Disclosures. Objectives. Novel Agents in the Systemic Management of Breast Cancer (Breast Cancer Update 2012) Peter Kabos, MD

Size: px

Start display at page:

Download "Disclosures. Objectives. Novel Agents in the Systemic Management of Breast Cancer (Breast Cancer Update 2012) Peter Kabos, MD"

Joan Powers
5 years ago
Views:

Mountain States Cancer Conference 2012 Novel Agents in the Systemic Management of Breast Cancer (Breast Cancer Update 2012) Peter Kabos, MD University of Colorado Denver Disclosures No relevant

1 Mountain States Cancer Conference 2012 Novel Agents in the Systemic Management of Breast Cancer (Breast Cancer Update 2012) Peter Kabos, MD University of Colorado Denver Disclosures No relevant disclosures Off label use: venlaflexine, gabapentin, clonidine, Bisphosphonates Objectives Screening Subtypes of breast cancer Advances in molecular classifications Novel therapies Common side effects Bone health

2 SCREENING FOR BREAST CANCER Question: What is the role of MRI in breast cancer screening? 1. Every patient should have MRI for breast cancer screening 2. Every patient younger than 40 should have screening MRI 3. High risk patients should have MRI screening 4. Patients with a palpable mass should have MRI screening 5. Patients with personal history of breast cancer Probability of Developing Breast Cancer by Age Percent >85 Age Screening Mammography Gold-standard Multiple studies with survival as endpoint Decreases the chance of dying of breast cancer by at least 30% Detection rate: 5-7/1000 for first mammogram 2-3/1000 for subsequent mammograms

Summary recommendations Normal Risk Mammography annually beginning at age 40 years Clinician exam Self-exam Summary recommendations High Risk Mammography annually beginning 10 years before age of

3 Summary recommendations Normal Risk Mammography annually beginning at age 40 years Clinician exam Self-exam Summary recommendations High Risk Mammography annually beginning 10 years before age of youngest diagnosed relative Clinician exam Self-exam Consider MRI if lifetime risk greater than 20% - (h/o LCIS, AH, FH) per ACS guidelines Molecular Subtypes of Breast Cancer and Relative Prognosis ( New prognostic features) Luminal A & B Her2+ TN/Basal Sorlie et al, PNAS 2001

New breast cancer biology in clinic Breast cancer is a systemic disease at diagnosis So1riou, NEJM 2009; Sorlie, PNAS 2001 Evolution of Chemotherapy for Breast Cancer

E 1199 ddac-p C 9741 CMF = cyclophosphamide, methotrexate, fluorouraci; CEF = cyclophosphamide, epirubicin, fluorouracil; FAC = fluorouracil, doxorubicin,

4 New breast cancer biology in clinic Breast cancer is a systemic disease at diagnosis So1riou, NEJM 2009; Sorlie, PNAS 2001 Evolution of Chemotherapy for Breast Cancer CMF Milan ACx4 B-15 ATx4 TACx4 CEF/FEC MA-5/ICCG FAC GEICAM TC US 9735 AC-P C 9344 B-28 FEC-T OR P PACS-01 TACx6 BCIRG 001 BCIRG 005 AC-T E 1199 BCIRG 005 B-30 AC-Pw E 1199 ddac-p C 9741 CMF = cyclophosphamide, methotrexate, fluorouraci; CEF = cyclophosphamide, epirubicin, fluorouracil; FAC = fluorouracil, doxorubicin, cyclophosphamide. Walshe et al, 2006; Ellis, 2006; Fumoleau et al, 2003; Roche et al, 2006; Eiermann et al, 2008; Mamounas, 2005; Joensuu et al, Modified from Hudis / Jones

ER+ breast cancer Standardized Quantitative Oncotype DX Assay Recurrence Score in Node -, ER+ patients Lower RS s Lower likelihood of recurrence Greater magnitude of TAM benefit Minimal, if any,

5 ER+ breast cancer Standardized Quantitative Oncotype DX Assay Recurrence Score in Node -, ER+ patients Lower RS s Lower likelihood of recurrence Greater magnitude of TAM benefit Minimal, if any, chemotherapy benefit 1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research ) Paik et al JCO 2006, 4) Gianni et al JCO 2005 Higher RS s Greater likelihood of recurrence Lower magnitude of TAM benefit Clear chemotherapy benefit Less is more, trying to decrease long term toxicity TC docetaxel / cyclophosphamide, AC doxorubicin/ cyclophosphamide Jones S et al. JCO 2009;27: by American Society of Clinical Oncology

6 Typhlitis in a patient on chemotherapy. d Almeida M et al. Radiographics 2008;28: by Radiological Society of North America Inhibi1on of Estrogen- Dependent Growth Tamoxifen, Fulvestrant Vasomotor Dysregulation Hot flashes/ flushes Cold sweats and chills Due to antiendocrine therapy or hormone alterations due to chemo Patients decide what is enough to treat Options: Accupuncture, biofeedback venaflexine (or other SSRIs) clonidine Gabapentin NO SYSTEMIC HORMONES

7 Small steps towards personalized medicine Gnant, Current Oncol Rep 2012 mtor inhibitor everolimus approved for metastatic breast cancer Baselga et al, NEJM 2012 HER2+ breast cancer

Immunoconjugate/ADC T-DM1: Trastuzumab Emtansine Antibody Drug Conjugate (ADC) Trastuzumab is linked to an antimicrotubule drug (maytansine or DM1) for a targeted and

8 Immunoconjugate/ADC T-DM1: Trastuzumab Emtansine Antibody Drug Conjugate (ADC) Trastuzumab is linked to an antimicrotubule drug (maytansine or DM1) for a targeted and antineoplastic effect Trastuzumab binds to HER2 cancer cells, is absorbed, and then releases DM1 Burris H, et al. JCO 2011;29(4): Triple negative breast cancer

First- line metasta1c 103 irinotecan- carbo +/- cetuximab Carey et al. Baselga et al.

cetuximab RR 18%, CBR 27%, OS 12 mos 173 cispla1n +/- cetuximab RR 20% v 10% (p=0.11), PFS 3.

032) Higher gr 3/4 toxicity Nega1ve for primary endpoint Patients "selected" for TNBC Need

Breast Cancer Res Treat 2007, Carey et al ASCO 2008 abstract 1009, Baselga et al.

9 EGFR inhibitors in TNBC Study Se<ng No. of Treatment Response (%) Comments with O'Shaughnessy et al. First- line metasta1c 103 irinotecan- carbo +/- cetuximab Carey et al. Baselga et al. Previously treated metasta1c Previously treated metasta1c (1 prior) RR 49% v 30% 102 carbo + cetuximab RR 18%, CBR 27%, OS 12 mos 173 cispla1n +/- cetuximab RR 20% v 10% (p=0.11), PFS 3.7mos v 1.5 mos (p = 0.032) Higher gr 3/4 toxicity Nega1ve for primary endpoint Patients "selected" for TNBC Need better patient selection strategies O'Shaughnessy et al. Breast Cancer Res Treat 2007, Carey et al ASCO 2008 abstract 1009, Baselga et al. ESMO 2010 abstract PARP inhibitors in TNBC Phase II Study of Olaparib in BRCA1/2 Mutated Advanced Breast Cancer Tutt et al 2010 Aurora kinases are integral in mito1c cell division Prophase Metaphase Anaphase Aurora A Aurora B Adapted from Keen et al. Nature Reviews Cancer 4: , 2004

10 Cancer-Related Fatigue An unusual, persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning and is different from usual fatigue as it is not relieved by rest and sleep What does it look like? Subjective and Objective components Physical weakness or tiredness Depression or negative alteration of mood Lack of normal motivation or initiative Impairment of cognitive function Alteration of ability to sustain social relationships Options for combating fatigue?drugs Rule out compounding issues Thyroid Anemia Vitamin D EXERCISE Walking yoga

Breast Cancer Treatment Related Bone Loss Zoladex Gonadotrophins (FSH + LH) Estrogens Ovary Tamoxifen LHRH (hypothalamus) Pituitary gland Adrenal glands Androgens Estrogens ACTH Anastrozole ACTH =

11 Breast Cancer Treatment Related Bone Loss Zoladex Gonadotrophins (FSH + LH) Estrogens Ovary Tamoxifen LHRH (hypothalamus) Pituitary gland Adrenal glands Androgens Estrogens ACTH Anastrozole ACTH = adrenocorticotrophic hormone; FSH = follicle-stimulating hormone; LH = luteinising hormone; LHRH = LH-releasing hormone Peripheral conversion (aromatase enzyme) Recommended management strategy for patients with diagnosed nonmetastatic breast cancer. Hillner B E et al. JCO 2003;21: by American Society of Clinical Oncology Osteoimmunologic interactions between osteoblasts and osteoclasts Terpos 2011

12 Monitoring for Metastatic Disease the asymptomatic patient NCCN and ASCO guidelines Physical exam q 6 months LFTs and CBC q 6-12 months No routine scans besides breast imaging No tumor markers or The best way to minimize treatment related side effects is to only give treatment to those patients who will truly benefit from it. Thank you

COME HOME Innovative Oncology Business Solutions, Inc.

COME HOME Innovative Oncology Business Solutions, Inc. Innovative Oncology Business Solutions, Inc. Breast Cancer Diagnostic/Therapeutic Pathway V11, April 2015 Required Structured Data Fields: ICD9 Code Stage Staging Components Performance Status Treatment