Cancer-free Women Research Articles

Assessing the Variations in Breast/Ovarian Cancer Risk for Chinese BRCA1/2 Carriers.

Background Cancer risks vary in different BRCA1/2 mutations. We are interested in identifying regions associated with elevated/reduced risks of breast/ovarian cancers in the Chinese population and comparing with previously reported Caucasian-based breast/ovarian cancer cluster regions (OCCR/BCCR). We also aim to characterize the distribution and estimate the cancer risks of different Chinese recurrent mutations. Methods A total of 3,641 cancer-free women and 4,278 female cancer patients were included in the study. Germline BRCA1/2 status was detected with amplicon-based next-generation sequencing. We calculated the odds ratio (OR) of breast cancer and OR of ovarian cancer, and their ratio of the two ORs (ROR) for each region. ROR >1 indicated elevated odds of breast cancer and/or decreasing odds of ovarian cancer, and vice versa. The frequency, distribution, and penetrance of six known Chinese founder mutations were characterized, respectively. Haplotype analysis and age estimation were performed on the most prevalent founder mutation BRCA1: c.5470_5477del. Results A total of 729 subjects were detected with germline BRCA1/2 deleterious mutations. The putative Chinese OCCR/BCCR partially overlapped with Caucasian-based OCCR/BCCR and shared structural-functional characteristics. The six known Chinese founder mutations greatly vary in both distribution and penetrance. The two widely spread mutations are estimated to convey low penetrance, while the area-restricted founder mutations seemed to confer higher/complete penetrance. BRCA1: c.5470_5477del is estimated to have emerged ∼2,090 years ago (70 B.C.) during the Han dynasty. Conclusions BRCA1/2 carriers with different genotypes have significantly different cancer risks. An optimal risk assessment should be mutation specific, rather than concerning a single figure.

Effect of inpatient breast cancer education and risk assessment on mammography utilization among hospitalized women post discharge

ABSTRACT Objective To evaluate prevalence of nonadherence to breast cancer screening guidelines after bedside educational intervention and informed individualized risk assessment score during an inpatient stay. Methods A prospective intervention study was conducted among 507 cancer-free (except skin cancer) women aged 50–75 years hospitalized to a general medicine service. Study intervention included one-on-one bedside education via handout and videos about breast cancer screening and informed individualized risk assessment using the Gail risk model to predict 5-year risk for breast cancer development. Study outcomes were measured using posthospitalization follow-up survey to determine if intervention resulted in improved adherence to breast cancer screening. Chi-square and unpaired t-tests were utilized to compare population characteristics. Results The mean age for the study population was 60.5 years (SD = 6.9), the mean 5-year Gail risk score was 1.77 (SD = 1), and 36% of women were African American. One hundred sixty nine (33%) hospitalized women were nonadherent to breast cancer screening recommendations. Only 15% of the nonadherent women were reachable for follow-up survey, and 42% of these women self-reported adherence to screening mammography after a mean follow-up period of 27 months. Conclusion This study provides evidence that most women who are nonadherent to breast cancer screening remain nonadherent after hospital discharge despite educational interventions. Our study intervention was only partially successful in enhancing breast cancer screening among hospitalized women who were overdue and at high risk. Further studies need to evaluate strategies to overcome the barriers and improve adherence whenever patients encounter health care system regardless of clinical locale.

AKR1B10 as a Potential Novel Serum Biomarker for Breast Cancer: A Pilot Study.

BackgroundAldo-keto reductase 1B10 (AKR1B10) is a secretory protein that is upregulated in breast cancer.ObjectiveThis case-controlled pilot study evaluated the serum level of AKR1B10 in healthy women and patients with a localized or metastatic breast cancer.MethodsAKR1B10 levels were measured by ELISA and IHC in several patient cohorts.ResultsOur data showed that serum AKR1B10 was significantly elevated in patients with localized (6.72 ± 0.92 ng/ml) or metastatic (7.79 ± 1.13 ng/ml) disease compared to cancer-free healthy women (1.69 ± 0.17 ng/ml) (p<0.001); the serum AKR1B10 was correlated with its expression in tumor tissues, but not with the tumor burden, molecular subtypes or histological stages. After surgical removal of primary tumors, the serum AKR1B10 was rapidly decreased within 3 days and plateaued at a level similar to that of healthy controls in most patients. ROC curve analysis suggested the optimal diagnostic cut-off value of serum AKR1B10 at 3.456 ng/ml with AUC 0.9045 ± 0.0337 (95% CI 0.8384 – 0.9706), sensitivity 84.75% (95% CI 73.01% to 92.78%), and specificity 93.88% (95% CI 83.13% to 98.72%).ConclusionsThese data indicate the potential value of serum AKR1B10 as a biomarker of breast cancer.

Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock

BackgroundA variety of epigenetic clocks utilizing DNA methylation changes have been developed; these clocks are either tissue-independent or designed to predict chronological age based on blood or saliva samples. Whether discordant tick rates between tissue-specific and general epigenetic clocks play a role in health and disease has not yet been explored.ResultsHere we analyze 1941 cervical cytology samples, which contain a mixture of hormone-sensitive cervical epithelial cells and immune cells, and develop the WID general clock (Women’s IDentification of risk), an epigenetic clock that is shared by epithelial and immune cells and optimized for cervical samples. We then develop the WID epithelial clock and WID immune clock, which define epithelial- and immune-specific clocks, respectively. We find that the WID-relative-epithelial-age (WID-REA), defined as the difference between the epithelial and general clocks, is significantly reduced in cervical samples from pre-menopausal women with breast cancer (OR 2.7, 95% CI 1.28-5.72). We find the same effect in normal breast tissue samples from pre-menopausal women at high risk of breast cancer and show that potential risk reducing anti-progesterone drugs can reverse this. In post-menopausal women, this directionality is reversed. Hormone replacement therapy consistently leads to a significantly lower WID-REA in cancer-free women, but not in post-menopausal women with breast or ovarian cancer.ConclusionsOur findings imply that there are multiple epigenetic clocks, many of which are tissue-specific, and that the differential tick rate between these clocks may be an informative surrogate measure of disease risk.

Abstract P3-12-19: Associations of alcohol consumption with benign breast tissue composition

Abstract Objectives: Alcohol is a known breast cancer risk factor and it is also associated with increased mammographic breast density, a well-established, strong breast cancer risk factor. Despite some evidence on the associations of alcohol use with tissue composition on mammograms, no studies have examined these associations using direct measurement of tissue composition in normal breast tissue of cancer-free women. We investigated the associations of recent and cumulative average alcohol use with percentage of epithelium, stroma, fibroglandular (epithelium+stroma), and fat tissue in benign breast biopsy samples. Methods: This study included 859 cancer-free women with biopsy-confirmed benign breast disease (BBD) within the Nurses’ Health Study and Nurses’ Health Study II cohorts. Percentage of each tissue type was measured on whole section images with a deep-learning technique. All tissue measures were log-transformed. The data on alcohol use was obtained from semi-quantitative food frequency questionnaires. Information on other covariates was collected on initial questionnaire and updated biennially thereafter. We examined associations for recent (at the time of biopsy) and cumulative average alcohol use (from all questionnaire preceding the biopsy), both of which were modeled as a continuous (g/day) and categorical (using various approaches: 0, 0-&amp;lt;5, and ≥5 g/day; non-drinkers, &amp;lt;11 g/day [&amp;lt;1 drink/day], 11-&amp;lt;22g/day [1-&amp;lt;2 drinks/day], and ≥ 22 g/day [≥2 dinks/day]; and quartiles based on the distribution in the study sample). Generalized linear regression was used to examine the associations of alcohol with % of tissue types, while adjusting for known breast cancer risk factors and BBD subtype. Results: In this study of 859 cancer-free women, 260 (30.3%) had non-proliferative disease, 485 (56.5%) had proliferative disease without atypia, and 114 (13.3%) had atypical hyperplasia, consistent with previously reported distributions of these BBD subtypes. In our study, 30.3% of women consumed ≥5 g/day of alcohol at the time of biopsy and 18.1% consumed ≥11 g (≥1 drinks) of alcohol per day. The average % of epithelium, stroma, and fat in our study was 9.0% (range 0.7-52.2%), 72.4% (range 23.6-99.0%), and 18.6% (range 0-71.3%), respectively. Both recent and cumulative alcohol use were inversely associated with % of stroma and fibroglandular tissue; these associations were most pronounced for recent use of ≥22 g (≥2 drinks) per day (stroma: β=-0.08, 95% Confidence Interval [CI] -0.13;-0.03; fibroglandular: β=-0.09, 95% CI -0.13;-0.04) and cumulative average use of ≥22 g (≥2 drinks) per day (stroma β=-0.08, 95% CI -0.13;-0.02; fibroglandular: β=-0.09, 95% CI -0.14;-0.04). Recent and cumulative average use of ≥22 g/day were also positively associated with % of fat (β=0.30, 95% CI 0.03; 0.57 for recent and β=0.32, 95% CI 0.04; 0.61 for cumulative average). In stratified analysis by menopausal status, recent and cumulative average alcohol use were inversely associated with % of stroma and fibroglandular tissue and positively associated with % of fat in postmenopausal women. The strongest associations were observed for recent alcohol use of ≥22 g/day (stroma: β=-0.12, 95% CI -0.21;-0.04; fat: β=0.67, 95% CI 0.23;1.12; fibroglandular: β=-0.15, 95% CI -0.23;-0.07) and cumulative average use of ≥22 g/day (stroma β=-0.14, 95% CI -0.23;-0.04; fat: β=0.53, 95% CI 0.03;1.03; fibroglandular: β=-0.16, 95% CI -0.25;-0.07). We found no associations of alcohol use with any of the tissue measures in premenopausal women. Conclusion: Our findings suggest that both recent and cumulative average alcohol consumption are associated with smaller proportion of stroma and fibroglandular tissue and a greater proportion of fat in postmenopausal women. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms. Citation Format: Lusine Yaghjyan, Rebecca Austin-Datta, Yujing J Heng, Gabrielle Baker, Bernard Rosner, Rulla Tamimi. Associations of alcohol consumption with benign breast tissue composition [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-19.

Obstetrical and Perinatal Outcomes in Female Survivors of Childhood and Adolescent Cancer: A Population-Based Cohort Study.

The likelihood of pregnancy and risk of obstetrical or perinatal complications is inadequately documented in female survivors of pediatric cancer. We assembled a population-based cohort of female survivors of cancer diagnosed at age 21 years and younger in Ontario, Canada, between 1985 and 2012. Survivors were matched 1:5 to women without prior cancer. Multivariable Cox proportional hazards and modified Poisson models assessed the likelihood of a recognized pregnancy and perinatal and maternal complications. A total of 4062 survivors were matched to 20 308 comparisons. Median (interquartile range) age was 11 (4-15) years at cancer diagnosis and 25 (19-31) years at follow-up. By age 30 years, the cumulative incidence of achieving a recognized pregnancy was 22.3% (95% confidence interval [CI] = 20.7% to 23.9%) among survivors vs 26.6% (95% CI = 25.6% to 27.3%) among comparisons (hazard ratio = 0.80, 95% CI = 0.75 to 0.86). A lower likelihood of pregnancy was associated with a brain tumor, alkylator chemotherapy, cranial radiation, and hematopoietic stem cell transplantation. Pregnant survivors were as likely as cancer-free women to carry a pregnancy >20 weeks (relative risk [RR] = 1.01, 95% CI = 0.98 to 1.04). Survivors had a higher relative risk of severe maternal morbidity (RR = 2.31, 95% CI = 1.59 to 3.37), cardiac morbidity (RR = 4.18, 95% CI = 1.89 to 9.24), and preterm birth (RR = 1.57, 95% CI = 1.29 to 1.92). Preterm birth was more likely in survivors treated with hematopoietic stem cell transplantation (allogenic: RR = 8.37, 95% CI = 4.83 to 14.48; autologous: RR = 3.72, 95% CI = 1.66 to 8.35). Survivors of childhood or adolescent cancer are less likely to achieve a pregnancy and, once pregnant, are at higher risk for severe maternal morbidity and preterm birth.

Residential ultraviolet radiation and breast cancer risk in a large prospective cohort.

Ambient ultraviolet (UV) radiation has been increasing due to climate change. While this may result in adverse health consequences such as an increased incidence of skin cancer, UV radiation is also a source of vitamin D, which has been hypothesized to be protective for breast cancer risk. Using a spatiotemporal kriging model, we estimated residential UV exposure levels for the enrollment addresses (2003-2009) of breast cancer-free women aged 35-74years participating in the Sister Study and living in the contiguous United States (N=48,450). Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk associated with UV exposure levels (mW/m2) categorized in quintiles. We examined the association for breast cancer overall (invasive and ductal carcinoma in situ) and by estrogen receptor (ER) status of the tumor. We considered effect modification by regular (≥4 times/week) vitamin D supplement use. Over a median of 10.5years of follow up, 3,510 incident breast cancer diagnoses were reported. We found no evidence of an association between living in areas with higher levels of UV radiation and overall breast cancer risk (HRQ5 vs. Q1=1.00, 95% CI: 0.90, 1.11). Higher UV levels were inversely associated with the risk of ER- breast cancer (HRQ5 vs. Q1=0.73, 95% CI: 0.55-0.99), but not ER+ (HR Q5 vs. Q1=1.04, 95% CI: 0.92-1.18). For ER- breast cancer, the inverse association was only evident in women who did not regularly take vitamin D supplements (HRQ5 vs. Q1=0.52, 95% CI: 0.33-0.81) compared with those who did regularly take vitamin D supplements (HRQ5 vs. Q1=1.02, 95% CI: 0.68-1.54; p-for-heterogeneity=0.12). The findings from this study support a role for UV exposure and vitamin D in the etiology of ER- breast cancer.

Associations between obesity, metabolic syndrome, and endometrial cancer risk in East Asian women.

ObjectiveThis study investigated the associations between obesity, metabolic syndrome (MetS), the combination of these two components as a metabolic obesity phenotype, and endometrial cancer risk in East Asian women.MethodsA total of 6,097,686 cancer-free women aged 40–74 years who underwent the National Health Insurance Service health examination between 2009 and 2010 were included. Cancer incidence was identified using the healthcare utilization database. Associations between baseline obesity (body mass index <23 kg/m2, 23–24.9 kg/m2, ≥25 kg/m2), MetS, each component of MetS, MetS stratified by obesity status, combination of obesity and MetS, and endometrial cancer risk were investigated using hazard ratios (HRs).ResultsObesity, each component of MetS, and MetS increased the endometrial cancer risk. After these factors were mutually adjusted for, the association did not change. When stratified by obesity, MetS and MetS components were not associated with endometrial cancer in normal-weight or overweight women. However, in obese women, MetS and MetS components increased the risk of endometrial cancer (HR=1.29; 95% confidence interval [CI]=1.20–1.39). Compared with normal-weight women without MetS, endometrial cancer risk was not increased in normal-weight women with MetS. Overweight women showed an increased risk of endometrial cancer irrespective of the presence of MetS (HR=1.37 and 1.38, respectively). The HR of obese women with MetS was higher than that of obese women without MetS (HR=2.18 and 1.75).ConclusionThe association between MetS and endometrial cancer was most prominent in obese women, suggesting that obese women with MetS would be more vulnerable to endometrial cancer.

Association of the Interaction Between Mammographic Breast Density, Body Mass Index, and Menopausal Status With Breast Cancer Risk Among Korean Women

Evidence suggests that breast density and body mass index (BMI) are strong breast cancer risk factors; however, their interactive associations are unknown. Elucidation of these interactive associations may help to increase understanding of the causes of breast cancer and find effective interventions for susceptible subgroups. To explore the association of the interaction of mammographic breast density and BMI with breast cancer risks among premenopausal and postmenopausal women. This prospective observational cohort study used population-based data of the Korean National Cancer Screening Program embedded in the National Health Insurance Service database to evaluate the breast cancer risk of 3 248 941 premenopausal cancer-free women and 4 373 473 postmenopausal cancer-free women aged 40 years or older who underwent mammographic screening between January 1, 2009, and December 31, 2013, and were followed up until December 31, 2018. Statistical analysis was performed from June 1 to July 15, 2021. Breast Imaging Reporting and Data System (BI-RADS)-defined breast density (with a scale from 1 to 4, where 1 indicates almost entirely fat, 2 indicates scattered fibroglandular densities, 3 indicates heterogeneously dense tissue, and 4 indicates extremely dense tissue) and BMI levels classified according to the World Health Organization Asia-Pacific Region classification. Adjusted relative risk (aRR) of breast cancer during the follow-up period and interactions in additive and multiplicative scales. The study end point was the development of breast cancer. Of 3 248 941 premenopausal women (mean [SD] age, 44.6 [4.3] years) and 4 373 473 postmenopausal women (mean [SD] age, 59.6 [8.4] years) aged 40 years or older, 34 466 cases of breast cancer were identified among the premenopausal women, and 30 816 cases of breast cancer were identified among the postmenopausal women. Increased breast density was associated with an increased risk of breast cancer in both premenopausal and postmenopausal women across the BMI categories. Among premenopausal women, those in BI-RADS category 4 had an approximately 2-fold higher risk of breast cancer irrespective of BMI (all women: aRR, 2.36 [95% CI, 2.24-2.49]; underweight: aRR, 1.80 [95% CI, 1.25-2.59]; normal weight: aRR, 2.10 [95% CI, 1.93-2.28]; overweight: aRR, 2.47 [95% CI, 2.27-2.68]; obese: aRR, 2.87 [95% CI, 2.49-3.32]) than those with underweight status and in BI-RADS category 1. However, an association between BMI and the risk of breast cancer was found only in the postmenopausal women in all breast density categories compared with underweight women with BI-RADS category 1 (BI-RADS category 4, all women: aRR, 2.91 [95% CI, 2.78-3.04]; underweight: aRR, 2.74 [95% CI, 1.89-3.98]; normal weight: aRR, 3.05 [95% CI, 2.82-3.30]; overweight: aRR, 2.85 [95% CI, 2.67-3.04]; obese: aRR, 2.52 [95% CI, 2.22-2.88]). When the combined associations of breast density and BMI with the risk of breast cancer were considered, a high breast density and high BMI had a significant positive interaction on the additive scale for both premenopausal and postmenopausal women, especially the latter (premenopausal women: adjusted relative excess risk due to interaction, 0.53 [95% CI, 0.35-0.71]; postmenopausal women: adjusted relative excess risk due to interaction, 1.68 [95% CI, 1.26-2.10]). This study suggests that breast density and BMI interact synergistically to augment breast cancer risk, with a stronger association found among postmenopausal women. Both factors should be incorporated into risk stratification in a population-based screening for public health significance. Women with overweight or obesity and dense breast tissue might benefit from tailored early screening strategies to detect breast cancer.

Early-life exposures and age at thelarche in the Sister Study cohort

BackgroundEarly age at breast development (thelarche) has been associated with increased breast cancer risk. Average age at thelarche has declined over time, but there are few established risk factors for early thelarche. We examined associations between pre- and postnatal exposures and age at thelarche in a US cohort of women born between 1928 and 1974.MethodsBreast cancer-free women ages 35–74 years who had a sister diagnosed with breast cancer were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported information on early-life exposures and age at thelarche, which we categorized as early (≤ 10 years), average (11–13 years), and late (≥ 14 years). For each exposure, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early and late thelarche using polytomous logistic regression, adjusted for birth cohort, race/ethnicity and family income level in childhood.ResultsEarly thelarche was associated with multiple prenatal exposures: gestational hypertensive disorder (OR = 1.25, 95% CI 1.09–1.43), diethylstilbestrol use (OR = 1.23, 95% CI 1.04–1.45), smoking during pregnancy (OR = 1.20, 95% CI 1.13–1.27), young maternal age (OR 1.30, 95% CI 1.16–1.47 for < 20 vs. 25–29 years), and being firstborn (OR = 1.25, 95% CI 1.17–1.33). Birthweight < 2500 g and soy formula use in infancy were positively associated with both early and late thelarche.ConclusionsAssociations between pre- and postnatal exposures and age at thelarche suggest that the early-life environment influences breast development and therefore may also affect breast cancer risk by altering the timing of pubertal breast development.

Incorporating Robustness to Imaging Physics into Radiomic Feature Selection for Breast Cancer Risk Estimation.

Simple SummaryMammographic density estimates can be combined with radiomic texture features to offer an even better assessment of breast cancer risk. However, some feature variations will be due to true parenchymal differences between women, but others will be due to imaging physics effects (contrast, noise, and image sharpness); features robust to imaging physics effects should better model risk. To investigate this, we imaged an anthropomorphic phantom at various x-ray technique settings, allowing us to directly measure the effects of imaging physics on feature values. We compared these variations, for each feature, with the inter-woman variation in a screening population (552 cancer-free women) and the intra-woman variation between each woman’s left and right breasts, to assess which features were relatively robust to physics settings. We then tested more- versus less-robust features in modeling cancer risk on an independent case-control data set, and demonstrated that more-robust features were indeed better at risk prediction.Digital mammography has seen an explosion in the number of radiomic features used for risk-assessment modeling. However, having more features is not necessarily beneficial, as some features may be overly sensitive to imaging physics (contrast, noise, and image sharpness). To measure the effects of imaging physics, we analyzed the feature variation across imaging acquisition settings (kV, mAs) using an anthropomorphic phantom. We also analyzed the intra-woman variation (IWV), a measure of how much a feature varies between breasts with similar parenchymal patterns—a woman’s left and right breasts. From 341 features, we identified “robust” features that minimized the effects of imaging physics and IWV. We also investigated whether robust features offered better case-control classification in an independent data set of 575 images, all with an overall BI-RADS® assessment of 1 (negative) or 2 (benign); 115 images (cases) were of women who developed cancer at least one year after that screening image, matched to 460 controls. We modeled cancer occurrence via logistic regression, using cross-validated area under the receiver-operating-characteristic curve (AUC) to measure model performance. Models using features from the most-robust quartile of features yielded an AUC = 0.59, versus 0.54 for the least-robust, with p < 0.005 for the difference among the quartiles.

Evaluation of health perceptions and healthcare utilization among population-based female cancer survivors and cancer-free women.

Cancer survivors are more likely to report having a poor health status when compared to the general population. Few studies have focused on the impact of cancer on health status and healthcare utilization/access outcomes among women from medically underserved populations. 25,741 women with and without a history of cancer from the National Health and Nutrition Examination Survey from 1999 to 2016 contributed data. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for associations between cancer status and perceived health and healthcare utilization/access outcomes stratified by race/ethnicity, poverty status, education, and comorbidities. 1,897 (7.0%) women had a history of cancer with breast cancer as the most common (n = 671, 35.7%). While most survivors were non-Hispanic white (69.4%), 13.9% were Hispanic, 12.0% were non-Hispanic Black, and 4.6% were additional racial/ethnic groups. Survivors were 1.32 times more likely to be hospitalized within the last year (95% CI 1.11-1.58) and 1.32 times more likely to see a mental health provider within the last year (95% CI 1.05-1.66) compared to cancer-free women. Race/ethnicity was a significant effect modifier in the association between being a survivor and seeing a mental health provider, with Hispanic survivors having the highest odds (aOR 3.44; 95% CI 2.06-5.74; p-interaction < 0.00). Our study identifies disparities in healthcare utilization among female cancer survivors, highlighting the importance of evaluating these associations among medically underserved populations. These findings can educate healthcare professionals working with these populations to inform gaps in survivorship care utilization/access.

The Use of Human Serum Samples to Study Malignant Transformation: A Pilot Study.

Obesity and excess adiposity account for approximately 20% of all cancer cases; however, biomarkers of risk remain to be elucidated. While fibroblast growth factor-2 (FGF2) is emerging as an attractive candidate biomarker for visceral adipose tissue mass, the role of circulating FGF2 in malignant transformation remains unknown. Moreover, functional assays for biomarker discovery are limited. We sought to determine if human serum could stimulate the 3D growth of a non-tumorigenic cell line. This type of anchorage-independent 3D growth in soft agar is a surrogate marker for acquired tumorigenicity of cell lines. We found that human serum from cancer-free men and women has the potential to stimulate growth in soft agar of non-tumorigenic epithelial JB6 P+ cells. We examined circulating levels of FGF2 in humans in malignant transformation in vitro in a pilot study of n = 33 men and women. Serum FGF2 levels were not associated with colony formation in epithelial cells (r = 0.05, p = 0.80); however, a fibroblast growth factor receptor-1 (FGFR1) selective inhibitor significantly blocked serum-stimulated transformation, suggesting that FGF2 activation of FGFR1 may be necessary, but not sufficient for the transforming effects of human serum. This pilot study indicates that the FGF2/FGFR1 axis plays a role in JB6 P+ malignant transformation and describes an assay to determine critical serum factors that have the potential to promote tumorigenesis.

Comparison of Incidental Thyroid Nodules Between Early Breast Cancer Patients and Healthy Controls: Higher Incidence and Thyroid Imaging Reporting and Data System (TI-RADS) Score of Patients with Cancer

Background: Breast and thyroid cancers remain among the most common malignancies in women. In previous studies, the co-occurrence of thyroid and breast cancers has been reported. Objectives: The aim of this study was to evaluate and compare the risk and incidence of incidental thyroid nodules (ITNs) between patients with breast cancer and healthy controls, based on the Thyroid Imaging Reporting and Data System (TI-RADS). Methods: This case-control study was conducted on 140 patients with breast cancer and 140 cancer-free women in a similar age range. Thyroid ultrasonography (US) was performed before the onset of treatment. The risk stratification of thyroid nodules was based on the TI-RADS. Results: The mean age of the participants was not significantly different between the case (43.35 ± 7.85 years) and control (42.11 ± 3.69 years) groups (P = 0.094). Invasive ductal carcinoma was the most frequent type of breast cancer in the patients. Normal thyroid US findings were significantly less frequent in patients with breast cancer (35.7%) compared to the healthy controls (76.4%) (P = 0.001). On the other hand, thyroid nodules were more frequent in the patients and associated with a higher risk of malignancy (i.e., high TI-RADS scores) compared to healthy women (P = 0.001 and P = 0.001, respectively). Besides, patients with breast cancer showed more thyroid abnormalities in the US examinations. Conclusions: A higher frequency of ITN, with an elevated TI-RADS score, which raised the suspicion of malignancy, was seen in patients with breast cancer. Overall, patients with breast cancer may benefit from a regular thyroid US examination.

THE CHARACTERISTICS AND PROGNOSIS OF HEART FAILURE ASSOCIATED WITH CHEMOTHERAPY FOR EARLY BREAST CANCER: A POPULATION-BASED MATCHED COHORT STUDY

THE CHARACTERISTICS AND PROGNOSIS OF HEART FAILURE ASSOCIATED WITH CHEMOTHERAPY FOR EARLY BREAST CANCER: A POPULATION-BASED MATCHED COHORT STUDY

Associations between obesity, metabolic health, and the risk of breast cancer in East Asian women.

This study examined the associations between metabolic syndrome(MetS), obesity, their combination as a metabolic obesity phenotype, and the risk of breast cancer in East Asian postmenopausal women. A total of 3,095,336 postmenopausal cancer-free women aged 40-79 years who underwent the National Health Insurance Service health examination between 2009 and 2010 were included. The incidence of invasive breast cancer was followed up until 2018. The presence of obesity (body mass index[BMI] ≥25 kg/m2), MetS, and each component of MetS was investigated. Obesity and MetS were associated with breast cancer risk, but when the effects of obesity and MetS were mutually adjusted, the associations were attenuated, especially for MetS. Only elevated fasting blood glucose levels and waist circumference increased the risk of breast cancer after adjusting for BMI. Compared to metabolically healthy normal-weight women, metabolically unhealthy normal-weight women, metabolically healthy obese, and metabolically unhealthy obese women had an increased risk of breast cancer. Obesity and MetS were independently associated with an increased risk of breast cancer in postmenopausal women, despite the relationship between MetS and breast cancer appearing to result from a partial association with BMI. Postmenopausal women should be encouraged to control their weight and metabolic health.

Information needs on breast cancer genetic and non-genetic risk factors in relatives of women with a BRCA1/2 or PALB2 pathogenic variant

ObjectivesComprehensive breast cancer (BC) risk models integrating effects of genetic (GRF) and non-genetic risk factors (NGRF) may refine BC prevention recommendations. We explored the perceived information received on BC risk factors, and related characteristics, in female relatives of women with a BRCA1/2 or PALB2 pathogenic variant, undergoing BC risk assessment using the CanRisk© prediction tool. MethodsOf 200 consecutive cancer-free women approached after the initial genetic consultation, 161 (80.5%) filled in questionnaires on their perception of information received and wished further information on BC risk factors (e.g., being a carrier of a moderate risk altered gene, personal genetic profile, lifestyles). Multilevel multivariate linear models were performed accounting for the clinician who met the counselee and exploring the effect of counselees’ socio-demographic, familial and psychological characteristics on the perceived extent of information received. ResultsPerceived no/little information received and wish for further information were more frequent for NGRF (>50%) than for GRF, especially high-risk genes (<20%). Perceived amount of information received and desire for further information were inversely correlated (p=<0.0001). Higher education level related to lower perceived levels of information received on GRF. Younger counselees' age (β = 0.13, p = 0.02) and less frequent engagement coping (e.g., inclination to solicit information) (β = 0.24, p = 0.02) related to lower perceived information received about NGRF. Other assessed counselees’ features were not found to be associated to GRF and NGRF information perception. ConclusionsAwareness of counselees’ perceived lack of information on BC risk factors indicates a need to enhance evidence-based information on BC NGRF especially.

Uncovering Microbial Composition in Human Breast Cancer Primary Tumour Tissue Using Transcriptomic RNA-seq.

Recent research studies are showing breast tissues as a place where various species of microorganisms can thrive and cannot be considered sterile, as previously thought. We analysed the microbial composition of primary tumour tissue and normal breast tissue and found differences between them and between multiple breast cancer phenotypes. We sequenced the transcriptome of breast tumours and normal tissues (from cancer-free women) of 23 individuals from Slovakia and used bioinformatics tools to uncover differences in the microbial composition of tissues. To analyse our RNA-seq data (rRNA depleted), we used and tested Kraken2 and Metaphlan3 tools. Kraken2 has shown higher reliability for our data. Additionally, we analysed 91 samples obtained from SRA database, originated in China and submitted by Sichuan University. In breast tissue, the most enriched group were Proteobacteria, then Firmicutes and Actinobacteria for both datasets, in Slovak samples also Bacteroides, while in Chinese samples Cyanobacteria were more frequent. We have observed changes in the microbiome between cancerous and healthy tissues and also different phenotypes of diseases, based on the presence of circulating tumour cells and few other markers.

Differences in heart rate variability and body composition in breast cancer survivors and women without cancer

The aim of this study was to explore cardiac autonomic changes assessed by linear and nonlinear indexes of heart rate variability (HRV) and body composition modifications in breast cancer survivors and cancer-free control women. Women who were breast cancer survivors (BCS, n = 27) and without cancer with similar characteristics (Control, n = 31) were recruited for this study. We calculated some relevant linear and nonlinear parameters of 5 min of RR interval time series such as mean RR interval (RRave), the corrected Poincaré index (cSD1/SD2), the sample entropy (SampEn), the long-term fractal scaling exponent (α2) and 2UV from symbolic dynamics. Additionally, we indirectly assessed body composition measures such as body weight, fat mass, visceral fat rating (VFR), normalized VRF (nVFR), muscle mass, metabolic age, and total body water. We found that diverse HRV indexes and only one body composition measure showed statistical differences (p < 0.05) between the BCS and Control groups. RRave: 729 (648–802) vs. 795 (713–852) ms; cSD2/SD1: 3.4 (2.7–5.0) vs. 2.9 (2.3–3.5); SampEn: 1.5 (1.3–1.8) vs. 1.7 (1.5–1.8); α2: 0.6 (0.3–0.6) vs. 0.5 (0.4–0.5); 2UV: 7.1 (4.3–11.5) vs. 10.8 (6.4–15.7) and nVFR 0.12 (0.11–0.13) vs. 0.10 (0.08–0.12) points/kg, respectively. The nVFR was strongly significantly correlated with several indexes of HRV only in the BCS group.Our findings suggest that BCS exhibit lower parasympathetic cardiac activity and changes in HRV patterns compared to Controls. A concomitant increase of visceral fat, among other factors, may contribute to cardiac autonomic disturbances and changes in HRV patterns in BCS.

A Randomized Trial of Calcium Plus Vitamin D Supplementation and Risk of Ductal Carcinoma In Situ of the Breast.

BackgroundThe effect of calcium plus vitamin D (CaD) supplementation on risk of ductal carcinoma in situ (DCIS) of the breast, a nonobligate precursor of invasive ductal carcinoma, is not well understood. In this secondary analysis, we examined this association in the Women’s Health Initiative CaD trial over approximately 20 years of follow-up.MethodsA total of 36 282 cancer-free postmenopausal women (50-79 years) were randomly assigned to daily (d) calcium (1000 mg) plus vitamin D (400 IU) supplementation or to a placebo. Personal supplementation with vitamin D (≤600 IU/d, subsequently raised to 1000 IU/d) and calcium (≤1000 mg/d) was allowed. The intervention phase (median = 7.1 years), was followed by a postintervention phase (additional 13.8 years), which included 86.0% of the surviving women. A total of 595 incident DCIS cases were ascertained. Hazard ratios (HRs) plus 95% confidence intervals (CIs) were calculated.ResultsThe intervention group had a lower risk of DCIS throughout follow-up (HR = 0.82, 95% CI = 0.70 to 0.96) and during the postintervention phase (HR = 0.76, 95% CI = 0.61 to 0.94). The group that used CaD personal supplements in combination with the trial intervention had a lower risk of DCIS compared with the trial placebo group that did not use personal supplementation (HR = 0.72, 95% CI = 0.56 to 0.91).ConclusionsCaD supplementation in postmenopausal women was associated with reduced risk of DCIS, raising the possibility that consistent use of these supplements might provide long-term benefits for the prevention of DCIS.