EARLY • Carika Fourie BREAST • Radiation CANCER Oncology CASE 14 February 2018 T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
CASE • 71 year old lady • Presentation: General practitioner with a painless breast lump in left breast for 3 months. • Referred to Pelonomi Hospital for work up. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
HISTORY: • Comorbidities: Hypertention on treatment for 10 years • Hydrochlorothiazide 25mg daily and Enalapril 5mg daily • Gyneacology: 3 children. No miscarriages. Never used hormonal contraception. Postmenopausal for 19 years. • Previous knee replacement in 2011. • Allergic to penicillin. • Social: smoker, 30 pack years • Family history: Parents: Hypertention. Father died of myocardial infarction at 57. Mother died of old age. Aunt: breast cancer at age 75. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
CLINICAL EXAM: • ECOG PS 1 • General: No lymphadenopathy, pallor or jaundice • Breast: L breast: 2 cm nodule in superolateral quadrant. No skin involvement. R breast: no masses • Chest: Good bilateral air entry. No added sounds • CVS: No tachycardia. S1S2 heart sounds normal. • Abdomen: Soft. No organomegaly. • Neuro: GCS 15/15. No localizing signs. Normal power in all limbs. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
HISTOLOGY: BIOPSY • Tru cut biopsy (6/9/17) • Grade 2 invasive ductal carcinoma • ER >90% • PR >90% • Her 2 negative Subsequently had a left mastectomy and axillary dissection. Patient chose not to have breast conservation. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
SPECIAL INVESTIGATIONS: • Mammogram: Bi-RADS B breast density. Poorly circumscribed lesion in the superolateral quadrant measuring 2 cm with increased density and pleomorphic calcifications. Ultrasound: Hypoechoic spiculated mass. Birads 4 lesion. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
HISTOLOGY: MASTECTOMY AND NODES Macroscopy: • Skin: Normal • Nipple: no Paget’s • Single tumor nodule in superolateral quadrant • Tumor size: 20 x 16 x14mm • Surgical margins: Uninvolved, 5mm from closest surgical margin T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
HISTOLOGY: MASTECTOMY AND NODES Microscopy: • No DCIS present • Lymphovascular invasion • 0/13 lymphnodes involved • Ki 67 : 40% pT1cpN0, ER/PR positive, HER2 Negative T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
PREDICT UK: • Age • Symptomatic/not • Tumor size • Histological grading • Nodal status • ER receptor status • Her 2 receptor status • Ki 67 T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
PREDICT UK: 5 year survival: • 87% with no adjuvant therapy • 89% with hormone therapy alone • 89% with chemotherapy and hormone therapy Ten year survival: • 68% with no adjuvant therapy • 71% with hormone therapy alone • 73% with chemotherapy and hormone therapy T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
1 . DO WE NEED A MIND SHIFT IN OUR APPROACH TO ADJUVANT CHEMOTHERAPY IN EARLY BREAST CANCER? 2. SHOULD GENETIC PROFILING BE DONE FOR ALL EARLY BREAST CANCER PATIENTS? WHAT ARE THE COST IMPLICATIONS? IS IT FEASIBLE, ESPECIALLY FOR STATE SECTOR? 3. WHAT IS THE ROLE OF KI-67 IN GENETIC PROFILING? 4. ARE WE FINALLY MOVING TOWARDS AN ERA OF INDIVIDUALIZED TREATMENT? 5. WHAT IS THE IDEAL THERAPY FOR THIS PATIENT?
TREATMENT: • No chemotherapy • No radiotherapy • Started on Tamoxifen 20mg daily orally for 10 years T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
IDEAL: • Recurrence Score(Oncotype Dx): Best validated. Place for adjuvant chemotherapy. Indicated: ER positive, node negative and HER2 negative. Low risk <18. 13 (Tailorx trial: intermediate and high RS cutoffs). Node positive: Plan B study, SWOG S1007 RxPONDER trial, ongoing. • EndoPredict • Predictor Analysis of Microarray 50 (PAM50): predict susceptibility of HER2 overexpressed tumors to respond to HER2 directed therapy. 14 • Breast Cancer index • Mammaprint: 70 gene prognostic profile. Node positive tumors. MINDACT trial: may identify a subset of patients with low likelihood of distant recurrence despite high risk features. 14 T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
Thank You T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
ADJUVANT THERAPY • Reduction in mortality • Overtreated T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
GENETICS • Prognostic and predictive markers • Risk profile • Determine benefit of adjuvant treatment • Prevent overtreatment of patients T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
PROGNOSTIC FACTORS: Clinical: • Age: <35 worse 5 year survival. 2 Elderly patients with hormone receptor positive breast cancer have a higher disease specific mortality 3 • Race: black women have a lower incidence of breast cancer than white women but a higher mortality 4 • Sigarette smoke: Increased mortality in smokers 5 Mammographic: • Screen detected breast cancer has improved overall survival compared to clinically detected. 6 T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
Pathological features: • Tumor size: Increased size correlates with worse prognosis and inflammatory breast cancer even worse. 7 • Nodal involvement: Even in patients with small tumors the prognosis is worse with nodal spread. 8 • Metastatic disease • Tumor morphology: ILC has a lower risk of recurrence than IDC 9 • Histological grade: Elston-Ellis grading system. Higher grade is associated with worse prognosis. 10 • Peritumoral lymphovascular invasion: Unclear T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
Tissue Markers: • Hormone receptors: Estrogen and progesterone receptors expression are ass with improved outcomes. • HER2 overexpression: Worse prognosis T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
GENOMIC PROFILES • Gene expression profiling: measures expression of thousands of genes in a breast cancer cell. • Identified subtypes with different prognoses. • Luminal subtypes: ass with luminal epithelial cells of normal breast tissue • Luminal A: (40%). High expression of ER related genes. Low Her2 gene expression and low expression of proliferative genes. 11 • Luminal B: (20%). Lower expression of ER related genes. Variable expression of Her2 gene clusters and high expression of proliferation genes. Worse prognosis than Luminal A. 12 • HER2 enriched: (10-15%). High expression Her2 cluster genes as well as proliferation gene clusters and low expression of luminal and basal clusters. Mostly ER and PR negative. And HER2 overexpressed. • ER negative subtypes: Basal-like, claudin-low and interferon rich among others. Basal type(15-20%). Typically triple negative T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
PROLIFERATIVE MARKERS: • Ki67: Higher relapse risk and worse overall survival. 16 Heterogeneity and inconsistence of methodology of laboratories. 17 ASCO does not recommend its use in assessment of prognosis. • Urokinase plasminogen activator system: needs validation • P53: due to false detection rate, not recommended. • Disseminated tumor cells: Assistance in determining role of adjuvant chemotherapy not established. 18 • Circulating tumor cells: Associated with poor prognosis 19 However, role in clinical care and monitoring is uncertain and not evaluated routinely. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
BIOMARKER ASSAYS • Recurrence Score(Oncotype Dx): Best validated. Place for adjuvant chemotherapy. Indicated: ER positive, node negative and HER2 negative. Low risk <18. 13 (Tailorx trial: intermediate and high RS cutoffs). Node positive: Plan B study, SWOG S1007 RxPONDER trial, ongoing. • EndoPredict • Predictor Analysis of Microarray 50 (PAM50): predict susceptibility of HER2 overexpressed tumors to respond to HER2 directed therapy. 14 • Breast Cancer index • Mammaprint: 70 gene prognostic profile. Node positive tumors. MINDACT trial: may identify a subset of patients with low likelyhood of distant recurrence despite high risk features. 14 T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
CONCLUSION • Prognostic and predictive factors are utilized to assist in treatment decisions. • Currently genomic testing assist in early breast cancer treatment. • Genomic testing is not readily available yet. • Potential markers need to demonstrate: Analytical validity, clinical validity and clinical utility. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
Recommend
More recommend
