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100 result(s) for "McCready, David R."
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Cancer-related fatigue and associated disability in post-treatment cancer survivors
Purpose Cancer-related fatigue (CRF) is the most prevalent and distressing symptom among cancer patients and survivors. However, research on its prevalence and related disability in the post-treatment survivorship period remains limited. We sought to describe the occurrence of CRF within three time points in the post-treatment survivorship trajectory. Methods A self-administered mail-based questionnaire which included the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and the World Health Organisation Disability Assessment Schedule 2.0 was sent to three cohorts of disease-free breast, prostate or colorectal cancer survivors (6–18 months; 2–3 years; and 5–6 years post-treatment). Clinical information was extracted from chart review. Frequencies of significant fatigue by diagnostic group and time cohorts were studied and compared. Multivariate logistic regressions were conducted to examine the associations between CRF and demographic, clinical, and psychosocial variables. Results One thousand two hundred ninety-four questionnaire packages were returned (63 % response rate). A total of 29 % (95 % CI [27 % to 32 %]) of the sample reported significant fatigue (FACT-F ≤34), and this was associated with much higher levels of disability ( p  < 0.0001). Breast (40 % [35 % to 44 %]) and colorectal (33 % [27 % to 38 %]) cancer survivors had significantly higher rates of fatigue compared with the prostate group (17 % [14 % to 21 %]) ( p  < 0.0001). Fatigue levels did not differ between the three time cohorts. The main factors associated with CRF included physical symptom burden, depression, and co-morbidity (AUC, 0.919 [0.903 to 0.936]). Conclusions Clinically relevant levels of CRF are present in approximately 1/3 of cancer survivors up to 6 years post-treatment, and this is associated with high levels of disability. Implications for Cancer Survivors Clinicians need to be aware of the chronicity of CRF and assess for it routinely in medical practice. While there is no gold standard treatment, non-pharmacological interventions with established efficacy can reduce its severity and possibly minimize its disabling impact on patient functioning. Attention must be paid to the co-occurrence and need for possible treatment of depression and other co-occurring physical symptoms as contributing factors.
Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study
Metformin may exert anti-cancer effects through indirect (insulin-mediated) or direct (insulin-independent) mechanisms. We report results of a neoadjuvant “window of opportunity” study of metformin in women with operable breast cancer. Newly diagnosed, untreated, non-diabetic breast cancer patients received metformin 500 mg tid after diagnostic core biopsy until definitive surgery. Clinical (weight, symptoms, and quality of life) and blood [fasting serum insulin, glucose, homeostasis model assessment (HOMA), C-reactive protein (CRP), and leptin] attributes were compared pre- and post-metformin as were terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Ki67 scores (our primary endpoint) in tumor tissue. Thirty-nine patients completed the study. Mean age was 51 years, and metformin was administered for a median of 18 days (range 13–40) up to the evening prior to surgery. 51 % had T1 cancers, 38 % had positive nodes, 85 % had ER and/or PgR positive tumors, and 13 % had HER2 overexpressing or amplified tumors. Mild, self-limiting nausea, diarrhea, anorexia, and abdominal bloating were present in 50, 50, 41, and 32 % of patients, respectively, but no significant decreases were seen on the EORTC30-QLQ function scales. Body mass index (BMI) (−0.5 kg/m 2 , p  < 0.0001), weight (−1.2 kg, p  < 0.0001), and HOMA (−0.21, p  = 0.047) decreased significantly while non-significant decreases were seen in insulin (−4.7 pmol/L, p  = 0.07), leptin (−1.3 ng/mL, p  = 0.15) and CRP (−0.2 mg/L, p  = 0.35). Ki67 staining in invasive tumor tissue decreased (from 36.5 to 33.5 %, p  = 0.016) and TUNEL staining increased (from 0.56 to 1.05, p  = 0.004). Short-term preoperative metformin was well tolerated and resulted in clinical and cellular changes consistent with beneficial anti-cancer effects; evaluation of the clinical relevance of these findings in adequately powered clinical trials using clinical endpoints such as survival is needed.
Regional Nodal Irradiation in Early-Stage Breast Cancer
Women with breast cancer who are undergoing breast-conserving surgery were assigned to receive whole-breast irradiation with or without regional nodal irradiation. At 10 years, disease-free survival in the nodal-irradiation group was improved but overall survival was not. Many women with early-stage breast cancer undergo breast-conserving surgery followed by whole-breast irradiation, which reduces the rate of local recurrence. 1 – 3 Radiotherapy to the chest wall and regional lymph nodes, termed regional nodal irradiation, which is commonly used after mastectomy in women with node-positive breast cancer who are treated with adjuvant systemic therapy, reduces locoregional and distant recurrence and improves overall survival. 4 – 6 An unanswered question is whether the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery has the same effect. Whole-breast irradiation may involve irradiation of the lower axillary and internal mammary lymph nodes. 7 However, regional . . .
Does oncoplastic surgery increase immediate (30-day) postoperative complications? An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database
Purpose Although there has been a significant increase in the use of oncoplastic surgery (OPS), data on the postoperative safety of this approach are limited compared to traditional lumpectomy. This study aimed to compare the immediate (30-day) postoperative complications associated with OPS and traditional lumpectomy. Methods An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was performed on women with breast cancer who underwent OPS or traditional lumpectomy. Logistic regression was used to explore the effect of type of surgery on the outcome of interest. Results A total of 109,487 women were analyzed of whom 8.3% underwent OPS. OPS had a longer median operative time than traditional lumpectomy. The unadjusted immediate (30-day) overall complication rate was significantly higher with OPS than traditional lumpectomy (3.8% versus 2.6%, p  < 0.001). After adjusting for baseline differences, overall 30-day postoperative complications were significantly higher amongst women undergoing OPS compared with traditional lumpectomy (OR 1.41, 95%CI 1.24–1.59). Factors that were independent predictors of overall 30-day complications included higher age, higher BMI, race, smoking status, lymph node surgery, neoadjuvant chemotherapy, ASA class ≥ 3, in situ disease, and year of operation. The interaction term between type of surgery and operative time was not statistically significant, indicating that operative time did not modify the effect of type of surgery on immediate postoperative complications. Conclusions Although there were slightly higher overall complication rates with OPS, the absolute rates remained quite low for both groups. Therefore, OPS may be performed in women with breast cancer who are suitable candidates.
Psychosocial Functioning in Women with Early Breast Cancer Treated with Breast Surgery With or Without Immediate Breast Reconstruction
Purpose To compare psychosocial function outcomes in early breast cancer patients treated with breast-conserving surgery (BCS), mastectomy alone (MA), and mastectomy with immediate breast reconstruction (IBR) at 1 year after surgery. Methods Early-stage (stage 0–2) breast cancer patients treated with BCS, MA, and IBR at the University Health Network, Toronto, Ontario, Canada between May 1 2015 and July 31 2016 were prospectively enrolled. Their changes in psychosocial functioning from baseline to 12 months following surgery were compared by using the BREAST-Q, Hospital Anxiety and Depression Scale, and Impact of Event Scale with ANOVA and linear regression. Results There were 303 early-stage breast cancer patients: 155 underwent BCS, 78 MA, and 70 IBR. After multivariable regression accounting for age, baseline score, income, education, receipt of chemoradiation or hormonal therapy, ethnicity, cancer stage, and unilateral versus bilateral surgery, breast satisfaction was highest in BCS (72.1, SD 19.6), followed by IBR (60.0, SD 18.0), and MA (49.9, SD 78.0) at 12 months, p  < 0.001. Immediate breast reconstruction had similar psychosocial well-being (69.9, SD 20.6) compared with BCS (78.5, SD 20.6), p  = 0.07. Sexual and chest physical well-being were similar between IBR, BCS, and MA, p  > 0.05. Conclusions Our study found that in a multidisciplinary breast cancer centre where all three breast ablative and reconstruction options are available to early breast cancer patients, either BCS or IBR can be used to provide patients with a higher degree of satisfaction and psychosocial well-being compared with MA in the long-term.
‘Taking Control of Cancer’: Understanding Women’s Choice for Mastectomy
Purpose Rates of both unilateral (UM) and contralateral prophylactic mastectomy (CPM) for unilateral early-stage breast cancer (ESBC) have been increasing since 2003. Recent studies suggest that this increase may be due to women choosing UM and CPM because of fear. We conducted an in-depth qualitative study to identify those factors influencing a woman’s choice for more extensive surgery. Methods Semi-structured interviews were conducted with breast cancer patients to examine the experiences, decision making, and choice of UM ± CPM for the treatment of ESBC. Purposive sampling identified suitable candidates for breast-conserving therapy (BCT) who underwent UM ± CPM. Interviews were guided by grounded theory methodology, and constant comparative analysis identified key concepts and themes. Results Data saturation was achieved after 29 interviews. ‘Taking control of cancer’ was the dominant theme. Fear of breast cancer was expressed at diagnosis and remained throughout decision making. Personal experiences of family or friends ‘living with cancer’ were the most influential source of information during the decision-making process. Fear translated into an overestimated risk of recurrence, contralateral breast cancer (CBC), and death. Despite surgeons discussing equivalent survival with BCT, UM ± CPM patients believed that by choosing UM ± CPM they would eliminate recurrence, CBC and live longer. By choosing more extensive surgery, women were actively trying to control cancer outcomes as more surgery was believed to offer greater survival. Conclusions Women seek UM and CPM to take control of cancer and manage their fear. It is important for surgeons to understand how personal experiences shape women’s choice for UM ± CPM to facilitate informed decision making.
Utilization of a rapid diagnostic centre during the COVID-19 pandemic reduced diagnostic delays in breast cancer
Access to breast imaging was restricted during the first wave of the COVID-19 pandemic. We assessed the impact of healthcare restrictions on the Gattuso Rapid Diagnostic Centre (GRDC) at the Princess Margaret Cancer Centre. A retrospective review of patients seen at the GRDC between March 12 - August 31, 2020 and the corresponding period from 2019 was performed. There was an 18.6% decrease in patients seen at the GRDC (n = 429 in 2020 vs. 527 in 2019). Time from the first abnormal breast image to diagnosis was significantly shorter (17.4 days [IQR 13.0–21.8] in 2020 vs. 25.9 days [21.0–30.8] in 2019; p = 0.020) with no appreciable difference in time from diagnosis to consult or from consult to surgery. The GRDC enabled patients with concerning breast symptoms to access breast imaging, which helped to ensure timely treatment during the first wave of the pandemic. [Display omitted] •The rapid diagnostic clinic ensured access to breast imaging during the pandemic.•A higher proportion of patients presented with palpable lesions.•Despite this change in presentation, there was no increase in cancer diagnoses.
Primary MALT lymphoma of the breast: pathological and radiological characteristics
Purpose Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. Methods This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. Results All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up. Conclusion Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. Trial registration number University Health Network Ethics Committee (CAPCR/UHN REB number 19–5844), retrospectively registered.
Evolving surgical treatment decisions for male breast cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database
BackgroundMale breast cancer (MBC) is a rare malignancy, and gender-specific treatment outcomes are currently lacking. The use of a large, multi-national surgical-outcomes database may provide a better understanding of treatment patterns and postoperative morbidity in men who undergo oncological breast surgery.MethodsA retrospective cohort analysis was conducted between 2007 and 2016 using the American College of Surgeons National Surgical Quality Improvement Program database (NSQIP), examining MBC treatment patterns and postoperative complication rates. All men undergoing surgery for the treatment of invasive or in situ carcinoma of the breast were identified. Clinical characteristics, demographics, and surgical treatment options most frequently used for this population were described. In addition, the 30-day postoperative complication rates in the surgical treatment of male breast cancer were evaluated.ResultsA total of 1773 MBC patients with a median age of 65 years (IQR 56–74 years) were included in this analysis. Mean body mass index (BMI) was 29.1 (IQR 25.4–33.8). In this study population, 177 (10.0%) had a diagnosis of in situ breast cancer, while the remaining 1596 (90.0%) had invasive disease. While most men underwent mastectomy, 282 (15.9%) had breast-conserving surgery. There were 74 (4.2%) patients who underwent immediate breast reconstruction. In addition, 118 (6.7%) patients elected to have a contralateral prophylactic mastectomy. Overall, the rate of morbidity was 4.6%, comprising mostly of wound complications (3.2%).ConclusionAnalysis of this large, prospective multi-institutional cohort revealed that complication rates are low and comparable to reported rates in the female breast cancer population. What is also significant about this analysis is that the cohort demonstrated the importance of cosmetic considerations in MBC patients, as some men decide to undergo breast-conserving surgery or immediate breast reconstruction. Contralateral prophylactic mastectomy in the treatment of MBC is also performed.
Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study
Introduction The antidiabetic drug metformin exhibits potential anticancer properties that are believed to involve both direct (insulin-independent) and indirect (insulin-dependent) actions. Direct effects are linked to activation of AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of rapamycin mTOR signaling, and indirect effects are mediated by reductions in circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling. However, the in vivo impact of metformin on cancer cell signaling and the factors governing sensitivity in patients remain unknown. Methods We conducted a neoadjuvant, single-arm, “window of opportunity” trial to examine the clinical and biological effects of metformin on patients with breast cancer. Women with untreated breast cancer who did not have diabetes were given 500 mg of metformin three times daily for ≥2 weeks after diagnostic biopsy until surgery. Fasting blood and tumor samples were collected at diagnosis and surgery. Blood glucose and insulin were assayed to assess the physiologic effects of metformin, and immunohistochemical analysis of tumors was used to characterize cellular markers before and after treatment. Results Levels of IR expression decreased significantly in tumors ( P  = 0.04), as did the phosphorylation status of protein kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2, T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) ( P  = 0.0001, P  < 0.0001, P  < 0.005 and P  = 0.02, respectively). All tumors expressed organic cation transporter 1, with 90% (35 of 39) exhibiting an Allred score of 5 or higher. Conclusions Reduced PKB/Akt and ERK1/2 phosphorylation, coupled with decreased insulin and IR levels, suggest insulin-dependent effects are important in the clinical setting. These results are consistent with beneficial anticancer effects of metformin and highlight key factors involved in sensitivity, which could be used to identify patients with breast cancer who may be responsive to metformin-based therapies. Trial registration ClinicalTrials.gov identifier: NCT00897884 . Registered 8 May 2009.