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Obesity and breast cancer: Risk, outcomes, and future considerations
Abstract
The proportion of adults who are obese has increased dramatically in the United States over the last 30 years. Obesity has been linked to an increased risk of developing a number of malignancies, including postmenopausal breast cancer. Evidence also suggests that obesity at the time of breast cancer diagnosis is linked to an increased risk of breast cancer-specific and overall mortality in both premenopausal and postmenopausal women with early-stage breast cancer. Obesity is linked to an increased risk of secondary malignancies in women with early breast cancer, and studies suggest that weight gain after diagnosis increases overall mortality. Despite the data linking obesity to poor outcomes in women with early breast cancer, there are currently no data from randomized trials testing the impact of weight loss on breast cancer outcomes. A number of recent randomized controlled trials have shown that weight loss interventions are feasible in obese survivors of breast cancer, yielding loss of 5% to 6% of body weight, and several ongoing randomized phase 3 clinical trials are evaluating the effect of weight loss interventions on breast cancer outcomes. These studies will help define the role of weight loss in the management of obese women with early breast cancer. © 2016, Millennium Medical Publishing, Inc. All rights reserved.
... Obesity and the metabolic consequences related to obesity have long been linked to increased incidence of cancer and worse cancer outcomes [1][2][3][4][5][6][7]. Obesity is an independent risk factor for at least 19 types of cancer, including breast cancer, in postmenopausal women [7]. ...
... Studies show that obesity is associated with worse overall and cancer-specific survival in breast cancer patients [3][4][5][6]10]. One meta-analysis of 213,075 women and 41,477 deaths showed that overweight increased the risk of total mortality and breast cancer-specific death by 41% and 35%, respectively [3]. ...
... One meta-analysis of 213,075 women and 41,477 deaths showed that overweight increased the risk of total mortality and breast cancer-specific death by 41% and 35%, respectively [3]. Findings from a systematic review of the literature demonstrated that breast cancer survivors with obesity had a greater risk of developing a new, second primary malignancy, and that obesity increased the risk of malignancy in the contralateral breast by 37% [4,11]. ...
Objective
Obesity is related to the recurrence of breast cancer. In‐person groups or individual telephone counseling currently comprise the behavioral weight loss (BWL) programs tested for cancer survivors. Group support via telehealth may be convenient and provide support from fellow survivors, but feasibility, acceptability, and efficacy testing are needed.
Methods
A single‐arm, 6‐month BWL program was conducted for female breast cancer survivors with an ECOG performance 0 or 1, BMI > 25 kg/m², and > 6 months from completion of adjuvant chemotherapy and/or radiation treatment. Participants attended 22 video group sessions over 6 months, completing acceptability ratings, weight measurements, Patient Health Questionnaire (PHQ‐9), City of Hope Breast Cancer Quality of Life Scale (QOL), and International Physical Activity Questionnaire. Changes in survey scores and weight (last‐observation carried forward) and differences in outcomes by patients' race were computed with paired t‐tests, ANCOVAs and Chi‐square tests.
Results
Twenty‐one (5 Black, 15 White, 1 Asian American; Mean (SD) = 60.7 (11.6) years; BMI 33.1 (5.9) kg/m²) survivors enrolled with 90% retention and 81.3% of sessions attended. Acceptability ratings were high (all > 4 on a five‐point scale). Mean (SD) weight loss was 5.9% (5.2%), with 60% losing ≥ 5% of baseline weight; White participants lost 7.5% and Black participants lost 1.9% (p = 0.04). Significant improvements were observed in mood (PHQ‐9; p = 0.01) and physical wellbeing QOL (p = 0.01). Physical activity did not change.
Conclusion
This telehealth group BWL program was feasible and acceptable for breast cancer survivors, yielding a clinically significant weight loss. Future studies should test this intervention in larger, more diverse samples.
Trail Registration
ClinicalTrials.gov identifier: NCT04855552, posted April 22, 2021
... Obesity, defined as BMI > 30 kg/m 2 , is associated with increased incidence and worse overall outcomes and cancer-specific survival in breast cancer patients as compared to breast cancer patients without obesity [1,2]. Breast cancer survivors (BCS) with obesity have an increased risk of total and breast cancer-specific mortality and developing a second primary breast cancer or contralateral breast cancer as compared to BCS without obesity [1,3]. ...
... Obesity, defined as BMI > 30 kg/m 2 , is associated with increased incidence and worse overall outcomes and cancer-specific survival in breast cancer patients as compared to breast cancer patients without obesity [1,2]. Breast cancer survivors (BCS) with obesity have an increased risk of total and breast cancer-specific mortality and developing a second primary breast cancer or contralateral breast cancer as compared to BCS without obesity [1,3]. ...
Purpose
Results from the pilot Group-basEd Telehealth behavioral Weight Loss (GET-WEL) Program (NCT04855552) showed that fewer Black breast cancer survivors (BCS) enrolled than White BCS. Black participants also lost less weight than White participants. Little is known about mitigating factors or how best to implement such programs equitably. In this study, we explored facilitators and barriers in Black and White BCS who did or did not participate in GET-WEL.
Methods
BCS who are overweight or obese (body mass index (BMI) ≥ 25 kg/m²) and who had previously been assessed for their willingness to participate in GET-WEL were invited to participate in a semi-structured telephone interview conducted from June to August 2023. Interviewees were purposefully sampled from those who did (participants) and did not (non-participants) enroll in GET-WEL. Interviews were coded and analyzed via comparative thematic analysis.
Results
Of the 24 interviewees, 9 (8 White, 1 Black) were GET-WEL participants, and 15 (8 White, 6 Black, 1 Asian) were non-participants. There were no thematic differences between Black and White BCS. Most non-participants lacked awareness that the Program was recruiting. Program accountability, session flexibility, and pre-existing exercise routines emerged as facilitators while inability to identify enjoyable physical activities, difficulty accessing healthy foods, and competing work/life priorities emerged as barriers.
Conclusion
Our results suggest that enhancing Program awareness and outreach may increase enrollment in minoritized BCS. Resources providing healthy foods and support to ease competing work/life priorities may help BCS maintain healthy lifestyles during and after GET-WEL. These results may help inform future large-scale GET-WEL implementation.
... Reproductive, hormonal factors, and unhealthy lifestyles that trigger obesity are considered significant risk factors for breast cancer [3]. Obesity represents a potentially modifiable risk factor that could increase the risk of breast cancer in women [4,5]. The biological association between obesity and disease risk, at least in part, may be related to circulating lipid levels and tissue lipid metabolism [6]. ...
... Diet and obesity are important risk factors for breast cancer development [5,32]. High cholesterol intake was found to be positively associated with the risk of breast cancer, mainly among postmenopausal women [33,34]. ...
Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer.
... Strong evidence links obesity (de ned by high body mass index (BMI) ≥ 25 kg/m 2 ) ; or indicators of body fat distribution, such as waist circumference (WC : men > 102 cm, women > 88 cm), hip circumference (HC), and waist-to-hip ratio (WHR : men > 0.90, women > 0.80)) with the risk of postmenopausal breast cancer (BC) [1][2][3][4], the most frequent cancer which represents an important public health problem in women [5][6][7][8][9]. ...
Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers.
The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio. The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions.
After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was mediated positively by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 12.2% (95% confidence intervals: -20.5% to -4.0%) and 11.4%(5.1% to 17.8%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8%(0.6% to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1%(-10.9% to -1.3%)).
Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of generally obese body shape and BC risk, while IGF-1 and SHBG may mediate the tall/lean body shape-BC risk association.
... Among the last years, several reports evidenced that various metabolic disturbances related to obesity may be associated with an increased risk of breast cancer [1,2]. Circulating lipids may be one of the factors that relate to these metabolic abnormalities and the disease risk [3]. ...
Plasma lipids are carried within lipoproteins with various apolipoprotein content. This study evaluates the interest of measuring the apolipoproteins of circulating lipoproteins in breast cancer. Patients with early-stage breast cancer (n = 140) were included. Tumors differed by the expression of estrogen and progesterone receptor (HR− and HR+ for negative and positive expression) and the proliferation marker Ki-67 (≤20% or ≥30%). Apolipoprotein concentrations were determined in plasma, HDL and non-HDL fractions, and results are given in mg/dL, median (25th–75th). Patients did not differ in their plasma and lipoprotein lipid concentrations. HDL apoC-I and non-HDL apoC-II were reduced (1.34 (1.02–1.80) vs. 1.61 (1.32–2.04), p = 0.04; 0.31 (0.18–0.65) vs. 0.63 (0.39–1.02), p = 0.01; respectively), in RH-/high Ki-67 patients in comparison to RH-/low Ki-67 patients, while plasma apoD and HDL apoD were higher (3.24 (2.99–4.16) vs. 3.07 (2.39–3.51), p = 0.04;2.74 (2.36–3.35) vs. 2.45 (2.01–2.99), p = 0.04; respectively). When RH+/high Ki-67 patients were compared with RH+/low Ki-67 patients, HDL apoC-I and HDL apoC-III were higher (1.56 (1.20–1.95) vs. 1.35 (1.10–1.62), p = 0.02; 2.80 (2.42–3.64) vs. 2.38 (1.69–2.96), p = 0.02; respectively). The distribution of exchangeable apolipoproteins, such as apoC-I, apoC-II, apoC-III, apoD, between lipoproteins is linked to the severity of breast cancer.
... Female gender, age, obesity, menarche (under 12 years of age), and radiation therapy to the chest or breasts are the main factors for breast cancer (BC) development [32][33][34]. One prevalent major risk factor among women was found to be overweight. ...
Recently, the rate of cancer deaths in less-developed countries such as Bangladesh has significantly increased day by day, making it a major health issue. The most predominant types of cancers among the populations of less-developed countries (especially Bangladesh) are lung, throat, colon, gastric, ovarian, breast, and skin cancers. The mortality rate is increasing for both males and females. The main common factors are smoking, use of tobacco leaves, bacterial or viral infection, hereditary disorders, food adulterations, and environmental factors, which are highly responsible for the development of carcinoma in the young to adult population in this region. Raising consciousness among people regarding early diagnosis, decreasing the use of chemicals such as formalin for food preservation, and reducing environmental pollution such as arsenic as well as air pollution might help to reduce the number of deaths. Education and public campaigns can also reduce the intensity of cancer occurrence. Breast, esophagus, and cervical cancer are common diseases in less-developed countries such as Bangladesh.
... Furthermore, we were unable to explore the effect of menopausal status on associations. Given that mechanisms linking obesity to breast cancer risk may differ between premenopausal and postmenopausal women [46], this question is worth exploring further. Lastly, though our cross-sectional study design prevents the possibility of causal interpretation, it does provide some future lines of questioning. ...
Background:
Mechanisms underlying the obesity-breast cancer link involve inflammation but need to be elucidated. Determining obesity by combining body mass index (BMI) with the waist circumference (WC) may clarify the role of inflammatory and hormonally related markers in breast cancer. We examined the effect of combining adiposity indices (BMI/WC) with the gene expression of several biomarkers involved in breast cancer.
Methods:
Expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), estrogen receptor-alpha (ER-α), allograft inflammatory factor 1 (AIF1), cyclooxygenase-2 (COX2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leptin (LEP) in 141 adipose breast tissues was quantified using qPCR method. BMI and WC were measured by a trained nurse and categorized using the median split, BMILOWCLO, BMILOWCHI, BMIHIWCLO, and BMIHIWCHI.
Results:
Gene expression of IL-6 (3-fold), TNF-α (2-fold), and LEP (2-fold) was higher in the breast adipose tissue of women with high WC regardless of BMI, that is, BMILOWCHI and BMIHIWCHI women (all P < 0.01). Compared to BMILOWCLO women, gene expression of CYP19A1, COX2, and AIF1 was increased by two-fold in breast adipose tissue of BMIHIWCHI women (P < 0.10). ER-α was not different across adiposity categories.
Conclusions:
The expression of some biomarkers, particularly those related to inflammation, is elevated in breast adipose tissue of women with a high WC independent of BMI. Obesity monitoring should also include women with normal or low BMI, but with central adiposity.
... Another study found that BMI can be a prognostic factor in both menopausal and premenopausal patients suffering from breast cancer and can also be used to determine the rate of recurrence and mortality [33]. Furthermore, there is a relationship between BMI and tumor size, resulting in larger tumors in patients with an obese nutritional status [34][35][36]. In a study by Biglia et al., there was no relationship between BMI and breast cancer assessment; however, obesity was linked to cancer size and invasive lymphovascular disease [29]. ...
Background:
Breast cancer, a global health problem with a high mortality rate, has several risk factors, including obesity and increased lipid profile. Postmenopausal obesity is associated with estrogen production from adipose tissue, while abnormal cell growth is triggered by insulin-like growth factor 1 (IGF-1) and insulin. Obesity could be assessed by measuring body mass index (BMI). An increase in lipid profile signifies an increased risk for breast cancer. Histopathological findings in the form of grading and differentiation can indicate how serious the condition is. Breast cancer with good differentiation is always associated with a positive prognosis.
Objective:
This observational analytic study aims to determine the relationship between BMI and cholesterol levels based on the menopausal status and the histopathological grading findings of breast cancer patients.
Methods:
The observational cross-sectional study analyzed histopathological grading, total cholesterol level, and body mass index. Data were analyzed with Spearman rank correlation statistical test, and the results are significant when the p-value is <0.05.
Results:
Analyzing the relationship between cholesterol levels and histopathological gradings indicated a moderate correlation. The results of another correlation test based on menopausal status showed a weak correlation value, while menopause was said to be significant, indicating a moderate correlation. However, results from the analysis of BMI data in the menopausal subject group were associated with histopathological assessment.
Conclusions:
There is a relationship between cholesterol levels and histopathological degrees in the two menopausal status groups. However, no relationship was found between BMI and the histopathological grades of breast cancer.
... The improved treatment modalities and early detection in developed countries have improved the mortality and survival rates; in developing countries, however, survival rates are lower due to late-disease presentation, lack of oncologic infrastructure, and lack of cost-effective treatment regimens [2]. Breast cancer is linked with a multitude of modifiable risk factors (e.g., alcohol, tobacco consumption, and obesity) that relate to lifestyle [4,5] and non-modifiable risk factors such as inherited gene mutation (e.g., BRCA 1/2), age, and familial risks [6][7][8]. ...
PurposeThis study aims to examine the burden of breast cancer in 185 countries in 2018.Methods
The estimates of incidence, mortality, and prevalence of breast cancer were drawn from GLOBOCAN 2018. The overall burden of breast cancer was gauged using breast cancer burden index (BRCBI)—a novel index comprising age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), mortality-to-incidence ratio (MIR), prevalence-to-incidence ratio (PIR), and prevalence-to-mortality ratio (PMR). The socioeconomic status of countries was measured using human development index (HDI)ResultsGlobally, breast cancer was responsible for an estimated 626,679 deaths at age-standardized rate of 13/100,000; there were 2.1 million cases diagnosed in 2018 at age-standardized rate of 46.3/100,000. The ASIR varied 22-fold from 5/100,000 (Bhutan) to 113.2/100,000 (Belgium). The ASMR varied 13-fold from 2.7/100,000 (Bhutan) to 36.9/100,000 (Fiji). The HDI exhibited a positive gradient with ASIR (r = 0.73), PIR (r = 0.98), and PMR (r = 0.85); with MIR, however, it exhibited a negative association (r = − 0.83). The BRCBI spanned from 0.70 in Somalia to 78.92 in South Korea and exhibited a positive association with HDI (r = 0.76). An additional 46,823 female lives in 2018 and a cumulative total of 333,304 lives could have been saved over 2013–2018, had countries performed as per their HDI.Conclusions
The substantial burden of breast cancer in developing and low-resource economies calls for a holistic approach to cancer management and control that includes oncologic infrastructure to provide cost-effective screening, diagnostic, therapeutic, and palliative services, greater breast cancer awareness, and mitigation of risk factors.
... The most compelling explanation for the U.S. old-age survival and lifespan inequality disadvantage for breast cancer may thus lie at the intersection of behavioural differences and social distribution mechanisms, such as accessibility of the health care system. Postmenopausal breast cancer has been associated with behavioural risk factors, including obesity and sedentary lifestyle (Levi et al. 2005;Menvielle et al. 2006;Yung and Ligibel 2016). While adult obesity prevalence increased in Canada and in the U.S. since the late 1970s, the gap between the two countries gradually widened with the highest proportion of overweight adult females being recorded in the U.S. (Alley et al. 2010). ...
The U.S. elderly experience shorter lifespans and greater variability in age at death than their Canadian peers. In order to gain insight on the underlying factors responsible for the Canada-U.S. old-age mortality disparities, we propose a cause-of-death analysis. Accordingly, the objective of this paper is to compare levels and trends in cause-specific modal age at death (M) and standard deviation above the mode (SD(M +)) between Canada and the U.S. since the 1970s. We focus on six broad leading causes of death, namely cerebrovascular diseases, heart diseases, and four types of cancers. Country-specific M and SD(M +) estimates for each leading cause of death are calculated from P-spline smooth age-at-death distributions obtained from detailed population and cause-specific mortality data. Our results reveal similar levels and trends in M and SD(M +) for most causes in the two countries, except for breast cancer (females) and lung cancer (males), where differences are the most noticeable. In both of these instances, modal lifespans are shorter in the U.S. than in Canada and U.S. old-age mortality inequalities are greater. These differences are explained in part by the higher stratification along socioeconomic lines in the U.S. than in Canada regarding the adoption of health risk behaviours and access to medical services.
... 11 Moreover, a strong correlation was demonstrated between obesity and the risk of breast cancer recurrence and death regardless of the fact that the patient was pre-or postmenopausal. 46 A meta-analysis of 12 studies, which included 23,832 women, showed that if body weight increased by at least 5% of initial body weight after the diagnosis of breast cancer, the patient was at an increased risk of death due to all causes compared to patients whose body weight did not change (HR, 1.12; 95% CI, 1.03-1. 22). ...
Introduction
Sarcopenic obesity (SO) is characterized as the cooccurrence of sarcopenia and obesity. It is associated with many adverse health consequences, also in oncological patients. The study aimed to assess the prevalence of SO in postmenopausal women with a history of breast cancer depending on adopted methodology.
Materials and Methods
The case–control study enrolled 103 women over the age of 50 with a history of breast cancer, including women who completed oncological treatment and had remained in remission for at least 5 years (group I, n=78) and women in whom the disease recurred (group II, n=25). The control group included women with no history of breast cancer (group III, n=73).
Results
In group II sarcopenia occurred significantly more commonly compared to both group I and the control group (for the skeletal muscle index (SMI) ≤29.20%: 13 (52%) in group II vs 16 (20.5%) in group I, p=0.004 and 3 (4.1%) in group III, p<0.001; for SMI ≤26.60%: 10 (40%) in group II vs 9 (11.5%) in group I, p=0.003 and 3 (4.1%) in group III, p<0.001; for SMI ≤33.87%: 17 (68%) in group II vs 21 (26.9%) in group I, p<0.001 and 5 (6.8%) in group III, p<0.001). Depending on the assessment criteria, SO was diagnosed in 0–11.5% of cases in group I, 0–40% of cases in group II and 0–4.1% in the control group. Intergroup differences were not statistically significant, irrespective of the adopted pair of diagnostic criteria. The highest detectability of SO was observed when SMI was combined with each of the diagnostic criteria for obesity used.
Discussion
SO diagnosis based on the percentage of fatty tissue mass in the body of >38% and SMI value were associated with a higher detection rate of SO in each study group, regardless of the adopted cut-off value. Similar results were obtained in each analyzed group when using the remaining diagnostic criteria for obesity and SMI value, regardless of the cut-off value.
... Contextually, this article is aiming to provide insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tool utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management [6]. To this end, innovative screening strategies should consider primary [11] and secondary [26] levels of predictive and preventive medical approach, including both non-modifiable and modifiable risk factors [27] based on comprehensive individual patient profiles that means application of multi-omics [28,29], big data processing [30] and artificial intelligence such as machine learning approach [5]. Table 1 summarizes the categories of women with the mammography screening applicability. ...
In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the “golden standard” approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.
... Each year, as many as 84,000 cancer diagnoses are attributed to obesity and being overweight and obesity are implicated in 15% to 20% of total cancer-related mortality [4]. Obesity has been found to be associated with increased incidence of a variety of cancers, including postmenopausal breast [5,6], prostate [6], colorectal [7,8], esophageal adenocarcinomas [9], gastric [9], pancreas [10], liver [11], and melanomas [12]. Cancer is predicted to overtake heart disease as the leading cause of death in the United States by 2030 [13]. ...
Background:
Although it is well known that obesity is a risk factor for gastrointestinal (GI) cancer, it is not well established if obesity can cause earlier GI cancer onset.
Methods:
A cross-sectional study examining the linked 2004-2008 California Cancer Registry Patient Discharge Database was performed to evaluate the association between obesity and onset age among four gastrointestinal cancers, including esophageal, gastric, pancreatic, and colorectal cancers. Regression models were constructed to adjust for other carcinogenic factors.
Results:
The diagnosis of obesity (BMI > 30) was associated with a reduction in diagnosis age across all four cancer types: 3.25 ± 0.53 years for gastric cancer, 4.56 ± 0.18 years for colorectal cancer, 4.73 ± 0.73 years for esophageal cancer, and 5.35 ± 0.72 for pancreatic cancer. The diagnosis of morbid obesity (BMI > 40) was associated with a more pronounced reduction in the age of diagnosis: 5.48 ± 0.96 years for gastric cancer, 7.75 ± 0.30 years for colorectal cancer, 7.67 ± 1.26 years for esophageal cancer, and 8.19 ± 1.25 years for pancreatic cancer. Both morbid obesity and obesity remained strongly associated with earlier cancer diagnosis for all four cancer types even after adjusting for other available cancer risk factors.
Conclusions:
The diagnosis of obesity, especially morbid obesity, was associated with a significantly earlier gastrointestinal cancer onset in California. Further research with prospective cohort data may be required to establish the causal relationship between obesity and cancer onset age.
... Aynı zamanda obezitenin meme kanseri rekürensini %35-40 oranlarında artırdığı ve düşük sağkalım ile ilişkili olduğu da belirtilmektedir (Jiralerspong and Goodwin 2016). Benzer şekilde 2016 yılında yayınlanan bir derlemede, erken tanı alan meme kanserli kadınlarda obezitenin ikincil kanserlerin riskinde de artışa neden olabileceği ve tanı sonrası ağırlık artışının toplam mortaliteyi de artırdığı belirtilmiştir (Yung and Ligibel 2016). ...
Meme kanseri, dünya genelinde ikinci sırada en sık g.rülen kanser iken, kadınlar arasında en sık g.rülen kanser türüdür. Hem gelişmiş hem de gelişmekte olan ülkelerde kadınlar arasında kansere bağlı .lüm nedenlerinde de ilk sırada yer almaktadır. Etiyolojisi çok fakt.rlüdür ve meme kanseri gelişimindeki birçok majör risk fakt.rü reprodüktif ve genetik gibi kolayca değiştirilemeyen değişkenlerdir. Değiştirilebilir faktörlerin belirlenmesi ve risk grupları için etkili tarama uygulamaları meme kanseri insidansını azaltıcı stratejilerinin geliştirilmesine katkı sağlayabilir. Bu derlemenin amacı, meme kanseri etiyolojisi ve risk faktörlerinin güncel literatür ile incelenmesidir.
... Clavel-Chapelon F et al. identified a significant dose-dependent association between the risk of developing TC and BMI, particularly in women who gained weight from menarche to adulthood [60]. Meanwhile, the role of obesity or a high BMI in the development of breast cancer has been well-known for years [61,62]. Moreover, weight loss interventions are recommended for patients with BC [63]. ...
Background:
Thyroid and breast cancer are two of the malignant diseases with highest incidence in females. Based on clinical experience, breast and thyroid cancer often occur metachronously or synchronously. Therefore, thyroid and breast cancer might share some common etiological factors. The relationship between these diseases has attracted substantial attention, and because these two glands are both regulated by the hypothalamic-pituitary axis, such a relationship is not surprising. A study of this relationship will be useful for obtaining a better understanding of the mechanism by which these two malignancies co-occur.
Main body:
This study reviewed the progress in research on the roles of iodine intake, folate metabolism, obesity, gonadal hormones, and thyroid hormone in thyroid and breast cancer. These studies evaluating the etiological roles of these factors in linking breast and thyroid cancer might also improve our understanding and identify new therapeutic approaches, such as sodium/iodide symporter-mediated radioiodine therapy and thyroid-stimulating hormone receptor antagonists, for breast cancer. In addition, some specific treatments for each cancer, such as radiotherapy for breast cancer or radioactive iodine therapy for thyroid cancer, might be risk factors for secondary malignances, including breast and thyroid cancer.
Conclusions:
Studies of the precise relationship between the co-occurrence of breast and thyroid cancer will certainly improve our understanding of the biological behaviors of these two malignancies and direct evidence-based clinical practice.
... Meta-analyses of case-control and cohort studies, which have been published in recent years [19,30], showed that excess of body mass increases the risk of cancer in postmenopausal women. Moreover, obesity in females with diagnosed breast cancer increases the risk of its recurrence [34]. On the other hand, we cannot rule out that large gain of abdominal fat in study participants took place after the diagnosis of breast cancer. ...
Background:
Wrong dietary practices and excessive body mass may not only influence the risk of primary breast cancer but also the risk of its recurrence.
Objective:
Evaluation of dietary practices and identification of nutritional factors which may influence the risk of tumor recurrence in women with prior breast cancer.
Materials and methods:
The case-control study involved 108 women aged 50 years and older with history of breast cancer who were divided into two categories: women after completed cancer treatment with no recurrence for minimum 5 years (group I, n=82) and women with diagnosed breast cancer recurrence (group II, n=26). A control group (n=74) constituted of subjects with no breast cancer diagnosis. In every subject anthropometric measurements were taken and dietary practices were evaluated by means of an original questionnaire.
Results:
Average BMI and hip circumference values were higher in the group II than in the group I. In both study groups the percentage of high WHR values was significantly higher than in the control group. Women with history of cancer consumed significantly fewer vegetable and fruit and more refined cereals, dairy products, meat and cold cuts than women in the control group. Group I responders more often declared implementation and maintenance of changes in their diet after diagnosis of cancer than women from group II. Subjects with cancer history consumed more alcohol and more often used supplements than females in the control group.
Conclusion:
Avoiding overweight and obesity along with following the principles of a healthy diet seems to reduce the risk of both breast cancer incidence and its recurrence.
... estrogen, testosterone). [7][8][9] Few studies have investigated the impact of body size on breast cancer risk among women with an inherited BRCA1 or BRCA2 mutation. [10][11][12][13][14] In the largest study conducted to date, which included 1073 matched pairs of BRCA mutation carriers, we previously reported that weight loss of at least 10 pounds in early adulthood (between the ages of 18 and 30) was associated with a 53% reduction in breast cancer diagnosed between ages 30 and 40 years (P ¼ 0.005). ...
Background:
Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers.
Methods:
Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires. Current BMI and weight change since age 18 were calculated from updated biennial follow-up questionnaires. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI).
Results:
Among 3734 BRCA mutation carriers, there were 338 incident breast cancers over a mean follow-up of 5.5 years. There was no association between height, current BMI or weight change and breast cancer risk. Women with BMI at age 18 ≥22.1 kg/m2 had a decreased risk of developing post-menopausal breast cancer compared with women with a BMI at age 18 between 18.8 and 20.3 kg/m2 (HR 0.49; 95% CI 0.30-0.82; P = 0.006). BMI at age 18 was not associated with risk of pre-menopausal breast cancer.
Conclusions:
There was no observed association between height, current BMI and weight change and risk of breast cancer. The inverse relationship between greater BMI at age 18 and post-menopausal breast cancer further supports a role of early rather than current or adulthood exposures for BRCA-associated breast cancer development. Future studies with longer follow-up and additional measures of adiposity are necessary to confirm these findings.
... Female gender, older age, obesity, menarche at <12 years of age, radiation therapy to the chest or breasts, having a first-degree relative with BC [14][15][16][17][18] etc. increases the risk of developing BC. One of the major risk factors (35.39%) prevailing among the respondents was found to be a BMI ≥25 (30.16% overweight and 5.23% obese). ...
Breast cancer (BC) is considered as one of the most prevalent cancers among women in Bangladesh. The aim of the present study was to investigate the knowledge about BC, risk factor prevalence and breast self-examination (BSE) practices among female populations of Bangladesh. After taking verbal consent, 1051 females of age ≥20 years from different districts of Bangladesh were interviewed using a pre-tested questionnaire in 2015. Among the respondents, three-forth (77.74%) knew (heard or read) about BC and their main source of information was electronic media (74.54%). Most of them could identify at least one sign and symptom (73.93%) and one risk factor of BC (71.55%). But only 34.16% and 52.14% correctly identified at least one option for early detection and treatment, respectively. Although early screening of BC was very important according to 58.90% respondents and BSE procedure was known to 21.69%, only 13.13% actually performed BSE. Major risk factors prevailing among the respondents were a BMI ≥25 (35.39%), menarche at <12 years age (21.03%), contact with radiation to chest or face (15.89%) and age ≥40years (20.08%). Using paired t-test, BC knowledge was found to be significantly (p<0.05) related to being unmarried, having higher education levels and positive family history. Practice of BSE was also significantly associated with increase in age, higher education levels, being married and perception of importance about early screening. The results of this study reflect the need for educating Bangladeshi women about BC to improve their knowledge level and to increase their practice of early screening strategies.
... Более того, у больных диабетом и ртм выявился больший Имт в сравнении с больными СД и рмЖ. оценивая полученные данные, следует отметить, что нарастающая распространенность повышенного Имт уже давно рассматривается как эпидемия, заслуживающая серьезного внимания [14], и является признанным фактором риска развития рака эндометрия [3,5,11], молочной железы в постменопаузе [29], а также сахарного диабета. ...
The article presents a comparative analysis of clinical and morphological characteristics of tumor process in patients with breast cancer and endometrial cancer with diabetes mellitus and without it. Previously little-known features of the tumor process in combination with diabetes were revealed. The data obtained indicated that in case of breast cancer the presence of diabetes for a number of signs influenced the course/characteristics of the disease: e.g., the tumor size was significantly greater than in patients without diabetes and highly differentiated Gl tumors were less common. In case of endometrial cancer, diabetes (but only in combination with obesity or postmenopausal period) was combined with more favorable characteristics of tumor indicating a diagnosis-specific effect of Type 2 diabetes in regard of the tumor process features. An evaluation of the role of antidiabetic therapy variant discovered that in patients with breast cancer metformin therapy was combined with more frequent detection of highly differentiated, hormone-positive tumors, which was not revealed in patients with endometrial cancer.
... In contrast, the prevalence of obesity in the study cohort was higher than expected for women between 45 and 64 years according to the data of the Brazilian Census (IBGE 2010). Indeed, obesity is a recognized risk factor for the development of breast cancer, especially among postmenopausal women (Yung & Ligibel 2016). ...
Breast cancer is the leading cancer among women, and its increasing incidence is a challenge worldwide. Estrogen exposure is the main risk factor, but obesity among postmenopausal women has been shown to favor disease onset and progression. The link between obesity and mammary carcinogenesis involves elevated estrogen production and proinflammatory stimuli within the adipose tissue, with activation of the cyclooxygenase-2 pathway. Here, we evaluate the impact of the four most common cyclooxygenase-2 gene polymorphisms (rs689465, rs689466, rs20417 and rs20417), in combination with obesity, on the risk of breast cancer progression in a cohort of Brazilian breast cancer patients (N = 1038). Disease-free survival was evaluated using Kaplan-Meier curves, with multivariate Cox proportional hazards regression models for calculation of adjusted hazard ratios (HRadj). Obesity did not affect disease progression, whereas rs689466 variant genotypes increased the recurrence risk among obese patients (HRadj = 2.5; 95% CI = 1.4-4.3), either for luminal (HRadj = 2.2; 95% CI = 1.1-4.2) or HER2-like and triple-negative tumors (HRadj = 3.2; 95% CI = 1.2-8.5). Likewise, the haplotype *4, which contains variant rs689466, was associated with shorter disease-free survival among obese patients (HRadj = 3.3; 95% CI = 1.8-6.0), either in luminal (HRadj = 3.5; 95% CI = 1.6-7.3) or HER2-like and triple-negative (HRadj = 3.1; 95% CI = 1.1-8.9) tumors. Such deleterious impact of variant rs689466 on disease-free survival of obese breast cancer patients was restricted to postmenopausal women. In conclusion, cyclooxygenase-2 genotyping may add to the prognostic evaluation of obese breast cancer patients.
... B reast cancer is the most common malignancy and the leading cause of cancerrelated death in women worldwide (1,2). In recent years, multiple reports have shown obesity as a serious risk factor for the development of breast cancer (3). However, the link between obesity and this deadly disease remains unclear. ...
Obesity is increasingly recognized as a risk factor for breast cancer development. However, the molecular basis of obesity-related breast carcinogenesis remains elusive. In this study, we have shown that obesity reduces the level of the tumor suppressor p16 INK4A protein in breast adipocytes, which showed active features and strong pro-carcinogenic potential both in vitro and in orthotopic tumor xenografts, as compared to mature adipocytes from lean women. Furthermore, obesity triggered epithelial-to-mesenchymal transition (EMT) in breast ductal epithelial cells. Interestingly, specific down-regulation of p16 INK4A increased the expression/secretion levels of various adipokines including leptin, and activated breast adipocytes from lean women. Consequently, like breast adipocytes from obese women, p16-deficient adipocytes induced EMT in normal primary breast luminal cells in a leptin-dependent manner, and enhanced tumor growth and angiogenesis. Additionally, we have shown that p16 INK4A negatively controls leptin at the mRNA level through miR-141 and miR-146b-5p, which bind the leptin mRNA at specific sequence in the 3’ UTR. These results show that obesity activates breast stromal adipocytes through p16 down-regulation, which up-regulates leptin and promotes procarcinogenic processes.
... The risk of developing BC is affected by some non-modifiable factors (e.g., age, genetic and familial risk) [23] and by others that can be modified, which are related to lifestyle (e.g., alcohol abuse, tobacco use, and body mass index) [24,25]. Prevention campaigns to reduce the risk attributable to modifiable risk factors should therefore be conducted in all countries. ...
Breast cancer (BC) is the most frequent tumour affecting women all over the world. In low- and middle-income countries, where its incidence is expected to rise further, BC seems set to become a public health emergency. The aim of the present study is to provide a systematic review of current BC screening programmes in WHO European Region to identify possible patterns. Multiple correspondence analysis was performed to evaluate the association among: measures of occurrence; GNI level; type of BC screening programme; organization of public information and awareness campaigns regarding primary prevention of modifiable risk factors; type of BC screening services; year of screening institution; screening coverage and data quality. A key difference between High Income (HI) and Low and Middle Income (LMI) States, emerging from the present data, is that in the former screening programmes are well organized, with approved screening centres, the presence of mobile units to increase coverage, the offer of screening tests free of charge; the fairly high quality of occurrence data based on high-quality sources, and the adoption of accurate methods to estimate incidence and mortality. In conclusion, the governments of LMI countries should allocate sufficient resources to increase screening participation and they should improve the accuracy of incidence and mortality rates.
... It has been reported that activation of NLRP3 inflammasome enhanced the proliferation and migration of A549 lung cancer cells [50] and that obesityassociated NLRC4 inflammasome activation/IL-1 signaling promoted breast cancer progression [51]. Obesity has been linked to an increased risk of developing breast cancer and worse clinical prognosis [52] and is a risk factor for TNBC [26]. Within the tumor microenvironment in the context of obesity, an increase in tumor-infiltrating myeloid cells is induced with an activated NLRC4 inflammasome, which, in turn, activates IL-1β, driving disease progression through enhancing the expression of adipocyte-mediated vascular endothelial growth factor A and angiogenesis. ...
Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice. Moreover, CS treatment also inhibited the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed HFD-induced NF-κB signaling in vivo and LPS-induced NF-κB activation as reflected by the fact that their phosphorylated forms and the ratios of pNF-κB/NF-κB, pIKK/IKK, and pIκB/IκB were all decreased in EAT from HFD-fed mice treated with CS as compared with those of HFD mice. Taking together, this study has revealed that CS effectively inhibits HFD-induced inflammation in adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and NF-κB signaling. Thus, CS can serve as a potential therapeutic drug in the prevention and treatment of inflammation-associated diseases.
Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association.
Purpose:
The aim of the study was to investigate the effects of body mass index (BMI) on the response to neoadjuvant chemotherapy (NACT) in Turkish patients with local and locally advanced breast cancer.
Methods:
The pathological responses for the breast and axilla were assessed according to the Miller-Payne grading (MPG) system. Tumors were grouped into molecular phenotypes and classified as response rates according to the MPG system after the completion of NACT. A 90% or greater reduction in tumor cellularity was considered a good response to treatment. Additionally, patients were grouped according to BMI into <25 (group A) and ≥25 (group B).
Results:
In total, 647 Turkish women with breast cancer were included in the study. In the univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and BMI were assessed to determine which of these factors were associated with a ≥90% response rate. Stage, HER2 positivity, triple-negative breast cancer (TNBC; ER-negative, PR-negative, and HER2-negative breast cancer), grade, Ki-67 levels, and BMI were found to be the statistically significant factors for a ≥90% response rate. In the multivariate analysis, grade III disease, HER2 positivity, and TNBC were found to be the factors associated with a high pathological response. Meanwhile, hormone receptor (HR) positivity and a higher BMI were associated with a decreased pathological response in patients receiving NACT for breast cancer.
Conclusion:
Our results show that a high BMI and HR positivity are associated with a poor response to NACT in Turkish patients with breast cancer. The findings presented in this study may guide novel studies to examine the NACT response in obese patients with and without insulin resistance.
hysical activity and the prevention of weight gain decrease breast cancer incidence and improve survival. Unraveling the biological mechanisms underlying these cancer prevention effects is difficult because activity and dietary restriction are often linked. The goal of this study was to determine whether physical activity (A), preventing weight gain via energy restriction (ER), or the combination was most effective in delaying tumor growth, reducing metastatic progression, and improving survival in the 4T1.2 mammary tumor model. Furthermore, we determined whether any of these interventions prevented the expansion of protumor immunosuppressive cells and altered the tumor microenvironment (TME). Female BALB/c mice (n = 7–20/group) were randomized to sedentary (SED) or A wheel cages and fed ad libitum (AL) or 90% of control food intake (ER). After 8 weeks on the interventions, mice were inoculated with 5 × 10⁴ 4T1.2luc cells into the 4th mammary fat pad and continued on their respective intervention. A+ER significantly delayed primary tumor growth (final tumor volume, 0.193 ± 0.042 vs. 0.369 ± 0.049 cm³, < 0.001), reduced metastatic burden in the lungs (0.72 ± 0.36 vs. 16.27 ± 6.98, = 0.054) and increased survival (median survival, 68 vs 40 days, = 0.043) compared with SED+AL mice. A+ER also reduced the expression level of metastatic and immunosuppressive genes and resulted in favorable changes in immune cell infiltrates in the tumor. These data suggest that both A and ER are needed to reduce tumor growth, delay metastatic progression, and improve survival, and that this protection is associated with changes in immune-mediated mechanisms.
Purpose
Physical activity and lower BMI have shown benefit for breast cancer survival, but the association between these factors, pathologic complete response (pCR), and chemotherapy completion is not clear. We evaluated whether BMI and physical activity are associated with pCR and chemotherapy completion during neoadjuvant breast cancer treatment.
Methods
We conducted a retrospective case–control study of women given neoadjuvant chemotherapy for stage I–III breast cancer between 2010 and 2016. A medical record review provided pCR, chemotherapy completion, and patient characteristics. A telephone survey assessed physical activity 1 year before diagnosis. Unconditional logistic regression models identified factors associated with pCR and chemotherapy completion.
Results
In our cohort (n = 243), the average age was 52.9 years (SD 13.0) and mean BMI was 29.5 kg/m² (SD 7.0). Seventy-five (31%) patients had pCR and 168 (69%) had residual disease. Patients with pCR had lower mean BMI than those with residual disease (28.2 (SD) vs. 30.1 (SD), P = 0.04). Exercise was associated with completion of chemotherapy (OR 7.6, 95% CI 1.4–41.2, P = 0.02).
Conclusions
Pathologic complete response was associated with lower BMI; chemotherapy completion was associated with exercising at CDC-recommended levels prior to breast cancer diagnosis.
Background:
This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis.
Methods:
Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG). The trial was powered for a main effects analysis of metformin vs placebo and weight loss vs control. All tests of statistical significance were two-sided.
Results:
A total of 313 women (94.0%) completed the six-month trial. High prescription adherence (ie, ≥80% of pills taken) ranged from 65.9% of participants in the metformin group to 81.3% of those in the placebo group (P < .002). Mean percent weight loss was statistically significantly higher in the weight loss group (-5.5%, 95% confidence interval [CI] = -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI = -3.5% to -1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG. Statistically significant group differences (ie, percent change in weight loss group minus placebo group) were -12.5% (95% CI = -19.6% to -5.3%) for insulin and 5.3% (95% CI = 0.2% to 10.4%) for SHBG.
Conclusions:
As adjuvant therapy, weight loss and metformin were found to be a safe combination strategy that modestly lowered estrogen levels and advantageously affected other biomarkers thought to be on the pathway for reducing breast cancer recurrence and mortality.
Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, and treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer metastasis. ACC1 phosphorylation was increased in invading cells both in murine and human breast cancer, serving as a point of convergence for leptin and transforming growth factor (TGF) β signaling. ACC1 phosphorylation was mediated by TGFβ-activated kinase (TAK) 1, and ACC1 inhibition was indispensable for the elevation of cellular acetyl-CoA, the subsequent increase in Smad2 transcription factor acetylation and activation, and ultimately epithelial-mesenchymal transition and metastasis induction. ACC1 deficiency worsened tumor recurrence upon primary tumor resection in mice, and ACC1 phosphorylation levels correlated with metastatic potential in breast and lung cancer patients. Given the demonstrated effectiveness of anti-leptin receptor antibody treatment in halting ACC1-dependent tumor invasiveness, our work defines a "metabolocentric" approach in metastatic breast cancer therapy.
Background
Reconstructive surgeons are encountering an increasing number of obese women requiring postmastectomy reconstruction. These patients are poor candidates for autologous and prosthetic-based reconstructions as they have a high rate of reconstructive failure, surgical complications, and poor aesthetic outcomes. We demonstrate here the utility of the previously described Goldilocks mastectomy with free nipple grafts as a safe bridge to second stage implant-based breast reconstruction.
Methods
Ten consecutive morbidly (BMI > 40) or super obese (BMI>50) women underwent bilateral Goldilocks mastectomy with free nipple grafts followed by second stage subpectoral implant placement at least three months postoperatively. Patients were assessed for implant-related complications including malposition, capsular contracture, dehiscence, and extrusion.
Results
Ten postmastectomy reconstructions in patients with BMIs ranging from 37 to 50 with a mean BMI of 45 underwent bilateral Goldilocks mastectomy with free nipple grafts. Two patients had wound healing complications after Goldilocks mastectomy but were completely healed within 8 weeks. There were no instances of delayed wound healing or reconstructive failure after prosthetic placement. With at least 9 months of follow-up on all patients, no patient has had a capsular contracture, significant malposition, or other complication requiring reoperation.
Conclusion
The obese patient poses a significant reconstructive challenge for which no reproducible approach has been described. Here, we present a 2-stage strategy: the previously described Goldilocks mastectomy with free nipple grafts followed by second stage subpectoral definitive implant placement. This is the first proposed description of a reliable strategy for postmastectomy reconstruction in the morbidly and super obese.
Background:
Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer–specific, all-cause mortality and recurrence outcomes.
Methods:
Electronic databases identified articles up through December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer–specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (≥5.0% body weight) and all-cause mortality; all tests were two-sided.
Results:
Twelve studies (n = 23 832) were included. Weight gain (≥5.0%) compared with maintenance (