Adverse effects of breast cancer treatment can negatively affect survivors' work ability. Previous reports lacked detailed clinical data or health-related patient-reported outcomes (PROs) and did not ...prospectively assess the combined impact of treatment and related sequelae on employment.
We used a French prospective clinical cohort of patients with stage I-III breast cancer including 1,874 women who were working and ≥ 5 years younger than legal retirement age (≤ 57 years) at breast cancer diagnosis. Our outcome was nonreturn to work (non-RTW) 2 years after diagnosis. Independent variables included treatment characteristics as well as toxicities (Common Toxicity Criteria Adverse Events CTCAE v4) and PROs (European Organization for Research and Treatment of Cancer EORTC Quality of life Questionnaires, Breast cancer module QLQ-BR23 and Fatigue module QLQ-FA12, Hospital Anxiety and Depression Scale) collected 1 year after diagnosis. Logistic regression models assessed correlates of non-RTW, adjusting for age, stage, comorbidities, and socioeconomic covariates.
Two years after diagnosis, 21% of patients had not returned to work. Odds of non-RTW were significantly increased among patients treated with combinations of chemotherapy and trastuzumab (odds ratio OR
chemotherapy-hormonotherapy: for chemotherapy-trastuzumab, 2.01; 95% CI, 1.18 to 3.44; for chemotherapy-trastuzumab-hormonotherapy, 1.62; 95% CI, 1.10 to 2.41). Other significant associations with non-RTW included grade ≥ 3 CTCAE toxicities (OR
no, 1.59; 95% CI, 1.15 to 2.18), arm morbidity (OR
no, 1.59; 95% CI, 1.19 to 2.13), anxiety (OR
no, 1.47; 95% CI, 1.02 to 2.11), and depression (OR
no, 2.29; 95% CI, 1.34 to 3.91).
Receipt of systemic therapy combinations including trastuzumab was associated with increased odds of non-RTW. Likelihood of unemployment was also higher among patients who reported severe physical and psychological symptoms. This comprehensive study identifies potentially vulnerable patients and warrants supportive interventional strategies to facilitate their RTW.
Background
Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor–positive breast cancer. This study evaluated differences in survival after DR in patients ...treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1‐98 trial.
Methods
BIG 1‐98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT). After a median follow‐up of 8.1 years, 911 of 8010 patients (T, 302; L, 285; TL, 170; and LT, 154) had DR as the site of first recurrence. Univariate and multivariate Cox analyses were performed to determine features associated with post‐DR survival.
Results
The median follow‐up time after DR was 59 months (interquartile range, 29‐88 months). Among all patients with DR, 38.1% were 65 years old or older at enrollment, 61.9% had tumors larger than 2 cm, and 69.7% were node positive. Neoadjuvant or adjuvant chemotherapy was administered to 35.6% of the patients. There was no difference in post‐DR survival by treatment arm (median survival, 20.8 months for T, 17.9 months for L, 17.3 months for TL, and 20.8 months for LT; P = .21). In multivariate analysis, older patients (hazard ratio HR, 1.35; 95% confidence interval CI, 1.15‐1.59) and patients with tumors larger than 2 cm (HR, 1.19; 95% CI, 1.00‐1.41), 4 or more positive nodes (HR, 1.31; 95% CI, 1.05‐1.64), progesterone receptor (PR)–negative tumors (HR, 1.25; 95% CI, 1.02‐1.52), or shorter disease‐free survival (DFS) had significantly worse post‐DR survival.
Conclusions
Treatment with adjuvant T, L, or their sequences was not associated with differences in survival after DR. Significant differences in survival were observed by age, primary tumor size, nodal and PR status, and DFS, and this suggests that traditional baseline high‐risk features remain prognostic in the metastatic setting.
In the Breast International Group 1‐98 study, no difference was observed in post–distant recurrence survival by adjuvant endocrine treatment arm. Older patients and patients with tumors larger than 2 cm, 4 or more positive nodes, progesterone receptor–negative tumors, or shorter disease‐free survival had significantly worse post–distant recurrence survival.
Objective
Cognitive complaints are more frequent in women with breast cancer (BC) than in healthy controls and can be present before any treatment. Findings regarding contributive factors remain ...inconsistent. This study aimed to identify different groups of patients with cognitive complaints at BC diagnosis and to determine whether these different groups were associated with demographic, medical, or psychological characteristics.
Methods
Cognitive complaints were assessed in a subset of 264 women from the French multicenter prospective CANTO cohort, at baseline before any treatment. Clustering analyzes were performed using the six‐cognitive dimension Costa's scoring of the FACT‐Cog V3. Univariable analyses were used to study how cognitive function (standardized neuropsychological tests, ICCTF), anxiety, depression, fatigue, and quality of life (HADS, FA12, QLQ‐C30) were associated with specific cognitive complaints groups.
Results
Results included 263 women (54±11 years), newly diagnosed with BC (69% stages I–III). Four distinct groups emerged, ranged from “no complaints” (22.8%), “low complaints” (55.1), “mixed complaints” (14.5%), to “consistent complaints” (7.6%). No significant differences were found in terms of demographic and medical factors between the four groups. However, the groups with higher proportions of patients with complaints were found to have more impairment in executive function, higher scores of anxiety, depressive symptoms, and fatigue, and lower quality of life, than the groups with lower proportions of cognitive complaints.
Conclusion
Using complete cognitive assessment prior to BC treatment, we identified four distinct cognitive complaints groups with specific characteristics. This work provides valuable clinical basis to further investigations for a better understanding of cognitive complaints and their associates.
Background
The diagnosis of mixed invasive ductal and lobular carcinoma (IDC‐L) in clinical practice is often associated with uncertainty related to its prognosis and response to systemic therapies. ...With the increasing recognition of invasive lobular carcinoma (ILC) as a distinct disease subtype, questions surrounding IDC‐L become even more relevant. In this study, we took advantage of a detailed clinical database to compare IDC‐L and ILC regarding clinicopathologic and treatment characteristics, prognostic power of histologic grade, and survival outcomes.
Materials and Methods
In this retrospective cohort study, we identified 811 patients diagnosed with early‐stage breast cancer with IDC‐L or ILC. Descriptive statistics were performed to compare baseline clinicopathologic characteristics and treatments. Survival rates were subsequently analyzed using the Kaplan–Meier method and compared using the Cox proportional hazards model.
Results
Patients with ILC had more commonly multifocal disease, low to intermediate histologic grade, and HER2‐negative disease. Histologic grade was prognostic for patients with IDC‐L but had no significant discriminatory power in patients with ILC. Among postmenopausal women, those with IDC‐L had significantly better outcomes when compared with those with ILC: disease‐free survival (DFS) and overall survival (OS; adjusted hazard ratio HR, 0.54; 95% confidence interval CI 0.31–0.95). Finally, postmenopausal women treated with an aromatase inhibitor had more favorable DFS and OS than those treated with tamoxifen only (OS adjusted HR, 0.50; 95% CI, 0.29–0.87), which was similar for both histologic types (p = .212).
Conclusion
IDC‐L tumors have a better prognosis than ILC tumors, particularly among postmenopausal women. Histologic grade is an important prognostic factor in IDC‐L but not in ILC.
Implications for Practice
This study compared mixed invasive ductal and lobular carcinoma (IDC‐L) with invasive lobular carcinomas (ILCs) to assess the overall prognosis, the prognostic role of histologic grade, and response to systemic therapy. It was found that patients with IDC‐L tumors have a better prognosis than ILC, particularly among postmenopausal women, which may impact follow‐up strategies. Moreover, although histologic grade failed to stratify the risk of ILC, it showed an important prognostic power in IDC‐L, thus highlighting its clinical utility to guide treatment decisions of IDC‐L. Finally, the disease‐free survival advantage of adjuvant aromatase inhibitors over tamoxifen in ILC was consistent in IDC‐L.
摘要
背景。临床实践中混合浸润性导管和小叶癌 (IDC‐L) 的诊断通常与其预后和系统治疗反应相关的不确定性有关。随着人们日益认识到浸润性小叶癌 (ILC) 是一种独特的疾病亚型，围绕 IDC‐L 而产生的问题变得更加相关。在本次研究中，我们利用详细的临床数据库来比较 IDC‐L 和 ILC 的临床病理和治疗特征、组织学分级的预后能力以及生存预后。
材料和方法。在本次回顾性队列研究中，我们找到了 811 名被诊断为患有 IDC‐L 或 ILC 的早期乳腺癌患者。我们执行了描述性统计，以比较基线临床病理特征和治疗。随后，我们使用Kaplan–Meier分析方法对生存率进行了分析，并使用Cox比例风险模型进行了比较。
结果。ILC 患者患有更常见的多灶性疾病，组织学分级介于低级至中级之间，且为 HER2 阴性。组织学分级对 IDC‐L 患者而言是预后因素，但在 ILC 患者中没有显著的区分能力。在绝经后女性中，IDC‐L 患者的预后明显好于 ILC 患者:无病生存期 (DFS) 和总生存期 OS；校正风险比 (HR)，0.54；95% 置信区间 (CI) 0.31–0.95。最后，采用芳香化酶抑制剂治疗的绝经后女性在 DFS 和 OS 方面比仅采用他莫昔芬治疗的绝经后女性更好(OS 校正 HR，0.50；95% CI，0.29–0.87)，后一种治疗方式对这两种组织学类型而言效果相似 (p = 0.212)。
结论。IDC‐L 肿瘤的预后要好于 ILC 肿瘤，尤其在绝经后女性中更是如此。在 IDC‐L(而非 ILC)中，组织学分级是一个重要的预后因素。
实践意义:本研究将混合浸润性导管和小叶癌 (IDC‐L) 与浸润性小叶癌(ILC)进行对比，以评估总体预后、组织学分级的预后作用以及系统治疗的反应。研究发现，IDC‐L 肿瘤患者的预后要好于 ILC 患者，尤其在绝经后女性中更是如此，这可能会影响随访策略。此外，尽管组织学分级未能对 ILC 的风险进行分层，但是，它在 IDC‐L 中显示出重要的预后能力，因而突显其指导 IDC‐L 治疗决策的临床实用性。最后，辅助芳香化酶抑制剂在 ILC 中相对于他莫昔芬的无病生存期优势与在 IDC‐L 中的优势是一致的。
In this retrospective analysis, a large, detailed, and curated single center database was used to compare clinicopathologic features and outcomes between invasive lobular carcinoma and mixed invasive ductal and lobular carcinomas, focusing on the prognostic implications of histological grade and taking into consideration the differences in systemic therapies.
Abstract Background Inflammation could be related to cancer-related cognitive impairment (CRCI) and might be used as a predictive marker of long-term CRCI. We evaluated associations between ...inflammatory markers assessed at diagnosis of breast cancer and CRCI two years afterwards. Methods Newly diagnosed stage I-III patients with breast cancer from the French CANTO-Cog (Cognitive sub-study of CANTO, NCT01993498) were included at diagnosis (baseline). Serum inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10, TNFα, CRP) were assessed at baseline. Outcomes at year 2 post-baseline included overall cognitive impairment (≥ 2 impaired domains) and the following domains: episodic memory, working memory, attention, processing speed, and executive functions. Multivariable logistic regression models evaluated associations between markers and outcomes, controlling for age, education, and baseline cognitive impairment. Results Among 200 patients, the mean age was 54 ± 11 years, with 127 (64%) receiving chemotherapy. Fifty-three (27%) patients had overall cognitive impairment at both timepoints. Overall cognitive impairment at year 2 was associated with high (> 3 mg/L) baseline CRP (OR = 2.84, 95%CI: 1.06–7.64, p = 0.037). In addition, associations were found between high CRP and processing speed impairment (OR = 2.47, 95%CI:1.05–5.87, p = 0.039), and between high IL-6 and episodic memory impairment (OR = 5.50, 95%CI:1.43–36.6, p = 0.010). Conclusions In this cohort, high levels of CRP and IL-6 assessed at diagnosis were associated with overall CRCI, processing speed and episodic memory impairments two years later. These findings suggest a potential inflammatory basis for long-term CRCI. CRP may represent an easily measurable marker in clinical settings and be potentially used to screen patients at greater risk of persistent CRCI.
Background
The authors used the French breast cancer Cancer and Toxicities (CANTO) cohort to study the associations between baseline quality of life and chemotherapy dose‐reductions (CDRs) or ...postchemotherapy‐toxicities (PCTs).
Methods
In total, 3079 patients with breast cancer who received chemotherapy were included in this analysis. The associations between baseline physical functioning (PF) and fatigue measured using the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire Core 30, and two endpoints—CDRs during adjuvant or neoadjuvant chemotherapy; and selected PCTs were estimated with odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) using logistic regression models.
Results
Among the 3079 patients from the CANTO cohort who were included, 718 (33.0%) received chemotherapy in the neoadjuvant setting, and 2361 (67.0%) received chemotherapy as adjuvant treatment. The chemotherapy included taxanes in 94.2% of patients and anthracyclines in 90.5% of patients. Overall, 15.5% of patients experienced CDRs and, 31.0% developed PCTs. Women with low baseline PF scores (<83) had higher multivariate odds of developing CDRs compared with those who had PF scores ≥83 (OR, 1.54; 95% CI, 1.13–2.09). The corresponding OR for PCTs was 1.50 (95% CI, 1.13–2.00). Women with high baseline fatigue scores had higher odds of CDRs (OR, 1.43; 95% CI, 1.13–1.76) and PCTs (OR, 1.32; 95% CI, 1.10–1.59).
Conclusions
By using the national CANTO cohort, baseline PF and fatigue were independently associated with CDRs and PCTs.
In the French national breast cancer Cancer and Toxicities cohort, the authors observed that baseline physical functioning and fatigue scores were independently associated with chemotherapy dose reductions and chemotherapy‐induced toxicities.
In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The ...influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity.
Using prospective data collected from 2012-2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction LVEF > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I-III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio OR 3.02; 95% CI 1.10-8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6-40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort.
In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498).
ClinicalTrials.gov NCT01993498.
Background
Although improvements in survival have been achieved for patients with metastatic breast cancer, some patients experience early death after diagnosis.
Patients and Methods
Using ...Surveillance, Epidemiology, and End Results data, we identified 26,538 patients with de novo metastatic breast cancer diagnosed between January 1, 2000 and June 30, 2011. We evaluated time trends for deaths at 1 and 6 months after diagnosis. We then restricted the cohort to patients diagnosed between 2010 and 2011 (n = 3,317), when human epidermal growth factor receptor 2 was routinely collected, and examined factors associated with early death.
Results
In 2000, 15.9% of patients died within 1 month of diagnosis and 33.2% within 6 months. In 2011, the proportion of women dying within 1 month decreased to 13.4% and 26.3% within 6 months (p < .001). Older age and uninsured status were associated with early death (at both time points, age ≥70 versus age <40 had >8.5 higher odds of dying, and uninsured versus insured patients had >2.5 higher odds of death). In addition, in some subgroups (e.g., no insurance and triple negative disease), more than half of patients died within 6 months. Region was also associated with early death.
Conclusion
Although we observed improvements in the proportion of patients experiencing early death, one quarter of patients with de novo metastatic disease diagnosed in 2011 died within 6 months of diagnosis. In addition to tumor factors and older age, geography and uninsured status were associated with early death. Our findings highlight the need for focused interventions for metastatic patients at highest risk for poor outcomes.
Implications for Practice
With nearly one quarter of patients in our dataset diagnosed in 2011 dying within 6 months of diagnosis, our findings highlight the persistent and critical need of further characterization and identification of patients who are risk for poor outcomes in order to optimize care, impact change, and improve outcomes for all women with metastatic breast cancer. Our data also emphasize the need for interventions among those at highest risk for early death. These interventions would likely promote immediate referral for clinical trial participation, early palliative care referrals, and additional supportive services, optimizing equitable patient access to cancer treatment and care.
Little is known about the rates of early breast cancer or the factors associated with early mortality due to metastatic breast cancer. Further insight into potentially modifiable factors that influence the likelihood of early death could improve outcomes. This study examined time trends of early mortality over the last decade and the factors associated with mortality at 1 and 6 months after diagnosis.
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