The Clinical Treatment Score post-5 years (CTS5) is a clinicopathological tool designed to estimate late distant recurrence (LDR) in hormone receptor-positive (HR+) breast cancer patients after 5 years of adjuvant endocrine therapy (ET). While intended as a prognostic algorithm, its predictive value for ET extension remains uncertain.

The score was calculated in 4931 patients from four prospective randomized ABCSG trials (ABCSG-6, -6a, -8, and -16) with 250 LDR events. We assessed its prognostic power, calibration accuracy, and predictive value. Time to LDR was analyzed using Cox regression models.

In our cohorts, the CTS5 provided prognostic information whether used as a continuous or categorical score. In the ABCSG-8 cohort (n = 2054) and the combined ABCSG-6+8 cohort (n = 3308), a higher continuous score was significantly associated with increased LDR risk. The categorical CTS5 showed that high-risk patients had significantly higher LDR rates compared to low- or intermediate-risk patients. The score slightly overestimated LDR risk, regardless of predicted risk. Although no significant predictive value was found on the relative scale, an absolute LDR risk reduction of 23.4 % was found in patients with a high CTS5 of 5 when extended ET was administered additional five than two years. In patients with a CTS5 of 2, no benefit was found when ET was extended to 10 instead of 7 years.

The CTS5 is a valid tool for LDR risk stratification in HR + breast cancer, but should be used cautiously for determining benefits from ET extension, as no significant predictive value was found.

Endocrine therapy for breast cancer may reduce the risk of contralateral breast cancer (CBC). However, there are no published estimates quantifying the lifetime outcomes by age at primary diagnosis, regimen, or duration. Here, we adapted an established Cancer Intervention and Surveillance Network (CISNET) model to simulate life histories of multiple US female birth-cohorts diagnosed with stage 0-III ER+/HER2- breast cancer receiving different durations (none, 2.5, 5, 10 years) of two endocrine therapy regimens (aromatase inhibitors or tamoxifen; including ovarian-function suppression for premenopausal women). As expected, greater duration of endocrine therapy led to more avoided CBC cases, as did aromatase inhibitors over tamoxifen, but the numbers varied greatly by the age of diagnosis. The maximum number of CBC were avoided using 10-year aromatase inhibitor regimens (6.0 vs. 11.2 for no adjuvant therapy, per 100 women with ER+/HER2- breast cancer). For the 5-year aromatase inhibitors therapy, women <45 years had the largest reduction in CBC cases (5.0/100), which dropped to 2.7/100 for women at 75+ years. Quantification of the lifetime risk of CBC for specific endocrine therapy types and duration is helpful for weighing therapeutic options. The risk of breast cancer death has a larger weight, but inclusion of the risk of CBC increases the separation between different therapy options.

This narrative review aims to determine the impact of postdiagnosis isoflavone intake, via supplements and foods, on breast cancer outcomes. Foods derived from soybeans are uniquely rich sources of isoflavones, naturally occurring compounds that can bind to estrogen receptors although the extent to which they exert estrogen-like effects in humans is unclear. Isoflavones have been rigorously investigated for a wide range of health benefits including breast cancer prevention. However, their classification as phytoestrogens has led to concern that isoflavones and hence, soy food consumption, could worsen the prognosis of women with breast cancer and interfere with the efficacy of endocrine therapy for this disease.

Research in athymic ovariectomized mice shows isoflavones stimulate the growth of existing estrogen-sensitive mammary tumors. However, extensive clinical research indicates that neither soy foods nor isolated isoflavones affect markers of breast cancer risk including mammographic density and breast cell proliferation. No effects are observed even when isoflavone exposure greatly exceeds typical intake in Asian countries. Furthermore, the results from epidemiologic studies indicate postdiagnosis isoflavone intake from soy foods reduces recurrence and possibly mortality from breast cancer. Additionally, the limited observational data do not show that isoflavones interfere with the efficacy of tamoxifen or aromatase inhibitors. Regardless of their treatment status, evidence indicates that women with breast cancer can safely consume soy foods. Limiting intake to no more than two servings of traditional Asian soy foods daily, an amount that provides approximately 50 mg isoflavones, is recommended, not because data indicate exceeding this amount is harmful, but because few population-based studies involved participants consuming more than this intake recommendation.

Though not specifically designed for cancer therapy, several FDA-approved drugs such as metformin, aspirin, and simvastatin have an effect in lowering the incidence of cancer. However, there is a great discrepancy between in vitro concentrations needed to eliminate cancer cells and the plasma concentration normally tolerated within the body. At present, there is no universal explanation for this discrepancy and several mechanisms have been proposed including targeting cancer stem cells (CSCs) or cellular senescence. CSCs are cells with the ability of self-renewal and differentiation known to be resistant to chemotherapy. Senescence is a response to damage and stress, characterized by permanent cell-cycle arrest and apoptotic resistance. Although, for both situations, there are few examples where low concentrations of the FDA-approved drugs were the most effective, there is no satisfactory data to support that either CSCs or cellular senescence are the target of these drugs. In this review, we concisely summarize the most used FDA-approved drugs for non-cancer conditions as well as their potential mechanisms of action in lowering cancer incidence. In addition, we propose that prolonged low-dose administration (PLDA) of specific FDA-approved drugs can be useful for effectively preventing metastasis formation in selected patients.

This study aimed to determine whether clinical treatment score post-5 years (CTS5) could predict the clinical benefits of extended endocrine therapy (ExET) in young and old patients.

We reviewed 2495 hormone receptor-positive breast cancer patients treated between 2001 and 2012 who were free from recurrence or death during the 5 years post-surgery in South Korea. The cohort was analyzed separately based on age (≤ 50 years and > 50 years). Multivariable analysis was conducted, and a cutoff of CTS5 < 3.13 was defined as the low group and CTS5 ≥ 3.13 as the intermediate/high (int/high) group.

The median follow-up duration was 115 months. Regardless of young and old age at diagnosis, the low group displayed considerably enhanced disease-free survival. Multivariate analysis revealed that the low group emerged as an independent and favorable prognostic factor for disease-free survival after adjusting for ExET use and prognostic parameters. Patients in the low group demonstrated a trend toward improved overall survival compared to those in the int/high group, reaching marginal statistical significance. ExET use demonstrated a significant correlation with improved disease-free survival, particularly in patients aged ≤ 50 years.

ExET should be considered in premenopausal and postmenopausal breast cancer patients with high CTS5 levels.

The plasma concentration of endoxifen, the active metabolite of tamoxifen, might be affected by different CYP2D6 genotypes in patients with breast cancer, but solid evidence is still lacking in Asian patients. This prospective study aimed to investigate the relationship between CYP2D6 genetic polymorphisms and endoxifen plasma concentrations among Chinese patients with breast cancer treated with tamoxifen.

From August 2015 to June 2018, 110 patients with breast cancer were enrolled. CYP2D6 variant alleles and endoxifen plasma concentration were determined using Sanger sequencing and high-performance liquid chromatography-tandem mass spectrometry, respectively.

The most frequent allele of CYP2D6 was *10 (56.4%). The most frequent genotype of CYP2D6 was *10/*10 (33%), *1/*10(28.2%) and *2/*10(14.5%). Sixty-four patients (58.2%) were Normal Metabolizers (NM), while 46 (41.8%) were Intermediate Metabolizers (IM). All patients except two had endoxifen concentrations above the threshold of 5.9ng/ml. The median endoxifen plasma concentrations for patients with CYP2D6 genotypes *1/*2 and *1/10 were higher compared to other genotypes (p = 0.012). The median endoxifen plasma concentration was higher in NM than in IM (18ng/ml vs. 13ng/ml, p = 0.0077). Patients with CYP2D6*10(T/T) had lower endoxifen concentrations than those with *10(C/T) and *10(C/C) but the difference was not significant. There were no significant differences in adverse events between patients in the NM and IM groups or between patients with the CYP2D6*10 (T/T) genotype and non-*10 (T/T) genotype.

Only CYP2D6 IMs and NMs were identified in this study. Almost all patients had the endoxifen concentrations above the threshold. The endoxifen plasma concentration was lower in CYP2D6 IMs than in NMs, but these variants did not compromise the adverse effects of tamoxifen in Asian patients with breast cancer.

The study protocol was approved by the institutional review boards of Sun YatSen University Cancer Center (Ethics approval number, B201506501,20160115).

Multiple trials have evaluated escalation strategies of endocrine therapy for early breast cancer, including ovarian function suppression (OFS) and aromatase inhibitors (AI) in premenopausal patients and extended endocrine therapy. However, several aspects remain controversial due to the heterogeneity of study designs and lack of statistical power in relevant subgroups. We aimed to investigate the optimal endocrine therapy strategy.

A systematic literature search was performed and last updated in August 2024 to identify randomized controlled trials (RCT) evaluating endocrine treatment strategies for hormone receptor positive breast cancer. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. In addition, an extracted individual patient data meta-analysis was conducted to estimate the absolute differences between treatments. Study endpoints were disease-free survival (DFS), overall survival (OS), and safety. PROSPERO: CRD42023447979.

A total of 37 RCT that had enrolled 107,684 patients were included in the study. During the first five years, OFS + AI was the most effective strategy in premenopausal women, while AI or switch strategy showed the better efficacy results in postmenopausal ones. Following five years of tamoxifen, continuation with five additional years of AI was associated with improved 8-year DFS (85.8%) compared to no extended therapy (78.1%) or five additional years of tamoxifen (81.0%). Following five years of AI or switch strategy, extended treatment with AI improved DFS (Hazard Ratio = 0.81, 95% Confidence Interval 0.73-0.90).

This study provides information regarding the optimal endocrine treatment strategies for patients with resected hormone receptor positive early breast cancer.

None.

Patients with estrogen receptor α positive (ERα+) breast cancer typically undergo surgical resection, followed by 5-10 years of treatment with adjuvant endocrine therapy. This prolonged intervention is associated with a host of undesired side effects that reduce patient compliance, and ultimately therapeutic resistance and disease relapse/progression are common. An ideal anticancer therapy would be effective against recurrent and refractory disease with minimal dosing; however, there is little precedent for marked tumor regression with a single dose of a small molecule therapeutic. Herein we report ErSO-TFPy as a small molecule that induces quantitative or near-quantitative regression of tumors in multiple mouse models of breast cancer with a single dose. Importantly, this effect is robust and independent of tumor size with eradication of even very large tumors (500-1500 mm3) observed. Mechanistically, these tumor regressions are a consequence of rapid induction of necrotic cell death in the tumor and are immune cell independent. If successfully translated to human cancer patients, the benefits of such an anticancer drug that is effective with a single dose would be significant.

Hormone receptor-positive, HER2-negative breast cancer is the most common subtype, with endocrine therapy as the standard treatment. Despite the advancements in adjuvant endocrine therapy, recurrence remains a challenge, particularly in high-risk patients. Recent trials on cyclin D kinase 4/6 (CDK4/6) inhibitors in adjuvant therapy have shown promise in reducing early recurrence and improving survival.

This review analyzes the clinical evidence supporting the use of CDK4/6 inhibitors, focusing on the NATALEE and monarchE trials, which demonstrate comparable efficacy and manageable safety profiles for ribociclib and abemaciclib.

Ribociclib, with its broader applicability and impact on the decision making for axillary lymph node surgery, may be the preferred option in high-risk populations. The review also addresses unanswered clinical questions and highlights the need for ongoing research to optimize the adjuvant therapy strategies.

Tamoxifen is one of the most widely used anticancer drugs in the world. It is a safe drug with generally well-tolerated side effects and has been prescribed for the treatment of early-stage and advanced-stage or metastatic estrogen receptor α (ERα/ESR1)-positive breast cancer. Tamoxifen therapy also provides a 38% reduction of the risk of developing breast cancer in women at high risk. With the advent of newer medications targeting ERα-positive breast cancer, tamoxifen is now mainly used as adjuvant therapy for lower-risk premenopausal breast cancer and cancer prevention. It is widely accepted that tamoxifen as a selective estrogen receptor modulator exerts its therapeutic effect by competitively binding to ERα, leading to the recruitment of corepressors and inhibition of transcription of genes involved in the proliferation of breast cancer epithelium. As such, expression of ERα in breast tumors has been considered necessary for tumors to be responsive to tamoxifen therapy. However, ERα-independent effects of tamoxifen in various in vitro and in vivo contexts have been reported over the years. Importantly, the recent discovery that ERα and estrogen receptor β (ERβ/ESR2) can bind tumor suppressor protein p53 with functional consequences has provided new insights into the mechanisms underlying response to tamoxifen therapy and resistance. Furthermore, these findings have paved the way for broadening the use of tamoxifen by potentially repurposing it to treat triple negative (negative for ERα, human epidermal growth factor receptor 2, and progesterone receptor) breast cancer. Herein, we summarize these developments and discuss their mechanistic underpinnings and clinical implications.

Approximately 40 000 individuals die from metastatic breast cancer each year. We examined what fractions of annual breast cancer-specific death are due to stage I, II, III, and IV disease and if these proportions changed over time.

We used data from Surveillance, Epidemiology, and End Results Program covering 1975-2017. After filtering for female sex at birth, 1 primary tumor type, surgery, American Joint Committee on Cancer Staging Manual (6th edition) stage above 0, no bilateral cancer, and survival data available, the final analysis included 972 763 patients. Temporal trends were assessed using a linear model and analysis of variance test.

The contribution of stage I and II cancers to breast cancer-specific death increased statistically significantly from 16.2% to 23.1% and from 30.7% to 39.5%, respectively, between 2000 and 2017. The contribution of stages III and IV cancers decreased from 36.4% to 30.3% and from 16.7% to 7.1%, respectively. In 2000, 0.92%, 4.0%, and 10.7% breast cancer-specific deaths were due to T1a, T1b, and T1c node-negative cancers, respectively, which increased significantly to 1.9%, 5.8%, and 14.7% by 2017. These temporal trends were similar for hormone receptor-positive and hormone receptor-negative cancers. The contribution of breast cancer-specific death to all-cause mortality declined from 23.9% to 16.6% for stage I and from 47.7% to 36.9% for stage II cancers by 2017.

Patients with stage I and II breast cancers have excellent prognosis, yet these cancers account for more than 60% of current breast cancer-specific death because of their large absolute numbers. To further reduce breast cancer death, strategies are needed to identify and treat patients with stage I and II disease who remain at risk for recurrence.

Breast cancer in young women (BCY) is associated with unfavourable tumour biology, worse pathological features, and poorer prognosis. There is limited data on the long-term survival outcomes in BCY patients who undergo breast conservation surgery (BCS). This study aims to determine the long-term survival outcome of BCY treated with BCS at our centre. Data was collected of BCY patients who underwent primary BCS at our centre from the 1st of January 2005 to the 31st of December 2008. Oncological event was defined as local, regional, or systemic recurrence, contralateral breast cancer and death. The primary and secondary objectives were to analyse the 15-year overall survival and the 15-year disease-free survival and local recurrence-free survival of BCY who underwent primary BCS respectively. The study enrolled 132 women with a median age of 35 years. No oncological event occurred in 71.2% of patients. Distant metastasis occurred in 14.4%, and one patient developed local recurrence and distant metastasis. Isolated local recurrence occurred in 10.6% of the patients. The contralateral primary was detected in 3.8% of the patients. The 5-, 10-, and 15-year overall survival were 79.5%, 71%, and 70.2%, respectively. The 5-, 10-, and 15-year disease-free survival were 78%, 66.7%, and 65.9%, respectively. The 5-, 10-, and 15-year local recurrence-free survival were 94.9%, 91.1%, and 85.7%, respectively. BCS in young women with breast cancer is oncologically safe with good long-term overall survival and disease-free survival outcomes and can be offered to young breast cancer patients suitable for BCS.

Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain.

The present systematic review, meta-analysis and expert panel review aimed to evaluate the strength of the available evidence on the risk of recurrence and mortality when TE is utilised in congruence with TAM or AI treatment, among BC survivors.

Six databases and two prospective registers, were interrogated from inception to January 3rd, 2024. Search terms were Breast cancer AND Hormone replacement therapy AND topical/vaginal oestrogen AND recurrence/mortality.

All study designs reporting the use vs. non-use of TE in breast cancer survivors receiving adjuvant endocrine treatment were included. Six observational studies were deemed eligible for inclusion.

Sources of heterogeneity were explored using subgroup analysis by risk of bias, median follow-up period, node positivity and menopausal status. Trial sequential analysis was performed to quantify outcome reliability. A global expert panel was called to deliberate on the data, pinpoint areas of limited understanding, and determine the most important areas for future research.

Risk ratio effect sizes (RR) and corresponding 95 % Confidence Intervals (CI) of breast cancer recurrence and mortality in survivors on endocrine treatment (TAM and/or AI) exposed to TE were reported. Expert panel appraisal of meta-analysis evidence with definition of current knowledge gaps and future research aims.

In 38 050 female patients receiving adjuvant endocrine treatment, of whom 1805 had been exposed to TE, TE exposure of those on AI, did not increase all-cause mortality (RR 0.99 [95 %CI 0.58, 1.69], I2 = 81 %, P = 0.96; moderate GRADE certainty). However, such exposure may convey an increased risk of recurrence (RR 2.51 [95 % CI 1.10, 5.72], I2 = 9 %, P = 0.03; low-GRADE certainty). Exposure to TE during TAM did not increase either recurrence risk or all-cause mortality. Clinical factors such as lymph node positivity at the time of diagnosis and menopausal status and follow-up time appeared to be significant confounders.

The use of TE does not appear to increase either recurrence or mortality risk among BC survivors treated with TAM. An increased recurrence risk, without an increase in mortality, cannot be ruled out when TE is used during AI.

Adjuvant CDK4/6 inhibitors abemaciclib and ribociclib improved disease-free survival (DFS) added to endocrine therapy in hormone receptor (HR)-positive HER2-negative early breast cancer (EBC), in monarchE (NCT03155997) and NATALEE (NCT03701334) trials respectively. We assessed the proportion and outcome of EBC patients qualifying for adjuvant CDK4/6 inhibitors in the real-world.

Consecutive female patients with HR-positive HER2-negative EBC between 1997 and 2017 from the Australian Capital Territory and South-East New South Wales Breast Cancer Treatment Group registry were analyzed. Patients eligible for abemaciclib had ≥4 axillary nodes involved or 1-3 nodes plus primary >5 cm or grade 3. Ribociclib eligibility was defined as node-positive and node-negative with primary >5 cm or >2 cm grade 3.

Of 3840 patients, 671 (17.5%) were abemaciclib-eligible and 1587 (41.3%) ribociclib-eligible . The 5-year DFS was 77% and 94% in abemaciclib-eligible and noneligible registry patients respectively (HR 2.6, 95% CI 2.26-3.05, P < .001). The 5-year DFS was 86% and 97% in ribociclib-eligible and noneligible registry patients respectively (HR 1.92, 95% CI 1.67-2.19, P < .001). Compared with monarchE trial patients, abemaciclib-eligible registry patients were older (median 55 years in registry vs. 51 years in trial), with lower nodal burden (≥4 nodes in 44% in registry vs. 60% in trial). There were more stage III cancers in NATALEE trial patients (60%) than ribociclib-eligible registry patients (24%).

Many women with EBC will qualify for adjuvant CDK4/6 inhibitors (17.5% abemaciclib, 41.3% ribociclib) with resource and workforce implications. In the real-world setting, a greater proportion of adjuvant CDK4/6-eligible patients have lower stage disease, therefore the absolute benefit from treatment may be smaller than estimated by the trials.

Extended endocrine therapy shows promise for reducing the recurrence of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, its benefits in patients with high-risk factors for late recurrence remain unclear, particularly in premenopausal patients. In this study, we aimed to explore the impact of extended endocrine therapy in patients with risk factors for late recurrence of postmenopausal and premenopausal ER-positive, HER2-negative breast cancer.

We retrospectively analyzed data from patients with ER-positive, HER2-negative breast cancer at Tohoku Kosai Hospital who were disease-free after 5 years of adjuvant endocrine therapy. The patients were classified as high risk based on lymph node positivity, tumor size > 2 cm, or high tumor grade. The high-risk group was further divided into extended therapy and stop groups. Propensity score matching was applied to balance baseline characteristics. Disease-free survival (DFS) was the primary endpoint.

Among the 1474 eligible patients, 224 received extended endocrine therapy, and 1250 stopped therapy. After propensity score matching, the high-risk group comprised 348 patients (n = 174 patients/group). The extended therapy group had significantly higher 10-year DFS and distant DFS rates than the stop group. The multivariate Cox model indicated a 69% reduction in recurrence risk in the extended therapy group.

Extended endocrine therapy can substantially improve DFS in patients with high-risk ER-positive, HER2-negative breast cancer, especially in those with large tumors, lymph node involvement, and high tumor grade. These findings support personalized treatment strategies for enhancing long-term outcomes.

To provide clinicians involved in managing menopause with a summary of current evidence surrounding menopause hormone therapy (MHT).

The authors evaluate and synthesize existing pooled evidence relating to MHT's clinical indications, efficacy, and safety and explore the limitations of existing data.

The review focuses on MHT-related outcomes in women with natural-timed menopause captured within observational studies, RCTs, and pooled data from pivotal meta-analyses and reviews.

Available published data are scrutinized. Available evidence and notably lacking data from women not adequately represented in published MHT trials, such as those with socioeconomic adversity, significant comorbidities, and minority ethnic backgrounds, are highlighted and deliberated.

The impact of MHT differs significantly between demographics. Current consensus recommendations for MHT emphasize the importance of tailoring type, route, dose, and duration of therapy to individual needs and risk/benefit ratio through shared decision-making. MHT impact can change over time. Current MHT data support its benefits for treating menopause symptoms and a potential window of opportunity in midlife to benefit skeletal health. Limitations of current evidence highlight menopause health inequalities and underscores the need for further research.

This review recommends tailored use of MHT for well-defined indications, recognizing its value for menopause symptom relief and skeletal benefits for many midlife women. MHT may be used as long as benefits outweigh risks, through shared decision-making. There is insufficient clinical evidence to support the long-term use of MHT in some contemporary cohorts of women accessing MHT in clinical practice.

Background: Breast cancer is a prevalent malignancy with rising incidence globally. Advances in endocrine therapy have improved outcomes for premenopausal women with hormone receptor-positive breast cancer. However, these treatments may induce menopause-like states, potentially elevating cardiovascular risks, including left ventricular (LV) dysfunction. This study aims to evaluate the impact of one year of adjuvant endocrine therapy with goserelin and tamoxifen on LV function in premenopausal breast cancer patients. Methods: The ISACS cardiovascular toxicity (NCT01218776) is a pilot multicenter registry of breast cancer patients referred to hospitals for routine surveillance, suspected, or confirmed anticancer-drug-related cardiotoxicity (ADRC). Patients may be enrolled retrospectively (1 year) and prospectively. The pilot phase focused on the available data on combined goserelin and tamoxifen therapy for breast cancer and its impact on LV disfunction at 1-year follow-up. Inverse probability of treatment weighting (IPTW) analysis of the ISACS registry was performed assigning 70 patients to combined endocrine therapy (goserelin and tamoxifen). Controls consisted of 120 patients with no adjuvant combined goserelin and tamoxifen therapy. None of the patients developed distant metastasis. Primary outcome measures were as follows: low LV function in women as defined by a left ventricular ejection fraction (LVEF) < 65% and subclinical LV dysfunction as defined by a 10-percentage point decrease in LVEF. Results: In the overall population, combined goserelin and tamoxifen therapy did not affect the mean LV function compared with controls at 3-, 6-, and 12-month follow-up (65.7 ± 2.7% versus 65.3 ± 2.1%, p value = 0.27; 65.5 ± 2.9% versus 65.1 ± 2.5%, p value = 0.34; 65.0 ± 3.2% versus 64.6 ± 3.1%, p value = 0.29, respectively). The mean LVEF reduction in patients who did or did not receive combination therapy for 12 months was small and approximately similar (1.03 ± 2.5% versus 1.16 ± 2.9%, p value = 0.73). Using IPTW analyses, there were no significant associations between combined therapy and low LV function (risk ratio [RR]: 1.75; 95% CI: 0.71-4.31) or subclinical LV dysfunction (RR: 1.50; 95% CI: 0.35-6.53) compared with controls. Conclusions: One year of endocrine therapy with goserelin and tamoxifen does not cause ADRC in patients with invasive breast cancer. Findings are independent of the severity of the disease. Results may not be definitive without replication in studies with larger sample size.

Patients with estrogen receptor (ER)-positive breast cancer (BC) can be treated with endocrine therapy targeting ER, however, metastatic recurrence occurs in 25% of the patients who have initially been treated. Secreted proteins from tumors play important roles in cancer metastasis but previous methods for isolating secretory proteins had limitations in identifying novel targets.

We applied an in situ secretory protein labeling technique using TurboID to analyze secretome from tamoxifen-resistant (TAMR) BC. The increased expression of LGALS3BP was validated using western blotting, qPCR, ELISA, and IF. Chromatin immunoprecipitation was applied to analyze estrogen-dependent regulation of LGALS3BP transcription. The adhesive and angiogenic functions of LGALS3BP were evaluated by abrogating LGALS3BP expression using either shRNA-mediated knockdown or a neutralizing antibody. Xenograft mouse experiments were employed to assess the in vivo metastatic potential of TAMR cells and the LGALS3BP protein. Clinical evaluation of LGALS3BP risk was carried out with refractory clinical specimens from tamoxifen-treated ER-positive BC patients and publicly available databases.

TAMR secretome analysis revealed that 176 proteins were secreted at least 2-fold more from MCF7/TAMR cells than from sensitive cells, and biological processes such as cell adhesion and angiogenesis were associated with the TAMR secretome. Galectin-3 binding protein (LGALS3BP) was one of the top 10 most highly secreted proteins in the TAMR secretome. The expression level of LGALS3BP was suppressed by estrogen signaling, which involves direct ERα binding to its promoter region. Secreted LGALS3BP in the TAMR secretome helped BC cells adhere to the extracellular matrix and promoted the tube formation of human umbilical vein endothelial cells. Compared with sensitive cells, xenograft animal experiments with MCF7/TAMR cells showed increased pulmonary metastasis, which completely disappeared in LGALS3BP-knockdown TAMR cells. Finally, higher levels of LGALS3BP were associated with poor prognosis in ER-positive BC patients treated with adjuvant tamoxifen in the clinic.

TAMR secretome analysis identified secretory proteins, such as LGALS3BP, that are involved in biological processes closely related to metastasis. Secreted LGALS3BP from the TAMR cells promoted adhesion of the cells to the extracellular matrix and vasculature formation, which may support metastasis of TAMR cells.

The aim of this study was to compare estimates of adherence to oral endocrine therapy (OET) based on real-world data (RWD) and on clinical evaluation in people diagnosed with breast cancer in the public healthcare system in Catalonia (Spain).

We conducted two retrospective cohort studies. Cohort 1 (RWD) consisted of women diagnosed with breast cancer in 2021 in the public healthcare system of Catalonia (Spain). Sources of RWD were the pharmacy billing register, hospital discharge records, and the Catalan health division's central insurance registry. Nonadherence was defined as below 80% adherence in the first year of treatment. Data for cohort 2 came from two population-based cancer registries in Girona and Tarragona (Catalonia), with diagnoses from 2007 to 2011. We evaluated the impact of variables missing from RWD, such as stage and hormonal status. Analyses were performed using a chi-square test and logistic regression, with results stratified by age group and drug type.

Nonadherence at one year was 10.9% in cohort 1 and 11.3% in cohort 2. When we reviewed the medical records of a selection of nonadherent women from cohort 1, we found only 59.4% had documented treatment interruptions. Reasons for interruptions in the patients from RWD cohort included adverse effects (48.8%), patient decision (40.0%), medical reasons (29.4%), and other clinical causes (14.7%). Women aged under 50 years and those receiving tamoxifen or a sequential regimen had lower adherence. Determinants associated with nonadherence were similar in both approaches used.

This study confirms the validity of estimating adherence with RWD from the Spanish national health system, although when combined with reviewing medical records, this may provide more reliable and higher-quality data. The RWD method provides valuable evidence to help oncologists discuss adherence with their patients.

Tamoxifen is the most prescribed drug used to prevent breast cancer recurrence, but patients show variable responses to tamoxifen. Such differential inter-individual response has a significant socioeconomic impact as one in eight women will develop breast cancer and nearly half a million people in the United States are treated with tamoxifen annually. Tamoxifen is orally delivered and must be activated by metabolizing enzymes in the liver; however, clinical studies show that neither genotype nor hepatic metabolic enzymes are sufficient to predict why some patients have sub-therapeutic levels of the drug. Here, using gnotobiotic- and antibiotics-treated mice, we show that tamoxifen pharmacokinetics are heavily influenced by gut bacteria and prolonged exposure to tamoxifen. Interestingly, 16S rRNA gene sequencing shows tamoxifen does not affect overall microbiota composition and abundance. Metabolomics, however, reveals differential metabolic profiles across the microbiomes of different donors cultured with tamoxifen, suggesting an enzymatic diversity within the gut microbiome that influences response to tamoxifen. Consistent with this notion, we found that β-glucuronidase (GUS) enzymes vary in their hydrolysis activity of glucuronidated tamoxifen metabolites across the gut microbiomes of people. Together, these findings highlight the importance of the gut microbiome in tamoxifen's pharmacokinetics.IMPORTANCEOne in eight women will develop breast cancer in their lifetime, and tamoxifen is used to suppress breast cancer recurrence, but nearly 50% of patients are not effectively treated with this drug. Given that tamoxifen is orally administered and, thus, reaches the intestine, this variable patient response to the drug is likely related to the gut microbiota composed of trillions of bacteria, which are remarkably different among individuals. This study aims to understand the impact of the gut microbiome on tamoxifen absorption, metabolism, and recycling. The significance of our research is in defining the role that gut microbes play in tamoxifen pharmacokinetics, thus paving the way for more tailored and effective therapeutic interventions in the prevention of breast cancer recurrence.

We sought to evaluate prognostic factors in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and their relationship with short- and long-term overall survival (OS).

Using the Surveillance, Epidemiology, and End Results (SEER) database, we evaluated patients with de novo HER2-positive MBC diagnosed from 2010 to 2018. Univariate analyses were performed to determine effect of each variable on OS. Significant variables were included in a multivariate Cox model for OS. Univariate and multivariate logistic regression were used to evaluate the association of each variable with short- (<2 years) and long- (≥5 years) term OS.

Overall, 5576 patients were included. Median follow up was 48 months (interquartile range 25-73 months), and median OS was 41 months. The proportion alive at 2, 5, and 8 years was 63.3% (95% confidence interval [CI] 62.0%-64.7%), 37.8% (95% CI, 36.2%-39.4%), and 26.8% (95% CI, 24.8%-28.9%), respectively. Factors associated with short-term OS were older age; Black race; nonductal nonlobular; brain, liver, or lung metastases; estrogen/progesterone receptor (ER/PR)-negative disease, and lower income (all P < .04). Number of metastatic organ sites was not significant. Factors associated with long-term OS were younger age, White race, fewer metastatic organ sites, ER/PR-positive disease, and higher income (all P < .02). Specific organ sites were not significant.

In this cohort with de novo HER2-positive MBC, OS improved significantly over the study period. We identified patient-specific and tumor-specific factors that were associated with short- and long-term survival in HER2-positive MBC.

Patients with estrogen receptor-positive breast cancer undergoing continuous adjuvant hormone therapy often experience delayed recurrence with tamoxifen use, potentially causing adverse effects. However, the lack of biomarkers hampers patient selection for extended endocrine therapy. This study aimed to elucidate the molecular mechanisms underlying delayed recurrence and identify biomarkers. When miRNA expression was assessed in luminal breast cancer tissues with and without delayed recurrence using NanoString, a significant increase in the expression of miR483-3p was observed in samples from patients with delayed recurrence compared with those without. miR483-3p expression was elevated in tamoxifen resistant (TAMR) EFM19 cells than in non-resistant EFM19 cells. Notably, genes associated with cancer metastasis (AMOTL2, ANKRD1, CTGF, and VEGF) were upregulated in TAMR EFM19 cells, although cell motility and proliferation were reduced. Transfection of miR483-3p mimics into both non-resistant EFM19 and MCF7 cells resulted in increased expression of cancer metastasis-related genes, but decreased proliferation and migration. Given that miR483-3p can bind to the 3'UTR region of O-GlcNAc transferase (OGT) and potentially affect its protein expression, we examined OGT protein levels and found that transfection with miR483-3p mimics selectively reduced OGT expression. Overall, breast cancer cells subjected to long-term hormone therapy displayed elevated miR483-3p expression, reducing motility and dormancy induction via decreased OGT expression. These findings suggest that miR483-3p is a potential biomarker for long-term endocrine therapy.

In-vivo proton magnetic resonance spectroscopy (MRS) is a non-invasive method of analyzing choline metabolism that has been used to predict breast cancer prognosis. A strong choline peak may be a surrogate for aggressive tumor biology but its clinical relevance is unclear. The present study assessed whether total choline (tCho), as measured by proton MRS, can predict late recurrence in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer.

The study cohort included 261 HR+/HER2- breast cancer patients who underwent diagnostic single-voxel proton MRS (3.0T scanner) prior to first-line surgery from March 2011 to July 2014. The relationships between tCho compound peak integral (tChoi) values and others prognostic factor were analyzed, as were the effects of tChoi on 10-year disease-free survival (DFS) and overall survival (OS). The clinical significance of tChoi was also analyzed using Harrell's C-index.

Mean tChoi in HR+/HER2- study group was 15.47 and we set the cut-off for tChoi at 15 for survival analysis. 10-year DFS differed significantly between tChoi <15 and ≥15 (p = 0.017), with differences differing significantly for late (5-10 years; p = 0.02) but not early (0-5 years; p = 0.323) recurrence. Cox regression analysis showed that tChoi was significantly predictive of 10-year DFS (p = 0.046, OR 2.69) and tended to be predictive of late recurrence (HR 4.36, p = 0.066). Harrell's C-index showed that the Ki-67 index (AUC = 0.597) and lymphovascular invasion (AUC = 0.545) were also predictive of survival, with the addition of normalized tChoi improving the AUC to 0.622 (p = 0.014), indicating better predictive power.

tChoi determined by in vivo MRS was predictive of prognosis in patients with HR+/HER2- early breast cancer. This parameter may serve as a valuable, non-invasive tool to predict prognosis when combined with other known prognostic factors.

Extracellular vesicles (EVs) play a crucial role in the occurrence and progression of cancer. The efficient isolation and analysis of EVs for early cancer diagnosis and prognosis have gained significant attention. In this study, for the first time, a rapid and visually detectable method termed freeze-thaw-induced floating patterns of gold nanoparticles (FTFPA) is proposed, which surpasses current state-of-the-art technologies by achieving a 100 fold improvement in the limit of detection of EVs. Notably, it allows for multi-dimensional visualizations of EVs through site-specific oligonucleotide incorporation. This capability empowers FTFPA to accurately identify EVs derived from subtypes of breast cancers with artificial intelligence algorithms. Intriguingly, learning the freezing-thawing-microstructures of EVs with a random forest algorithm is not only able to distinguish their original cell lines (with an accuracy of 95.56%), but also succeed in processing clinical samples (n = 156) to identify EVs by their healthy donors, breast lump and breast cancer subtypes (Luminal A, Triple-negative breast cancer, and Luminal B) with an accuracy of 83.33%. Therefore, this AI-empowered micro-visualization method establishes a rapid and precise point-of-care platform that is applicable to both fundamental research and clinical settings.

There has been over 130 years of research into the treatment of breast cancer using approaches that target oestrogen receptor signalling. Here, we summarise the development of the key pillars of such endocrine therapy, namely, oestrogen deprivation, achieved through ovarian suppression and/or aromatase inhibition, and oestrogen receptor blockade, through selective oestrogen receptor modulators, downregulators and novel compounds entering early phase development. The translation of these compounds from advanced to early breast cancer settings is discussed with a focus on the placebo-controlled breast cancer prevention studies to most accurately describe the side effect profiles of the main approaches.

The DREAM (dimerization partner, RB-like, E2F, and multi-vulval class B) complex is an evolutionarily conserved transcriptional repression complex that coordinates nearly one thousand target genes, primarily associated with the cell cycle processes. The formation of the DREAM complex consequently inhibits cell cycle progression and induces cellular quiescence. Given its unique role in cell cycle control, the DREAM complex has gained significant interest across various physiological and pathological contexts, particularly in conditions marked by dysregulated cell cycles, such as cancer. However, the specific cancer types most significantly affected by alterations in the DREAM complex are yet to be determined. Moreover, the possibility of restoring or pharmacologically targeting the DREAM complex as a therapeutic intervention against cancer remains a relatively unexplored area of research and is currently under active investigation. In this review, we provide an overview of the latest advances in understanding the DREAM complex, focusing on its role in cancer. We also explore strategies for targeting the DREAM complex as a potential approach for cancer therapeutics. Advances in understanding the precise role of the DREAM complex in cancer, combined with ongoing efforts to develop targeted therapies, may pave the way for new options in cancer therapy.

Single cell sequencing and related databases have been widely used in the exploration of cancer occurrence and development, but there is still no in-depth explanation of specific and complicated cellular protein modification processes. Ubiquitin-Proteasome System (UPS), as a specific and precise protein modification and degradation process, plays an important role in the biological functions of cancer cell proliferation and apoptosis. Proteasomes, vital multi-catalytic proteinases in eukaryotic cells, play a crucial role in protein degradation and contribute to tumor regulation. The 26S proteasome, part of the ubiquitin-proteasome system. In this study, we have enrolled a common SITP process including analysis of single cell sequencing to elucidate a flow that can capture typical proteasome markers in the oncogenesis and progression of breast cancer. PSMD11, a key component of the 26S proteasome regulatory particle, has been identified as a critical survival factor in cancer cells. Results suggest that PSMD11's rapid degradation is linked to acute apoptosis in cancer cells, making it a potential target for cancer treatment. Our study explored the potential mechanisms of PSMD11 in breast cancer development. The findings revealed the feasibility of disclosing ubiquitinating biomarkers from public database, as well as presented new evidence supporting PSMD11 as a potential therapeutic biomarker for breast cancer.

This register-based study investigates the probability of a livebirth after cancer during the female reproductive age.

The study population, derived from the DANAC II cohort, included women aged 18-39 diagnosed with cancer between 1978 and 2016, matched with 60 undiagnosed women each from the general population. Primary outcome was a livebirth after cancer with follow-up until death, emigration, or end of follow-up. Hazard ratios (HR) were calculated using multivariable Cox regression analyses.

The population included 21,596 women with cancer and 1,295,760 without. The 20-year cumulative incidence of livebirth after cancer/study entry was lower among women with cancer (0.22 [95% CI 0.22-0.22]) compared to those without (0.34 [95% CI 0.34-0.34]). The HR of a livebirth after cancer was 0.61 [95% CI 0.59-0.63]; highest at age 18-25 (HR = 0.72 [95% CI 0.68-0.76]); and lowest at age 33-39 (HR = 0.50 [95% CI 0.47-0.54]). Nullipara women had higher HR of a livebirth than those with children (HR = 0.72 [95% CI 0.69-0.75] vs. HR = 0.48 [95% CI 0.46-0.51]). HR was lowest for women with breast, gynecological, central-nerve-system cancer, and leukemia. Women with/without cancer were comparable in assisted reproductive technology initiation after cancer/study entry, but HR was higher among nullipara than in those with prior children.

Cancer during reproductive years significantly and negatively impacts HR of a livebirth after cancer, particularly as age at diagnosis increases. Low HR of livebirth is observed in specific cancer groups.

Results underscore the importance of oncofertility counseling at diagnosis, referral to fertility specialist before treatment, and follow-up after cancer, focusing on cancer type, parity status, and age at diagnosis.

Breast cancer remains one of the most prevalent and lethal malignancies in women, particularly the estrogen receptor-positive (ER+) subtype, which accounts for approximately 70% of cases. Traditional endocrine therapies, including aromatase inhibitors, selective estrogen receptor degraders/antagonists (SERDs), and selective estrogen receptor modulators (SERMs), have improved outcomes for metastatic ER+ breast cancer. However, resistance to these agents presents a significant challenge. This study explores a novel therapeutic strategy involving the simultaneous inhibition of the estrogen receptor (ER) and the chaperone protein Hsp90, which is crucial for the stabilization of various oncoproteins, including ER itself. We employed a hybrid, hierarchical in silico virtual screening approach to identify new dual ER/Hsp90 inhibitors, utilizing the Biotarget Predictor Tool (BPT) for efficient multitarget screening of a large compound library. Subsequent structure-based studies, including molecular docking analyses, were conducted to further evaluate the interaction of the top candidates with both ER and Hsp90. Supporting this, molecular dynamics simulations demonstrate the high stability of the multitarget inhibitor 755435 in complex with ER and Hsp90. Our findings suggest that several small molecules, particularly compound 755435, exhibit promising potential as dual inhibitors, representing a new avenue to overcome resistance in ER+ breast cancer.

Mammalian target of rapamycin (mTOR) inhibitors have been used clinically as anticancer and immunosuppressive agents for over 20 years, demonstrating their safety after long-term administration. These inhibitors exhibit various effects, including inhibition of cell proliferation, interaction with the oestrogen and progesterone pathways, immunosuppression, regulation of angiogenesis, and control of autophagy. We evaluated the potential of mTOR inhibitors as therapeutic agents for endometriosis, examined the secondary benefits related to reproductive function, and assessed how their side effects can be managed. We conducted a thorough review of publications on the role of the mTOR pathway and the effectiveness of mTOR inhibitors in endometriosis patients. These results indicate that the mTOR pathway is activated in endometriosis. Additionally, mTOR inhibitors have shown efficacy as monotherapies for endometriosis. They may alleviate resistance to hormonal therapy in endometriosis, suggesting a potential synergistic effect when used in combination with hormonal therapy. The potential reproductive benefits of mTOR inhibitors include decreased miscarriage rates, improved implantation, and prevention of age-related follicular loss and ovarian hyperstimulation syndrome. Activation of the mTOR pathway has also been implicated in the malignant transformation of endometriosis. Preclinical studies suggest that the dosage of mTOR inhibitors needed for treating endometriosis may be lower than that required for anticancer or immunosuppressive therapy, potentially reducing dosage-dependent side effects. In conclusion, while mTOR inhibitors, which allow for pregnancy during oral administration, show potential for clinical use in all stages of endometriosis, current evidence is limited to preclinical studies, and further research is needed to confirm clinical effectiveness.

Oral adjuvant endocrine therapy (AET) reduces the risk of cancer recurrence and death for women with hormone receptor-positive (HR+) breast cancer. Because of adverse symptoms and socioecologic barriers, AET adherence rates are low. We conducted post hoc analyses of a randomized trial of a remote symptom and adherence monitoring app to evaluate characteristics associated with higher app use, satisfaction, and how app use was associated with AET adherence.

Patients prescribed AET were randomly assigned to receive one of three intervention conditions: app, app + feedback, or enhanced usual care. Baseline and 6-month follow-up surveys, app use, and pillbox-monitored AET adherence data for app and app + feedback participants were used. Logistic regression evaluated the association between sociodemographic/clinical characteristics and app utilization and satisfaction, and how app use was associated with AET adherence (>80%).

Overall, 163 women with early-stage HR+ breast cancer were included; 35.0% had high app use (≥75% of weeks enrolled). No sociodemographic characteristics were associated with app use. Satisfaction with the app was higher among those who were younger (88.9% for age 31-49 years v 54.9% for age 65+ years, P < .001), identified as White (76.8% v 60.1% for Black, P = .045), had lower health literacy (85.4% v 68.2% with higher health literacy, P = .017), or were nonurban residents (85.7% v 68.6% for urban, P = .021). Most participants (90.3%) with high app use were AET-adherent compared with 66.8% for those with lower app use (P < .001).

Use of a remote monitoring app was similar across sociodemographic characteristics, and more frequent app use was associated with a higher likelihood of 6-month AET adherence. Encouraging women to monitor medication adherence and communicate adverse symptoms could improve AET adherence.

Breast cancer belongs to the most commonly diagnosed malignancies worldwide, with its increasing incidence paralleled by advances in early diagnostics and effective treatments resulting in significantly improved survival rates. However, breast cancer survivors often experience significantly reduced quality of life linked to the long-term health burden as a consequence of aggressive oncological treatments applied. Their most frequently recorded complains include chronic fatigue, reduced physical activity, disordered sleep, chronification of pain, and severe mental health impairments-all per evidence are associated with compromised mitochondrial health and impaired homeostasis. Self-report of a breast cancer survivor is included in this article to illustrate currently uncovered patient needs. This article highlights mechanisms behind the suboptimal health of breast cancer survivors associated with mitochondrial damage, and introduces a novel, mitochondria-based holistic approach addressing rehabilitation concepts for breast cancer survivors following advanced principles of predictive, preventive and personalised medicine (3PM). By operating via mitochondrial function, the proposed holistic approach triggers systemic effects at molecular, sub/cellular and organismal levels positively affecting energy metabolism, repair mechanisms as well as physical and mental health creating, therefore, highly effective rehabilitation algorithms tailored to an individualised patient profile. The proposed methodology integrates mitochondrial health assessments utilising mitochondrial homeostasis biomarkers in tear fluid as a non-invasive diagnostic tool, tailored nutraceuticals and lifestyle adjustments. The introduced approach aligns with advanced principles of 3PM, offering a holistic and proactive framework for managing persistent post-treatment symptoms of suboptimal health in the cohort of cancer survivors. Furthermore, presented approach is also applicable to pre-habilitation programmes considering needs of other patient cohorts affected by chronic diseases such as CVD and orthopaedic disorders with planned major surgical incisions, who require individually adapted pre- and rehabilitation programmes. Implementing such innovative pre- and rehabilitation strategies may lead to a full recovery, sustainable health conditions and, therefore, facilitating patients' comeback to normal daily activities, family and professional life. Contextually, presented approach is considered a 'proof-of-principle' model for the 3PM-related paradigm shift from reactive medicine to a cost-effective holistic health management in both primary and secondary care benefiting a large spectrum of affected patient cohorts, individuals in suboptimal health conditions as well as society at large.

This research aims to optimize adjuvant ovarian function suppression (OFS) for premenopausal Indian women with hormone receptor-positive (HR+) /human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). To address specific challenges identified in clinical practice, a comprehensive questionnaire consisting of 21 statements was developed. These statements were reviewed and validated by a scientific committee, ensuring their accuracy and relevance to the study's objectives. A panel of 46 Indian experts and one global expert in the field of eBC were asked to rate their level of agreement/disagreement with each statement. Consensus was defined as achieving ≥80% agreement among participants. Following two rounds of the modified Delphi technique, a consensus was achieved on 19 out of 21 statements addressing critical aspects of premenopausal HR+ HER2- eBC management. The expert panel strongly recommended comprehensive risk stratification for premenopausal patients with HR+ HER2- eBC, highlighting age ≤40 as a high-risk factor and advising composite assessments for patients ≥40 years. For high-risk patients, OFS coupled with an aromatase inhibitor emerged as the recommended therapeutic strategy. The panel recommended a potential duration of up to five years for OFS, provided tolerability is maintained. For patients under 40, simultaneous OFS and chemotherapy is advised when needed. For those over 40, sequential initiation is acceptable. Triptorelin is preferred among luteinizing hormone-releasing hormone analogs, though all options have similar efficacies. The outcomes of this consensus offer valuable clinical guidance, enabling individualized and evidence-based approaches for OFS in Indian patients with HR+ HER2- eBC.

Breast cancer (BC) is the most common female cancer worldwide, and the burden is increasing across sub-Saharan Africa. For women with hormone receptor-positive (HR+) cancers, endocrine therapy (ET) taken for 5-10 years can reduce the risk of recurrence by half. We explored experiences with ET and barriers to utilization among survivors in Botswana.

We recruited women with nonmetastatic disease from a survivorship cohort who had undergone mastectomy within 1-5 years for semi-structured interviews to explore experiences with treatment. This thematic content analysis focused on ET, so the sample included women with HR+ cancer who should have received ET and HR- women who reported taking ET.

We analyzed interviews with 19 women (mean age 54 years, 42% stage I/II, 58% stage III). Three key themes were identified: (1) limited provider counseling, (2) challenges refilling prescriptions at public pharmacies, and (3) high medication and transportation costs associated with private pharmacies. Subthemes included immunohistochemistry result communication, lack of knowledge, frequent public pharmacy stockouts, inconvenient prescription refill policies, and medication switching and discontinuation, especially among participants with low socioeconomic positions (SEPs). Women's persistence, SEP, and financial support facilitated refills. Although some experienced side effects, they were not a common reason for discontinuation.

BC survivors in Botswana face multilevel barriers to accessing and adhering to ET. Provider and health system improvements are needed to effectively communicate ET importance and increase access to consistently available and affordable medication.

Patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (HR+ BC) with unfavorable features have an increased risk of relapse and are currently candidate for additional treatment strategies. We evaluated the real-world clinicopathological characteristics, treatment patterns and survival outcomes of these patients within the CANcer TOxicities study (CANTO, NCT01993498).

This is a retrospective analysis of the prospective data collected within CANTO between 2012 and 2022. Patients with high-risk HR+ BC were defined either by the identification of at least four positive axillary lymph nodes (LNs) or one to three positive axillary LNs with a tumor size ≥5 cm or histologic grade 3 (cohort 1). The definition 1-3 positive LNs with Ki-67 ≥20% was also considered (cohort 2). The Kaplan-Meier method was used for survival analysis.

Patients with high-risk HR+ BC represented 15.0%-19.6% of HR+ BC (cohort 1 and 2, respectively) in the CANTO cohort. Of the 1266 patients in cohort 1, 617 patients (49.0%) had ≥4 LNs, 327 (26.0%) had tumor ≥5 cm and 727 (57.6%) had grade III tumors. 79.9% had a favorable Charlson comorbidity score and 88.1% stage II/IIIA. Patients with ≥10 LNs accounted for 11.8%. (Neo)adjuvant chemotherapy was administered in 94.2%. Endocrine therapy was prescribed in 97.3%, mostly with aromatase inhibitors and discontinued in 34.3%, mainly for adverse events. Patients enrolled at least 6 years before data extraction had a 5-year invasive disease-free survival and 5-year distant relapse-free survival of 79.9% [95% confidence interval (CI) 77.2% to 82.4%] and 83.5% (95% CI 80.9% to 85.7%), respectively.

This real-world study confirms that patients with HR+ BC and unfavorable clinicopathological features are at risk of relapse early in their adjuvant treatment trajectory, despite (neo)adjuvant chemotherapy. It is imperative to implement innovative treatment approaches for high-risk patients, ideally adding them as early as possible to the adjuvant treatment.

To examine utilization of a dedicated menopause symptoms after cancer clinic (MSAC) and to determine whether women referred to the MSAC for management of severe hot flush symptoms are more likely to adhere to endocrine therapy compare to those with severe symptoms not referred to MSAC.

Breast cancer patients prescribed endocrine therapy with a diagnosis of estrogen-receptor positive breast cancer between January 2003 and December 2011 were identified from the Royal Perth Hospital Breast Unit database. Details of breast cancer pathology, endocrine therapy, endocrine therapy related side effects, referral to MSAC and patient reported adherence to endocrine therapy for up to 4 years were ascertained from the database and medical records systems. For those with severe vasomotor symptoms, total duration of endocrine therapy was compared between women referred to MSAC and those who were not referred to MSAC.

About 1275 women were identified from the database, with the cohort followed up until Dec 2016. Of these women, 120 (9.4%) were referred to MSAC and 1155 (90.1%) received usual care. In total, 147 reported severe vasomotor symptoms of whom almost half (71) were referred to MSAC. Women with severe vasomotor symptoms managed by MSAC were less likely to discontinue endocrine therapy (15.5%) compared with those managed with usual care (26.3%). However, this difference was not statistically significant (chi-square test statistic = 2.584, 1df, P = .1).

Management of severe vasomotor symptoms at a dedicated menopause clinic may increase adherence to endocrine therapy for breast cancer.