Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer.Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides.Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36–0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36–0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60–2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients—halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.
Background The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only. Methods The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/− whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group. Discussion This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM. Results The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden. Trial registration ClinicalTrials.gov, NCT 03116412. Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412
The benefit of imaging in the follow-up setting for high-risk melanoma patients is uncertain, and even less is known about the impact of intensive follow-up on the patient´s quality of life. In 2017, a Swedish prospective randomized multicenter study started, in which high-risk melanoma patients are randomly assigned 1:1 to follow-up by physical examinations +/− whole-body imaging. The first-year examinations are scheduled at 0, 6 and 12 months. The aim of this study was to investigate whether the patients´ health-related quality of life (HRQoL) and levels of anxiety and depression were affected at 1 year by imaging. Anxiety/depression and HRQoL were assessed at 0 and 12 months by the questionnaires Hospital Anxiety and Depression (HAD) scale and EORTC QLQ-C30 version 3. Expected baseline QLQ-C30 values for the patients were calculated using data from the general population. In total, 204 patients were analyzed. Mean differences in subscale scores at 1 year were not statistically significant either for HRQoL or for anxiety/depression. Baseline HRQoL did not differ from expected values in the general Swedish population. In conclusion, the patients in general coped well with the situation, and adding whole-body imaging to physical examinations did not affect the melanoma patients’ HRQoL or levels of anxiety or depression.
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