Razi Journal of Medical Sciences

fa سرطان سینه: همه‌گیری‌شناسی، عوامل خطر و نوآوری‌ها در پزشکی شخصی‌سازی‌ شده Breast Cancer: Epidemiology, Risk Factors, and Innovations in Personalized Medicine خون و انکولوژی Hematology & oncology مروري review article <div style="text-align: justify;">سرطان پستان شایع‌ترین تومور بدخیم و یکی از علل اصلی مرگ ‌و میر زنان در سطح جهان است که شیوع آن به‌طور مداوم در حال افزایش است. عوامل خطر شامل جهش‌های ژنتیکی، تغییرات هورمونی و سبک زندگی ناسالم می‌باشد. این عوامل همراه با افزایش سن، بار جهانی این بیماری را تشدید کرده‌اند. تشخیص زودهنگام از طریق ماموگرافی،Magnetic resonance imaging (MRI) و بیوپسی‌های مایع نقشی حیاتی در کاهش مرگ‌ و میر دارد. این روش‌ها به شناسایی سریع‌تر بیماری کمک کرده و درمان مؤثرتر را امکان‌پذیر می‌کنند. با این حال، در کشورهای کم‌درآمد و متوسط، ضعف زیرساخت‌های بهداشتی-درمانی مانع از دسترسی کافی به برنامه‌های غربالگری شده و منجر به تشخیص‌های دیرهنگام و پیامدهای ضعیف‌تر می‌گردد. پیشرفت‌های درمانی شامل استفاده از داروهای هدفمند برای انواع خاص سرطان سینه می‌باشد. درمان‌هایی مانند تراستوزوماب برای Human epidermal growth factor receptor 2 (HER2) مثبت و ترکیب شیمی‌درمانی با ایمونوتراپی برای (TNBC) Triple-negative breast cancer، نتایج چشمگیری در بهبود بقا داشته‌اند. همچنین، داروهای جدید مانند مهارکننده‌های CDK4/6 و PARP به بهبود درمان‌های فعلی کمک کرده‌اند. جراحی و رادیوتراپی همچنان ارکان اصلی درمان هستند و در کنار درمان‌های سیستمیک برای کاهش عود و متاستاز استفاده می‌شوند. آینده درمان سرطان پستان بر توسعه درمان‌های شخصی‌سازی‌شده، شناسایی اهداف ژنتیکی جدید و ارتقای دسترسی به فناوری‌های پیشرفته متمرکز است. این رویکردها، همراه با تاکید بر پیشگیری و تشخیص زودهنگام، می‌توانند نتایج درمان را بهبود بخشیده و بار جهانی سرطان سینه را کاهش دهند. هدف درمان‌های آینده، شخصی‌سازی درمان‌ها و تنظیم شدت آن‌ها بر اساس زیست‌شناسی سرطان و واکنش اولیه بیمار به درمان است. این مقاله، به مروری بر عوامل مختلف تاثیرگذار بر سرطان سینه در مناطق مختلف جهان و روش‌های تشخیصی و درمانی این بیماری می‌پردازد. <div style="text-align: justify;"></div></div> <div style="text-align: justify;">Breast cancer is the most common malignant neoplasm and a primary cause of mortality among women worldwide. In recent decades, its prevalence has consistently risen, resulting in an escalating public health challenge, especially in low- and middle-income countries (LMICs), where healthcare systems frequently lack the requisite infrastructure and resources to address the increasing demand for cancer treatment. This difference emphasizes the critical need for equal access to preventive, early detection, and treatment methods to address this global health crisis comprehensively. The increasing prevalence of breast cancer is linked to various factors. Demographic changes, including population aging and shifts in reproductive behaviors, such as delayed childbirth and reduced breastfeeding duration, have significantly impacted this trend. Lifestyle factors, including rising obesity rates, physical inactivity, and alcohol consumption, have exacerbated the risk. In high-income countries, especially the United States and Europe, dietary patterns marked by high-fat consumption and the prevalence of obesity have become significant contributors to the disease burden. In contrast, low- and middle-income countries (LMICs) in Asia and Africa encounter specific challenges, such as cultural barriers that hinder early detection initiatives and restricted access to screening programs. These limitations frequently lead to diagnoses at higher levels and lower clinical outcomes. The risk factors for breast cancer are multifaceted, involving both genetic and environmental components. Approximately 5–10% of breast cancer cases are attributable to inherited genetic mutations, most notably in the BRCA1 and BRCA2 genes, which can increase the lifetime risk of developing breast and ovarian cancer to as high as 80%. Advances in genetic screening have made it possible to identify high-risk individuals, enabling the implementation of preventive strategies, such as prophylactic surgeries, that significantly reduce cancer risk. In addition to genetic predisposition, lifestyle factors that can be considerably modified influence susceptibility to breast cancer. Behaviors including alcohol consumption, smoking, obesity, physical inactivity, and poor dietary habits are significantly linked to an increased risk of the disease. Hormonal factors, such as extended exposure to estrogen resulting from early menarche, late menopause, or hormone replacement therapy, significantly contribute to the development of breast cancer. The complex link among genetic, hormonal, and lifestyle factors highlights the importance of thorough preventive strategies that combine lifestyle changes with specific interventions for individuals at elevated genetic risk. Diagnosing breast cancer requires a synthesis of precise imaging techniques, histopathological analysis, and genetic testing. Mammography is fundamental for early detection, especially in asymptomatic women, and has significantly contributed to decreasing mortality rates in high-income nations. Access to mammography is frequently restricted in low- and middle-income countries (LMICs), resulting in diagnoses at more advanced stages and inferior results. Recent innovations, including magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and contrast-enhanced mammography, have increased the accuracy of breast cancer detection, particularly in women with dense breast tissue, where conventional techniques may be inadequate. Moreover, innovative instruments like liquid biopsies, which identify circulating tumor DNA (ctDNA), provide promising opportunities. These non-invasive tests promote early recognition and generate significant insights into treatment efficacy and the existence of residual disease. These discoveries can change breast cancer treatment globally, especially by reducing gaps in diagnostic availability in resource-constrained environments.  Breast cancer treatment has significantly improved, proceeding closer to personalized strategies based on the molecular profile of individual tumors. Breast cancer is categorized into subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC), which form the basis for targeted treatment approaches. Hormone receptor-positive cancers, including luminal A and B subtypes, show a positive response to endocrine therapies, such as selective estrogen receptor modulators (SERMs) and aromatase inhibitors, which inhibit estrogen's contribution to tumor proliferation. HER2-positive breast cancers, defined by HER2 protein overexpression, have seen improved treatment outcomes due to the introduction of targeted therapies including trastuzumab, pertuzumab, and newer agents like trastuzumab deruxtecan. These therapies have changed the management of HER2-positive disease, leading to notable modifications in survival rates and patient quality of life. This progress illustrates the significance of a precision medicine approach in the management of breast cancer. Triple-negative breast cancer (TNBC) poses a considerable challenge due to its absence of hormone receptors and HER2 expression, making it resistant to numerous targeted therapies that have altered the treatment of other subtypes. TNBC has been defined by its rapid growth and increased recurrence rates, leading to more intensive and multifaceted treatment strategies. Recent advancements in immunotherapy, especially regarding the use of immune checkpoint inhibitors, have shown improved survival rates for patients with TNBC. Ongoing research is exploring innovative strategies, including the combination of chemotherapy with immunotherapy, and investigating targeted therapies such as PARP inhibitors for patients with BRCA-mutated TNBC. These developments enable modern methods to address this challenging subtype and enhance outcomes for affected individuals. Breast cancer treatment generally includes local and systemic treatments, providing a holistic strategy for controlling the disease. Surgery plays an essential role in treatment, with different options from breast-conserving surgery (lumpectomy) to mastectomy, according to tumor features and patient preferences. After treatment, radiation is frequently advised for individuals after breast-conserving surgery to decrease the risk of local recurrence. Systemic treatments, including chemotherapy, hormone therapy, and targeted therapies, are important for inhibiting the metastasis of cancer to other parts of the body. Recent advances in molecularly targeted therapies have markedly enhanced results, especially for HER2-positive and hormone receptor-positive breast tumors. The addition of CDK4/6 inhibitors, including palbociclib and ribociclib, along with endocrine therapy has significantly improved therapeutic efficacy for hormone receptor-positive breast cancer, promising patients with higher prospects for sustainable control and survival. The future of breast cancer treatment relies mainly on the advancement of personalized medicine. Improvements in genetic and molecular profiling, accelerated by next-generation sequencing technology, have exposed new targets for therapy and facilitated more precise treatments. PI3K inhibitors, aimed at PIK3CA-mutated tumors, represent a notable transition for improving the genetic mechanisms of cancer instead of depending exclusively on standard chemotherapy, therefore providing patients with more personalized and less toxic options for therapy. Immunotherapy promises to be a potential field of advancement, especially for TNBC. Immune checkpoint drugs, including pembrolizumab and atezolizumab, have demonstrated promising outcomes in advanced-stage TNBC, with current clinical trials studying their application in earlier disease stages. Studies that merge immunotherapy with chemotherapy and targeted medicines are in growth, to enhance the immune system's efficacy in attacking cancer. These discoveries indicate a new era in breast cancer treatment, offering promise for better results and an improved quality of life for patients. In conclusion, breast cancer is a significant worldwide health challenge, influenced by increasing incidence and the complex interaction of genetic, environmental, and lifestyle conditions. However, advances in early detection, molecular profiling, and personalized treatment options offer an opportunity for better results. Reducing breast cancer globally requires expanding access to these technologies, especially in low-resource areas, and refining therapy techniques. The final goal of breast cancer research is to increase survival rates, prevention, early detection, and long-term outcomes, giving hope for a managed and preventive future.  </div> سرطان سینه, اپیدمیولوژی, عوامل خطر, عوامل پیش‌بینی‌کننده و پیش‌آگهی, رویکردهای درمانی Breast cancer, Epidemiology, Risk factors, Predictive and prognostic factors, Therapeutic approaches 1 17 http://rjms.iums.ac.ir/browse.php?a_code=A-10-8286-2&slc_lang=fa&sid=1 Farideh Hashemi فریده هاشمی 3900319475328460087803 3900319475328460087803 No Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran گروه پزشکی مولکولی، دانشکده فناوری‌های نوین، دانشگاه علوم پزشکی ایران، تهران، ایران Vahid Babaei وحید بابایی 3900319475328460087804 3900319475328460087804 No Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran گروه ژنتیک پزشکی و بیولوژی مولکولی، دانشکده پزشکی، دانشگاه علوم پزشکی ایران، تهران، ایران Ayna Yazdanpanah آینا یزدان‌پناه 3900319475328460087805 0009-0008-5699-6077 No Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran گروه مهندسی بافت و سلول‌های بنیادی، دانشکده فناوری‌های نوین، دانشگاه علوم پزشکی ایران، تهران، ایران Mansoureh Akouchekian منصوره آکوچکیان akouchekian.m@iums.ac.ir 3900319475328460087806 3900319475328460087806 Yes Assistant Professor of Medical Genetics, Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran دانشیار، گروه ژنتیک پزشکی و بیولوژی مولکولی، دانشکده پزشکی، دانشگاه علوم پزشکی ایران، تهران، ایران