipulation is only seen in OR-positive DCIS tumours. Any clinical value of antioestrogen therapy is likely to be restricted to this group.