Malignant Breast Disease Past Paper PDF - RCSI 2024

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Malignant Breast Disease Class Year 2 Course Pathology Lecturer Prof Paul Murray Date February 2024 LEARNING OBJECTIVES List and discuss malignant breast disease Describe the epidemiology of breast...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Malignant Breast Disease Class Year 2 Course Pathology Lecturer Prof Paul Murray Date February 2024 LEARNING OBJECTIVES List and discuss malignant breast disease Describe the epidemiology of breast cancer (i.e. risk factors) List the different types of breast cancers Discuss the prognosis of breast cancer Discuss the management of breast cancer BREAST CARCINOMA The most common non-skin cancer in females 2nd most common cause of cancer mortality in females Incidence is increasing Lifetime risk 1:9 Aetiology unknown- major risk factors: – Excess oestrogen – Genetic factors  RISK FACTORS FOR BREAST CARCINOMA Female gender Increasing age (70% of cases are in females >50 years) Early menarche and late menopause Nulliparity and first birth after 35 years Radiation exposure Post menopausal obesity Pregnancy and lactation have a protective effect against breast cancer. During pregnancy, oestrogen levels rise, but they are counteracted by higher levels of progesterone. Additionally, during lactation, the breast tissue undergoes changes that make it less susceptible to the development of cancer. Women who have delayed pregnancies or remain nulliparous do not experience these protective effects. RISK FACTORS FOR BREAST CARCINOMA Dietary fat Alcohol Race Geographic influence – Migrants tend to adopt pattern of host country Exposure to oestrogen Genetics RISK FACTORS FOR BREAST CARCINOMA Carcinoma of the contra-lateral breast or endometrium Atypical epithelial hyperplasia – 1.5- 2x relative risk epithelial hyperplasia of usual type – 4-5x relative risk atypical ductal hyperplasia – Double relative risk with positive family history AETIOLOGY AND PATHOGENESIS Hormonal- sporadic Genetics- hereditary HORMONAL- SPORADIC Age at menarche and menopause, reproductive history, breast feeding (protective) Exogenous oestrogens – Hormone replacement therapy Relative risk increases by 1.02/year of treatment Risk persists for 5 years after cessation Type of preparation important (e.g. type of progestogen) – Oral contraceptive pills or the injectable contraceptive Depo- Provera - very small increased risk OESTROGEN INCREASES THE RISK OF BREAST CANCER Mechanisms – Oestrogen→ proliferation of pre-malignant lesions and cancers – Metabolites of oestrogen – Most hormonal sporadic cancers occur in postmenopausal women and are ER positive Metabolites of oestrogen can contribute to the development of breast cancer by promoting the growth and proliferation of breast cells. Oestrogen is metabolized in the liver into various metabolites, including 2-hydroxyestrone (2-OHE1) and 16α- hydroxyestrone (16α-OHE1). 2-OHE1 is considered to have a protective effect against breast cancer, as it has weaker oestrogenic activity and is less likely to promote the growth of breast cells. In contrast, 16α-OHE1 has stronger oestrogenic activity and has been shown to promote the growth and proliferation of breast cells.  HEREDITARY BREAST CANCER BRCA1 High risk also for ovarian cancer Carriers susceptible to other cancers (colon, prostate and pancreas) Breast cancers tend to have medullary features, ER-, Her2- Difficult to visualise on mammogram BRCA2 Higher risk of male breast cancer Carriers susceptible to other cancers (colon, prostate and pancreas) Breast cancers more similar to sporadic cancers Visible on mammogram TP53 Li-Fraumeni syndrome PTEN Cowden disease GENETIC FACTORS - HEREDITARY BREAST CANCER Suspect familial syndrome if: – Multiple first-degree relatives of breast carcinoma – Tumour at pre-menopausal age (less than 40) – Multiple tumours Bilateral breast cancer, breast and ovarian cancer, male breast cancer, breast cancer