Breast Cancer Diagnosis, Prognosis, and Precision Medicine L2 PDF

Presentation by: Dr Temba Mudariki Insights into Breast Cancer Molecular Medicine XY3121 2024  Learning Outcomes 1. Understand the epidemiological significance of breast cancer, including its incidence, mortality, and global impact. 2. Recognize the anatomical considera...

Presentation by: Dr Temba Mudariki Insights into Breast Cancer Molecular Medicine XY3121 2024  Learning Outcomes 1. Understand the epidemiological significance of breast cancer, including its incidence, mortality, and global impact. 2. Recognize the anatomical considerations and pathophysiological aspects of breast cancer. 3. Evaluate the risk factors and protective factors influencing breast cancer development and progression. 4. Discuss the significance of screening tools and diagnostic procedures for early detection and accurate diagnosis of breast cancer. 5. Analyse the impact of genetic and molecular profiling in predicting treatment responses and guiding personalized therapeutic decisions in breast cancer patients.  Overview A.Introduction B. Anatomy and Pathophysiology of Breast Cancer C. Disease Progression and Metastasis of Breast Cancer D.Risk Factors and Protective Factors of Breast Cancer E. Screening and Diagnosis  Overview F. Prognostic and Predictive Factors G. Genetic and Molecular Profiling H. Posttherapy Considerations I. Case Studies and Clinical Applications J. Future Directions and Research Implications  Introduction to Breast Cancer ❖ Most common cancer in women ❖ Breast Cancer Incidence -2.3 million new cases in 2020 globally ❖ Breast Cancer mortality-685 000 deaths globally ❖ Epidemiological significance- (2021): 280K invasive, 49K non-invasive ❖ Estimated deaths – 2021, 44K deaths in the USA ❖ Prevalence- 3.8 million women in USA have history of breast cancer Anatomy and Pathophysiology of Breast Cancer ❖ Anatomy of the Breast: Composed of glandular tissue, ducts, connective tissue, blood vessels, and lymphatics. Located anterior to the pectoral muscles and extends from the second to the sixth rib and from the sternum to the mid-axillary line. Anatomy and Pathophysiology of Breast Cancer ❖ Key Structures in the Breast: Glandular tissue: The breast consists of lobes, lobules, and milk ducts responsible for producing and transporting milk. Lymph nodes: The axillary lymph nodes, located in the armpit, are crucial for draining lymphatic fluid from the breast. Cooper's ligaments: These connective tissue strands provide structural support to the breast. Anatomy and Pathophysiology of Breast Cancer ❖ Breast Cancer Development: Originates in the cells lining the milk ducts or the lobules. Abnormal changes in these cells can lead to the development of tumours. Over time, cancer cells can invade surrounding tissues and potentially spread to other parts of the body through the lymphatic or blood vessels. Anatomy and Pathophysiology of Breast Cancer ❖ Types of Breast Cancer: Ductal Carcinoma: The most common type, originating in the cells lining the milk ducts. Lobular Carcinoma: Arises from the cells in the lobules. There are also less common types, such as inflammatory breast cancer and Paget's disease of the breast. Anatomy and Pathophysiology of Breast Cancer ❖ Pathophysiology of Breast Cancer: Genetic mutations: Alterations in certain genes, such as BRCA1 and BRCA2, can increase the risk of developing breast cancer. Hormonal factors: Oestrogen and progesterone receptors play a role in the growth and proliferation of breast cancer cells. HER2/neu gene: Amplification or overexpression of this gene is associated with more aggressive breast cancers. Anatomy and Pathophysiology of Breast Cancer ❖ Disease Progression and Metastasis: Breast cancer can progress through stages, from localised to regional and metastatic disease. Metastasis occurs when cancer cells spread to distant organs, such as the bones, liver, lungs, or brain. The process of metastasis involves invasion of blood vessels or lymphatics and subsequent dissemination to other parts of the body. Anatomy and Pathophysiology of Breast Cancer ❖ Inflammatory Breast Cancer (IBC): IBC is a rare and aggressive form of breast cancer. It typically presents with symptoms such as redness, swelling, and warmth of the breast. IBC is characterized by cancer cells blocking lymph vessels in the skin, leading to the appearance of an inflamed breast. Disease Progression and Metastasis of Breast Cancer ❖ Disease Progression ✓ Local, Regional and Metastatic ❖ Metastasis in Breast Cancer ✓ Blood vessels or Lymphatic system ❖ Metastatic Sites ✓ Bones, Liver, Lung and Brain  Disease Progression and Metastasis of Breast Cancer ❖ Mechanisms of Metastasis: The process of metastasis is complex and involves several steps. Invasion: Cancer cells acquire the ability to invade nearby tissues, breaking through the extracellular matrix and basement membrane. Intravasation: Cancer cells invade blood vessels or lymphatics, entering the circulation. Circulation: Cancer cells travel through the bloodstream or lymphatic system to reach distant organs. Extravasation: Cancer cells exit the circulation and invade the surrounding tissues at the metastatic site. Formation of metastatic tumours: Cancer cells proliferate and establish secondary tumours in the distant organs. Disease Progression and Metastasis of Breast Cancer ❖ Clinical Implications of Metastasis: Metastatic breast cancer is generally more challenging to treat than localized disease. The presence of metastasis often indicates a poorer prognosis and may require systemic treatment approaches, such as chemotherapy, targeted therapy, or hormone therapy. The identification and monitoring of metastatic sites are crucial for determining the most appropriate treatment strategies. Risk Factors and Protective Factors of Breast Cancer ❖ Risk Factors for Breast Cancer – Genetic Factors: Inherited gene mutations –BRCA1 and BRCA2 ❖ Age and Gender - increases with age, and being a woman ❖ Family History – Close relative with breast cancer ❖ Personal History - previous breast cancer diagnosis or certain non- cancerous breast conditions ❖ Hormonal Factors- Prolonged exposure to oestrogen and progesterone Early menstruation Late menopause Hormone replacement therapy Risk Factors and Protective Factors of Breast Cancer Lifestyle Factors-Obesity, sedentary lifestyle, alcohol consumption, and tobacco BRCA1 Mutation: estimated lifetime risk 55%-72% BRCA2 Mutation: estimated lifetime risk 45% to 69% Germline mutation in the genes BRCA1 and BRCA2 – constitute 5% to 10% of women with breast cancer Risk Factors and Protective Factors of Breast Cancer ❖ Genetic Susceptibility: Inherited gene mutations, such as BRCA1 and BRCA2, significantly increase the risk of breast cancer. Genetic testing can identify individuals with these mutations, enabling targeted surveillance and preventive measures. Other gene mutations, such as TP53 and PTEN, also contribute to breast cancer risk, albeit less frequently. Risk Factors and Protective Factors of Breast Cancer ❖ Hormonal Influences: Oestrogen and progesterone play critical roles in breast cancer development. Early menarche (onset of menstruation) and late menopause increase the cumulative exposure to these hormones. Hormone replacement therapy (HRT) with oestrogen and progesterone after menopause may also elevate the risk, particularly with long-term use. Risk Factors and Protective Factors of Breast Cancer ❖ Lifestyle Factors: Obesity: Excess body weight, particularly after menopause, is associated with an increased risk of breast cancer. Physical Activity: Regular exercise and an active lifestyle have been linked to a reduced risk of breast cancer. Alcohol Consumption: Higher alcohol intake is associated with an increased risk of breast cancer. Tobacco Use: Smoking has been linked to an increased risk of various cancers, including breast cancer. Risk Factors and Protective Factors of Breast Cancer ❖ Protective Factors: Hormone Use: Certain hormonal factors can be protective. Early age at first childbirth, longer duration of breastfeeding, and use of oral contraceptives have been associated with a reduced risk of breast cancer. Physical Activity: Engaging in regular physical activity and maintaining a healthy weight can help reduce the risk of breast cancer. Reproductive History: Early first childbirth, multiple pregnancies, and a younger age at menopause have been associated with a lower risk of breast cancer. Risk Factors and Protective Factors of Breast Cancer ❖ Protective Interventions: Chemoprevention: Medications such as selective oestrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) can be used to reduce the risk of breast cancer in high-risk individuals. Lifestyle Modifications: Encouraging healthy lifestyle choices, such as maintaining a healthy weight, regular exercise, limiting alcohol consumption, and avoiding tobacco use, can help mitigate the risk of breast cancer.  Screening and Diagnosis ❖ Early Detection ❖ Mammography ❖ Ultrasonography  Screening and Diagnosis ❖Diagnostic Procedures: If an abnormality is detected during screening or based on clinical examination, further diagnostic procedures are performed to confirm the diagnosis and determine the extent of the disease. Biopsy and magnetic resonance imaging (MRI) are two important diagnostic procedures used in breast cancer diagnosis and staging. ❖ Biopsy: Gold standard confirming breast cancer Core needle biopsy, vacuum-assisted biopsy, surgical biopsy  Screening and Diagnosis ❖Magnetic Resonance Imaging (MRI)- extent of breast cancer, assessing the involvement of lymph nodes, and screening high-risk individuals ❖Staging- determines the extent and spread of the disease: (TNM system (Tumour, Node, Metastasis). ❖Multidisciplinary Approach ✓Radiologists, pathologists, surgeons, medical oncologists, and radiation oncologists ✓Accurate diagnosis and appropriate treatment planning.  Prognostic and Predictive Factors ❖Prognostic Factors: Prognostic factors provide information about the likelihood of disease recurrence, progression, and overall survival. Clinical factors, such as age, tumour size, lymph node involvement, and histological grade, influence prognosis. Pathological factors, including hormone receptor status, HER2/neu status, and presence of lymphovascular invasion, also impact prognosis.  Prognostic and Predictive Factors ❖Hormone Receptor Status: Oestrogen receptor (ER) and progesterone receptor (PR), is an essential prognostic factor. Patients with hormone receptor-positive breast cancer tend to have a better prognosis and may benefit from hormone-targeted therapies. ❖ HER2/neu Status: Amplification or overexpression of the HER2/neu gene is associated with aggressive breast cancer. HER2-positive breast cancer patients may benefit from targeted therapies, such as trastuzumab (Herceptin®) and pertuzumab (Perjeta®).  Prognostic and Predictive Factors ❖Histological Grade: Histological grade reflects the degree of differentiation and aggressiveness of the tumour. High-grade tumours are associated with a poorer prognosis compared to low-grade tumours. ❖Lymphovascular Invasion: Lymphovascular invasion refers to the presence of tumour cells within lymphatic or blood vessels. Its presence indicates a higher risk of metastasis and poorer prognosis.  Prognostic and Predictive Factors ❖Predictive Factors: Predictive factors help determine the likelihood of response to specific treatments. Molecular profiling and gene expression assays provide valuable information in this regard.  Prognostic and Predictive Factors ❖Molecular Profiling: Molecular profiling involves the analysis of specific genes and molecular pathways in breast cancer. It provides insights into the tumour’s behaviour, response to treatment, and prognosis. Examples of molecular profiling tests include Oncotype DX, MammaPrint, and Prosigna.  Prognostic and Predictive Factors ❖Gene Expression Assays: Gene expression assays measure the activity levels of multiple genes in a tumour sample. These assays help predict the risk of recurrence and guide treatment decisions. Commonly used gene expression assays include the Breast Cancer Index and PAM50.  Prognostic and Predictive Factors ❖Treatment Response Prediction: Molecular profiling and gene expression assays help predict the response to specific treatments. For example, Oncotype DX can guide the decision to use chemotherapy in hormone receptor-positive, HER2-negative breast cancer. ❖ Precision Medicine: The integration of prognostic and predictive factors allows for precision medicine approaches in breast cancer. Tailoring treatments based on individual patient characteristics and tumour biology improves outcomes.  Genetic and Molecular Profiling ❖Genetic Testing: Genetic testing plays a crucial role in identifying inherited mutations that increase the risk of breast cancer. It helps identify mutations in genes like BRCA1 and BRCA2, which are associated with a significantly higher risk of breast and ovarian cancer.  Genetic and Molecular Profiling ❖BRCA1 and BRCA2 Mutations: BRCA1 and BRCA2 mutations are the most well-known and extensively studied genetic mutations associated with breast cancer. These mutations significantly increase the lifetime risk of developing breast and ovarian cancer. Individuals with BRCA1 or BRCA2 mutations may consider risk- reducing strategies such as prophylactic surgeries or enhanced surveillance.  Genetic and Molecular Profiling ❖Implications of BRCA1 and BRCA2 Mutations ✓ Inform decisions regarding surgical interventions, targeted therapies, and counselling for family members ❖Molecular Profiling ✓ guide personalized treatment decisions and improves patient outcomes. ❖MammaPrint ✓ Classifies tumours into high- and low-risk prognostic categories based on a 70-gene signature ❖Oncotype DX ❖Predict the likelihood of disease recurrence and guides decisions on adjuvant chemotherapy in hormone receptor-positive, HER2-negative breast cancer.  Genetic and Molecular Profiling ❖Treatment Decision-Making ✓MammaPrint and Oncotype DX aid in treatment decision-making ✓Provide valuable information on the tumour’s aggressiveness and response to specific therapies ✓Help identify patients who may benefit from chemotherapy ❖Precision Medicine Approach ✓Genetic testing and molecular profiling contribute to the precision medicine ✓Treatment can be tailored to the individual patient, improving outcomes and minimizing side effects  Posttherapy Considerations Breast Cancer Treatment and Hormonal Changes ✓ Surgery, chemotherapy, and endocrine therapy, can lead to hormonal changes and menopausal symptoms ❖ Hormone Replacement Therapy (HRT) ✓ Contraindicated in breast cancer survivors due to concerns about hormone-related cancer recurrence ❖ Evolving Perspectives on HRT ✓ Decision to use HRT should be individualized ✓ Age ✓ Type of breast cancer ✓ Treatment received ✓ Overall health  Posttherapy Considerations ❖Patient-Centred Care ✓ Open communication, shared decision-making ✓ Tailoring interventions to the individual patient's needs, preferences, and goals ❖Assessing Risks and Benefits ✓ Severity of menopausal symptoms, impact on quality of life, risk of cancer recurrence, and overall health status. ❖Personalized Interventions ✓ Tailored to the patient's specific needs and preferences  Posttherapy Considerations Shared Decision-Making Multidisciplinary Approach Survivorship Programs  Case Studies and Clinical Applications ❖Case Study 1: Genetic Profiling and Targeted Therapy Description: This case study focuses on a patient with advanced breast cancer who underwent genetic profiling. Results of the genetic profiling revealed a specific mutation, guiding the selection of targeted therapy. The case study will showcase the patient's response to the targeted therapy and the improvement in disease control.  Case Studies and Clinical Applications ❖Case Study 2: BRCA1/BRCA2 Mutation and Risk Management Description: This case study centres around a patient with a strong family history of breast and ovarian cancer. Genetic testing identified a BRCA1 mutation in the patient, leading to risk-reducing strategies and heightened surveillance. The case study will demonstrate the impact of early intervention and personalized risk management on the patient's outcomes.  Case Studies and Clinical Applications ❖Case Study 3: Molecular Profiling and Treatment Selection Description: This case study focuses on a patient with early-stage breast cancer who underwent molecular profiling. The molecular profile test, such as MammaPrint or Oncotype DX, assisted in determining the patient's risk of recurrence. The case study will highlight how the molecular profile results influenced the treatment decision-making process and optimized the patient's therapy.  Case Studies and Clinical Applications ❖Case Study 4: Personalized Treatment Approach Description: This case study illustrates the importance of a personalized treatment approach in breast cancer management. It will showcase a patient with unique characteristics, such as hormone receptor status, HER2 expression, and genomic alterations. The case study will emphasize how a comprehensive understanding of the patient's molecular profile guided the selection of tailored therapies, resulting in improved outcomes.  Case Studies and Clinical Applications ❖Case Study 5: Long-Term Survivorship Care Description: This case study focuses on the long-term survivorship care of a breast cancer patient. It will explore the role of ongoing genetic and molecular profiling in monitoring the patient's disease status and optimizing follow-up care. The case study will highlight how genetic and molecular profiling contribute to personalized survivorship care and the early detection of potential recurrences.  Future Directions and Research Implications ❖Precision Medicine in Breast Cancer: Precision medicine aims to tailor medical treatment to individual patients based on their unique characteristics, such as genetic makeup, molecular profile, and lifestyle factors. In breast cancer management, precision medicine holds promise for optimizing therapy selection, treatment response prediction, and personalized survivorship care.  Future Directions and Research Implications ❖ Genomic and Molecular Profiling ❖ Liquid Biopsies and Circulating Tumour DNA (ctDNA) ❖ Immunotherapy and Targeted Therapies ❖ Artificial Intelligence (AI) and Machine Learning ❖ Long-Term Survivorship Care ❖ Clinical Trials and Collaborative Research ❖ Ethical Considerations and Patient Empowerment End of Session