scholarly journals Pilot Study of Anti-Th2 Immunotherapy for the Treatment of Breast Cancer-Related Upper Extremity Lymphedema

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 934
Author(s):  
Babak J. Mehrara ◽  
Hyeung Ju Park ◽  
Raghu P. Kataru ◽  
Jacqueline Bromberg ◽  
Michelle Coriddi ◽  
...  

Recent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer–related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months. We measured limb volumes, bioimpedance, and skin tonometry, and analyzed the quality of life (QOL) using a validated lymphedema questionnaire (Upper Limb Lymphedema 27, ULL-27) before treatment, immediately after treatment, and 4 months following treatment withdrawal. We also obtained 5 mm skin biopsies from the normal and lymphedematous limbs before and after treatment. Treatment was well-tolerated; however, one patient with a history of cellulitis developed cellulitis during the trial and was excluded from further analysis. We found no differences in limb volumes or bioimpedance measurements after drug treatment. However, QBX258 treatment improved skin stiffness (p < 0.001) and improved QOL measurements (Physical p < 0.05, Social p = 0.01). These improvements returned to baseline after treatment withdrawal. Histologically, treatment decreased epidermal thickness, the number of proliferating keratinocytes, type III collagen deposition, infiltration of mast cells, and the expression of Th2-inducing cytokines in the lymphedematous skin. Our limited study suggests that immunotherapy against Th2 cytokines may improve skin changes and QOL of women with BCRL. This treatment appears to be less effective for decreasing limb volumes; however, additional studies are needed.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 44-44 ◽  
Author(s):  
Jacques Raphael ◽  
Sunil Verma ◽  
Paul Hewitt ◽  
Andrea Eisen

44 Background: In May 2013, AJ revealed to the media that she had undergone preventive double mastectomy. The actress had a family history of breast and ovarian cancer and tested positive for the BRCA1 gene mutation. Media coverage has been extensive, but it’s not clear what messages the public and professional medical staff took from this personal story that sometimes could be misleading. Methods: We conducted a retrospective review in our centre using data from the clinical database of the Familial Cancer Program in a tertiary care cancer centre. The impact of AJ’s story on genetic counseling referrals was assessed by comparing the number of referrals made 6 months before and after the story. In addition, the quality of referrals was reported by comparing the number of patients who qualified for genetic testing as defined by the Ontario Ministry of Health and Long Term Care and the ones who carried a BRCA1/2 mutation before and after the media release. Results: The number of women referred for genetic counseling increased by 85% after the release of AJ’s story (479 before versus 887 after). This translated to an increase of 99% in the number of women who qualified for a genetic testing (211 before versus 419 after). Among them, 120 and 254 women had a history of breast and ovarian cancer in their family, 16 and 37 women had a history of male breast cancer in their family, and 28 and 15 women were diagnosed with breast cancer at the age of 35 or less before and after AJ’s story respectively. Furthermore, the number of BRCA1/2 carriers identified increased by 107% (29 (14 BRCA1, 15 BRCA2) before and 60 (32 BRCA1, 28 BRCA2) after). Conclusions: This study clearly shows that the number of genetic referrals doubled after AJ’s story. Nevertheless, the quality of referral remained the same with nearly the same percentage of patients who qualified for genetic testing and who were identified as BRCA1/2 carriers. The challenge is to meet the increased demand for cancer genetic services including screening, counseling, testing, and preventive surgery. After AJ’s story the current model of genetic counseling may need to be revisited.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2506
Author(s):  
Mark van Barele ◽  
Bernadette A. M. Heemskerk-Gerritsen ◽  
Yvonne V. Louwers ◽  
Mijntje B. Vastbinder ◽  
John W. M. Martens ◽  
...  

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Roger Hesselstrand ◽  
Jörg H. W. Distler ◽  
Gabriela Riemekasten ◽  
Dirk M. Wuttge ◽  
Marie Törngren ◽  
...  

Abstract Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia (n = 3) and headache (n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration ClinicalTrials.gov, NCT01487551. Registered on 7 September 2011


2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Imran Rafi ◽  
Susmita Chowdhury ◽  
Tom Chan ◽  
Ibrahim Jubber ◽  
Mohammad Tahir ◽  
...  

2017 ◽  
Vol 5 (2) ◽  
pp. 29
Author(s):  
Muhammad Taukhid

Background : Fatigue is feeling tired physically, psychologically, cognitively perceived cancer patients while undergoing therapies for the disease, including chemotherapy. The purpose of this study was to determine differences in the level of fatigue in cancer patients between before and after aerobic exercise combined with relaxation techniques of yoga. Methods :  This study used Quasi-experimental design with pretest-posttest control group in patients with breast cancer in the course of chemotherapy. The sampling methods used purposive sampling. The fatigue level was collected by subjective instruments Pipper Fatigue Scale (PFS), and then analyzed by the Independent and Dependent T test, and multivariate analysis used linear regression with a significance value of α 0.05. Results :  There were differences in the level of fatigue post-test between the intervention group and the control group with a difference of 1.25 (p = 0.013). History of previous exercise may explain the 17.8% level of fatigue that occurs in patients with breast cancer in the course of chemotherapy, the rest was explained by other variables. Conclusion : There were a decrease in the level fatigue statistically, however clinically the level of fatigue remain the same catagories.


Author(s):  
Helena Carreira ◽  
Rachael Williams ◽  
Harley Dempsey ◽  
Susannah Stanway ◽  
Liam Smeeth ◽  
...  

Abstract Purpose There is limited high-quality evidence on quality of life, anxiety, and depressive symptoms in breast cancer survivors and women with no history of cancer. We aimed to address this by comparing patient-reported outcomes between breast cancer survivors and women with no history of breast cancer. Methods Breast cancer survivors and women with no prior cancer were selected from the UK Clinical Practice Research Datalink GOLD primary care database, which includes population-based primary care electronic health record data. Breast cancer survivors and controls were frequency matched by age and primary care practice. Outcomes were assessed with validated instruments via postal questionnaire. Linear and logistic regression models were fitted to estimate adjusted associations between breast cancer survivorship and outcomes. Results A total of 356 breast cancer survivors (8.1 years post diagnosis) and 252 women with no prior cancer participated in the study. Compared with non-cancer controls, breast cancer survivors had poorer QoL in the domains of cognitive problems (adjusted β (aβ) = 1.4, p = 0.01), sexual function (aβ = 1.7, p = 0.02) and fatigue (aβ = 1.3, p = 0.01), but no difference in negative feelings, positive feelings, pain, or social avoidance. Breast cancer survivors had higher odds of borderline-probable anxiety (score ≥ 8) (adjusted OR = 1.47, 95%CI:1.15–1.87), but no differences in depression. Advanced stage at diagnosis and chemotherapy treatment were associated with poorer QoL. Conclusions Compared with women with no history of cancer, breast cancer survivors report more problems with cognition, sexual function, fatigue, and anxiety, particularly where their cancer was advanced and/or treated with chemotherapy. Implications for Cancer Survivors Breast cancer survivors with more advanced disease and/or treated with chemotherapy should be closely monitored and, when possible, offered evidence-based intervention for fatigue, cognitive dysfunction, and sexual problems.


2021 ◽  
Author(s):  
Jenny Eva Maria Heiman ◽  
Aron Onerup ◽  
David Bock ◽  
Eva Haglind ◽  
Roger Olofsson Bagge

Abstract PurposeWe conducted a randomised controlled trial (PhysSURG-B) to assess the short- and long-term effects of a non-supervised physical activity intervention at the time of breast cancer surgery. Here we report a secondary outcome, quality of life (QoL).MethodsFemale patients planned for surgery were randomly assigned to either an intervention of 30 minutes of self-administered physical aerobic activity daily 2 weeks before and 4 weeks after surgery, or control. QoL was assessed with questionnaires at baseline, 4 weeks and 12 months postop using the instruments FACT-B, RAND-36 and EQ-VAS.ResultsOut of 354 included participants at 12 months follow-up after surgery, 287 were available for QoL analysis. Comparing intervention to control, the results for the FACT- B score at 4 weeks showed an odds ratio (OR) of 0.975 (95% CI 0.636-1.495) and at 12 months an OR of 0.883 (95% CI 0.581-1.342). The subgroup of patients receiving adjuvant chemotherapy had significantly lower FACT-B at 12 months compared to no chemotherapy (OR 0.475, 95% CI 0.300-0.735). EQ-VAS showed OR 1.163 (95% CI 0.760-1.779) and 0.817 (95% CI 0.536-1.244) at 4 weeks and 12 months, respectively. RAND-36 domains “role limitations due to physical health” and “pain” showed a decrease at 4 weeks in both groups, returning towards baseline at 12 months follow-up.ConclusionAn intervention of non-supervised physical activity before and after surgery for breast cancer had no effect on QoL. Patients receiving adjuvant chemotherapy had significantly lower QoL, regardless of study group.Trial registrationClinicalTrials.gov registration number: NCT 02560662. Registered 25 September, 2015.


The Breast ◽  
2010 ◽  
Vol 19 (5) ◽  
pp. 404-409 ◽  
Author(s):  
M. de Kok ◽  
T. van der Weijden ◽  
A.G.H. Kessels ◽  
C.D. Dirksen ◽  
H.J.M. Sixma ◽  
...  

2008 ◽  
Vol 26 (2) ◽  
pp. 86-93 ◽  
Author(s):  
Michele Alem ◽  
Maria Salete Costa Gurgel

Objective To evaluate the effect of acupuncture on rehabilitation of motor function, reduction in lymphoedema and improvement in perceived heaviness and tightness in the arms of women who had undergone breast cancer surgery. Subjects and Methods Twenty nine women who had had mastectomy or segmentectomy with axillary dissection, presenting with lymphoedema and/or a decrease in movement amplitude of the upper limb ipsilateral to surgery were studied. The patients underwent 24 acupuncture sessions once a week from February to December 2004. The movement amplitude of shoulder flexion and abduction and circumferential measurements of the arm, forearm and wrist were evaluated before and after one, three and six months of treatment. Statistical analysis was performed by Friedman's test. Results Significant improvements in range of movement of shoulder flexion and abduction (P<0.001), degree of lymphoedema (P=0.016), and sense of heaviness and tightening (P<0.001) in the affected limb after six months of therapy were observed. For circumferential measurements of the arm, forearm and wrist, no significant improvement between the different periods of treatment was observed. Conclusions Acupuncture in rehabilitation after breast cancer surgery was shown to be associated with improvements in movement amplitude of the shoulder, symptoms of heaviness and tightness in the arm, and the degree of lymphoedema. However, controlled trials should be performed to ascertain whether the results were due to the natural history of the complaint or the acupuncture treatment.


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