Breast Cancer Webinar Topic PDF

MINDANAO STATE UNIVERSITY GENERAL SANTOS CITY COLLEGE OF MEDICINE BREAST CANCER WEBINAR TOPIC: MEdicine II September 26, 2024  introduction/background Breast cancer is a malignant proliferation of epithelial cells lining t...

MINDANAO STATE UNIVERSITY GENERAL SANTOS CITY COLLEGE OF MEDICINE BREAST CANCER WEBINAR TOPIC: MEdicine II September 26, 2024  introduction/background Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. Epithelial malignancies of the breast PICTURE DEPENDS ON YOUR are the most common cause of cancer DISCRETION in women (excluding skin cancer) Accounting for about 1/3 of all cancer in women. Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622) Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  introduction/background Subtypes: Expression of the estrogen receptor (ER) Human epidermal growth factor receptor type 2 (HER2) Germline or somatic mutations in inherited tumor suppressor genes, such as BRCA1 and BRCA2. PICTURE DEPENDS ON YOUR DISCRETION Somatic mutations: mammalian target of rapamycin (mTOR) cyclin-dependent kinase 4 and 6 (CDK4/6) S-phosphatidylinositol-4,5- bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  EPIDEMIOLOGY & RISK FACTORS Clinical, Hormonal, and Other Nongenetic Risk Factors Age: 75% of all breast cancers occur in women aged >50 years, Risk is higher in women with early menarche (35 years) Sex: Female-to-male ratio is ~150:1. Hormonal exposure: Relative exposure to both endogenous and exogenous estrogens increases risk of breast cancer. Hormone replacement therapy (HRT) with conjugated equine estrogens plus progestins increases the risk of breast cancer. Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  EPIDEMIOLOGY & RISK FACTORS Clinical, Hormonal, and Other Nongenetic Risk Factors Central obesity, metabolic syndrome, and type 2 diabetes mellitus Moderate alcohol intake Depression Benign breast pathologic findings, such as atypical hyperplasia and radial scars Prior radiation 30yo - minimal carcinogenic effect on the breast. Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  EPIDEMIOLOGY & RISK FACTORS INHERITED GERMLINE SUSCEPTIBILITY FACTORS Family history A woman with a first-degree history of breast cancer has an increased relative risk of approximately 30–50% Inherited, germline genetic differences among individuals Often called mutations but are properly termed single nucleotide polymorphisms (SNPs) If an SNP leads to an amino acid substitution that alters the protein function or results in complete cessation of transcription or translation (a “stop” codon), it is considered deleterious and leads to higher susceptibility to developing cancer. Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  EPIDEMIOLOGY & RISK FACTORS INHERITED GERMLINE SUSCEPTIBILITY FACTORS Acquired, somatic genetic changes within cancers. Somatic genetic changes that are not inherited, including: mutations amplifications insertions deletions translocations Others responsible for the malignant behavior of a cancer Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  EPIDEMIOLOGY & RISK FACTORS The BRCA1 and BRCA2 genes located on chromosomal loci 17q21 and 13q12, respectively are the best characterized breast cancer susceptibility genes and have the greatest clinical importance Women who inherit mutated alleles at least a 60–80% lifetime chance of developing breast cancer about a 33% chance of developing ovarian cancer. Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  EPIDEMIOLOGY & RISK FACTORS BRCA1 BRCA2 Patients are almost exclusively Patients are more likely to be ER negative for ER, progesterone positive. receptor (PgR), and HER2 (so-called The incidence of BRCA2 mutations “triple-negative” breast cancers). is much higher than BRCA1 in men Men who carry a mutant allele of who develop breast cancer the gene have an increased incidence of breast and also prostate cancers Other inherited germline mutations in known or putative tumor-suppressor genes: p53 - accounts in part for the Li-Fraumeni familial cancer syndrome PTEN - accounts for Cowden’s syndrome PALB1 Harrison, T. R., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.). (2022). Harrison's principles of internal medicine (21st ed.). McGraw-Hill Education. (page 621-622)  EPIDEMIOLOGY & RISK FACTORS Panel assays Has a family member who has been tested and found to harbor a deleterious SNP in a germline tumor-suppressor gene. Any breast cancer patient with a triple- negative breast cancer