Breast cancer is most common in women, and in most cases there is no evidence of spread and the primary tumor is removed, resulting in a \'cure\'. However, in 10% to 30% of these women, distant metastases recur after years to decades. This is due to breast cancer cells disseminating to distant organs and lying quiescent. This is called metastatic dormancy. Dormant cells are generally resistant to chemotherapy, hormone therapy and immunotherapy as they are non-cycling and receive survival signals from their microenvironment. In this state, they are clinically irrelevant. However, risk factors, including aging and inflammation can awaken dormant cells and cause breast cancer recurrences, which may happen even more than ten years after the primary tumor removal. How these breast cancer cells remain in dormancy is being unraveled. A key element appears to be the mesenchymal stem cells in the bone marrow that have been shown to promote breast cancer metastatic dormancy in recent studies. Indirect co-culture, direct co-culture and exosome extraction were conducted to investigate the modes of signal operation. Multiple signaling molecules act in this process including both protein factors and microRNAs. We integrate these studies to summarize current findings and gaps in the field and suggest future research directions for this field.

Following metastatic spread, many hormone receptor positive (HR+) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR+ breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure on representative HR+ breast cancer cell lines through protein and gene expression analysis. Proteomics results demonstrated that 540 total proteins and 1473 phospho-proteins significantly changed due to FSS exposure and pathways of interest included early and late estrogen response. The impact of FSS on response to 17β-estradiol (E2) was next evaluated and gene expression analysis revealed repression of ER and E2-mediated genes (PR and SDF1) following exposure to FSS. Western blot demonstrated enhanced phosphorylation of mTOR following exposure to FSS. Taken together, these studies provide initial insight into the effects of FSS on HR signaling in metastatic breast cancer.

UNASSIGNED: Since the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources.
UNASSIGNED: A monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options.
UNASSIGNED: All patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs. all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs. 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs. 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time.
UNASSIGNED: Patients and practitioners prefer oral antitumor therapy-both continuous and 21/7 regimens-over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer.

Multiple primary malignancies (MPMs) occur when an individual develops two or more distinct primary cancers. These are categorized as synchronous or metachronous based on the timing of their diagnosis. Patients previously diagnosed with cancer face increased risks due to exposure to carcinogenic factors and treatments such as chemotherapy and radiotherapy. Individuals with a history of breast cancer are known to have elevated risks for secondary malignancies compared to the general population. However, cases of squamous cell carcinoma (SCC) of the eyelid in this group are exceedingly rare. Here, we present a case report describing a young female patient who sequentially developed metachronous breast cancer, and a human papillomavirus (HPV)-associated SCC of the eyelid. To the best of our knowledge, this case report represents the first documented instance of this specific combination of primary neoplasms in medical literature.

OBJECTIVE: Eribulin is used in taxane and anthracycline refractory HER2-negative metastatic breast cancers (MBC). Patients treated in pivotal clinical trials achieved low survival rates, therefore, the identification of prognostic criteria for long progression-free survival (PFS) is still an unmet medical need. In this study, we sought to determine potential prognostic criteria for long-term eribulin response in HER2-negative MBC.
METHODS: Our retrospective cohort includes female patients with HER2-negative MBC treated with eribulin in Franche-Comté, France. We defined a long-term response as at least 6 months of eribulin treatment. The primary endpoint was the analysis of criteria that differ according to the progression-free survival. Secondary outcomes concerned overall survival and response rate.
RESULTS: From January 2011 to April 2020, 431 patients treated with eribulin were screened. Of them, 374 patients were included. Median PFS was 3.2 months (2.8-3.7). Eighty-eight patients (23.5%) had a long-term response to eribulin. Four discriminant criteria allowed to separate PFS in 2 arms (PFS < 3 months or > 6 months) with a 78% positive predictive value: histological grade, absence of meningeal metastasis, response to prior chemotherapy, and OMS status. We have developed a nomogram combining these 4 criteria. Median overall survival was 8.5 months (7.0-9.5).
CONCLUSIONS: Eribulin response in MBC can be driven by clinical and biological factors. Application of our nomogram could assist in the prescription of eribulin.

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UNASSIGNED: There is no clear information in the literature about the relationship between the efficacy of CDK 4/6i combined with ET and HR positivity. However, we know that the longest overall survival was in the ER-strong positive/PR intermediate or strong positive groups. Therefore, we aimed to investigate CDK4/6i treatments that create positivity in HR.
UNASSIGNED: Patients with the diagnosis of HR+/HER2- MBC who were treated with CDK 4/6i and HR >10% were retrospectively evaluated. To analyze the role of HR positivity, ER was moderately positive (10-49%) and ER was strongly positive (50-100%); PR was grouped as moderately positive (10-49%) and PR strongly positive (50-100%).
UNASSIGNED: Median follow-up of 150 patients included in the study was 15.2 months (95% CI, 2.1-40.9 months). The highest response in the whole group was obtained in the ER-strong positive/PR moderate or strong positive group, and the ER moderate positive/PR moderate or strong group. This was followed by the ER strong positive/PR negative group, and then the ER moderate positive/PR negative group. Although these advantages were not statistically significant, they were numerically higher (ORR: 83.8% vs. 83.3% vs. 77.4% vs. 62.5%, p=0.488, respectively). The highest survival in the whole group was achieved in the ER strong positive/PR moderate or strongly positive group, followed by the ER moderately positive/PR moderate or strongly positive group, the ER strongly positive/PR negative group followed by the ER moderate positive/PR negative group, respectively(p=0.410). However, these advantages were not statistically significant.
UNASSIGNED: As a result, HR+/HER2- MBC patients receiving CDK 4/6i combined with ET suggest that the percentage of HR positivity may have a predictive and prognostic role.

Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions.

UNASSIGNED: The role of surgery in metastatic breast cancer (MBC) is currently controversial. Several novel statistical and deep learning (DL) methods promise to infer the suitability of surgery at the individual level.
UNASSIGNED: The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.
UNASSIGNED: We introduced the deep survival regression with mixture effects (DSME), a semi-parametric DL model integrating three causal inference methods. Six models were trained to make individualized treatment recommendations. Patients who received treatments in line with the DL models\' recommendations were compared with those who underwent treatments divergent from the recommendations. Inverse probability weighting (IPW) was used to minimize bias. The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.
UNASSIGNED: In total, 5269 female patients with MBC were included. DSME was an independent protective factor, outperforming other models in recommending surgery (IPW-adjusted hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.19-0.78) and type of surgery (IPW-adjusted HR = 0.66, 95% CI: 0.48-0.93). DSME was superior to other models and traditional guidelines, suggesting a higher proportion of patients benefiting from surgery, especially breast-conserving surgery. The debiased effect of patient characteristics, including age, tumor size, metastatic sites, lymph node status, and breast cancer subtypes, on surgery decision was also quantified.
UNASSIGNED: Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed. This method can facilitate the development of efficient, reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

Background and Objectives: Patients with human epidermal growth factor receptor 2 (HER2) -positive, hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) usually undergo trastuzumab emtansine (T-DM1) therapy in subsequent lines. Combining endocrine therapy (ET) with T-DM1 can improve treatment outcomes in this subtype. Therefore, this study aimed to investigate the benefits of using T-DM1 with ET in HER2-positive and HR-positive MBC. This study was the first to investigate the benefits of combining ET with T-DM1. Material and Methods: This study analyzed the medical records of patients with HER2-positive and HR-positive MBC who were treated with T-DM1 from June 2010 to December 2021. The patients were divided into groups based on whether they received concomitant ET with T-DM1. The primary endpoint was to determine the progression-free survival (PFS), while the secondary endpoints were overall survival (OS), objective response rate, and safety of the treatment. Results: Our analysis examined 88 patients, of whom 32 (36.4%) were treated with T-DM1 in combination with ET. The combination therapy showed a significant improvement in median PFS (15.4 vs. 6.4 months; p = 0.00004) and median OS (35.0 vs. 23.1 months; p = 0.026) compared to T-DM1 alone. The ORR was also higher in the combination group (65.6% vs. 29.3%; p = 0.026). Patients treated with pertuzumab priorly had reduced median PFS on T-DM1 compared to those who were not treated with pertuzumab (11.7 vs. 5.4 months, respectively; p < 0.01). T-DM1 demonstrated better median PFS in HER2 3+ patients compared to HER2 2+ patients, with an amplification ratio of >2.0 (10.8 vs 5.8 months, respectively; p = 0.049). The safety profiles were consistent with previous T-DM1 studies. Conclusions: The combination of T-DM1 with ET can significantly improve PFS and OS in patients with HER2-positive and HR-positive MBC. Our study suggests that prior pertuzumab treatment plus trastuzumab treatment might decrease T-DM1 efficacy.