Lower Risk Of Breast Cancer Research Articles

Benefit of systemic therapy in MINDACT patients with small, ER-positive, HER2-negative breast cancers

Small, hormone receptor-positive (HR+), HER2-negative (HER2-), lymph node-negative breast cancers are associated with relatively low rates of disease recurrence and have therefore been underrepresented in clinical trials assessing the effects of systemic therapy. Consequently, it remains uncertain if this patient population derives benefit from these treatments. For this exploratory analysis, we selected MINDACT (NCT00433589) patients with a HR+, HER2-, T1ab (≤1 cm) tumor and negative lymph nodes. Patients with discordant clinical risk and MammaPrint genomic risk classification were randmomized to receive chemotherapy based on either the clinical or the genomic risk assessment. Endocrine therapy treatment was based on local guidelines. 715/6693 (10.7%) MINDACT patients had HR+, HER2-, T1abN0 breast cancer and were included in this analysis. All were clinically low-risk, 124/715 (17.3%) were genomic high-risk. For genomic high-risk tumors, 8-year distant metastasis-free survival (DMFS) was 92.9% (95% CI 86.2–96.4%) compared to 95.0% (95% CI 92.8–96.6%) for genomic low-risk tumors. For genomic high-risk tumors treated with or without chemotherapy, 8-year DMFS was 89.2% (95% CI 73.6–95.8%) and 94.1% (95% CI 82.9–98.1%), respectively. For genomic low-risk tumors, the 8-year DMFS and disease-free survival (DFS) were 96.1% (95% CI 93.4–97.6%) and 89.3% (95% CI 85.5–92.2%) when treated with endocrine therapy and 92.9% (95% CI 87.9–95.9%) and 79.4% (95% CI 72.5–84.8%) without. In conclusion, although the number of randomized patients is small, patients with small, genomic high-risk breast cancer did not seem to derive benefit from chemotherapy. Endocrine therapy was associated with improved outcomes even in genomic low-risk breast cancers.

Can Ki-67 serve as a suitable marker to indicate the necessity of staging diagnostics in cases of low-risk breast cancer?

For many years, staging tests have not been routinely employed for low-risk early breast cancer (EBC). However, the role of Ki-67 in determining the need for staging tests in low-risk EBC remains unclear. Our study aimed to assess the number and types of staging diagnostics, additional imaging, false-positive results, and rate of distant metastases in low-risk EBC with low and high Ki-67 (< / ≥ 25%). This is a retrospective, single institution cohort study. All patients with newly diagnosed low-risk breast cancer at the University Medical Center in Freiburg in 2017 and 2021 were included. Low-risk was defined as clinical tumor stage T1/2, node negative (N0), hormone receptor positive, HER2 negative, asymptomatic EBC. Information on demographics, clinical and pathological characteristics, as well as number and type of performed staging diagnostics was obtained. Rate and type of additional imaging or follow-up diagnostics due to suspicious findings was analyzed. The patients were divided into two groups (Ki-67 < and ≥ 25%) and rates of distant metastases, performed staging diagnostics and false positive rates were compared. A total of 189 patients with low-risk EBC were identified, with 54% (n = 102) having Ki-67 < 25% and 46% (n = 87) having Ki-67 ≥ 25%. Risk for distant metastases was 0% in Ki-67 < 25% and 1.1% in patients with Ki-67 ≥ 25% (p = 0.46). Due to suspicious findings in the initial staging diagnostic, additional imaging was required for 11.8% (n = 12) of patients with Ki-67 < 25% compared to 19.5% (n = 17) of patients with Ki-67 ≥ 25% (p = 0.16). False positive rates did not differ significantly between the two groups (7.6% in Ki-67 < 25% vs. 9.8% in Ki-67 ≥ 25%; p = 0.55). Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.

Childhood-to-adulthood body size trajectory and cancer risk: a prospective cohort study

Abstract Background While excess weight in adulthood and childhood has been associated with increased cancer risk, the link between childhood-to-adulthood body size trajectories and cancer risk requires further investigation. Methods We used data from the UK Biobank, a prospective population-based cohort study. The main exposure was childhood-to-adulthood body size trajectory, constructed from self-reported body at age 10 (categories: thinner, average, and plumper than average) and measured body mass index (BMI) at recruitment (normal weight, overweight, and obese). Primary outcome was obesity-related cancer (13 different cancer types). Results During a median follow-up of 11.7 years, 21,289 participants developed obesity-related cancers. Having a larger body size at age 10 was strongly associated with being overweight or obese in adulthood. Compared to participants with average childhood to normal adulthood body size trajectory, all trajectories ending in overweight or obesity in adulthood were strongly associated with an increased risk of obesity-related cancers. The strength of the association was mostly determined by adulthood BMI, and similar patterns were observed for colorectal, endometrial, kidney, pancreatic and esophageal cancer. However, a larger body size in childhood was associated with a lower risk of postmenopausal breast cancer. Conclusions Although a larger body size in childhood predisposes to overweight and obesity in adulthood, it does not necessarily predispose to an increased obesity-related cancer risk if measures to maintain a healthy weight are taken in adulthood. Key messages • While larger body size in childhood predisposes individuals to overweight and obesity in adulthood, maintaining a healthy weight in adulthood may help mitigate the risk of obesity-related cancers. • Our findings highlight the importance of preventing and reducing overweight and obesity in adulthood for primary cancer prevention.

Physical activity during adolescence and early adulthood and breast cancer risk before age 40 years.

Breast cancer (BC) incidence is increasing in women under age 40 years, underscoring the need for research on BC risk factors for younger women. We used data from an international family cohort (n=26,348) to examine whether recreational physical activity (RPA) during adolescence and early adulthood are associated with BC risk before age 40. The cohort includes 2,502 women diagnosed with BC before age 40, including 2,408 diagnosed before study enrollment (68% within 5 years of enrollment). Women reported their average hours-per-week of moderate and strenuous RPA during adolescence (12-17 years) and early adulthood (25-34 years), which were converted to total age-adjusted metabolic equivalents-per-week and categorized into quartiles. We conducted attained age analyses until age 40 (follow-up time began at age 18) using Cox proportional hazards regression models adjusted for study center, race and ethnicity, and education. Being in the highest versus lowest quartile of RPA during adolescence and early adulthood were respectively associated with 12% [HR (95% CI): 0.88 (0.78, 0.98)] and 16% [HR (95% CI): 0.84 (0.74, 0.95) lower BC risks before age 40. Being in the highest quartile of RPA during both adolescence and early adulthood (Pearson correlation=0.52) versus neither timepoint was associated with a 22% lower risk [HR (95% CI): 0.78 (0.68, 0.89)]. Findings suggest that RPA during adolescence and early adulthood may lower BC risk before age 40. Policies promoting physical activity during adolescence and early adulthood may be important for reducing the growing burden of breast cancer in younger women.

Reimagining Deintensification for Low-Risk Breast Cancer

As outcomes for low-risk breast cancer continue to improve, research and clinical paradigms are increasingly focused on appropriate deintensification with the goal of improving the therapeutic ratio of breast cancer treatment. These deintensification approaches span across disciplines including breast surgery, radiation therapy, and systemic therapy. With regard to breast surgery, studies have continued to push deintensification when it comes to surgical margins with breast conservation, reducing re-excision rates, whereas deintensification of axillary surgery has reduced the rates of axillary lymph node dissection and increasingly the need for any axillary surgery, including sentinel lymph node biopsy for low-risk patients. With regard to radiation therapy, studies have allowed for a drastic reduction in treatment duration, whereas approaches that reduce the target of treatment have led to a change from from treatment daily for 5-7 weeks to many low-risk patients completing treatment in just five treatments. With regard to systemic therapy, use of genomic assays and tumor biology has led to reduced utilization of cytotoxic chemotherapy, with studies also allowing for dose reduction of endocrine therapy for patients with ductal carcinoma in situ. Moving forward, greater focus should be placed on interdisciplinary deintensification approaches such as the consideration of radiation therapy alone as compared with endocrine therapy alone for low-risk breast cancers.

BREATH TEST TO DETECT WOMEN AT LOW RISK FOR BREAST CANCER: POTENTIAL CLINICAL AND ECONOMIC BENEFITS.

A breath test for volatile organic compounds has identified biomarkers associated with breast cancer. We evaluated the potential clinical and economic benefits of a breath test to detect women at low risk for breast cancer by comparing its negative predictive value (NPV) to the NPV of screening mammography. Sensitivity and specificity values for screening mammography were obtained from the Food & Drug Administration Mammography Quality Standards Act; Amendments to Part 900 Regulations Docket No. FDA-2013-N-0134. The high values were sensitivity = 79.0%, specificity = 88.9% and the low values were sensitivity = 66.0%, specificity = 88.9%. In two previous studies of 771 women undergoing mammography, breath testing identified breast cancer with sensitivity=84% and specificity = 68.6% in 178 asymptomatic women, and sensitivity=82% and specificity = 77% in 593 who were symptomatic. These values were projected to a hypothetical screening population of 100,000 asymptomatic women with average breast cancer prevalence of 450/100,000, in order to estimate the NPV and PPV (positive predictive value) for breath testing and screening mammography respectively. Breath test in asymptomatic women: NPV = 99.895% and PPV = 1.19%; in symptomatic women: NPV = 99.895% and PPV = 1.59%. For screening mammography, NPV = 99.83% and PPV = 2.82% (low values), increasing to NPV= 99.89% and PPV = 3.12% (high values). A negative breath test identified 68.3% of the screening population as having low risk of breast cancer, with NPV similar to mammography. Based on Medicare reimbursement rates, elimination of mammography in women with a negative breath test could reduce the annual cost of breast cancer screening by 38.9. In a hypothetical screening population, a negative breath test ruled out breast cancer with the same accuracy as a negative mammogram. A screening breath test could potentially eliminate the need for two thirds of all mammograms and reduce the costs of screening without increasing the risk of false-negative findings. If applied in clinical practice, this approach could potentially reduce the costs and burdens of breast cancer screening services, and benefit women by lessening the discomfort, anxiety, radiation exposure, and costs associated with mammography.

Association between dietary factors and breast cancer risk: a matched case-control study in Vietnam

BackgroundThe role of diet in breast cancer prevention is controversial and limited in low-middle-income countries (LMICs). This study aimed to investigate the association between different dietary factors and breast cancer risk in Vietnamese women.MethodsThree hundred seventy newly histologically confirmed breast cancer cases and 370 controls matched by 5-year age from September 2019 to March 2020 in Ho Chi Minh City were recorded dietary intake using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated using conditional logistic regression and adjusted with potential confounders.ResultsCompared to the lowest quartile of intake, we found that the highest intake of vegetables, fruit, soybean products, coffee, and egg significantly decreased breast cancer risk, including dark green vegetables (OR 0.46, 95% CI 0.27-0.78, ptrend=0.022), legumes (OR 0.19, 95% CI 0.08-0.44, ptrend <0.001), starchy vegetables (OR 0.37, 95% CI 0.21-0.66, ptrend=0.003), other vegetables (OR 0.46, 95% CI 0.28-0.77, ptrend=0.106), fruits (OR 0.44, 95% CI 0.26-0.74, ptrend <0.001), soybean product (OR 0.45, 95% CI 0.24-0.86, ptrend=0.311), coffee (OR 0.47, 95% CI 0.23-0.95, ptrend 0.004), and egg (OR 0.4, 95% CI 0.23-0.71, ptrend=0.002).ConclusionGreater consumption of vegetables, fruit, soybean products, coffee, and eggs is associated with a lower risk of breast cancer. This study provides evidence of breast cancer prevention by increasing the intake of these dietary groups, especially in LMICs.

Comparative analysis of GLP-1 receptor agonists versus metformin on cancer outcomes in patients with polycystic ovarian syndrome: A real-world multi-center cohort study in the United States.

402 Background: To compare the effects of GLP-1 receptor agonists (GLP1RA) versus metformin on incident cancer outcomes in the female polycystic ovarian syndrome (PCOS) population. Methods: This retrospective cohort study utilized electronic health records from over 50 U.S. healthcare organizations (TriNetX). The baseline cohort comprised females aged ≥ 18 with ≥ two prescriptions for GLP1 RAor metformin following a diagnosis of PCOS, between May 1, 2005 (first GLP1 RA approval date), and December 31, 2021. All cancer types were identified using ICD-10 codes. The index date was the initiation of GLP1RA or metformin. We performed a 1:1 propensity score matched based on demographics, comorbidities, socioeconomic factors, healthcare utilization, and biomarkers (HbA1c, LDL, HDL, triglycerides, and cholesterol), insulin use and PCOS medications before index date. Analysis was performed with intention-to-treat approach. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the comparison groups were calculated by the Cox regression model. Patients were followed and censored upon meeting any of the following criteria: development of an outcome, the study end date of May 19, 2024, or loss to follow-up, whichever occurred first. Results: A total of 8,223 pairs of GLP1RA initiators and metformin initiators were included. Compared to metformin, GLP1RA was associated with a lower risk of incident colorectal cancer (HR 0.35, 95% CI 0.22-0.57) and breast cancer (HR 0.55, 95% CI 0.39-0.78). There were no significant differences in risk between the GLP1RA group and metformin group for endometrial (HR 0.82, 95% CI 0.49-1.37), cervical (HR 1.17, 95% CI 0.64-2.12), ovarian (HR 1.09, 95% CI 0.56-2.11), respiratory (HR 0.32, 95% CI 0.17-0.60), skin (HR 0.51, 95% CI 0.37-0.69), kidney cancer(HR 0.99, 95% CI 0.33-3.06), thyroid cancer (HR 1.37, 95% CI 0.88-2.13), other endocrine (HR 0.81, 95% CI 0.15- 0.44), leukemia and lymphoma (HR 1.03, 95% CI 0.91-1.16), brain (HR 0.97, 95% CI 0.24-3.96), pancreatic cancer(HR 0.50, 95% CI 0.16-1.55), esophageal cancer (HR 1.99, 95% CI 0.24-16.18), stomach cancer (HR 0.33, 95% CI 0.07-1.47), and intrahepatic cancer (HR 0.89, 95% CI 0.40-1.99). Conclusions: GLP-1 receptor agonists were associated with a lower risk of colorectal and breast cancer compared to metformin in females with PCOS, with no significant differences in risk for other cancer types.Further investigation is necessary to verify the underlying therapeutic mechanisms.

Dietary soluble, insoluble, and total fiber intake and their dietary sources in association with breast cancer

BackgroundA few studies have examined the association between different types of dietary fiber as well as their sources and the risk of breast cancer (BC) and the present study aimed to investigate these associations in a case-control study among Iranian women.MethodsA total of 464 women with pathologically confirmed breast cancer within the past year and 498 age-matched healthy controls were included. Dietary intakes were assessed using a 168-item food frequency questionnaire. The association between dietary soluble, insoluble, total dietary fiber, as well as, fiber from fruits, vegetables, legumes, cereals, and nuts intake with odds of breast cancer was assessed using multivariate logistic regression analysis.ResultsMean total dietary fiber intake of patients with and without cancer were 33.1 ± 15.3 g per day (g/d) and 34.2 ± 16.5 (g/d), respectively. Dietary total fiber (OR = 0.65; 95%CI: 0.47–0.90, Ptrend = 0.01), insoluble fiber (OR = 0.68; 95%CI: 0.49–0.93, Ptrend = 0.01), fruits’ fiber (OR = 0.68; 95%CI: 0.49–0.94, Ptrend = 0.02), and vegetables’ fiber (OR = 0.66; 95%CI: 0.48–0.91, Ptrend = 0.01) were significantly associated with reduced likelihood of developing breast cancer in all participants. Furthermore, dietary total and insoluble fiber, as well as, fiber from fruits were significantly associated with lower odds of breast cancer in premenopausal women (P < 0.05). In contrast, cereals’ fiber significantly increased the risk of breast cancer by 84% in premenopausal women (OR = 1.84; 95%CI: 1.18–2.86, Ptrend = 0.009). In postmenopausal women, cereals’ fiber had a significant inverse association with odds of breast cancer (OR = 0.56; 95%CI: 0.31–1.03, Ptrend = 0.04). Also, fiber from vegetables was significantly associated with a lower risk of breast cancer in postmenopausal women (OR = 0.53; 95%CI: 0.30–0.94, Ptrend = 0.03).ConclusionDietary fiber intake and more specifically insoluble, fruits’, and vegetables’ fiber intake might be associated with a reduced breast cancer risk, particularly in premenopausal women. Future prospective investigations are needed to confirm these findings.

Regular whole blood donation and gastrointestinal, breast, colorectal and haematological cancer risk among blood donors in Australia

AbstractBackground and ObjectivesSeveral studies have suggested that blood donors have lower risk of gastrointestinal and breast cancers, whereas some have indicated an increased risk of haematological cancers. We examined these associations by appropriately adjusting the ‘healthy donor effect’ (HDE).Materials and MethodsWe examined the risk of gastrointestinal/colorectal, breast and haematological cancers in regular high‐frequency whole blood (WB) donors using the Sax Institute's 45 and Up Study data linked with blood donation and other health‐related data. We calculated 5‐year cancer risks, risk differences and risk ratios. To mitigate HDE, we used 5‐year qualification period to select the exposure groups, and applied statistical adjustments using inverse probability weighting, along with other advanced doubly robust g‐methods.ResultsWe identified 2867 (42.4%) as regular high‐frequency and 3888 (57.6%) as low‐frequency donors. The inverse probability weighted 5‐year risk difference between high and low‐frequency donors for gastrointestinal/colorectal cancer was 0.2% (95% CI, −0.1% to 0.5%) with a risk ratio of 1.25 (0.83–1.68). For breast cancer, the risk difference was −0.2% (−0.9% to 0.4%), with a risk ratio of 0.87 (0.48–1.26). Regarding haematological cancers, the risk difference was 0.0% (−0.3% to 0.5%) with a risk ratio of 0.97 (0.55–1.40). Our doubly robust estimators targeted minimum loss‐based estimator (TMLE) and sequentially doubly robust (SDR) estimator, yielded similar results, but none of the findings were statistically significant.ConclusionAfter applying methods to mitigate the HDE, we did not find any statistically significant differences in the risk of gastrointestinal/colorectal, breast and haematological cancers between regular high‐frequency and low‐frequency WB donors.

Acceptability of de-intensified screening for women at low risk of breast cancer: a randomised online experimental survey

BackgroundRisk-stratified approaches to breast screening show promise for increasing benefits and reducing harms. But the successful implementation of such an approach will rely on public acceptability. To date, research suggests that while increased screening for women at high risk will be acceptable, any de-intensification of screening for low-risk groups may be met with less enthusiasm. We report findings from a population-based survey of women in England, approaching the age of eligibility for breast screening, to compare the acceptability of current age-based screening with two hypothetical risk-adapted approaches for women at low risk of breast cancer.MethodsAn online survey of 1,579 women aged 40–49 with no personal experience of breast cancer or mammography. Participants were recruited via a market research panel, using target quotas for educational attainment and ethnic group, and were randomised to view information about (1) standard NHS age-based screening; (2) a later screening start age for low-risk women; or (3) a longer screening interval for low-risk women. Primary outcomes were cognitive, emotional, and global acceptability. ANOVAs and multiple regression were used to compare acceptability between groups and explore demographic and psychosocial factors associated with acceptability.ResultsAll three screening approaches were judged to be acceptable on the single-item measure of global acceptability (mean score > 3 on a 5-point scale). Scores for all three measures of acceptability were significantly lower for the risk-adapted scenarios than for age-based screening. There were no differences between the two risk-adapted scenarios. In multivariable analysis, higher breast cancer knowledge was positively associated with cognitive and emotional acceptability of screening approach. Willingness to undergo personal risk assessment was not associated with experimental group.ConclusionWe found no difference in the acceptability of later start age vs. longer screening intervals for women at low risk of breast cancer in a large sample of women who were screening naïve. Although acceptability of both risk-adapted scenarios was lower than for standard age-based screening, overall acceptability was reasonable. The positive associations between knowledge and both cognitive and emotional acceptability suggests clear and reassuring communication about the rationale for de-intensified screening may enhance acceptability.

29 Additional Benefit of Endocrine Therapy to Rt in Postmenopausal Patients with Low-Risk Breast Cancer

29 Additional Benefit of Endocrine Therapy to Rt in Postmenopausal Patients with Low-Risk Breast Cancer

Single pre-operative radiation therapy (SPORT-CK) trial for low-risk breast cancer: Early results of a phase 2 study

Background and purposePreoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI. Materials and MethodsIn this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1–2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence. ResultsTwenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences. ConclusionPreoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population.

Single preoperative radiation therapy with delayed surgery for low-risk breast cancer: Oncologic outcome, toxicity and cosmesis of the SPORT-DS phase I trial

BackgroundA novel approach using single-fraction preoperative partial breast irradiation (PBI) for low-risk breast cancer is under study. We sought to investigate the rate of pathologic response (pR), toxicities and cosmetic results related to this new treatment strategy. MethodsWomen of 65 years or older with stage I unifocal luminal A breast cancer were eligible for inclusion in this phase I prospective trial. Patients received a single 20 Gy dose of PBI followed by breast-conserving surgery (BCS) 3 months later. The primary endpoint was the pR rate, and the secondary endpoints were radiation therapy-related toxicity and cosmetic results. ResultsThirteen patients were treated, with a median age of 71. Eleven patients (84.6 %) had pR with a median residual cellularity of 1 % (range: 0–10 %). At median follow-up of 48.5 months, no recurrences or cancer-related deaths were recorded. Acute radiation therapy-related toxicity were limited to grade 1 dermatitis and breast pain. At the 1-year follow-up, there were one grade 2 fat necrosis and two grade 3 toxicities (wound infection and hematoma). Only grade 1 toxicities remained at 2 years, but one grade 2 toxicity (fibrosis/induration) developed by the 3-year follow-up. Three-year patient-reported cosmetic outcomes were good or excellent in 60 % of patients. ConclusionsSingle-fraction preoperative PBI preceding BCS for low-risk breast cancer is feasible, relatively well tolerated and leads to a high level of pR. The 3-month interval after PBI seems to place surgery in a post-radiation inflammatory phase. Further delay between PBI and surgery could improve pR and cosmetic outcome. NCT03917498.

Injectable Biomimetic Hydrogel Constructs for Cell-Based Menopausal Hormone Therapy with Reduced Breast Cancer Potential.

Hormone replacement therapy (HRT) has been a primary method in menopausal women and patients with ablated ovaries, but safety has been a concern. Cell-based HRT has emerged as an alternative approach without side effects causing pharmaceutical HRT via 3-dimensionally engineered constructs layering ovarian hormone-producing cells. In this study, we applied micro-sized ovarian cell-laden hydrogel beads as an approach to cell-based HRT using a minimally invasive method in the menopausal rat model. Here, we constructed GC/TC-laden microbeads (GTBs; GC, granulosa cell; TC, theca cell) that allow crosstalk between endocrine cells, encapsulating multiple beads for the figuration of the original ovary. We assessed the ovarian hormone production function of GTB through invitro culture for 90 days. We applied it to a menopausal rat model and confirmed that GTB-injected rats restored their endocrine function, leading to the regeneration of the thinned endometrium and the maintenance of regular estrous cycles in some individuals. Additionally, it was observed to alleviate menopausal symptoms, including body weight gain and osteoporosis. Notably, the GTB-injected rats did not show mammary gland hyperplasia observed in the pharmaceutical HRT groups and exhibited fewer p53- and KI67-positive and an increase in phosphatase and tensin homolog-positive mammary gland epithelial cells compared to pharmaceutical hormone-treated rats. These results suggest that GTB-based HRT could present a lower risk of breast cancer compared to conventional pharmaceutical-HRT use. Our study highlights the potential of cell-based HRT using an injectable artificial ovary, offering a safer alternative for women requiring HRT.

Macronutrient composition of plant-based diets and breast cancer risk: the E3N prospective cohort study.

Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach. This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high). A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk. These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations. The protocol is registered at clinicaltrials.gov as NCT03285230.

Atorvastatin lowers breast cancer risk by reversing an early tumorigenic signature

Breast cancer remains a significant health challenge with complex molecular mechanisms. While many studies have explored genetic markers in breast carcinogenesis, few have studied the potential impact of pharmacological interventions such as Atorvastatin on its genetic landscape. This study aimed to elucidate the molecular distinctions between normal and tumor-adjacent tissues in breast cancer and to investigate the potential protective role of atorvastatin, primarily known for its lipid-lowering effects, against breast cancer. Searching the Gene Expression Omnibus database identified two datasets, GSE9574 and GSE20437, comparing normal breast tissues with tumor-adjacent samples, which were merged, and one dataset, GSE63427, comparing paired pre- and post-treated patients with atorvastatin. Post-ComBat application showed merged datasets' consistency, revealing 116 DEGs between normal and tumor-adjacent tissues. Although initial GSE63427 data analysis suggested a minimal impact of atorvastatin, 105 DEGs post-treatment were discovered. Thirteen genes emerged as key players, both affected by Atorvastatin and dysregulated in tumor-adjacent tissues. Pathway analysis spotlighted the significance of these genes in processes like inflammation, oxidative stress, apoptosis, and cell cycle control. Moreover, there was a noticeable interaction between these genes and the immunological microenvironment in tumor-adjacent tissues, with Atorvastatin potentially altering the suppressive immune landscape to favor anti-tumor immunity. Survival analysis further highlighted the prognostic potential of the 13-gene panel, with 12 genes associated with improved survival outcomes. The 13-gene signature offers promising insights into breast cancer's molecular mechanisms and atorvastatin's potential therapeutic role. The preliminary findings advocate for an in-depth exploration of atorvastatin's impact on.

Sleep traits and breast cancer risk: a two-sample Mendelian randomization study

Globally, breast cancer continues to be the leading cause of cancer-related incidence and mortality among females. Research has shown that sleep patterns significantly influence tumor onset and progression. In this research, the association was examined through the application of a two-sample Mendelian randomization (MR) approach. For the analysis of seven sleep patterns, genetic tools were sourced from both the UK Biobank and 23andMe, including morning/evening person (chronotype) n = 177,604, morning person (chronotype) n = 248,094, daytime dozing/sleepiness n = 193,472, getting up in the morning n = 193,717, and sleeplessness n = 193,987; sleep duration n = 192,810; and nap during the day n = 166,853. The Breast Cancer Association Consortium (BCAC) supplied genome-wide association studies (GWAS) data, including 133,384 breast cancer cases and 113,789 controls, alongside subtype-specific data with 106,278 cases and 91,477 controls. We discovered that chronotype encompasses both morning and evening types contributes to the risk of overall breast cancer. While daytime dozing and morning person (chronotype) are linked to a lower risk of breast cancer in general, In subtype-specific analyses, morning person (chronotype) was negatively associated with luminal B, HER2-negative-like, and daytime dozing was negatively correlated with luminal A-like, luminal B-like, and HER2-enriched-like. The study corroborates that chronotype is a danger element for breast cancer, aligning with previous observational findings. The association between being a morning person (chronotype) or having daytime dozing and a decreased risk of breast cancer underscores the significance of sleep patterns in formulating strategies for cancer prevention.

Mammography Screening Preferences Among Screening-Eligible Women in Their 40s : A National U.S. Survey.

The U.S. Preventive Services Task Force (USPSTF) recently changed its recommendation for mammography screening from informed decision making to biennial screening for women aged 40 to 49 years. Although many women welcome this change, some may prefer not to be screened at age 40 years. To conduct a national probability-based U.S. survey to investigate breast cancer screening preferences among women aged 39 to 49 years. Pre-post survey with a breast cancer screening decision aid (DA) intervention. (ClinicalTrials.gov: NCT05376241). Online national U.S. survey. 495 women aged 39 to 49 years without a history of breast cancer or a known BRCA1/2 gene mutation. A mammography screening DA providing information about screening benefits and harms and a personalized breast cancer risk estimate. Screening preferences (assessed before and after the DA), 10-year Gail model risk estimate, and whether the information was surprising and different from past messages. Before viewing the DA, 27.0% of participants preferred to delay screening (vs. having mammography at their current age), compared with 38.5% after the DA. There was no increase in the number never wanting mammography (5.4% before the DA vs. 4.3% after the DA). Participants who preferred to delay screening had lower breast cancer risk than those who preferred not to delay. The information about overdiagnosis was surprising for 37.4% of participants versus 27.2% and 22.9% for information about false-positive results and screening benefits, respectively. Respondent preferences may have been influenced by the then-current USPSTF guideline. There are women in their 40s who would prefer to have mammography at an older age, especially after being informed of the benefits and harms of screening. Women who wanted to delay screening were at lower breast cancer risk than women who wanted screening at their current age. Many found information about the benefits and harms of mammography surprising. National Cancer Institute.

Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta-analysis.

The MRE11, RAD50, and NBN genes encode the MRN complex sensing DNA breaks and directing their repair. While carriers of biallelic germline pathogenic variants (gPV) develop rare chromosomal instability syndromes, the cancer risk in heterozygotes remains controversial. We performed a systematic review and meta-analysis of 53 studies in patients with different cancer diagnoses to better understand the cancer risk. We found an increased risk (odds ratio, 95% confidence interval) for gPV carriers in NBN for melanoma (7.14; 3.30-15.43), pancreatic cancer (4.03; 2.14-7.58), hematological tumors (3.42; 1.14-10.22), and prostate cancer (2.44, 1.84-3.24), but a low risk for breast cancer (1.29; 1.00-1.66) and an insignificant risk for ovarian cancer (1.53; 0.76-3.09). We found no increased breast cancer risk in carriers of gPV in RAD50 (0.93; 0.74-1.16; except of c.687del carriers) and MRE11 (0.87; 0.66-1.13). The secondary burden analysis compared the frequencies of gPV in MRN genes in patients from 150 studies with those in the gnomAD database. In NBN gPV carriers, this analysis additionally showed a high risk for brain tumors (5.06; 2.39-9.52), a low risk for colorectal (1.64; 1.26-2.10) and hepatobiliary (2.16; 1.02-4.06) cancers, and no risk for endometrial, and gastric cancer. The secondary burden analysis showed also a moderate risk for ovarian cancer (3.00; 1.27-6.08) in MRE11 gPV carriers, and no risk for ovarian and hepatobiliary cancers in RAD50 gPV carriers. These findings provide a robust clinical evidence of cancer risks to guide personalized clinical management in heterozygous carriers of gPV in the MRE11, RAD50, and NBN genes.