Increased Incidence Of Breast Cancer Research Articles

Latcripin-7A, derivative of Lentinula edodes C91-3, reduces migration and induces apoptosis, autophagy, and cell cycle arrest at G1 phase in breast cancer cells.

Due to the high mortality rate and an increase in breast cancer incidence, it has been challenging for researchers to come across an effective chemotherapeutic strategy with minimum side effects. Therefore, the need for the development of effective chemotherapeutic drugs is still on the verge. Consequently, we approached a new mechanism to address this issue. The naturally available peptide named latcripin-7A (LP-7A), extracted from a mushroom called Lentinula edodes, provided us promising results in terms of growth arrest, apoptosis, and autophagy in breast cancer cells (MCF-7 and MDA-MB-231). Expressions of protein markers for apoptosis, autophagy, and cell cycle were confirmed via Western blot analysis. Migration and invasion assays were performed to analyze the anti-migratory and anti-invasive properties of LP-7A, while cell cycle analysis was performed via flow cytometry to evaluate its affect over cell growth. Supportive assays were performed like acridine orange, Hoechst 33258 stain, DNA fragmentation, and mitochondrial membrane potential (MMP) to further confirm the anticancer effectof LP-7A on breast cancer cell lines. It is concluded that LP-7A effectively reduces migration and promotes apoptosis as well as autophagy in MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell growth arrest at G0/G1 phase and decreasing mitochondrial membrane potential without adverse effects on MCF-10A normal breast cells. KEY POINTS: • In this study, we have investigated the anti-cancer activity of novel latcripin-7A (LP-7A), a protein extracted as a result of de novo characterization of Lentinula edodes C91-3. • We conclude in our research work that LP-7A can initiate diverse cell death-related events, i.e., apoptosis and autophagy in both triple-positive and triple-negative breast cancer cell lines by interacting with different nodes of cellular signaling that can further be investigated in vivo to gain a better understanding.

Liothyronine Use in Hypothyroidism and its Effects on Cancer and Mortality.

Background: The prescription of liothyronine (LT3) to treat hypothyroidism is increasing worldwide; however, the long-term safety of LT3 use has yet to be determined. Previous studies have suggested a possible association between LT3 use and breast cancer. The aim of this study was to examine the effects of LT3 use on cancer incidence and mortality. Methods: Our sample included the full adult population of individuals living in Sweden with at least three purchases of thyroid hormone therapy between July 2005 and December 2017. Individual-level data on drug purchases were linked to registry data on cancer incidence and mortality. There were 575,461 individuals with at least three purchases, of which 11,147 had made at least three purchases of LT3, including combinations of levothyroxine (LT4) and LT3. Individuals were followed for a median follow-up time of 8.1 years. We applied Cox regression with a time-varying exposure variable, comparing LT3 users (individuals with at least three cumulative purchases of LT3) with LT4-only users (the rest). Outcomes included breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, and breast cancer mortality. We adjusted for age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose in multivariate analyses. Results: Multivariate analyses produced a hazard ratio of 0.93 (95% confidence interval [0.75-1.15]) for breast cancer incidence (only females), 0.97 (0.87-1.08) for any cancer incidence, 0.69 (0.61-0.77) for all-cause mortality, 0.78 (0.62-0.98) for any cancer mortality, and 0.91 (0.50-1.66) for breast cancer mortality (only females). Conclusions: In this large, Swedish, long-term registry-based study, the use of LT3 did not lead to increased breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality compared with LT4 use. Somewhat surprisingly, there was evidence of lower mortality in LT3 users in models adjusting for dose, potentially an artifact of underlying associations between dose and health status/diagnosis.

Mammographic Breast Density and Acculturation: Longitudinal Analysis in Chinese Immigrants.

Breast cancer is the most common cancer in women. Asian American women have experienced steadily increasing breast cancer incidence rates over the past several decades. The increased rate might be in part due to acculturation. We tested the hypothesis that higher level of acculturation was associated with higher mammographic breast density (MBD), an indicator of breast cancer risk, in a cohort of 425 premenopausal Chinese immigrant women in Philadelphia. Generalized estimating equations accounted for repeated observations and adjusted for age, type of mammographic image, body mass index, months of breastfeeding, number of live births, age at first birth, and menopausal stage (pre, early peri, late peri, post). Results indicated that acculturation level was not associated with any of the MBD measures. Findings were contrary to our hypothesis and previous, cross-sectional studies. In this study population, reproductive factors had a greater effect on MBD than acculturation-related behaviors in adulthood.

Analysis on long-term trend of mortality and years of life lost of breast cancer in women in Tianjin, 1999-2017

Objective: To analyze the trends of mortality and years of life lost (YLL) of breast cancer in women in Tianjin and provide references for the development of intervention strategies. Methods: The crude mortality rate, standard mortality rate, cumulative rate (0-74 years old) and truncated rate (35-64 years old) of breast cancer in women in Tianjin from 1999 to 2017 were calculated. The annual percentage change of the mortality rate and YLL rate were analyzed by Joinpoint regression. Results: From 1999 to 2017, a total of 8 356 deaths of breast cancer were reported in Tianjin, resulting in a YLL of 262 835.53 person-years. The average crude mortality rate was 9.15/100 000. The average age standardized rate(ASR) (World) was 6.14/100 000. The ratio of ASR (World) between urban and rural areas was 1.73∶1. The peak mortality ratio of age groups between urban area and rural area was 3.13∶1. From 1999 to 2017, both the crude mortality rate and ASR of breast cancer in Tianjin had rising trends. In 2017, the crude mortality rate and the ASR of breast cancer increased by 113.7% and 44.4% respectively compared with 1999. The increase of urban mortality mainly came from elderly group aged ≥75 years, and the mortality of young age groups in rural area showed an fast increases, which was most obvious in age group 45-59 years (average annual percentage change=3.6%, P<0.01). Conclusions: The mortality rate of breast cancer and disease burden in women in Tianjin are still in rapid increase. We should continue to implement the prevention and control strategies such as lifestyle intervention and screening of key groups. More attention need to be paid to the increase of breast cancer incidence in rural area.

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey.

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.”

90 YEARS OF PROGESTERONE: Progesterone and progesterone receptors in breast cancer: past, present, future.

Progesterone and progesterone receptors (PR) have a storied albeit controversial history in breast cancers. As endocrine therapies for breast cancer progressed through the twentieth century from oophorectomy to antiestrogens, it was recognized in the 1970s that the presence of estrogen receptors (ER) alone could not efficiently predict treatment responses. PR, an estrogen regulated protein, became the first prognostic and predictive marker of response to endocrine therapies. It remains today as the gold standard for predicting the existence of functional, targetable ER in breast malignancies. PRs were subsequently identified as highly structured transcription factors that regulate diverse physiological processes in breast cancer cells. In the early 2000s, the somewhat surprising finding that prolonged use of synthetic progestin-containing menopausal hormone therapies was associated with increased breast cancer incidence raised new questions about the role of PR in 'tumorigenesis'. Most recently, PR have been linked to expansion of cancer stem cells that are postulated to be the principal cells reactivated in occult or dormant disease. Other studies establish PR as dominant modulators of ER activity. Together, these findings mark PR as bona fide targets for progestin or antiprogestin therapies, yet their diverse actions have confounded that use. Here we summarize the early history of PR in breast cancer; debunk the theory that progesterone causes cancer; discuss recent discoveries that PR regulate cell heterogeneity; attempt to unify theories describing PR as either good or bad actors in tumors; and discuss emerging areas of research that may help explain this enigmatic hormone and receptor.

XPC as breast cancer susceptibility gene: evidence from genetic profiling, statistical inferences and protein structural analysis.

Gene polymorphisms that affect nucleotide excision repair (NER) pathway may link with higher susceptibility of breast cancer (BC); however, the significance of these associations may vary conferring to the individual ethnicity. Xeroderma pigmentosum complementation gene (XPC) plays a substantial role in recognizing damaged DNA during NER process. To estimate the relationship among XPC polymorphisms and breast cancer (BC) risk, we carried out a case-control-association study with 493 BC cases and 387 controls using TETRA-ARMS-PCR. Distributional differences of clinical features, demographic factors and XPC polymorphisms among BC cases and controls were examined by conditional logistic regression model. Kaplan-Meier test was applied to predict survival distributions and protein structure was predicted using computational tools. Obesity, consanguinity, positive marital status and BC family history were associated (P ≤ 0.01) with higher BC risk. Genotyping revealed significant involvement (P ≤ 0.01) of two XPC polymorphisms rs2228001-A > C (OR = 3.8; CI 1.9-7.6) and rs2733532-C > T (OR = 2.6; CI 1.4-5.03) in BC development, asserting them potential risk factors for increased BC incidence. However, no association (P > 0.05) was detected for overall or progression free survival for both XPC polymorphisms possibly due to shorter follow-up time (45months). As compared to normal XPC structure, pronounced conformational changes have been observed in the C-terminus of XPCQ939K, bearing rs2228001-A > C substitution. In XPCQ939K, two additional α-helices were observed at A292-E297 and Y252-R286, while L623-M630 and L649-L653 helices were converted into loop conformation. In conclusion, both XPC polymorphisms confer significant association with increased BC risk. rs2228001 substitution may change the structural and functional preferences of XPC C-terminus, while rs2733532 may have regulatory role thereby leading to potential BC risk.

Abstract D096: Disparities in toxic heavy metal burden and breast cancer risk: Findings from the Metropolitan Chicago Breast Cancer Registry

Abstract BACKGROUND: Evidence regarding associations of ambient toxic heavy metals (THMs) and breast cancer (BC) incidence is mixed. Observed inconsistencies may be a consequence of utilizing ambient THM levels collected close to time of BC diagnosis, and not incorporating an appropriate latent period. In addition, most studies have not examined associations of ambient THMs and BC incidence stratified by estrogen receptor (ER) and menopausal status, and have examined relatively homogenous populations of non-Hispanic White (nHW) women. We examined time-to-event associations of ambient THM concentrations and BC subtypes among women enrolled in the racially/ethnically diverse Metropolitan Chicago Breast Cancer Registry (MCBCR) cohort. METHODS: Using the Environmental Protection Agency’s 2005 National Air Toxics Assessment (NATA), we examined census tract-level ambient concentrations for 11 THMs (antimony, arsenic, beryllium, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, and selenium). For women enrolled in MCBCR between 2003-2007, residential addresses were geocoded and matched to census-tract estimates of the ambient THM concentrations. Women were followed to time of BC diagnosis or December 31, 2014. Cox proportional hazards (PH) regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI), adjusted for age and race. RESULTS: Over a mean follow up time of 10 years, there were 6,579 incident BC cases (with a mean time to diagnosis of 3 years) and 205,095 cancer-free women in the cohort. Over a quarter of our study population was African American (AA), and nearly 10% were Hispanic. Compared to nHW women, AA women were more likely to reside in census tracts with higher quartile ambient concentrations of beryllium, cadmium, chromium, cobalt, lead, manganese, and mercury (p&amp;lt;0.001 for all). Similarly, Hispanic women were more likely to reside in census tracts characterized by higher quartile oncentrations of beryllium, cadmium, chromium, lead, manganese, mercury, and nickel (p&amp;lt;0.001 for all). In age and race adjusted models, compared to women residing in census tracts with the lowest quartile of ambient concentrations, increased BC incidence was observed for women residing in census tracts with the highest quartile of ambient concentrations of antimony (HR=1.08, 95% CI 1.00-1.17), beryllium (HR=1.09, 95% CI 1.01-1.18), cadmium (HR=1.07, 95% CI 1.00-1.17), lead (HR=1.18, 95% CI 1.09, 1.28), and nickel (HR=1.24, 95% CI 1.15-1.33). In models stratified by ER status and menopausal status, associations with beryllium, lead, and nickel were stronger for ER positive post-menopausal BC. Associations with antimony and cadmium were stronger for ER-negative BC risk. DISCUSSION: We found that African American and Hispanic women were disproportionately exposed to higher levels of ambient THMs, which in turn were associated with specific subtypes of BC. Future studies will focus on determinants of these observed environmental disparities in the MCBCR cohort. Citation Format: Alpana Kaushiva, Jacob Kresovich, Serap Erdal, Garth Rauscher. Disparities in toxic heavy metal burden and breast cancer risk: Findings from the Metropolitan Chicago Breast Cancer Registry [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D096.

Association between metabolic syndrome and breast cancer.

Metabolic syndrome is a set of risk factors associated with cardiovascular disease and diabetes. In Mexico, its prevalence has been reported up to 49.8%, significantly higher than in other countries. In the last 30 years there has been an increase in breast cancer incidence in Mexico, becoming the most frequent and deadly neoplasm in 2018. Since the late 1990s, several observational studies have identified an association between metabolic syndrome and an increased risk of breast cancer. At least 3 interrelated mechanisms that explain the risk increase of cancer associated with metabolic syndrome are postulated: the increase in estrogen levels derived from adipose tissue, hyperinsulinemia and its anabolic effect on epithelial cells and the endocrine effect of abdominal fat. The components of metabolic syndrome associated with an increased risk of breast cancer are: type 2 diabetes with a relative risk of 1.27 (95% CI: 1.16-1.39), obesity in postmenopausal women with a relative risk of 1.39 (95% CI: 1.14-1.70) and low HDL cholesterol levels have demonstrated an increased risk.

Correlation between breast cancer and lifestyle within the Gulf Cooperation Council countries: A systematic review.

BACKGROUNDIn the six Gulf Cooperation Council countries (GCCCs), Bahrain, Saudi Arabia, Kuwait, Oman, Qatar and the United Arab Emirates, breast cancer (BC) is the greatest cause of cancer incidence and mortality. Obesity and physical inactivity are established risk factors for BC globally and appear to be more of a problem in high income countries like the GCCCs.AIMTo determine whether obesity and physical inactivity are associated with BC incidence in the GCCCs using the United Kingdom as a comparator.METHODSThis systematic review was carried out according to PRISMA guidelines. A cancer registry and a statistical data search was done to identify the BC incidence over the past two decades and the prevalence of obesity and physical inactivity in the GCCCs. Additionally, a systematic search of the databases, MEDLINE, Web of Science, and PubMed between 1999 and 2019 was performed to determine whether obesity and physical inactivity are risk factors for BC in the GCCCs. All papers were critically appraised according to their research methods and were assessed for quality and risk of bias.RESULTSBC was the top malignancy in each GCC country. Women tended to be diagnosed with BC at a younger age than women in the United Kingdom. The greatest 10-year increase in BC incidence was seen in Saudi Arabia (54.2%), approximately seven times the rate of increase seen in the United Kingdom (7.6%). The prevalence of obesity and physical inactivity was greater in all the GCCCs in comparison to the United Kingdom. A total of 155 full studies were reviewed of which 17 were included. Of those, eight looked at the prevalence of obesity and physical inactivity in the Gulf States and nine looked at these as risk factors for BC. Only one study found an association between BC and obesity (odds ratio = 2.29). No studies looked solely at the link between physical inactivity and BC.CONCLUSIONThe prevalence of obesity and physical inactivity was high within the GCCCs, but the majority of the included studies found no positive correlation between obesity or physical inactivity and BC. A high proportion of women in this study were pre-menopausal which could contribute to the negative findings.

FABP4: A New Player in Obesity-Associated Breast Cancer

Obesity is known to increase breast cancer incidence and mortality, but the underlying mechanisms remain unsolved. Recent studies demonstrate that adipose fatty acid binding protein (FABP4) promotes obesity-associated breast cancer development, thus suggesting FABP4 as a novel player linking obesity and breast cancer risk.

Forty-year trends in menopausal hormone therapy use and breast cancer incidence among postmenopausal black and white women.

After reports from the Women's Health Initiative randomized trial evaluating estrogen plus progestin, there was a sudden, substantial, and sustained decrease in all categories of menopausal hormone therapy, and the first reduction in age-adjusted breast cancer incidence in more than 20years was seen in 2003-2004 among US women 50 years of age or older. Subsequent trends in breast cancer incidence have been described, but most reports have not focused on the postmenopausal age group or fully engaged the potential influence of reduced hormone therapy on breast cancer incidence trends by race/ethnicity. To address this gap, this commentary examines trends for annual age-adjusted breast cancer incidence over a 40-year period from 1975 to 2015 for white and black women on the basis of findings from the Surveillance, Epidemiology, and End Results 9 registries. Overall, the sharp decline in breast cancer incidence seen in 2003-2004 was followed in the subsequent decade by a continued low breast cancer incidence plateau in white women that has largely persisted. In contrast, a new discordance between breast cancer incidence trends in black and white women has emerged. In the 2005-2015 decade, a sustained increase in breast cancer incidence in black women has resulted in annual incidence rates comparable, for the first time, to those in white women. This commentary explores the hypothesis that the over-decade-long and discordant changes in breast cancer incidence rates in postmenopausal black and white women are, to a large extent, associated with changes in hormone therapy use in these 2 groups.

Trends in Parity and Breast Cancer Incidence in US Women Younger Than 40 Years From 1935 to 2015

During the past several decades, breast cancer incidence has been increasing for women younger than 40 years. The increase matches the decrease in parity, an established breast cancer risk factor, but secular trends in incidence have not been examined prior to the 1970s. To examine whether secular trends in parity explain the increase in breast cancer incidence among US women aged 25 to 39 years from 1935 to 2015. This population-based cohort study used population-based aggregate-level data from the Connecticut Tumor Registry (CTR) to examine breast cancer incidence and age-standardized rates among women aged 25 to 39 years from 1935 to 2015. National mean live births were calculated using birth data from the National Vital Statistics System (NVSS) from 1930 to 2015 (allowing for 5-year lag). Linear regression was used to compare a baseline model of year estimating age-adjusted breast cancer incidence rate with a model that adjusted for parity constructs. Breast cancer incidence rates among women aged 25 to 39 years from 1935 to 2015. Among women in Connecticut aged 25 to 39 years from 1935 to 2015, incidence of breast cancer for women aged 25 to 39 years increased 0.65% (95% CI, 0.53%-0.77%) per year, from 16.3 breast cancer diagnoses per 100 000 women in 1935 to 38.5 breast cancer diagnoses per 100 000 women in 2015. This increase began nearly 4 decades before the secular decrease in parity (mean [SD] parity peaked at 2.26 [0.87] live births per woman in 1966 and in 2010 had decreased to 1.41 [0.71] live births per woman). Age-specific parity trends explained only 0% to 4% of the variability in incidence over time. These findings suggest that breast cancer incidence for women aged 25 to 39 years has been significantly increasing since the 1930s and cannot be attributed to changes in parity over time.

Temporal trends in age at menarche and age at menopause: a population study of 312 656 women in Norway.

STUDY QUESTIONHave mean age at menarche or mean age at natural menopause changed from the 1939 birth cohort to the 1964 birth cohort?SUMMARY ANSWERWe estimated a minor decrease in mean age at menarche and an increase by nearly 3 years in mean age at natural menopause.WHAT IS KNOWN ALREADYIn the Western world, age at menarche decreased across birth cohorts from the early 1800s until the 1950s. Whether mean age at menarche has continued to decrease in birth cohorts after the 1950s remains uncertain. It is also uncertain whether mean age at natural menopause has changed across birth cohorts.STUDY DESIGN, SIZE, DURATIONWe performed a retrospective population study of 312 656 women who were born in Norway during the years 1936–1964.PARTICIPANTS/MATERIALS, SETTING, METHODSThe data were obtained by two self-administered questionnaires from women who participated in the Norwegian breast cancer screening program (BreastScreen Norway) during the years 2006–2014. We used flexible parametric survival models with restricted cubic splines to estimate mean age at menarche, mean age at menopause and mean number of years between menarche and menopause according to the women’s year of birth. The women who were still having menstrual periods contributed with follow-up time until the time of data collection, and the women who had reported surgical removal of the uterus and/or both ovaries prior to natural menopause contributed with follow-up time until the time of surgery.MAIN RESULTS AND THE ROLE OF CHANCEThe mean age at menarche was 13.42 years (95% CI: 13.40–13.44 years) among women born during 1936–1939, and it was 13.24 years (95% CI: 13.22–13.25 years) among women born during 1960–1964. The mean age at natural menopause increased from 50.31 years (95% CI: 50.25–50.37 years) among women born during 1936–1939 to 52.73 years (95% CI: 52.64–52.82 years) among women born during 1960–1964. The mean number of years between menarche and menopause increased from 36.83 years (95% CI: 36.77–36.89 years) to 40.22 years (95% CI: 40.11–40.34 years).LIMITATIONS, REASONS FOR CAUTIONInformation about age at menarche and age at menopause was based on self-reports.WIDER IMPLICATIONS OF THE FINDINGSLate menopause is associated with increased risk of breast cancer but also with increased life expectancy. Thus, higher mean age at menopause may partly explain the increase in breast cancer incidence after menopause and the increase in life expectancy in recent time. Also, a longer interval between menarche and menopause could suggest that the number of years of female fecundity has increased.STUDY FUNDING/COMPETING INTEREST(S)This work was funded by the South-Eastern Norway Regional Health Authority [grant number 2016112 to M.S.G.] and by the Norwegian Cancer Society [grant number 6863294-2015 to E.K.B.]. The authors declare no conflicts of interest.

Abstract GS5-00: Long-term influence of estrogen plus progestin and estrogen alone use on breast cancer incidence: The Women's Health Initiative randomized trials

Abstract Background: Breast cancer outcomes from the Women’s Health Initiative (WHI) Estrogen plus Progestin and Estrogen-alone trials have been reported but issues remain regarding long- term, post-intervention influence on breast cancer incidence and the influence of time from menopause to hormone therapy initiation (gap time) on breast cancer findings. Design and methods: Postmenopausal women aged 50 to 79 years with no prior breast cancer and with mammogram clearance enrolled in one of two randomized clinical trials at 40 US centers from 1993 to1998, with follow up through September, 2016. The randomized, placebo-controlled trial interventions were: conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) vs placebo (n = 8,102) for 5.6 years (median) for women with a uterus or CEE-alone (n = 5,310) vs placebo (n = 5,429) for 7.2 years (median) for women with prior hysterectomy. Annual mammography was mandated through the originally specified completion date in both trials (March 31, 2005). Incident breast cancers were verified by medical record review. Hazard ratios (HRs) were estimated using multi-variable Cox proportional hazards models. The primary outcome for these analyses was time-specific invasive breast cancer incidence rates. In each trial, participants were instructed to stop all study pills coincident with the publication of each trial’s results, in 2002 and 2004, respectively. Results: During the intervention period, with 238 incident breast cancers, CEE-alone significantly reduced breast cancer incidence (hazard ratio [HR] 0.76 95% confidence interval [CI] 0.58, 0.98, P = 0.04). As previously reported, subgroup analyses indicated CEE-alone was particularly beneficial for women with no prior HT use (interaction P = 0.04) and women with gap time &amp;gt;= 5 years (interaction P = 0.01). Post-intervention, through 16.1 years of cumulative follow-up, with 520 incident breast cancers, CEE-alone use continued to significantly reduce breast cancer incidence (HR 0.77 95% CI 0.65-0.92, P = 0.005) while subgroup differences were attenuated and were no longer statistically significant. During the intervention period, with 360 incident breast cancers, CEE plus MPA use significantly increased breast cancer incidence (HR 1.26 95% CI 1.02, 1.56, P = 0.04) with increase in breast cancer incidence greater in women with prior HT use (interaction P = 0.02) and women with gap time &amp;lt; 5 years (interaction P = 0.002). Post-intervention, through 18.3 years cumulative follow-up, with 1,003 incident breast cancers, CEE plus MPA continued to significantly increase breast cancer incidence (HR 1.29 95% CI 1.14, 1.47, P &amp;lt; 0.001) while subgroup differences were attenuated and were no longer statistically significant. Conclusions: CEE-alone and CEE plus MPA use have opposite effects on breast cancer incidence. CEE alone significantly decreases breast cancer incidence which is long term and persists over a decade after discontinuing use. CEE plus MPA use significantly increases breast cancer incidence which is long term and persists over a decade after discontinuing use. As a result of the attenuation of subgroup interactions: all postmenopausal women with prior hysterectomy using CEE-alone have the potential benefit of experiencing a reduction in breast cancer incidence while all postmenopausal women using CEE plus MPA have the potential risk of experiencing an increase in breast cancer incidence. Citation Format: Rowan T Chlebowski, Garnet L Anderson, Aaron K Aragaki, JoAnn E Manson, Marcia Stefanick, Kathy Pan, Wendy Barrington, Lewis H Kuller, Michael S. Simon, Dorothy Lane, Karen C Johnson, Thomas E. Rohan, Margery L.S. Gass, Jane A Cauley, Electra D. Paskett, Maryam Sattari, Ross L Prentice. Long-term influence of estrogen plus progestin and estrogen alone use on breast cancer incidence: The Women's Health Initiative randomized trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-00.

Abstract P4-17-10: Obesity increases the risk of male breast cancer and protects against triple negative male breast cancer

Abstract Introduction: Male breast cancer (MaBC) is an uncommon disease that represents less than 1% of all breast cancers. Obesity has been associated with increased breast cancer incidence in post-menopausal women. Overweight and obese rates have almost tripled since the 1990’s in the U.S. In 2016, 68% of Texas adults were classified as overweight or obese. The Rio Grande Valley (Cameron, Hidalgo, Starr and Willacy counties) is one of the areas with the highest levels of obesity in the country (37% of the population). The aim of this exploratory retrospective population-based study is to analyze the incidence of MaBC in Texas and the Rio Grande Valley (RGV), as well as to compare the association of obesity with triple negative MaBC. Methods: Retrospectively, we reviewed available data from the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, and Texas Department of State Health Services from the years 2011-2016 of patients with a diagnosis of invasive MaBC. The incidence of MaBC was examined according to sex, stage, tumor subtypes (HR+, HER2-Neu, Triple Negative) and BMI in Texas and the RGV. Some cases were excluded due to issues with data quality regarding BMI. Results: Between 2011-2016, there were 869 patients diagnosed with MaBC in Texas. The incidence of MaBC almost doubled during this time period. MaBC with distant metastasis had a downward trend (&amp;lt; 10% of cases). Evaluating MaBC tumor markers, there was no increase in the number of triple negative MaBC cases in Texas or the RGV despite a dramatic increase in MaBC cases. Furthermore, the number of triple negative MaBC cases in the RGV was significantly less than Texas’s, despite the RGV having higher levels of obesity (see table 1).A total of 495 cases of MaBC in Texas and 18 cases in the RGV had good quality data regarding BMI for analysis. There was a significant increase in the incidence of MaBC associated with obesity (BMI &amp;gt;30), which almost tripled in Texas and the RGV during the years studied. In the RGV, there was a trend to zero cases of MaBC in patients who were underweight and normal weight, see table 2. Conclusion: (1)There is a significant increase in MaBC, as well as in MaBC associated with obesity between the years 2011-2016 in Texas and the RGV. (2)There is no increase in the incidence of triple negative MaBC in Texas or the RGV despite a significant increase in obesity associated MaBC. (3)There is no increase in the incidence of MaBC in patients who are underweight or normal weight in the RGV. (4)Obesity appears to be a protective factor for the development of triple negative MaBC. Table 1. Male Breast Cancer Cases between 2011-2016 in Texas and the RGV201120122013201420152016Incidences of MaBC (Texas)104117121133202192MaBC Triple Negative (Texas)511556Incidences of MaBC (RGV)434366MaBC Triple Negative (RGV)001000 Table 2. Male Breast Cancer Cases by BMI between 2011-2016 in Texas and the RGVTexas Statewide2011-2016201120122013201420152016Underweight (&amp;lt;18.5)7111211Normal Weight (18.5–24.9)98768202928Overweight (25–29.9)167101617225547Obese (≥30)223151921416562Total49533424785150138Rio GrandeValley2011-2016201120122013201420152016Underweight (&amp;lt;18.5)0000000Normal Weight (18.5–24.9)3111000Overweight (25–29.9)4020011Obese (≥30)11002234Total18133245 Citation Format: Nicolas Restrepo, Kristina Vatcheva, Katia Moreno, Aimee Trejo, Alvaro Restrepo. Obesity increases the risk of male breast cancer and protects against triple negative male breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-10.

Return to Work of Breast Cancer Survivors: Perspectives and Challenges for Occupational Physicians.

Breast cancer is one of the most common diseases worldwide, mainly affecting the female gender. Considering the increase of breast cancer incidence and the decrease of mortality due to news diagnostic and therapeutic tools, the return to work issue after treatment is going to be very common in the next years. Occupational physicians therefore need to face the return to work and the fitness for work of workers previously diagnosed with breast cancer with a sufficient cultural and technical background. In addition to individual characteristics preceding the diagnosis, clinical outcome, lifestyles and occupational variables are the most impactful factors on return to work that need to be taken into account. The aim of this work is to analyze these factors and discuss the central role of occupational physicians in the decision-making process of returning to work in breast cancer survivors.

Genetic Profiling of Breast Cancer with and Without Preexisting Metabolic Disease

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women. Various mechanisms are involved in the initiation and progression of breast cancer. Metabolic dysregulation has been associated with increasing breast cancer incidence and mortality. However, little is known about how metabolic disease regulates the development and progression of breast cancer at the molecular level. Here, using a hybridization capture-based panel including 124 cancer-associated genes, we performed targeted next-generation sequencing of tumor tissues and matched blood samples from 20 postmenopausal patients with primary breast cancer, in which 6 cases suffered from preexisting metabolic disorders including hypertension, type 2 diabetes, and coronary heart disease. We took only the protein-altering variants and identified 170 somatic mutations of 59 genes. Among these, 40 mutated genes were found in the metabolic disease group, and 33 mutated genes were found in the non–metabolic disease group. Importantly, nonsynonymous mutations of 26 genes (MSH3, BRAF, MLH3, MTOR, DDR2, ALK, etc.) were uniquely present in the metabolic disease group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to investigate biological functions and key pathways of somatic mutations. TP53, PIK3CA, and PTEN were the top three commonly mutated genes at a higher frequency compared with the Cancer Genome Atlas (TCGA) data, and several novel but infrequent mutations in other genes were also found. Although further studies are required to validate these variants, our results are the first to suggest a specific molecular profile of breast cancer with preexisting metabolic disease.

Diagnosis and Treatment of Breast Cancer in Young Women.

Despite the increase of breast cancer incidence with age, approximately 7 to 10% ofwomen diagnosed with breast cancer are younger than the age 40. This subgroup ofpatients has different risk factors, tumour biology, clinical outcomes, and specific psy- chosocial issues, such as fertility preservation, family planning, and job reintegration. However, age alone should not be the main consideration when choosing the aggressive- ness of the treatment, as other factors must be considered, including the biologic aggressiveness of the tumour, potential long-term toxicities, and the preferences of the patient. Fertility preservation techniques should be discussed with the patient before starting any cancer treatment. Despite the significant percentage of breast cancer patients younger than age 40, fewclinical studies have specifically investigated disease characteristics and outcomes of this population, and most therapies routinely administered to these younger women were tested in older patients. Moreover, young women who have breast cancer are at a greater risk of sexual and psychological distress, and clinicians should address these issues in order to properly support patients during the long diagnostic and therapeutic journey. Consequently, it is essential to follow diagnostic and treatment guidelines specificallyaddressed to young women. Additional specific procedures should be followed to treat pregnant patients with breast cancer.

Bilateral breast cancer: a case study

AbstractBackground:Breast cancer is the most common cancer among females worldwide. Increasing breast cancer incidence rates, improved diagnosis and management modalities and growing life expectancy have resulted in increasing numbers of women at risk of developing contralateral primary breast cancer. Bilateral breast cancer can occur synchronously or metachronously.Material and methods:This study reports three cases of bilateral breast cancer patients treated at our oncology department between March 2018 and March 2019. The features of presentation, investigation, diagnosis and follow-up care are the highlights of this study.Results:Bilateral breast cancer was noted in three patients among the study population in the age group of 35 –55 years. Two of these patients had metachronous bilateral breast cancer, and one patient developed cancer in the second breast during the course of management. The second breast cancers differed histologically from primary breast cancer.Conclusion:Poor awareness on breast cancer care and the lack of national screening guidelines and programmes, and poor infrastructure, all contribute to late presentation and difficult breast cancer management. Proper history, clinical examination and imaging of opposite breast should be done to ensure adequate and timely management of bilateral breast cancer.