Mental health outcomes in older breast cancer survivors: Five-year follow-up from the CLIMB study.

BACKGROUND: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis. METHODS: Women aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up. RESULTS: In total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002). DISCUSSION: Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.

Association between endocrine therapy and cognitive decline in older women with early breast cancer: Findings from the prospective CLIMB study.

INTRODUCTION: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by the older population. Specifically, concerns have been raised regarding the detrimental effects of endocrine therapy (ET) on cognition. Therefore, we investigated cognitive functioning over time and predictors for cognitive decline in older women treated for early breast cancer. METHODS: We prospectively enrolled Dutch women aged ≥70 years with stage I-III breast cancer in the observational CLIMB study. The Mini-Mental State Examination (MMSE) was performed before ET initiation and after 9, 15 and 27 months. Longitudinal MMSE scores were analysed and stratified for ET. Linear mixed models were used to identify possible predictors of cognitive decline. RESULTS: Among the 273 participants, the mean age was 76 years (standard deviation 5), and 48% received ET. The mean baseline MMSE score was 28.2 (standard deviation 1.9). Cognition did not decline to clinically meaningful differences, irrespective of ET. MMSE scores of women with pre-treatment cognitive impairments slightly improved over time (significant interaction terms) in the entire cohort and in women receiving ET. High age, low educational level and impaired mobility were independently associated with declining MMSE scores over time, although the declines were not clinically meaningful. CONCLUSION: Cognition of older women with early breast cancer did not decline in the first two years after treatment initiation, irrespective of ET. Our findings suggest that the fear of declining cognition does not justify the de-escalation of breast cancer treatment in older women.

Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study.

BACKGROUND: A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline. METHODS: Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed. RESULTS: A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline -11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes. DISCUSSION: Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer.

PURPOSE: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL). METHODS: Patients aged ≥ 70 years with stage I-III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time. RESULTS: Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = - 4.37; 95% CI - 7.96 to - 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = - 11.10; 95% CI - 18.80 to - 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement. CONCLUSION: A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.

Differences in treatment and survival of older patients with operable breast cancer between the United Kingdom and the Netherlands - A comparison of two national prospective longitudinal multi-centre cohort studies.

BACKGROUND: Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. OBJECTIVES: We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. METHODS: Women diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. RESULTS: 3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0-81.0) and 75.0 (IQR: 72.0-81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9-5.4) in Age Gap and 4.3 years (IQR 2.9-5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74-1.17, p = 0.568). CONCLUSIONS: In contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation.

Partial mastectomy and m. latissimus dorsi reconstruction for radiation-induced fibrosis after breast-conserving cancer therapy.

BACKGROUND: Patients with severe complaints of radiation-induced fibrosis after breast-conserving therapy and not responding to conservative therapy, were treated by partial mastectomy and m. latissimus dorsi reconstruction. METHOD: To determine the feasibility and outcome of this approach, a retrospective study of nine patients was carried out. RESULTS: After a mean follow-up of 46 months, eight of the nine patients experienced improvement of their complaints and shape of the breast. In only one case did the procedure fail, as evidenced by continuation of all complaints. CONCLUSIONS: Partial mastectomy and m. latissimus dorsi reconstruction is the ultimate option in the treatment of radiation fibrosis. The procedure is safe with satisfying results.

Chest wall resection for adult soft tissue sarcomas and chondrosarcomas: analysis of prognostic factors.

BACKGROUND: Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited. METHODS: Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test. RESULTS: With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death. CONCLUSIONS: CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis.

Sternal resection for sarcoma, recurrent breast cancer, and radiation-induced necrosis.

BACKGROUND: The purpose of this study was to investigate the long-term outcome and technical feasibility of sternal resection. METHODS: We performed a 25-year retrospective study of 68 patients who underwent a sternectomy for sarcoma, recurrent breast cancer (BC) or radiation-induced necrosis between 1981 and 2006 in two tertiary referral centres (Erasmus Medical Center/Daniel den Hoed Cancer Center and Netherlands Cancer Center/Antoni van Leeuwenhoek Hospital, Netherlands). Patients were treated with curative intent and followed until May 2009. Medical records were reviewed for patient characteristics, indications for surgery, surgical technique, postoperative complications, and survival. RESULTS: Sternal resection was performed in 43 sarcoma patients, 17 recurrent BC and 8 patients with radiation-induced necrosis with additional rib resection in the majority of patients and with clavicle resection in 13% of patients. Additional scapula, lung, breast or axilla resection, or both, was performed in 10%. Two patients died postoperatively (3%). Mild complications occurred in 24%, and severe complications (namely, pulmonary complications and reinterventions) in 16% of patients. Radical resection was achieved in 80% and 53% of sarcoma and recurrent BC patients, respectively. Five-year overall survival was 64% and 40% in sarcoma and recurrent BC patients, respectively, with 5-year disease-free survivals of 52% and 15%, respectively. CONCLUSIONS: Sarcomas, recurrent BC, and radiation-induced necrosis can be successfully managed by sternal resection and reconstruction with curative intent. Low mortality and acceptable morbidity rates justify this operation in a palliative setting as well. Disease-free survival is poor among recurrent BC patients.

Prognostic factors in 77 curative chest wall resections for isolated breast cancer recurrence.

BACKGROUND: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent. METHODS: BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed. RESULTS: Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2 (P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses. CONCLUSIONS: CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >or= 10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients.

Complications in wound healing after chest wall resection in cancer patients; a multivariate analysis of 220 patients.

BACKGROUND: Extensive chest wall resections can provoke a wide variety of complications, in particular, complicated wound healing. A lower complication rate will be achieved when local factors contributing to wound healing can be identified and improved. The aim of this study is to describe these factors, irrespective of prognosis, survival, or systemic complications. METHODS: Retrospectively, the files of all patients undergoing an extended chest wall resection in a single institute during a 20-year period were retrieved. Patient demographics, use of preoperative therapy, tumor histology, the type of prosthesis (if any), and postoperative wound complications were recorded. Univariate and multivariate analysis were performed to identify factors contributing significantly to wound healing problems. RESULTS: From January 1987 to December 2006, 220 patients underwent a chest wall resection, defined as resection of at least one rib, and/or part of the sternum. In 145 patients (66%) this procedure was uneventful. Multivariate analysis showed that ulceration of tumor and the use of omentum for soft tissue reconstruction comprised independent factors contributing to impaired wound healing. CONCLUSION: Several factors leading to wound healing problems exist preoperatively. In a multidisciplinary setting, these factors should be weighed carefully against the possible benefits of an extended chest wall resection. Especially when ulceration of a tumor exists, or when omentum is considered for soft tissue reconstruction, increased risk on wound healing problems occurs. For the majority of patients chest wall resection will remain a safe and suitable procedure.

Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts.

Interferon-inducible protein 10 (IP-10) is an immunomodulatory chemokine recently recognized to have potent antiangiogenic activity in vivo. Due to difficulties in the stability, manufacture and chronic administration of recombinant forms of endogenous antiangiogenic proteins, antiangiogenic gene therapy has emerged as a promising new form of cancer treatment. We retrovirally transduced A375 human melanoma cells with the human IP-10 gene and injected cells subcutaneously into nude mice. IP-10-transduced cells also were mixed with null-transduced cells in varying proportions before injection. In vivo growth of IP-10-transduced melanoma cells was markedly diminished compared to parental or null-transduced cells (p = 0.0002, Kruskal-Wallis test). This growth inhibition was associated with a marked reduction in microvessel density. The degree of growth inhibition of tumors following injection of a mixed population of null- and IP-10-transduced cells was directly associated with the fraction of IP-10-transduced cells present. We conclude that retroviral transduction of human melanoma cells with the IP-10 gene leads to sufficient protein secretion to inhibit angiogenesis and tumor growth. These findings suggest that IP-10 gene therapy might be an effective therapy in patients with cancer.