Chromium as a Risk Factor for Breast Cancer: A Meta-Analysis

Background: Chromium (Cr) is a transition metal, natural element. Chromium is the 21st most abundant element in Earth’s crust. Cr is found in soil, rocks and living organisms. It may have various oxidation states, from -2 to +6, but most of these states are too unstable to exist in any significant quantities. The purpose of this review and meta-analysis is to critically assess the scientific evidence on the carcinogenic effects of chromium (Cr) and to determine whether there is currently sufficient evidence to suggest that that there is a link between chromium levels in hair and blood serum and breast cancer in women. Material and methods: Research on the relationship between heavy metal chromium and the risk of developing breast cancer has been searched in PubMed, EMBASE, Web of Science, Scopus among papers published between January 2000 and September 2020. The search used the following terms (MeSH): breast cancer, women, trace elements, metals, chromium, chemically-induced, hair, serum using additional terms. Results: In the second group of comparisons of women from “ecologically clean” districts of Aktobe Region, there were significantly lower indicators of the microelements in tumor tissue. The amount of Fe ranges from 38.46 to 65.39 ug/g (average 49.56±5.81 ug/g), Cu from 2.8 to 6.69 ug/g (average 5.06±1.01 ug/g), Zn from 1.89 to 5.38 ug/g (average 3.88±0.89 ug/g), Cr from zero to 6,1 ug/g (average 2.13±1.29 ug/g), Ni from 0.11 to 0.42 ug/g (average 0.28±0.067 ug/g) и Pb from zero to 0.19 ug/g (average 0.098±0.06 ug/g). Conclusion: The article established that women who live or work in ecologically polluted areas or have problems with micronutrient exchange need in-depth screening and more frequent screening for early detection of pre- and breast cancer.     

Refusal of Cancer-Directed Surgery by Breast Cancer Patients: Risk Factors and Survival Outcomes

Background

It has been reported that some patients with breast cancer may refuse cancer-directed surgery, but the incidence in the United States is not currently known. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with refusal of recommended breast cancer–directed surgery.

Survival Outcomes of Patients With Breast Cancer Diagnosed Using Vacuum-Assisted Biopsy: A Nationwide Study From the Korean Breast Cancer Society

PurposeBreast cancer is mainly diagnosed using core needle biopsy (CNB), although other biopsy methods, including vacuum-assisted biopsy (VAB), may also be used. We compared differences in clinical characteristics and prognoses of patients with breast cancer according to biopsy methods used for diagnosis.MethodsA total of 98,457 patients who underwent various biopsy methods (CNB, fine-needle aspiration [FNA], VAB, and excisional biopsy) for diagnosing breast cancer were recruited. Using CNB as a reference, related clinicopathological factors and prognostic differences between biopsy methods were analyzed retrospectively using large-scale data from the Korean Breast Cancer Society Registration System. The associations between biopsy methods and clinicopathological factors were compared using multinomial logistic regression analysis, and the prognoses of patients undergoing the different biopsy methods, as breast cancer-specific survival (BCSS) and overall survival (OS), were compared using the Kaplan-Meier method and Cox proportional hazard model.ResultsUnivariate and multivariate analyses showed that unlike FNA, both VAB and excisional biopsy were significantly associated with tumor size, palpability, tumor stage, and histologic grade as relatively good prognostic factors compared to CNB. In particular, VAB showed lower odds ratios for these factors than excisional biopsy. In the univariate analysis, the prognosis of patients undergoing VAB was better than that of those undergoing CNB with respect to BCSS (hazard ratio [HR], 0.188, p < 0.001) and OS (HR, 0.359; p < 0.001). However, in the multivariate analysis, there were no significant prognostic differences from CNB in both BCSS and OS; differences were only evident for FNA.ConclusionIn this study, we showed that the characteristics of breast cancer differed according to various biopsy methods. Although VAB is not a standard method for breast cancer diagnosis, it showed no prognostic differences to CNB.     

Vascular Invasion as an Independent Prognostic Factor in Lymph Node Negative Invasive Breast Cancer

Introduction: Identification of simple and measurable prognostic factors is an important issue in treatmentevaluation of breast cancer. The present study was conducted to evaluate the prognostic role of vascular invasion inlymph node negative breast cancer patients. Methods: in a retrospective design, we analyzed the recorded profilesof the 1,640 patients treated in the breast cancer department of Motahari clinic affiliated to Shiraz Universityof Medical Sciences, Shiraz, Iran, from January 1999 to December 2012. Overall and adjusted survivals wereevaluated by the Cox proportional hazard model. All the hypotheses were considered two-sided and a p-valueof 0.05 or less was considered as statistically significant. Results: Mean age in lymph node negative and positivepatients was 50.0 and 49.8 respectively. In lymph node negative patients, the number of nodes, tumor size,lymphatic invasion, vascular invasion, progesterone receptor, and nuclear grade were significant predictors.In lymph node and lymphatic negative patients, vascular invasion also played a significant prognostic role inthe survival which was not evident in lymph node negative patients with lymphatic invasion. Discussion: Theresults of our large cohort study, with long term follow up and using multivariate Cox proportional model andcomparative design showed a significant prognostic role of vascular invasion in early breast cancer patients.Vascular invasion as an independent prognostic factor in lymph node negative invasive breast cancer     

Alcohol Consumption as a Risk Factor for Breast Cancer Development: A Case-Control Study in Brazil

Background: Alcohol consumption is a well-established risk factor for breast cancer, but the evidence is mostlyfrom developed countries. Brazil is going through a rapid demographic expansion, and studies of this relationship arealso needed in such unexplored settings. Methods: We assessed the relationship between alcohol consumption andbreast cancer risk among 1,506 Brazilian women (406 cases and 1,100 controls). Regression models were used tocalculate odds ratios (OR) and 95% confidence intervals (CI). All statistical tests were two-tailed. Results: The meanage of the 1,506 women was 42.0 (standard deviation, ±15.0) years. There was a significant association between breastcancer and age, body mass index, age at menarche, menstrual flow and menstrual cycle. Multivariate analysis showedan increased risk of invasive breast cancer in regular alcohol consumers (years old: OR 3.9; 95% CI 1.2–13.4) compared with abstainers or occasional drinkers. Women with a regular alcoholintake for 10 years or more who were less than 50 years old had a threefold higher risk of developing breast cancer(OR 3.0; 95% CI 1.2–7.6). Conclusion: Regular alcohol consumption increases the risk of breast cancer mainly amongwomen less than 50 years old.     

COVID-19 Outcomes Among Patients With Cancer: Observations From the University of California Cancer Consortium COVID-19 Project Outcomes Registry

BackgroundThe risks associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated illness, coronavirus disease 2019 (COVID-19), among patients with a cancer diagnosis have not been fully characterized. This study leverages data from a multi-institutional cohort study, the University of California Cancer COVID Consortium, to evaluate outcomes associated with SARS-CoV-2 infection among patients with cancer.MethodsClinical data were collected from March to November 2020 and included patient demographics, cancer history and treatment, SARS-CoV-2 exposure and testing, and COVID-19 clinical management and outcomes. Multivariate ordinal logistic regression permitting unequal slopes was used to evaluate the impact of demographic, disease, and treatment factors on SARS-CoV-2 related hospitalization, intensive care unit (ICU) admission, and mortality.FindingsAmong all evaluated patients (n = 303), 147 (48%) were male, 118 (29%) were older adults (≥65 years old), and 104 (34%) were non-Hispanic white. A subset (n = 63, 21%) had hematologic malignancies and the remaining had solid tumors. Patients were hospitalized for acute care (n = 79, 26%), ICU-level care (n = 28, 9%), or died (n = 21, 7%) due to COVID-19. Patients with ≥2 comorbidities were more likely to require acute care (odds ratio [OR] 2.09 [95% confidence interval (CI), 1.23-3.55]). Cough was identified as a significant predictor of ICU hospitalization (OR 2.16 [95% CI, 1.03-4.57]). Importantly, mortality was associated with an active cancer diagnosis (OR 3.64 [95% CI, 1.40-9.5]) or advanced age (OR 3.86 [95% CI, 1.2-12.44]).InterpretationThis study observed that patients with active cancer or advanced age are at an increased risk of death from COVID-19. These study observations can inform risk counseling related to COVID-19 for patients with a cancer diagnosis.     

Clinical Risk Factor Analysis for Breast Cancer: 568,000 Subjects Undergoing Breast Cancer Screening in Beijing, 2009

Objectives: Although there are many reports about the risk of breast cancer, few have reported clinicalfactors including history of breast-related or other diseases that affect the prevalence of breast cancer. This studyexplores these risk factors for breast cancer cases reported in Beijing in 2009. Materials and Methods: Datawere derived from a Beijing breast cancer screening performed in 2009, of 568,000 women, from 16 districts ofBeijing, all aged between 40 and 60 years. In this study, multilevel statistical modeling was used to identify clinicalfactors that affect the prevalence of breast cancer and to provide more reliable evidence for clinical diagnosticsby using screening data. Results and Conclusion: Those women who had organ transplants, compared withthose with none, were associated with breast cancer with an odds ratio (OR) = 65.352 [95% confidence interval(CI): 8.488-503.165] and those with solid breast mass compared with none had OR = 1.384 (95% CI: 1.022-1.873). Malignant tendency was strongly associated with increased risk of breast cancer, OR = 207.999(95%CI: 151.950-284.721). The risk of breast cancer increased with age, OR1 = 2.759 (95% CI: 1.837-4.144, 56-60 vs.40-45), OR2 = 2.047 (95% CI: 1.394-3.077, 51-55 vs. 40-45), OR3 = 1.668 (95% CI: 1.145-2.431). Normal resultsof B ultrasonic examination show a lower risk among participants, OR= 0.136 (95% CI: 0.085-0.218). Thosewomen with ductal papilloma compared with none were associated with breast cancer, OR=6.524 (95% CI:1.871-22.746). Therefore, this study suggests that clinical doctors should pay attention to these high-risk factors.     

Multiple Sexual Partners as a Potential Independent Risk Factor for Cervical Cancer: a Meta-analysis of Epidemiological Studies

It’s known that having multiple sexual partners is one of the risk factors of human papillomavirus (HPV)infection which is a major cause of cervical cancer. However, it is not clear whether the number of sexual partnersis an independent risk factor for cervical cancer. We identified relevant studies by searching the databases ofMEDLINE, PubMed and ScienceDirect published in English from January 1980 to January 2014. We analyzedthose studies by combining the study-specific odds ratios (ORs) using random-effects models. Forty-one studieswere included in this meta-analysis. We observed that the number of sexual partners was associated with theoccurrence of non-malignant cervical disease (OR=1.82, 95%CI 1.63-2.00) and invasive cervical carcinoma(OR=1.77, 95%CI 1.50-2.05). Subgroup analyses revealed that the association remained significant aftercontrolling for HPV infection (OR=1.52, 95%CI 1.21-1.83 for non-malignant disease; OR=1.53, 95%CI 1.30-1.76 for invasive cervical carcinoma). We found that there was a non-linear relation of the number of sexualpartners with both non-malignant cervical disease and invasive cervical carcinoma. The risk of both malignantand non-malignant disease is relatively stable in women with more than 4-7 sexual partners. Furthermore, thefrequency-risk of disease remained significant after controlling for HPV infection.The study suggested thath aving multiple sexual partners, with or without HPV infection, is a potential risk factor of cervical cancer.     

Bioimpedence to Assess Breast Density as a Risk Factor for Breast Cancer in Adult Women and Adolescent Girls

Although high mammographic density is one of the strongest predictors of breast cancer risk, X-ray based mammography cannot be performed before the recommended screening age, especially not in adolescents and young women. Therefore, new techniques for breast density measurement are of interest. In this pilot study in Guam and Hawaii, we evaluated a radiation-free, bioimpedance device called Electrical Breast Densitometer™ (EBD; senoSENSE Medical Systems, Inc., Ontario, Canada) for measuring breast density in 95 women aged 31-82 years and 41 girls aged 8-18 years. Percent density (PD) was estimated in the women’s most recent mammogram using a computer-assisted method. Correlation coefficients and linear regression were applied for statistical analysis. In adult women, mean EBD and PD values of the left and right breasts were 230±52 and 226±50 Ω and 23.7±15.1 and 24.2±15.2%, respectively. The EBD measurements were inversely correlated with PD (rSpearman=-0.52, p<0.0001); the correlation was stronger in Caucasians (rSpearman=-0.70, p<0.0001) than Asians (rSpearman=-0.54, p<0.01) and Native Hawaiian/Chamorro/Pacific Islanders (rSpearman=-0.34, p=0.06). Using 4 categories of PD (<10, 10-25, 26-50, 51-75%), the respective mean EBD values were 256±32, 249±41, 202±46, and 178±43 Ω (p<0.0001). In girls, the mean EBD values in the left and right breast were 148 40 and 155±54 Ω; EBD values decreased from Tanner stages 1 to 4 (204±14, 154±79, 136±43, and 119±16 Ω for stages 1-4, respectively) but were higher at Tanner stage 5 (165±30 Ω). With further development, this bioimpedance method may allow for investigations of breast development among adolescent, as well as assessment of breast cancer risk early in life and in populations without access to mammography.     

Periodontitis as a Risk Factor for Breast Cancer – What We Know Till Date?

A healthy microbiome is important for human health because it exhibits a variety of functions in the human body wherein the microbiome dysbiosis can lead to a variety of diseases, including cancer. Recent advances in technology and cost reduction of sequencing have made it possible and much easier for researchers to investigate the role of the microbiome in carcinogenesis. Furthermore, modulation of microflora may serve as an effective adjunct to conventional anticancer therapy that is very important to improve the patient’s quality of life. Additionally, microbiome biomarkers can also be used as a diagnostic tool for cancer. So far the association between oral microbial consortia and their interactions with the host in maintaining the human health and the pathogenesis of multiple cancers has gained much popularity in the scientific research community. While the interactions of oral microflora are better established in cancer- like gastric cancer, it is far less understood in others like breast cancer. Therefore, this review briefly outlines the current information on the role of oral microbiota in breast cancer with emphasis on the mechanisms of oral microflora induced carcinogenesis and discusses the emerging role of periodontitis as a risk factor for breast cancer. Clinical relevance; Periodontitis is a very common disease that is characterized by chronic polymicrobial infection and inflammation of gingiva. It might be associated as a risk factor for breast cancer. If this association is validated in large cohort studies, it would serve as a non-invasive biomarker for breast cancer.     

Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis

Purpose

Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer.

Methods

We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression.

Results

There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73).

Conclusion

Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes.     

Medical radiation exposure and breast cancer risk: findings from the Breast Cancer Family Registry

Moderate to high-dose radiotherapy is known to increase the risk of breast cancer. Uncertainties remain about the effects of low-dose chest X-rays, particularly in individuals at increased genetic risk. We analyzed case-control data from the Breast Cancer Family Registry. Self-reported data on therapeutic and diagnostic radiation exposures to the chest were available for 2,254 breast cancer cases and 3,431 controls (1,556 unaffected sisters and 1,875 unrelated population controls). We used unconditional logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with radiation exposure, after adjusting for age, study center, country of birth, and education. Increased risks for breast cancer were found for women who had radiotherapy for a previous cancer (OR=3.55, CI=1.47-8.54) and diagnostic chest X-rays for tuberculosis (OR=2.49, CI=1.82-3.40) or pneumonia (OR=2.19, CI=1.38-3.47). Risks were highest for women with a large number of exposures at a young age or exposed in earlier calendar years. There was no evidence of increased risk associated with other diagnostic chest X-rays (not including tuberculosis or pneumonia), both in women with and without indicators of increased genetic risk (i.e., diagnosed at age <40 years or family history of breast cancer). Given the widespread and increasing use of medical diagnostic radiation, continued surveillance of breast cancer risk is warranted, particularly in women at specific genetic risk, such as those carrying mutations in BRCA1 or BRCA2.     

Survival Outcomes for Patients with Metastatic Triple-Negative Breast Cancer: Implications for Clinical Practice and Trial Design

BackgroundClinical experience suggests that many women with triple-negative metastatic breast cancer (MBC) relapse quickly. This has implications for clinical practice and trial design. We evaluated the duration of first-, second-, and third-line chemotherapy as a surrogate for duration of treatment response.Patients and MethodsWe performed a retrospective multicenter chart review of patients with triple-negative MBC receiving palliative chemotherapy. Primary outcome was duration of palliative chemotherapy, and secondary outcome was to identify prognostic variables.ResultsA total of 111 patients were analyzed. Median age at diagnosis was 51 years (range, 26–82 years). Fourteen percent of patients presented with MBC. Twenty-seven percent received neoadjuvant chemotherapy, and 48% received adjuvant chemotherapy. Median distant disease-free interval (DDFI) was 18 months (range, 0–172 months). At presentation of MBC, 68% had visceral and 71% had multiple sites of disease. Median survival with MBC was 13.3 months (range, 0.8–99.8 months). Median duration of first-line palliative therapy was 11.9 weeks (range, 0–73.1 weeks). Eighty-seven patients (78%) went on to receive second-line therapy with a median duration of 9 weeks (range, 0–120.9 weeks), and 55 (49%) received third-line therapy with a median duration of 4 weeks (range, 0–59 weeks). Multivariate analysis revealed that age < 50 years, ALP > 120 U/L, history of previous chemotherapy, DDFI < 12 months, and visceral presentation were all independently associated with a poor prognosis.ConclusionDespite the poorer overall prognosis of patients with triple-negative disease, there remains considerable heterogeneity in individual outcomes. Many women with recurrent triple-negative disease will progress quickly on first-, second-, and third-line palliative treatment. Future clinical trials in this population must take into account their shorter time to progression when determining optimal trial design.     

Race is a Risk Factor for the Deferral of Resection and Radiation for Early-Stage Lung Cancer

PURPOSEThere remain profound race-related disparities in the treatment of non-small cell lung cancer (NSCLC). Deferral of operative management for early-stage disease is recognized as driver of this disparity. Black race has been associated with higher rates of surgical deferral. It remains unclear how race impacts likelihood of receiving radiation therapy after declining surgical management of NSCLC.PATIENTS AND METHODSA retrospective cohort analysis was completed using data from the National Cancer Database (NCBD) for patients 18 and over with stage I NSCLC offered surgical resection from 2004 to 2015 (N = 89,462). Multivariable logistic regression identified predictors of surgical deferral and predictors for deferral of radiation after deferral of surgery. Kaplan-Meier survival analysis with log-rank tests and multivariable Cox proportional hazards regressions were performed.RESULTS87,293 (97.6%) patients underwent surgery, 2169 (2.4%) deferred. Patients who deferred had 2.1 times higher hazard ratio for mortality, (HR = 2.08, [1.97, 2.29], P < .001). Of those that deferred, 1250 (57.6%) received postdeferral radiation. Compared to White patients, Black patients had OR of 1.82 for deferring both surgery and radiation (aOR: 1.82, [1.31, 2.53], P < .001) and Asian and Pacific Island (API) patients had an OR of 2.67 (aOR: 2.67, [1.27, 4.64], P = .008). Other predictors of deferral of therapy included: Medicare or lack of insurance, and treatment at nonacademic medical centers.CONCLUSIONInsurance status and Black race, and API race are associated with deferring surgical therapy and radiation therapy for NSCLC. These findings are consistent with the large body of work showing worse outcomes for treatment of NSCLC in minority patients.     

Type 2 Diabetes Mellitus as a Risk Factor for Female Breast Cancer in the Population of Northern Pakistan

Background: There has been much research work in the past to ascertain the association between type 2 diabetes mellitus and breast cancer, but definitive evidence has been scanty. The present study was carried out to determine the association of type 2 diabetes mellitus with breast cancer in the female population of Northern Pakistan. Materials and Methods: This casecontrol study was carried out in the Oncology Department of NORI Hospital. A total of 400 patients were included. Data were entered into PSPP 0.8.1. Twotailed significance tests were used and a pvalue of 0.05 was considered significant. Results: There were a higher percentage of postmenopausal women in the diabetic breast cancer patients group as compared to the nondiabetic subset. The odds ratio for the association between diabetes and risk of developing breast cancer was elevated with statistical significance (OR 2.96; 95 % CI 1.36.3; pvalue0.004). The results of our study showed that diabetes is associated with a risk of developing breast cancer, especially in postmenopausal women (OR 4.928; 95 % CI 2.111.3; pvalue0.001). The association was particularly marked in obese subjects (OR 31.49; 95 % CI 1.8 536; p value0.01), as compared to nonobese subjects (OR 0.642; 95 % CI 0.21.7). Conclusions: Diabetes is strongly associated with obesity and it tends to increase the risk of breast Cancer, especially in postmenopausal women. A highrisk subset for breast cancer comprised postmenopausal, diabetic and overweight women.