Breast Cancer In Postmenopausal Women Research Articles

Engineered Porous Beta-Cyclodextrin-Loaded Raloxifene Framework with Potential Anticancer Activity: Physicochemical Characterization, Drug Release, and Cytotoxicity Studies.

Cancer ranks as the second most common cause of mortality as depicted by the World Health Organization, with one in six deaths being cancer-related mortality. Taking the lead in females, breast cancer is the most common neoplasm. Raloxifene, a selective estrogen receptor modulator, has been utilized as a chemotherapeutic agent for the treatment of breast cancer in postmenopausal women. However, its poor aqueous solubility hinders its clinical applications. Beta-cyclodextrin-based framework is a novel class of nano-vectors that used to potentiate the solubility and dissolution rate of poorly soluble drugs. The present study investigates the solubility and dissolution rate enhancement as well as the potential cytotoxic activity of raloxifene-loaded nanosponges formulation. The fabrication and optimization of cyclodextrin nanosponges crosslinked with diphenyl carbonate was portrayed through stoichiometric selection of cyclodextrin-to-crosslinker ratio. The complexation phenomenon and nanosponges formation were validated using FTIR, PXRD, TEM, and SEM examination. Raloxifene-loaded nanosponges exhibited a 440±8.5 nm particle size, a negative zeta potential of 25.18±2.3 mV and a partial drug incorporation. Moreover, the drug loaded nanosponges demonstrated an in-vitro significantly enhanced dissolution behavior. Furthermore, the in-vitro cytotoxicity of the raloxifene-loaded nanosponges on MCF-7 breast cancer cell lines was statistically significant compared to the complex-free raloxifene. The cytotoxic behavior provided evidence that the incorporation of raloxifene within the nanosponges structure enhanced its anticancer activity and represents a potential nanocarrier for anticancer agent delivery.

Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study

BackgroundBreast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients.MethodsPlasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements.ResultsBefore initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ2 = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15–48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy.ConclusionPostmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy.Trial registration The clinical trial (registration number NCT03784651) was registered on www.clinicaltrials.gov on 24 December 2018.

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.

Side Effect Profile of Arimidex vs. Femara: A Comparison Study

Background: Background: Aromatase inhibitors, Arimidex (anastrozole) and Femara (letrozole), are commonly used in the treatment of hormone receptor-positive (HR+) breast cancer in postmenopausal women. Despite similar efficacy, these drugs have different side effect profiles that impact patient compliance and quality of life.Objective: To compare the incidence and severity of side effects between Arimidex and Femara in postmenopausal women with HR+ breast cancer.Methods: A retrospective cohort study was conducted involving 1,000 postmenopausal women with HR+ breast cancer from multiple oncology centers. Participants were divided into two groups: Arimidex (n=500) and Femara (n=500). Side effects were assessed via patient self-reports, clinical evaluations, and standardized questionnaires. Data were analyzed using chi-square tests, t-tests, and logistic regression models, with p-values &lt;0.05 considered significant.Results: Arimidex was associated with higher rates of joint pain (45% vs. 30%, p&lt;0.001) and muscle pain (38% vs. 25%, p&lt;0.01). Femara showed increased rates of hypertension (28% vs. 20%, p&lt;0.05) and significant bone density loss (18% vs. 12%, p&lt;0.05).Conclusion: Arimidex and Femara exhibit distinct side effect profiles, suggesting the need for personalized treatment approaches based on patient risk factors.

Development of a Breast Cancer Risk Prediction Model Integrating Monogenic, Polygenic, and Epidemiologic Risk.

Breast cancer has been associated with monogenic, polygenic, and epidemiologic (clinical, reproductive, and lifestyle) risk factors, but studies evaluating the combined effects of these factors have been limited. We extended previous work in breast cancer risk modeling, incorporating pathogenic variants (PV) in six breast cancer predisposition genes and a 105-SNP polygenic risk score (PRS), to include an epidemiologic risk score (ERS) in a sample of non-Hispanic White women drawn from prospective cohorts and population-based case-control studies, with 23,518 cases and 22,832 controls, from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium. The model predicts 4.4-fold higher risk of breast cancer for postmenopausal women with no predisposition PV and median PRS, but with the highest versus lowest ERS. Overall, women with CHEK2 PVs had >20% lifetime risk of breast cancer. However, 15.6% of women with CHEK2 PVs and a family history of breast cancer, and 45.1% of women with CHEK2 PVs but without a family history of breast cancer, had low (<20%) predicted lifetime risk and thus were below the threshold for MRI screening. CHEK2 PV carriers at the 10th percentile of the joint distribution of ERS and PRS, without a family history of breast cancer, had a predicted lifetime risk similar to the general population. These results illustrate that an ERS, alone and combined with the PRS, can contribute to clinically relevant risk stratification. Integrating monogenic, polygenic, and epidemiologic risk factors in breast cancer risk prediction models may inform personalized screening and prevention efforts.

Does vaginal estrogen therapy increase risk of breast cancer in postmenopausal women?

Does vaginal estrogen therapy increase risk of breast cancer in postmenopausal women?

Association between body mass index combined with high-sensitivity C-reactive protein and the risk of postmenopausal breast cancer: A prospective cohort study.

The present study aimed to assess the risk of postmenopausal breast cancer in women based on a combination of body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) levels. A total of 20,400 participants were investigated as part of the 'Kailuan Study' clinical trial. Participants were classified into four groups based on BMI (BMI ≥24 or <24 kg/m2) and hs-CRP level (hs-CRP ≥3 or <3 mg/l). Cox proportional hazards models were used to evaluate the association between the combination of BMI and hs-CRP and the risk of postmenopausal breast cancer. A total of 19,540 participants met the inclusion criteria. The median follow-up time was 14.97 years, with a cumulative follow-up period of 283,599.43 person-years. Among the participants, 269 individuals were diagnosed with postmenopausal breast cancer. Individuals with a high BMI (BMI ≥24 kg/m2) and a high hs-CRP level (hs-CRP ≥3 mg/) had a greater risk of postmenopausal breast cancer compared with individuals with a low BMI (BMI <24 kg/m2) and a low hs-CRP level (<3 mg/l) (hazard ratio, 1.75; 95% confidence interval, 1.25-2.47). The sensitivity analysis showed findings consistent with the primary results. In conclusion, the combination of high BMI and high hs-CRP level is associated with an increased risk of postmenopausal breast cancer. The present study is part of the Kailuan Study. Trial registration number: ChiCTRTNCR11001489 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/showproj.html?proj=8050). Date of registration: 19/07/2015.

Preoperative plasma fibrinogen level is a risk factor for the long-term survival of postmenopausal women after surgery for breast cancer

BackgroundStudies have indicated an association between fibrinogen levels and the prognosis of breast cancer patients. However, fibrinogen levels are notably susceptible to fluctuations due to the menstrual cycle. This study explored the relationship between preoperative plasma fibrinogen levels and the prognosis of postmenopausal breast cancer women after surgery. Method855 patients with postmenopausal breast cancer were monitored for 10 years. Cox proportional hazards regression models were used to perform univariate and multivariate analyses to identify factors that are of substantial prognostic value. ResultsThe median follow-up was 77 months (51–105 months), and the maximum 142 months. Over the follow-up period, 65 deaths (7.6 %) were recorded. Multivariate Cox regression results show that preoperative plasma fibrinogen level (hazard ratio [HR] =1.615, 95 % confidence interval [CI]: 1.233–2.115) and age (HR = 1.626, 95%CI: 1.250–2.116) were independent risk factors for 10-year overall survival after surgery in postmenopausal breast cancer patients, while endocrine therapy (HR = 0.414, 95%CI: 0.202–0.846) was an independent protective factor. Multivariate Cox regression results also show preoperative plasma fibrinogen level was an independent risk factor for 10-year disease-free survival (HR = 1.398, 95 % CI: 1.137–1.719) and 10-year distant metastasis-free survival (HR = 1.436, 95%CI: 1.153–1.787). ConclusionElevated pretreatment plasma fibrinogen levels are associated with a poorer long-term prognosis in postmenopausal breast cancer patients following surgical treatment.

Efficacy of antiobesity medications among breast cancer survivors taking aromatase inhibitors.

Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment. This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%). We included 124 patients: 62 in the AOM/AI group (63.6 ± 10years, body mass index [BMI] 34.3 ± 7.1kg/m2) and 62 in the AOM group (62.8 ± 9.9years, BMI 34.6 ± 6.5kg/m2). The mean time of follow up was 9.3 ± 3.5months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI.

Evaluation of some proinflammatory cytokines and biochemical parameters in pre and postmenopausal breast cancer women

The study was planned to evaluate the differences in certain proinflammatory cytokines(IL-6, TNF-α) with CRP and biochemical parameters (E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid), between women with pre- and postmenopausal breast cancer and seemingly healthy women in Iraqi women as controls; at medical city in teaching Oncology hospital,70 breast cancer patients women their ages ranged (47.51 ± 1.18) and 20 healthy women with age (44.45 ± 2.66) begun from September (2020) to February (2021). The aims of this study to investigate the evaluation of chemotherapy effects especially doxorubicin and cyclophosphamide only use in this study in pre and postmenopausal breast cancer women on proinflammatory cytokines(IL-6, TNF-α) with CRP and on biochemical parameters(E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid) in pre and postmenapausal breast cancer women. The patients were divided into five groups and each group contains 14 patients women with breast cancer during pre and postmenopausal periods. The control groups were divided into 10 pre and 10 postmenopausal women(Fig. 1). The results of proinflammatory cytokines of and biochemical parameters in premenopausal groups were as the levels of IL-6 (pg/ml),TNF-α(pg/ml) and CRP (ng/ml) showed significant increase differences (P < 0.01)among breast cancer treated (BCT) groups in comparison with control groups,While the Liver enzymes GGT,LDH and TSB showed highly significant increase (P < 0.01) in BCT groups, Estrogen levels (pg/ml) and D3(ng/ml) increased significantly (P < 0.01)among BCT groups. Blood serum calcium and phosphorus with uric acid levels (mg/dl) showed significant difference (P < 0.01); While the result in postmenopausal of IL-6(pg/ml), TNF-α (pg/ml) and CRP (ng/ml) showed highly significant differences (P < 0.01)among BCT groups.While GGT(IU/L), LDH(IU/L) and TSB (mg/dl) enzymes were increased significantly (p < 0.01), Estrogen (pg/ml) and D3(ng/ml) levels showed significant increase (P < 0.01) among BCT groups.Blood calcium and phosphorus showed significant increase (P < 0.01) while uric acid was non-significant increase (P > 0.05).

Abstract PS10-03: Impact of Baseline Oestradiol and Testosterone on the Preventive Effect of Anastrozole

Abstract It is well known that serum levels of oestradiol and testosterone, esp free hormone levels, influence the risk of developing breast cancer in postmenopausal women (Thomas et al 1997, Hankinson et al 1998, Kaaks et al 2005, Tin Tin et al 2021). However very little is known about how these hormone levels influence the effectiveness of aromatase inhibitors. In the IBIS-II Prevention Trial we compared anastrozole to placebo in 3864 women at high risk of breast cancer (Cuzick et al 2020). Of these women 3644 (94.3%) had a baseline blood sample. In those with a valid blood sample, 72 in the anastrozole arm and 142 in the placebo arm developed breast cancer (including DCIS) after 12.9 years of follow up (OR = 0.49, 95% CI 0.37–0.66 P&amp;lt; 0.0001). For each case two controls were selected, matched on age, treatment arm and follow up longer than the matching case. In these women oestradiol (E2), testosterone (Testo) and SHBG were measured by liquid chromatography – tandem mass spectroscopy, and E2/SHBG and Testo/SHBG ratios were computed to approximate free hormone levels, and analysed in quartiles. Hormone replacement therapy was not allowed during the trial, and women with use within 3 months prior to entry or outlier hormone values were excluded from these analyses. In the placebo arm higher levels of both of these ratios were associated with a higher breast cancer rate (OR per quartile 1.25 (1.04-1.59), P=0.018) for E2/SHBG and (OR per quartile 1.22 (1.02-1.47), P = 0.032) for Testo/SHBG), whereas no significant effect was seen in the anastrozole arm (OR = 1.05 (0.81-1.37), and 1.16 (0.90-1.49), resp) (Table). Neither treatment interaction was significant. Absolute numbers of cases were similar between the anastrozole and placebo arms in the lowest quartile of E2/SHBG (18 anastrozole, 22 placebo), but higher numbers were seen in the placebo arm for the other quartiles. Similar results were seen for testo/SHBG, and supportive, but weaker results were seen for these two hormones without an SHBG adjustment, SHBG and BMI at entry. Adjusting for other risk factors had no influence on these findings. Effect sizes were similar during the 5 year treatment period and thereafter. There were too few ER negative cases to compare results by receptor status. Vasomotor side effects were higher with increasing E2/SHBG levels in both arms, but no other hormone showed an effect, and no hormone level was significantly associated with gynaecologic or musculoskeletal side effects. As aromatase inhibitors effectively eliminate the production of oestradiol in postmenopausal women, these results suggest they may be more effective in postmenopausal women with high oestradiol or testosterone levels, and raise questions about their value in women in the lower quartile of serum levels for these hormones for prevention and possibly adjuvant treatment. Table: Risk of breast cancer by quartiles of the oestradiol/SHBG in ratio high risk women treated with anastrozole or placebo. Citation Format: Jack Cuzick, Kim Chu, Brian Keevil, Antony Howell, Bernardo Bonanni, Evans Gareth, Kaija Holli, Sibylle Loibl, Nicholas Zdenkowski, Steven Cummings, Mitch Dowsett. Impact of Baseline Oestradiol and Testosterone on the Preventive Effect of Anastrozole [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-03.

A highly sensitive first derivative synchronous spectrofluorimetric approach for the simultaneous analysis of the anti-breast cancer co-administered drugs, letrozole and tramadol in dosage forms and human plasma at nanogram levels

Letrozole is an anticancer medication prescribed for the management of estrogen receptor-positive breast cancer in postmenopausal women. Chronic pain is prevalent in patients receiving chemotherapy, leading to the use of adjuvant analgesics such as tramadol. This work introduces the first analytical approach for the concurrent quantification of letrozole and tramadol, two co-administered drugs, employing a rapid, highly sensitive, eco-friendly, and cost-effective first derivative synchronous spectrofluorimetric technique. The fluorescence of tramadol and letrozole was measured at wavelengths of 235.9 nm and 241.9 nm, respectively using a wavelength difference (Δλ) of 60.0 nm. The developed approach demonstrated exceptional linearity (r ˃ 0.999) within the specified concentration ranges for tramadol (10.0–1200.0 ng/mL) and letrozole (1.0–140.0 ng/mL). The results demonstrated that the proposed technique exhibits a high level of sensitivity, with detection limits of 0.569 and 0.143 ng/mL for tramadol and letrozole, respectively, indicating the good bioanalytical applicability. The within-run precisions, both intra-day and inter-day, for both analytes, were less than 0.71 % RSD. The developed approach was effectively applied to simultaneously estimate the mentioned drugs in their tablets and human plasma samples, achieving high percentage recoveries and low % RSD values. In order to assess the environmental sustainability of the developed approach, Analytical GREEnnessNNESS (AGREE) and the Green Analytical Procedure Index (GAPI) metric tools were employed. Both tools revealed that the developed approach is excellent green, suggesting its usage as an environmentally-friendly alternative for the routine assayof the investigated pharmaceuticals. The developed approach was validated according to the ICHQ2 (R1) requirements.

Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.

Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report

BackgroundLetrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.Case presentationAn 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.ConclusionsAlthough TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.

How does weight gain since the age of 18 years affect breast cancer risk in later life? A meta-analysis

Early life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and all were of moderate to high quality with NOS scores ranging from 5 to 8. We included 17 studies (11 case-control, 6 cohort) in final analysis. In case-control studies, weight gain after age 18 was associated with an increased risk of breast cancer (odds ratio [OR] = 1.25; 95% CI = 1.07–1.48), when comparing the highest versus the lowest categories of weight gain. Menopausal status was a source of heterogeneity, with weight gain after age 18 associated with an increased risk of breast cancer in postmenopausal women (OR = 1.53; 95% CI = 1.40–1.68), but not in premenopausal women (OR = 1.01; 95% CI = 0.92–1.12). Additionally, a 5 kg increase in weight was positively associated with postmenopausal breast cancer risk (OR = 1.12; 95%CI = 1.05–1.21) in case-control studies. Findings from cohort studies were identical, with a positive association between weight gain after age 18 and breast cancer incidence in postmenopausal women (relative risk [RR] = 1.30; 95% CI = 1.09–1.36), but not in premenopausal women (RR = 1.06; 95% CI = 0.92–1.22). Weight gain after age 18 is a risk factor for postmenopausal breast cancer, highlighting the importance of weight control from early adulthood to reduce the incidence of postmenopausal breast cancer.

Pro-vegetarian dietary pattern and risk of breast cancer: a case-control study.

There are afew conflicting results from studies assessing the association between plant-based diets, particularly pro-vegetarian dietary pattern (PDP), and breast cancer (BC) incidence. Therefore, this study aimed to investigate the association between PDP and BC odds in the Iranian population. This case-control study was conducted on 134 women with BC and 265 without cancer (control). Participants were selected from two referral hospitals in Tehran, Iran. Also, a validated food frequency questionnaire was used to collect food information. Logistic regression was used to assess the association between PDP and BC and the association between PDP and BC by menopausal status. It was observed that in two models of logistic regression, the chance of BC was lower in the second and last tertile (T) than in the first tertile of PDP (model 1-T2: odds ratio (OR) = 0.39; 95% confidence interval (CI): 0.23-0.67; P = 0.001, and T3: OR = 0.43; 95% CI: 0.26-0.73; P = 0.002-model 2: T2: OR = 0.42; 95% CI: 0.24-0.74; P = 0.003, and T3: OR= 0.49; 95% CI: 0.27-0.88; P = 0.017). Also, according to menopausal status, the odds of developing BC in post-menopausal women in the second and last tertile of PDP was significantly lower than the first tertile in both logistic regression models. The findings revealed that Iranian women who followed PDP had a lower chance of developing BC. Also, we found that a diet high in plant-based foods and low in animal products is beneficial for reducing BC odds, particularly for post-menopausal women.

Body mass index and altered lipid profile as major risk markers for breast cancer progression: a cross-sectional study of postmenopausal women in Pakistan

BackgroundIn Pakistan, the death rate for post-menopausal women with breast cancer is significant due to late detection and delayed referral to proper facilities. There are a few reports on Pakistan’s epidemiology and breast cancer risk factors. There are modifiable and non-modifiable risk factors associated with the development of breast carcinoma; of which body mass index (BMI), central obesity, and lipid profile are considered as major risk markers.MethodsThis was a cross-sectional analytical study. A total of 384 women constituted the present study sample. Purposive sampling was used to collect 192 confirmed new breast cancer cases throughout the study. By using basic random sampling, an equal number of controls were chosen. Studied parameters included age, fasting blood sugar, cholesterol, triglyceride, serum high-density lipoprotein, cholesterol, serum low-density lipoprotein cholesterol, weight, height, BMI, waist circumference, and waist-to-hip ratio. The inclusion criteria of this study were post-menopausal women (45–65 years) in Pakistan. The confirmation of breast carcinoma was done through histopathology. Breast cancer occurrence was taken as a dependent variable, whereas BMI, central obesity, and lipid profile were taken as independent variables.ResultsStudied risk factors (cholesterol, BMI, and central obesity) significantly correlated with breast cancer. Cholesterol has a significantly high positive correlation (0.646) with breast cancer. BMI has a positive significant correlation (0.491) with breast cancer, and central obesity has a low but positive significant correlation (0.266) with breast cancer. Moreover, the binary logistic regression model also showed a significant association between biochemical factors and breast cancer occurrence. Regression analysis depicted a linear relationship between a dependent variable (breast cancer occurrence) and independent variables (central obesity, cholesterol, BMI).ConclusionPostmenopausal overweight (central obesity), increased BMI and high cholesterol levels are major risk factors for breast cancer. Moreover, high total cholesterol proved to be the most significant risk marker for the occurrence of breast cancer in post-menopausal women of Pakistan.

Preventing Breast Cancer in Postmenopausal Women

Preventing Breast Cancer in Postmenopausal Women

Human epidermal growth receptor polymorphisms (HER1-rs11543848 and HER2-rs1136201) exhibited significant association with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan.

Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1-rs11543848 and HER2-rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1-rs11543848 and HER2-rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. A total of 314 women including 164 breast cancer patients and 150 age and gender-matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra-ARMS-PCR for genotyping and gel electrophoresis. Our results indicated that HER1-rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258-5.6756, p = 0.0833). Similarly, the HER2-rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876-6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p < 0.005) with family history, metastasis, stage, luminal B, and TNBC. In conclusion, HER1-rs11543848 and HER2-rs1136201 polymorphisms are significantly associated with the higher risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. These findings advocate for further exploration with larger datasets, offering promising avenues for personalized approaches in breast cancer research and potentially enhancing clinical practices for better risk assessment and targeted management strategies.

Towards a New Generation of Hormone Therapies: Design, Synthesis and Biological Evaluation of Novel 1,2,3-Triazoles as Estrogen-Positive Breast Cancer Therapeutics and Non-Steroidal Aromatase Inhibitors.

Aromatase inhibitors (AIs) show promising features as drugs to treat estrogen-responsive breast cancer as they block aromatase activity, the key enzyme in estrogen synthesis. The current AIs approved by the Food and Drug Administration for breast cancer treatment present severe adverse effects. For these reasons, it is important to develop of new AIs that are more specific and sensitive. In this paper, we report the synthesis and the characterization of new nonsteroidal aromatase AIs containing triazoles moieties for the treatment of hormone-dependent breast cancer in post-menopausal women. A new series of 1,2,3-triazole based molecules were successfully synthetized and their chemical structures were determined from the spectral data (FT-IR, 13C NMR, 1H NMR, mass spectroscopy) and micro-analytical data. Additionally, the physical properties of the newly synthesized derivatives were reported. The novel compounds were also tested for their anticancer activity in both breast cancer (MCF7 and T-47D) and normal breast (MCF 10A) cell lines, evaluating their effect on cell proliferation, migration, and invasion. The results revealed that the compounds exhibited promising and specific anti-cancer action.