Kembara Xtra - Medicine - Breast Cancer
Introduction The second most common cause of CA death for American women and the cancer (CA) in which women are most frequently diagnosed. In the United States, women have a 2.6%, or 1 in 39, risk of dying from breast cancer. Malignant neoplasm of breast-specific cells, whether stromal, glandular, or epithelial. Types: phyllodes tumor, inflammatory breast cancer (BC), angiosarcoma, infiltrating ductal carcinoma, infiltrating lobular carcinoma, Paget disease Incidence and prevalence in Epidemiology Incidence Estimated new female DCIS: 49,290; invasive BC: 281,550 in 2021 Estimated deaths in 2021: females Recent years have seen an increase in BC incidence rates of 0.5% each year. Prevalence In the US, there are over 3.8 million breast cancer survivors. Pathophysiology BRCA1 and BRCA2 are tumor-suppressor genes that cause cell cycle progression and restrictions on DNA repair when they are mutated. Mutations in estrogen/progesterone cause the production of cyclin D1 and c-Myc, which promotes cell cycle progression. Epidermal growth factor receptors (EGFR) and other cancers (33%) may interact, resulting in comparable aberrant cellular replication. Genetics BC (breast cancer) at age 50 years BC at any age Criteria for extra risk evaluation/gene testing in afflicted BC (breast cancer) individuals 1 member of the family has ovarian/fallopian tube/primary peritoneal CA or BC 50 years of age. Two family members suffer with BC or pancreatic CA. Population at increased risk (e.g., Ashkenazi Jews with BC or ovarian CA at any age) - Triple-negative BC (ER, PR, HER2) - Two BC primaries - Ovarian/fallopian tube/primary peritoneal CA - 1 family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, central nervous system, diffuse gastric, aggressive prostate (Gleason >7), leukemia, Criteria for additional risk assessment/gene testing in unaffected BC individuals - First- or second-degree relative with BC 45 years of age - Two breast primaries in one person - One ovary, one fallopian tube, and one primary peritoneal cancer from the same side of the family - Two with breast primaries on the same side of the family - One family member with BC and cancers of the thyroid, adrenal cortex, endometrium, pancreas, - A BRCA mutation increases the risk from 7% at age 70 to 45–65% today. Risk Factors Hormone replacement therapy during perimenopause (combination estrogenprogesterone and estrogen only agents [but not vaginal estrogen]) raises the risk of breast cancer for ten years after the prescription is stopped. Relative risk (RR) >4.0: >65 years old - Atypical hyperplasia was detected by a biopsy. - DCIS - Lobular cancer in situ (LCIS) - BRCA mutation - A 40-year personal history with early-onset BC - Early diagnosis in 2 first-degree relatives (RR 2.1–4.0) - A 40+ year personal history of BC - First-degree relative of BC who is postmenopausal, has radiation history, and has an RR of 1.1 to 2.0: - Ashkenazi use of alcohol Jewish ancestry - Exposure to diethylstilbestrol - Early menarche (age 12 or younger) - Late menopause (over the age of 55) High socioeconomic status - First pregnancy at or after 30 years of age - Proliferative breast disease without atypia (ductal hyperplasia or fibroadenoma) - Dense breast tissue (> 50%) - Obesity history - Nulliparous/no history of full-term pregnancies - No history of breastfeeding - Endometrial or ovarian CA history The use of hormone replacement treatment - Recent usage of an oral contraceptive pill - Height: tall Patients with a 20–25% lifetime risk should start getting an MRI every year at age 30: - A first-degree relative who has the BRCA mutation - Radiation history between the ages of 10 and 30 Patients having a 15-20% lifetime risk: - Li-Fraumeni or Cowden syndrome, or first-degree relatives with the same: - A history of dense or unevenly thick breasts, including BC, DCIS, LCIS, atypical ductal hyperplasia, and atypical lobular hyperplasia Prevention Maintain a healthy weight—obesity raises the risk of BC; a balanced diet and regular exercise are essential. Limit your alcohol consumption to one serving each day. Consider vitamin D supplementation; high serum 25-OH vitamin D levels are associated with a decreased risk of breast cancer. The U.S. Preventative Services Task Force (USPSTF) advises clinicians to offer to prescribe risk-reducing drugs, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for negative drug effects (B recommendation). – Risk can be calculated using the National Cancer Institute Risk Assessment Tool. – Where the risk of medication hazards is modest, greater risk was considered as >3%. The American Cancer Society no longer advises routine monthly breast self-examinations (BSE). Clinical breast examination (CBE) Inadequate evidence to evaluate clinical benefits and hazards, according to the USPSTF - American Cancer Society (ACS): There are no systematic recommendations or obvious benefits for women at average risk. Mammography: The USPSTF recommends that women have a biennial mammography starting at age 50 and continuing until age 74. According to the American Cancer Society, women should begin having annual mammograms at age 45 and continue doing so until they are 54. After that, women should get biennial mammograms until they are 55. Women between the ages of 40 and 44 can choose to start getting yearly screening mammograms. Accompanying Conditions Genetic disorders and mutations like Li-Fraumeni, BRCA1, BRCA2, and Cowden disease A history of high-risk breast abnormalities, such as LCIS, atypical lobular hyperplasia, and atypical ductal hyperplasia Skin swelling, thickness, redness, or dimpling; a painless lump in the breast or axilla; a nipple discharge that is bloody, eroding, or retracts; abnormal findings or calcifications on screening mammography clinical assessment Look for skin dimpling, peau d'orange, and asymmetry while picturing the patient's breasts while they are seated and lying down. Examination involves the cervical, supraclavicular, infraclavicular, and axillary lymph nodes as well as palpation of all four breast quadrants. Benign breast disease differential diagnosis: - Fibroadenoma - Fibrocystic illness - Intraductal papilloma (bleeding from the nipples) Duct ectasia and an easy cyst Fat necrosis (history of serial/parallel breast trauma) and sclerosing adenosis An infection (mastitis, cellulitis, abscess) Diagnostic tests and lab investigations Mammography (MMG) is one of the initial tests (lab and imaging) The American Radiology Society has produced a quality assurance (QA) technique called BI-RADS: Breast Imaging-Reporting and Data System. Breast US and MRI interpretation are now included with BI-RADS. – Parts of the BI-RADS report: The purpose of the study and the sort of test The general makeup of the breasts, especially breast density Uses common BI-RADS descriptions to describe anomalies and significant findings: A—almost completely fatty tissue in the breasts; B—scattered patches of fibroglandular density; C—heterogenously dense; D—extremely dense. Comparing current photos to earlier ones and providing a summary report that includes the final BI-RADS assessment category BI-RADS 0: incomplete; more imaging evaluation is required; frequently seen in screening studies BI-RADS 1: unfavorable Maintain the current screening recommendations BI-RADS 2: benign; no further treatment is required; BI-RADS 3: likely benign; 2% chance of malignancy For the first year, follow-up imaging should be done every six months; for the following year, imaging should be done every six to twelve months. If the patient is worried or the follow-up is unknown, biopsy may be considered. The patient and doctor should talk about potential management strategies and probably a biopsy. Diagnostic imaging is required, followed by a biopsy, and BI-RADS 5: highly suggestive of malignancy. BI-RADS 6: known biopsy—proven malignancy. Calcifications on screening mammography need to be investigated with diagnostic mammography (Dx MMG) and stereotactic guided biopsy. This group of patients also includes those who have yet to have surgical removal of malignancies that have been detected by biopsy. Examining palpable masses - Palpable bulk 30 years or older To distinguish between cystic and solid conditions, obtain Dx MMG and US. Get a US biopsy if BI-RADS 1 to 3 are present. If the BI-RADS score is between 4 and 6, a surgical excision should be performed. - Palpable bulk 30 years or older Get a US diagnosis of MMG and a biopsy. If there is little clinical suspicion, one or two menstrual cycles may be used to monitor for improvement. Natural, repeatable nipple discharge: Obtain US Dx MMG. If the test is negative, you might want to pursue an MRI or surgical excision. - 30 year old with asymmetric thickening/nodularity: obtain US; diagnose MMG; biopsy. - 30-year-old with asymmetric thickening/nodularity: get a Dx MMG+ US biopsy. - Skin alterations, peau d'orange: Obtain a US biopsy for an underlying mass with a diagnosis of MMG. Perform a punch biopsy of the skin change if there is no mass. Get a CT scan of your chest, abdomen/pelvis, and bones if you have palpable lymph nodes. Tests in the Future & Special Considerations Stage IIIA or higher disease (advanced disease): Most common sites of metastasis are the lungs, liver, bone, and brain. Diagnostic tests include a bone scan if there is localized bone pain or elevated alkaline phosphate, an abdominal or pelvic CT if there are abdominal symptoms, elevated alkaline phosphate, or abnormal LFTs, a chest CT if there are pulmonary symptoms, and a brain or spine MRI if there are CNS/spinal cord symptoms. Other/Diagnostic Procedures When performing a workup, axillary lymph nodes should be ultrasounded, and if any worrisome nodes are found, a core needle biopsy or FNA should be performed. Otherwise, the index procedure should include a sentinel lymph node biopsy. Bruising, reactive lymph nodes, or hematoma Results from surgical pathology should be noted when interpreting tests: – Ductal/lobular/other - Intrusive vs. nonintrusive the margins - Nodal participation ER, PR, and HER2 assay results for tumor receptor status Neoadjuvant chemotherapy is one form of treatment. Early operable BC that is locally progressed (large tumor and/or positive lymph nodes) to enable breast conserving surgery - Triple negative BC and tumor size greater than 0.5 cm - HER2 (+) cancers smaller than 2 cm and lymph nodes that are positive In ER/PR(+) tumors with () nodes, the 21-gene PT-PCR assay should be taken into consideration. Dose-dense treatment shows an overall survival advantage in early BC. - For HER2 negative BC, doxorubicin/cyclophosphamide (AC) weekly or every two weeks paclitaxel HER2/neu-positive individuals with anti-HER2/neu antibodies (such as trastuzumab with or without pertuzumab) ISSUES FOR REFERRAL Prior to starting chemotherapy, premenopausal women should be sent to a reproductive specialist. Further Treatments Patients undergoing breast conservation treatment (BCT) should be administered whole breast radiation following surgery and chemotherapy before beginning endocrine therapy. - The overall survival after mastectomy and lumpectomy plus RT is comparable. - Postmastectomy RT is an option if the tumor is more than 5 cm, less than one lymph node is affected, the chest wall or skin is implicated, or clear margins cannot be obtained. DCIS and hormone treatment for ER+ tumors: Tamoxifen 200mg per day for five years Age 60 and postmenopausal: aromatase inhibitors (AI) may be used. Age > 60: Equal efficacy of selective estrogen receptor modulator (SERM) or AI – aggressive cancer Premenopausal at diagnosis; SERM (tamoxifen 20 mg QD); 5-year treatment; consider an additional 5-year course. Postmenopausal women should take aromatase inhibitors (anastrozole 1 mg QD, letrozole 2.5 mg QD, and exemestane 25 mg QD) for five years after receiving endocrine therapy for 4.5 to six years or for up to ten years. Advanced disease: Cytotoxic treatment and hormone therapy - Skeletal issues associated with bisphosphonates - Anti-HER2/neu antibody in a subset of HER2/neupositive individuals - Anti-vascular endothelial growth factor (anti-VEGF) antibody pregnant women's issues The type of treatment changes every trimester. Breast conservation surgery (BCT), which can be performed at any point during pregnancy, may necessitate delaying adjuvant radiation therapy (RT). Surgical Techniques If negative margins can be obtained, breast-conserving therapy (lumpectomy) is recommended, and the patient will additionally get adjuvant RT. Multicentric disease, a significant tumor-to-breast ratio, inflammatory BC, T4 disease, contraindication to RT, and patient desire all call for mastectomy. All individuals with clinically suspect axillary nodes should have their axillary nodes evaluated with preoperative ultrasound and biopsy. An axillary node dissection should be done if the biopsy results are positive. No evidence exists to support the use of routine complete blood counts, LFTs, "tumor markers," bone scans, chest x-rays, liver ultrasounds, CT scans, MRIs, or PET scans. Annual gynecologic examination for women on endocrine medication; baseline and follow-up measurements of bone mineral density while taking aromatase inhibitors or having ovarian failure as a result of treatment Active living, a balanced diet, and moderate alcohol consumption 5-year survival prediction (SEER 18, all genders, all races) Localized:98.8%; Regional:85.5%; Faraway:27.4%; Unknown:54.5%; All stages:89.9%
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