Bone is a major target for metastases in the most frequent solid tumors, which result in severe complications and are a major cause of pain. A bone metastasis gene expression signature was identified using human breast cancer cells in a mouse model. The bone metastasis-related genes encode secretory and cell surface proteins implicated in bone-homing (CXCR4), angiogenesis (CTGF and FGF5), invasion (MMP-1 and ADAMTS1), and osteoclast recruitment (IL11). This signature superimposes on the 70-gene poor prognosis gene expression signature for breast cancer, and only ADAMTS1, CTGF and IL11 were found to be overexpressed in human primary breast cancers with bone relapse. We analyzed the expression of the six bone metastasis-related genes in bone metastases from patients with different types of solid tumors, to assess its relevance in human clinical samples. MMP-1, CXCR4, FGF5 and CTGF were found to be overexpressed in tumor cells of human bone metastases when compared to a human normal epithelial cell line. All the analyzed genes were overexpressed in the tumor cells of breast cancer bone metastases when compared to normal breast tissue. We did not detect any differences between the expression of these genes in bone metastases from breast cancer or from other types of solid tumors. Importantly, there was a significant correlation between the expressions of IL11/CTGF, IL11/ADAMTS1, CTGF/CXCR4, CTGF/ADAMTS1, and MMP-1/ADAMTS1, supporting the cooperative function of these proteins in the bone microenvironment, and the potential functional role of these genes in the establishment of bone metastases in vivo.
1004 Background: Studies of checkpoint inhibitor monotherapy show only modest activity in HR+ MBC. We report data from the first randomized study comparing E plus P versus E alone in HR+/HER2- MBC. Methods: Eligible patients (pts) had HR+/HER2- MBC, ≥2 lines of hormonal therapies and 0-2 lines of chemotherapy for MBC. Pts were randomized 1:1 to E 1.4mg/m2 intravenously (IV) on d1 and d8 with P 200 mg/m2 IV on d1 of a 21-day cycle (Arm A) or E alone (Arm B). At time of progression, pts in arm B could crossover and receive P alone. Primary endpoint was progression-free survival (PFS). Key secondary endpoints were: objective response rate (ORR) and overall survival (OS). Exploratory analyses assessed the association between PFS and PD-L1 status, tumor-infiltrating lymphocytes (TILs), neutrophil-lymphocyte ratio (NLR), tumor mutation burden (TMB), and genomic alterations by next generation sequencing on archival tissue. Results: 88 pts initiated protocol therapy; the median age was 58, median prior lines of chemotherapy 1, prior lines of hormonal therapy 2. Median follow-up was 6.3 months. Median PFS and ORR were not different between Arms A and B (PFS 4.1 vs 4.2 months p = 0.38; ORR 25% and 34% respectively (p = 0.49). 14 patients initiated crossover treatment with pembrolizumab; 1 patient experienced a PR (ORR 7%). All-cause AEs occurred in 100% of pts (G3-4, 54.6%) including 2 treatment related deaths on Arm A, both from known AEs attributed to both drugs. PD-L1 assay was performed in 65 pts: 24 (36.9%) had PD-L1 positive ( > 1% with 22C3, centrally tested) tumors. PD-L1 status, TILs, NLR, TMB, and genomic alterations were not associated with PFS (Table). Updated data, including OS and genomic results, will be presented. Conclusions: Among pts with HR+/HER2- MBC, the combination of E and P was not associated with longer PFS than E alone in the ITT or PD-L1+ population, though the PD-L1+ subgroup had very limited power to assess P benefit. Clinical trial information: NCT03051659. [Table: see text]
561 Background: Cognitive impairment has been reported among breast cancer (BC) patients (pts) after adjuvant chemotherapy. However, very few studies focused on cognitive function at diagnosis. Here we aimed to describe cognitive impairment among recently diagnosed BC before any treatment. Methods: A predefined sub-study of the French national prospective cohort of cancer and toxicities performed extensive objective and subjective cognitive assessment before any BC treatment (surgery or neo-adjuvant treatment). This study included a group of pts with newly diagnosed invasive Stage I-III BC and a group of healthy control (HC) women matched on age and education level. Episodic and working memory, executive functions, processing speed, attention, cognitive complaints (FACT-COG), anxiety and depression (HADS) and fatigue dimensions (FA12) were assessed with neuropsychological tests and the referred self-report questionnaires. Objective and cognitive impairment were defined according to International Cognition and Cancer Task Force recommendations. Results: 264 women (median age 54±11 years) recently diagnosed (average of 37 days after initial diagnosis) with invasive BC (stage I-II, 69%) and 132 matched HC participated in this study. Impaired working memory (20% vs 4%), information processing speed (36% vs 17%), attention (16% vs 1%) and executive function (21% vs 8%) were higher among pts than in HC (p < 0.001). In addition, 24% (n = 64) of pts reported cognitive complaints versus 12% of HC (n = 16, p < 0.01). Emotional and cognitive fatigue were higher in pts than HC (mean 24 vs 15 and 18 vs 11, p < 0.01). Similarly, higher levels of anxiety and depression were observed in patients when compared with HC (respectively in 41% and 3% of patients vs 10 and 1% for HC, p < 0.001). Objective cognitive impairment was not associated with cognitive complains. Both objective and subjective cognitive impairment were not associated with anxiety or depression. However cognitive complain was associated with fatigue (p < 0.001). Conclusions: In this large study, compared to HC, patients recently diagnosed with a localized BC reported more cognitive complains and objective cognitive impairment before surgery, without link with emotional status, but with fatigue. Further understanding of the biology and correlates of cognitive dysfunction at BC diagnosis is needed (CANTO-NCT01993498).
10069 Background: A substantial proportion of breast, colo-rectal and prostate cancer patients (pts) can expect long term disease free survival after their primary treatment. Among those, fatigue commonly persists after diagnosis (dx) and can be debilitating. In this study, we evaluated the incidence of fatigue 2 years (y) after cancer dx and its association with health behaviors. Methods: We used a French population based cross-sectional study, which included a representative sample of pts from 12 cancer types (VICAN2). VICAN2 surveyed 4347 pts 2 y after dx. There is a 99% completion rate of fatigue related questions. For this study, we included 2017 pts with breast (1237), colo-rectal (348) and prostate (432) cancer without evidence of metastases at dx or relapse 2y after dx and with fatigue information. Severe fatigue was defined as average score of EORTC QLQC30 fatigue subscale ≥40 at 2y after dx. There were <1% of missing values in the evaluated covariates. Multivariate logistic regression models looked at associations of fatigue with heatlh behaviors (Δ in exercise since dx, exercise at diagnosis, body mass index (BMI), Δ since dx, smoking), age, gender, comorbidities, education, employment, cancer type, radiation, chemotherapy, hormonal therapy. Results: 52% of pts reported severe fatigue at 2 y after dx (median fatique score: 44, range: 0-100). 2 y after dx, 47% of pts either stopped or decrease exercise and 16% had a ≥ 10% change in BMI. Factors associated with fatigue included health behaviors (Table), but also age (adjusted odds ratio [ aOR] for severe fatigue, 95% confidence interval [95% CI]: 0.97, 0.96-0.98), gender ( aOR, 95 CI male vs. female: 0.5, 0.3-0.8), comorbidities ( aOR, 95 CI yes vs. no: 2.0, 1.6-2.4) and treatment type ( aOR, 95 CI radiation vs. no: 1.5, 1.1-2.0). Conclusions: Fatigue continues to be a substantial problem for cancer survivors 2 y after dx. Some factors that may contribute to persistent fatigue (health behaviors) may be amenable to interventions. [Table: see text]
221 Background: Optimal comprehensive survivorship care, beyond screening of recurrences and new cancers, and including health promotion, management of physical as well as psychosocial needs and chronic conditions is insufficiently delivered. To increase patient (pt) empowerment and maximize the uptake of multidisciplinary strategies serving all survivorship needs, we implemented a proactive survivorship care pathway offered for pts with early BC at the end of their primary treatment phase (surgery, chemotherapy, radiotherapy). Methods: The pathway consisted of the following components: 1) receipt of a personalized survivorship care plan (SCP), 2) invitation to attend face-to-face group seminars focused on specific themes and a comprehensive survivorship consultation for multidisciplinary referrals (”the transition day”) 3) access to a mobile application (app) delivering personalized education according to symptoms reported and 4) decision aids for helping physicians to manage prevalent symptoms and side effects related to BC treatment. Administrative data were collected. A pre-specified post-experience survey was sent to all pts four weeks post pathway delivery to inform program implementation with a minimum requirement of 50 responses. BC physicians and members of the multidisciplinary implementation team (MIT) answered a dedicated survey. For the overall pathway and each of its components we descriptively evaluated the following domains: satisfaction (primary outcome), uptake, perceived usefulness, barriers for delivery, and suggestions for improvement. A 70% satisfaction rate would define a positive experience. Results: From October 2021 to April 2022, 241 SCP were delivered, and 98 pts attended the “transition day”. 62 pts replied to the survey, 42 (67%) had received the SCP, 34 (55%) attended the “transition day”, 36 (57%) accessed the app. Only 21 pts (34%) who answered the survey received the full pathway, 81% of whom were very or completely satisfied with it. Perceived usefulness of individual components and for pts that received the full pathway were, respectively: 64% and 90% for the SCP, 91% and 95% for the “transition day”, 72% and 90% for the app. Among 14 BC physicians, agreement regarding the usefulness of the components was: 93% for the SCP, 86% for the decision aids, 93% for the “transition day”, and 86% for the app. The MIT (n = 13) reported high engagement and satisfaction (100%). Main actionable points for improvement included: automated screening and SCP preparation, virtual “transition day”, increase physicians’ awareness. Conclusions: In this pilot phase, pts were satisfied with receiving a proactive survivorship care pathway and the majority reported that the components were useful for supporting their needs. This study informed improvements on program penetration. Evolution towards sustainability phase is ongoing including dissemination to other cancers and centers.
512 Background: We recently witnessed a trend to de-escalate CT and escalate ET in adjuvant BC treatment (tx). However, there has been limited prior research investigating the differential impact on QoL of tx classes. We aimed to test the impact of CT and ET on QoL PROs 2 yrs after diagnosis (dx). Methods: CANTO (NCT01993498) is a multicenter prospective longitudinal study of stage I-III BC pts that characterizes long-term toxicities of BC tx. For this analysis we included 4262 pts recruited from 2012-14. QoL was extensively evaluated using the EORTC QLQ C30 and BR23. Linear regression modeling was performed, adjusting for demographic and clinical factors, with use of CT and/or ET as independent variables. Analyses were stratified by menopausal status due to different tx patterns and sequelae of CT. Results: Median age at dx was 56 yrs, 63% of pts were post (PostM) and 37% premenopausal (PreM), 80% had Charlson score 0, 91% stage I-II. 26% received mastectomy, 52% CT (preM 68%, postM 44%; 86% anthracycline+taxane) and 82% ET (preM 89% tamoxifen; postM 88% aromatase inhibitor). 32% preM pts had menses 1 year after ET initiation. Overall, QoL deteriorates 2 yrs after dx. ET negatively impacts more QoL domains than CT at 2 yrs. Also, young age, smoking, income, aggressive local tx and physiological distress are often associated with low QoL. In the stratified analyses, in postM pts, mostly ET (not CT) is associated with deteriorated QoL. In contrast, in preM pts, mostly CT (not ET) is associated with deteriorated QoL. Table shows eg of associations. Conclusions: In a large prospective cohort of BC survivors, detrimental QoL 2 yrs after dx is mostly associated with ET; however, negative effects of CT persist on preM. This differential effect on QOL should be considered when choosing optimal adjuvant therapy and appropriate selection of pts for ET escalation should be a research priority. [Table: see text]
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