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Breast cancer is a significant global health concern, and the discovery of endocrine therapy has played a crucial role in the treatment of estrogen-positive breast cancer. However, these therapies are often associated with osteoporosis-related adverse events, which increase the risk of fractures in breast cancer patients and can result in limited m...
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Context 1
... combined with aromatase, these drugs work by blocking the conversion of androgens into estrogen in the body, which reduces the estrogen levels and ultimately inhibits the growth of tumor cells. However, the use of aromatase inhibitors exacerbates the age-related reduction in BMD (16) due to the link between estrogen levels and bone health (Table 1) (20). Anastrozole, letrozole, and exemestane are frequently used aromatase inhibitors, with the latter being a steroid. ...Citations
... Aromatase inhibitors are chosen as the primary treatment for postmenopausal women by blocking the production of estrogen from androgens [80,82]. Endocrine therapy is used to inhibit the growth of tumor cells by reducing the levels of estrogen. ...
... Endocrine therapy is used to inhibit the growth of tumor cells by reducing the levels of estrogen. This therapy will prevent estrogen from binding to estrogen receptors on tumor cells [82]. However, the reduced estrogen levels stimulate osteoporosis-the loss of bone density with decreased estrogen levels-in older women and hinder bone formation and growth [82]. ...
... This therapy will prevent estrogen from binding to estrogen receptors on tumor cells [82]. However, the reduced estrogen levels stimulate osteoporosis-the loss of bone density with decreased estrogen levels-in older women and hinder bone formation and growth [82]. This development is commonly induced by the anti-estrogenic drugs and aromatase inhibitors mentioned previously [82]. ...
Breast cancer is the leading cancer found in females today. Although breast cancer can be broken down into various subtypes, the most prominent type is hormone receptor (HR) breast cancer. Hormones especially effective in females, such as progesterone and estrogen, may stimulate cancer cell proliferation. The four main breast cancer subtypes are HR+/HER2-, HR-/HER2+/−, HR-/HER2+, and HR-/HER2-, each characterized by the presence or absence of certain hormone receptors. HR breast cancers, due to high levels of progesterone and estrogen that promote cell proliferation and human epidermal growth factor receptors, grow by controlling gene transcription, cell division, and migration. Estrogen, a sex hormone primarily found in the female ovaries, binds to its associated receptors throughout the menstrual cycle and pregnancy. Various genes encode estrogen receptors, which regulate the expression of their respective genes. Estrogen causes ER-positive breast cancer growth via the continual binding of the hormone to cancer cell receptors. Conversely, ER-negative breast cancers are tumors that form due to the depletion of estrogen receptors from cancer cells. These cancers are regulated by two receptor types: ERα and ERβ. Recent treatment includes endocrine therapy, surgery, and epigenetic therapy.
... This can be associated with the clinical knowledge that breast carcinoma frequently metastasizes to bone (approximately 70% of patients with breast cancer have bone metastases), and endocrine therapy to treat breast cancer can cause osteoporosis. [33][34][35] For measurement, ionized calcium is one of the main indicators of OP, 36 and glycated hemoglobin (HbA1c) can increase by the abuse of GC. 37,38 Most relevant procedures include dual energy X-ray absorptiometry (DEXA) for diagnosing osteoporosis, followed by multiple imaging techniques to screen bone abnormalities. In the external validation, GC prescription pattern, several types of arthritis, and gastric disease (GERD with esophagitis) were also important, but unlike the internal validation, pneumonia, chronic obstructive pulmonary disease (COPD), and asthma were included in the top 10. ...
Background
Pretraining electronic health record (EHR) data using language models by treating patient trajectories as natural language sentences has enhanced performance across various medical tasks. However, EHR pretraining models have never been utilized in adverse drug event (ADE) prediction. We constructed and externally validated the EHR pretraining model for several ADE prediction tasks and qualitatively analyzed the important features of each ADE cohort.
Methods
A retrospective study was conducted on observational medical outcomes partnership (OMOP)-common data model (CDM) based EHR data from two separate tertiary hospitals. The data included patient information in various domains such as diagnosis, prescription, measurement, and procedure. For pretraining, codes were randomly masked, and the model was trained to infer the masked tokens utilizing preceding and following history. In this process, we adopted domain embedding (DE) to provide information about the domain of the masked token, preventing the model from finding codes from irrelevant domains. For qualitative analysis, we identified important features using the attention matrix from each finetuned model.
Results
510,879 and 419,505 adult inpatients from two separate tertiary hospitals were included in internal and external datasets. EHR pretraining model with DE outperformed all the other baselines in all cohorts. For feature importance analysis, we demonstrated that the results were consistent with priorly reported background clinical knowledge. In addition to cohort-level interpretation, patient-level interpretation was also available.
Conclusions
EHR pretraining model with DE is a proper model for various ADE prediction tasks. The results of the qualitative analysis were consistent with background clinical knowledge.
... Of all breast cancer patients, 70-80% suffer from a hormone receptor positive disease and therefore require endocrine therapy [11]. It is known that endocrine therapy with aromatase inhibitors in hormone receptor positive breast cancer patients leads to osteoporosis [12]. Estrogen reduces osteoclast-mediated resorption of the bone and promotes osteoblast-mediated bone formation [13]. ...
... Estrogen reduces osteoclast-mediated resorption of the bone and promotes osteoblast-mediated bone formation [13]. With the inhibition of the aromatase enzyme, estrogen levels fall and therefore bone renewal and strengthening are reduced [12]. Furthermore, chemotherapy with anthracyclines and taxanes in breast cancer patients was associated with a worsening of bone mineral density within 6 months and an elevated risk of major osteoporotic fractures at 10 years [14]. ...
... Nevertheless, the rate of vitamin D deficiency at the baseline assessment of the BEGYN-1 study was still very high, with a median serum 25(OH)D level of 24 ng/mL and therefore below the recommended minimal level of 30 ng/mL [16]. As oncological treatments like chemotherapy and endocrine therapy aggravate issues in bone metabolism, ensuring adequate vitamin D levels for breast cancer patients is crucial for the prevention of osteoporosis and the benefit of bone health [12,14]. For this reason, routine control, as well as the adequate substitution of vitamin D and calcium during oncological therapies, especially during endocrine therapy with aromatase inhibitor or ovarian function suppression, is recommended by national and international oncological guidelines [27,28]. ...
(1) Background: Vitamin D levels in patients remain inadequately understood, with research yielding inconsistent findings. Breast cancer patients, particularly due to oncological therapies, face an increased risk of osteopenia, which can be exacerbated by a vitamin D deficiency. (2) Methods: The prospective observational “BEGYN-1” study assessed serum 25(OH)D levels at baseline and quarterly thereafter. Clinical, pathological, nutritional, vitamin supplementation, and lifestyle data were recorded. (3) Results: Before treatment, 68.5% of patients were vitamin D deficient (<30 ng/mL), with 4.6% experiencing severe deficiency (<10 ng/mL). The median baseline 25(OH)D levels were 24 ng/mL (range: 4.8 to 64.7 ng/mL). Throughout the study, the median vitamin D levels increased to 48 ng/mL (range: 22.0 to 76.7 ng/mL). Before diagnosis, 16.7% received vitamin D substitution, and 97.8% received vitamin D substitution throughout the year with a median weekly dose of 20,000 IU. It took at least three quarterly assessments for 95% of patients to reach the normal range. A multiple GEE analysis identified associations between 25(OH)D levels and supplementation, season, age, VLDL, magnesium levels, and endocrine therapy. (4) Conclusions: Physicians should monitor 25(OH)D levels before, during, and after oncological therapy to prevent vitamin D deficiency and to adjust substitution individually. While variables such as seasons, age, VLDL, magnesium, diet, and oncological interventions affect 25(OH)D levels, supplementation has the greatest impact.
The raising number of older patients who are diagnosed with breast cancer represents a significant medical and societal challenge. Aromatase inhibitors (AI), which are commonly utilized to treat this condition in these patients have significant adverse events on bone and muscle health. Falling estrogen production leads to an increase in RANKL secretion by osteoblasts with accelerated bone remodeling due to osteoclast activity. Furthermore, estrogen deficiency reduces skeletal muscle strength and mass. The humanized monoclonal antibody, denosumab, neutralizes RANKL, thereby inhibiting osteoclast formation, function and survival and ultimately exerting powerful anti-resorptive effects.. In this study, we report on the efficacy of denosumab in mitigating aromatase inhibitor-induced bone loss (AIBL) and sarcopenia in older women with breast cancer. From January 2022 to January 2023, we enrolled 30 patients (female sex, ≥ 65 years) diagnosed with non-metastatic breast cancer undergoing adjuvant endocrine therapy; patients received, as per clinical practice, primary bone prophylaxis with denosumab (60 mg via subcutaneous injection every 6 months) according to oncologic guidelines. This group was matched with 30 patients with non-metastatic breast cancer, who were treated with biphosphonates (BF) therapy (oral alendronate 70 mg/week). For each patient bone mineral density (BMD) and bone quality in terms of trabecular bone score (TBS) in addition to body composition and Relative Skeletal Muscle Index (RSMI) was assessed by bone densitometry at baseline and after one year of treatment. Significant improvements in TBS at the lumbar spine, RSMI and whole-body composition (arms, legs, and trunk) were observed in the denosumab group compared with the BF group. These findings underscore the role of denosumab as an effective strategy in managing AIBL and osteosarcopenia in older women with breast cancer and undergoing adjuvant endocrine therapy, which is crucial for improving quality of life, preventing functional decline, and optimizing treatment outcomes.
