scholarly journals Impact of BMI for clinical outcomes in Japanese breast cancer patients

2020 ◽  
Vol 50 (3) ◽  
pp. 230-240
Author(s):  
Naomi Gondo ◽  
Masataka Sawaki ◽  
Masaya Hattori ◽  
Akiyo Yoshimura ◽  
Haruru Kotani ◽  
...  

Abstract Objective The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. Methods Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is <18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, >30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. Results From the database of our institution, we identified 3223 patients. The median follow-up period was 57 months (1–149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38–4.28; P < 0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15–6.44; P = 0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11–3.02; P = 0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15–11.04; P < 0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52–13.34; P < 0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02–4.89; P = 0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. Conclusion Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.


1997 ◽  
Vol 15 (4) ◽  
pp. 1385-1394 ◽  
Author(s):  

PURPOSE Adjuvant tamoxifen has been shown to reduce relapse and mortality among node-positive post-menopausal breast cancer patients. The value of adding chemotherapy to tamoxifen is controversial. PATIENTS AND METHODS Between July 1986 and April 1993, 1,266 postmenopausal breast cancer patients with node-positive disease were randomly assigned to receive one of four adjuvant therapy regimens: (A) tamoxifen alone for 5 years; (B) tamoxifen plus three courses of early cyclophosphamide, methotrexate, and fluorouracil (CMF) on months 1, 2, and 3; (C) tamoxifen plus delayed single courses of CMF on months 9, 12, and 15; (D) tamoxifen plus early and delayed CMF on months 1, 2, 3, 9, 12, and 15. The two-by-two factorial design allowed two direct comparisons: early CMF (B and D) versus no early CMF (A and C), and delayed CMF (C and D) versus no delayed CMF (A and B). Estrogen receptor (ER) status was known for all patients and was used to stratify the randomization. A total of 1, 212 patients (96%) were eligible and assessable. The median follow-up duration was 60 months. RESULTS The results of the two-by-two factorial comparisons were as follows: (1) early CMF added to tamoxifen significantly improved 5-year disease-free survival (DFS; 64% v 57%; hazards ratio [HR], 0.79; 95% confidence interval [CI], 0.66 to 0.95; P = .01); and (2) delayed CMF added to tamoxifen did not improve DFS (5-year DFS, 61% v 60%; HR, 0.97; 95% CI, 0.81 to 1.17; P = .77). For patients with ER-positive tumors, the addition of CMF, either early or delayed or both, reduced the relative risk of relapse by 22% to 36%. In contrast, for patients with ER-negative tumors, tamoxifen with delayed CMF was associated with a nonsignificant increased risk of relapse (HR, 1.27; 95% CI, 0.92 to 1.76; P = .15). CONCLUSION Postmenopausal patients with node-positive breast cancer should be offered combination chemotherapy in addition to tamoxifen. Tamoxifen should not be initiated before CMF, as this might be detrimental, especially for patients with ER-negative tumors.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19109-e19109
Author(s):  
Nathalie LeVasseur ◽  
Kaylie Willemsma ◽  
Caroline A. Lohrisch ◽  
Nafisha Lalani ◽  
Stephen K. L. Chia ◽  
...  

e19109 Background: Estrogen positive (ER) advanced breast cancers (ABC) are associated with a longer survival compared to other subtypes. However, clinical equipoise remains for the management of oligometastatic disease. While recent phase I and II data support the use of metastasis-directed therapy, breast cancer patients remain underrepresented and real-world outcomes for breast cancer patients with directed treatment for oligometastases is lacking. Methods: The BC Cancer Breast Cancer Outcomes Unit (BCOU) database was utilized to identify patients with ER positive breast cancer referred to BC Cancer from 2005-2014 with documented metastases. Baseline clinical, pathological and treatment data were compiled. Overall survival (OS) was compared between the group with oligometastatic disease(OM) (defined as < = 5 foci of metastases) and the group with non-oligometastatic disease (defined as > = 6 foci of metastases) using Kaplan-Meier survival curves. Key secondary endpoints included metastasis-directed treatment impact, based on the site of metastasis, local control (LC) and distant failure (DF) rate. Results: A total of 938 patients met the inclusion criteria. Of these, 191 (20.4%) had OM and 747 (79.6%) had widespread disease at 1st diagnosis of ABC. The groups were well balanced for clinical characteristics (all p > 0.05), with a median age of 59yrs (23-99). 84% were ductal carcinomas, 14% were also HER2 positive. Sites of oligometastases were bone (66.5%), liver (12.0%), brain (8.4%) and lung (5.8%). Median follow-up was 7.4 yrs. Median OS was 24 mo (95% CI 20.2, 27.8) for patients with OM and 11 mo (9.5, 12.5) for those with widespread disease (p < 0.0001). In the OM group, 114 (59.7%) of patients received metastasis-directed treatment, whereas 77 (40.3%) did not. Treatment modalities included radiation in 53.4% of patients, surgery in 8.9% of patients and stereotactic body radiotherapy (SBRT) in 3.7%. Median OS was 24 mo (18.3, 29.7) for patients who received metastasis-directed treatment and 23 mo (17.5, 28.5) for those who did not (p = 0.954). Patients with bone-only metastases had a median OS of 27mo with directed treatment and 25mo without directed-treatment (p = 0.334). Conclusions: Oligometastatic state was associated with a significantly better OS. Metastasis-directed treatment was associated with a non-significant OS difference in patients with bone-only metastases in a real world cohort. However, the impact of modern systemic treatment and SBRT methods are evolving. Large prospective randomized studies of this approach merit further study.


Tumor Biology ◽  
2020 ◽  
Vol 42 (6) ◽  
pp. 101042832092530
Author(s):  
A Ianza ◽  
F Giudici ◽  
C Pinello ◽  
SP Corona ◽  
C Strina ◽  
...  

A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival ( p = 0.009) and overall survival ( p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Anna Morra ◽  
Maria Escala-Garcia ◽  
Jonathan Beesley ◽  
Renske Keeman ◽  
Sander Canisius ◽  
...  

Abstract Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6591-6591
Author(s):  
H. T. Gold ◽  
H. T. Do

6591 Background: The objective of this study is to understand the impact of timely radiotherapy on disease-free survival (DFS) in early breast cancer patients ages 65 and above. Methods: The study population is women diagnosed from 1991–1999 in the linked SEER-Medicare database who underwent breast-conserving surgery and radiotherapy within 6 months of diagnosis. Median followup varies from 4 years for ductal carcinoma in situ (DCIS)(n=1,185) to 5 years for Stage 1 disease (n=7,481), and ranges from 0–11 years. Descriptive and proportional hazards analysis of this longitudinal cohort were conducted. Covariates include age, race, poverty, marital status, comorbidity, rurality, radiation completion and delay, elapsed time since diagnosis, comedo necrosis histology (DCIS only), and chemotherapy receipt (Stage 1 only). Subjects were censored at end of followup (including enrolling in Medicare managed care from Medicare fee-for-service) or death. Treatment delay is defined as radiotherapy beginning 8+ weeks post-surgery without chemotherapy or 4+ weeks after chemotherapy ends; other definitions also were explored. Radiotherapy is considered complete if the patient received greater than 16/22 of expected treatments, based on scientific literature. Results: DFS is negatively associated with radiation delay (OR=1.24, p=0.003 for Stage 1; OR=1.40, p=0.054 for DCIS) and Klabunde's inpatient comorbidity index (OR=1.32, p=0.004 for Stage 1; OR=1.66, p=0.065 for DCIS). Additional analyses suggest that a longer delay of 12+ weeks post-surgery (16+ weeks post-chemotherapy) further reduces DFS (OR=4.66, p<0.0001 for Stage 1; OR=12.4, p<0.0001 for DCIS). Non-white women with Stage 1 disease are more likely to delay radiotherapy (p<0.0001), but are not more likely to have worse outcomes (p>0.3). Conclusions: Delayed initiation of radiation therapy is associated with decreased DFS following radiotherapy for early breast cancer and DCIS. Non-white race is associated with delay, but not reduced DFS. Programs targeting referring physicians and patients should be developed to promote timely receipt of radiotherapy by early breast cancer patients, thereby reducing the risk of adverse health outcomes. No significant financial relationships to disclose.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Tone Frost Bathen ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
...  

Abstract Background The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Methods The study setting was on university hospital level with primary and secondary care functions in south-west Norway. Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n = 25) or standard pre-operative fasting (n = 35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n = 18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p = 0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r = 0.680; p = 0.002). In all tumors (n = 29), glutamate was increased in tumors with high proliferation (t-test; p = 0.009), independent of intervention group. Moreover, there was a positive correlation between tumor size and proliferation markers in the carbohydrate group only. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Trial of registration ClinicalTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.


2000 ◽  
Vol 15 (2) ◽  
pp. 135-138 ◽  
Author(s):  
J.-L. Floiras ◽  
K. Hacene ◽  
F. Turpin ◽  
F. Spyratos

The impact of ER levels on the response to tamoxifen was evaluated in 1,623 postmenopausal primary breast cancer patients treated at our center (median follow-up 8.2 years). In patients receiving adjuvant tamoxifen a significantly longer disease-free survival (DFS) was observed when ER levels were elevated (p<0.00001). Very high ER (>424 fmol/mg protein) appeared to be detrimental in node-negative patients not treated with tamoxifen.


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