Search

Purpose: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. Methods: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). Results: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. Conclusion: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC. [ABSTRACT FROM AUTHOR]

Background: Treatment of breast cancer includes many options and shared decision making is becoming standard practice. Within the context of treatment individualization, the omission of radiotherapy (RT) can be considered. It is thereby of great importance to correctly foresee the side effects attributed to RT. Data from longitudinal studies with contemporary techniques however are sparse. The purpose of the present study was to evaluate patient-reported outcome measures (PROMs) and long-term aesthetic outcome (AO) related to RT in the breast-conserving therapy (BCT) setting for breast cancer over time.Methods: Patients treated with BCT between April 2015 and April 2016 were prospectively included in the cohort. Evaluations were made at six time points: at baseline (before RT), during and at the end of RT, between 3 and 6 months, 1 year and 2 years after RT. AO was scored by the patient and by the BCCT.core software. Further PROMs were measured with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30/-BR23 and the Body Image after Breast Cancer Questionnaire BIBCQ. Patients were evaluated over 2 years. First, we assessed the evolution in time. Second, we tested the differences in mean scale scores of the PROMs between patients with a favourable and an unfavourable AO.Results: One hundred seventy-five patients were included in the analysis. At baseline, unsatisfactory levels were already present for several scales. Most unsatisfactory PROMs improved up to 1 year after RT. Complaints of fatigue increased at the start but decreased up to a lower level than that at baseline up to 1 year after RT (mean difference (MD) 7.6, - 12.3, respectively). Cognitive functioning showed a small decrease at the start with no further significant decrease (MD - 4.73, - 0.21, respectively). Breast symptoms significantly increased during RT but decreased afterwards up to 2 years after RT to lower values than those at baseline and were then considered satisfactory (MD 15.6, - 19.7, - 4.1, respectively). AO scored as PROM associated with BCCT.core and with the body image measures.Conclusions: The study suggests that quality of life and body image are temporarily impaired due to RT. Around one third of patients score their long-term AO as unfavourable. These results should be discussed with the patient and could help in the decision making of the treatment plan and in the clarification of the patient's expectations. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to estimate the probability of an unfavourable aesthetic outcome (AO) 2 years after breast-conserving therapy (BCT) and evaluate the possible influence of brachytherapy (BT) and external beam radiotherapy (EBRT) boost on patient-reported outcomes (PROs) and AO.Patients and Methods: Patients treated with BCT starting April 2015 were prospectively included. Selection of the boost technique followed an in-house flowchart based on the depth of the tumour bed. An electron boost was performed for a superficial clinical target volume (maximum 28 mm under the epidermis), a BT boost was proposed in all other cases. Patients were followed-up for 2 years. AO was scored by the BCCT.core software and the patient. Further PROs were measured with the EORTC QLQ-C30, QOL-BR23 and the BIBCQ questionnaires.Results: The analysis included 175 patients, 80 received a BT boost and 95 an EBRT boost. BT patients were significantly older; had a higher breast cup and band size, body mass index and surgical specimen weight of the wide excision; more seroma at baseline and less positive surgical section margins than patients in the EBRT group, and more patients drank alcohol. Cancer- and breast cancer-specific quality of life (QOL) and body image did not differ between the boost techniques over time. Although mean scores for breast symptoms and sexual enjoyment did differ significantly over time (p = 0.05 and < 0.01, respectively), the effect was due to differences before boost administration. Measured with BCCT.core, AO was unfavourable in 28% of patients 2 years after treatment (31% scored by the patient) and results were similar in the BT and EBRT groups.Conclusion: Using the presented flowchart (See Verhoeven et al. [16]), AO and PROs on QOL or body image up to 2 years after BCT are not influenced by the boost technique. [ABSTRACT FROM AUTHOR]

Purpose: Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. Because it is not well known whether this is subtype dependent, we studied the association between body mass index (BMI) and age at breast cancer diagnosis, or the probability of being diagnosed with a specific breast cancer phenotype, by menopausal status.Methods: All patients with non-metastatic operable breast cancer from the University Hospital Leuven diagnosed between January 1, 2000 and December 31, 2013 were included (n = 7020) in this cross-sectional study. Linear models and logistic regression were used for statistical analysis. Allowing correction for age-related BMI-increase, we used the age-adjusted BMI score which equals the difference between a patient’s BMI score and the population-average BMI score corresponding to the patient’s age category.Results: The quadratic relationship between the age-adjusted BMI and age at breast cancer diagnosis (p = 0.0207) interacted with menopausal status (p < 0.0001); increased age at breast cancer diagnosis was observed with above-average BMI scores in postmenopausal women, and with below-average BMI scores in premenopausal women. BMI was linearly related to the probabilities of Luminal B and HER2-like breast cancer phenotypes, but only in postmenopausal women. The relative changes in probabilities between both these subtypes mirrored each other.Conclusion: BMI associates differently before and after menopause with age at breast cancer diagnosis and with the probability that breast cancer belongs to a certain phenotype. The opposite effect of increasing BMI on relative frequencies of Luminal B and HER2-like breast cancers suggests a common origin. [ABSTRACT FROM AUTHOR]

Purpose: Discordances between the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), expression between primary breast tumors and their subsequent brain metastases (BM) were investigated in breast cancer patients.Methods: We collected retrospective data from 11 institutions in 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution’s ethical research committee.Results: A total of 167 breast cancer patients with BM were included. 25 patients out of 129 with a complete receptor information from both primary tumor and BM (ER, PR, HER2) available, had a change in receptor status: 7 of 26 (27%) ER/PR-positive/HER2-negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR-positive/HER2-positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost both ER/PR and HER2); one of 33 (3%) ER/PR-negative receptor/HER2-positive primaries (gained ER); and 7 of 39 (18%) triple-negative primaries (5 gained ER/PR and 2 gained HER2).Conclusions: The majority of breast cancer patients with BM in this series had primary HER2-enriched tumors, followed by those with a triple-negative profile. One out of 5 patients had a receptor discrepancy between the primary tumor and subsequent BM. Therefore, we advise receptor status assessment of BM in all breast cancer patients with available histology as it may have significant implications for therapy. [ABSTRACT FROM AUTHOR]

Aromatase inhibitor (AI) therapy for estrogen receptor-positive breast cancer is known to induce or enhance musculoskeletal problems. We have previously reported that loss of grip strength is more pronounced in AI-users with extremes in BMI. We here report results from a larger prospective study. Postmenopausal early breast cancer patients scheduled to start AI or tamoxifen therapy were recruited. A functional assessment grip strength test was performed at baseline, 3, 6, and 12 months of therapy. BMI was assessed, and a rheumatologic questionnaire was completed at each visit. 188 patients on an AI and 104 patients on tamoxifen were enrolled. 74 % of AI-users reported new/worsened musculoskeletal complaints compared with 37 % in the tamoxifen group. This was translated in a larger grip strength decrease in patients experiencing AI-induced pain opposed to patients without new/worsened complaints ( p = 0.0002). 15 % of AI-users discontinued therapy due to musculoskeletal symptoms, who were characterized by a larger grip strength reduction versus adherent patients ( p = 0.0107). Young age ( p = 0.0135), taxane-based chemotherapy ( p = 0.0223), and baseline VAS score >4 ( p = 0.0155) were predictors for AI-related musculoskeletal pain. In addition, a quadratic trend of BMI with grip strength change ( p = 0.0090) and probability of discontinuation was observed ( p = 0.0424). Musculoskeletal events were a substantial problem in AI-treated patients and an important reason for treatment discontinuation. The decrease in grip strength was larger in AI- than in tamoxifen-users, with a more pronounced change in symptomatic patients. The inverse relationship between BMI extremes and grip strength change was confirmed in this large group of AI-patients. [ABSTRACT FROM AUTHOR]

Retrospective studies suggest that single nucleotide polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene predict reduced tamoxifen metabolism, better tolerance and worse treatment outcome. We hypothesized that women with this genotype lack tamoxifen-induced endometrial and biochemical changes in follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG). We identified 56 breast cancer patients attending the follow-up clinic with a homozygous mutant (HM) status for the CYP2D6*4 null variant. Here, we report a detailed assessment of tamoxifen activity in 19 CYP2D6 HM women, while they were using tamoxifen either for metastatic ( n = 5) or for early disease ( n = 14). We assessed response to tamoxifen in metastatic disease. Endometrial appearances and serum levels of FSH and SHBG were assessed from retrospective and prospective testing. Our findings do suggest that the presence of two CYP2D6*4 alleles does not exclude a durable response of tamoxifen in metastatic breast cancer. The transvaginal ultrasonographic appearance of the endometrium in CYP2D6*4/*4 patients on tamoxifen is similar as seen in the normal population of tamoxifen users. The endometrium is increased in thickness with subepithelial cysts and endometrial polyps. Serum levels of FSH and SHBG in CYP2D6*4 HM tamoxifen users were in the range of what would be expected during tamoxifen treatment in the general population. Our findings do show CYP2D6*4/*4 carriers to have activity of tamoxifen on breast cancer, endometrium and serum levels of FSH and SHBG. They support clinical trials prospectively testing the effect of CYP2D6 genetic variability in response to tamoxifen before denying this drug to breast cancer patients only based on their CYP2D6*4 status. [ABSTRACT FROM AUTHOR]