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Breast Cancer: Updates in systemic therapy options

Breast Cancer: Updates in systemic therapy options. Hope Qamoos, NP Breast Oncology Stanford Hospital and Clinics. Breast Cancer: Updates in systemic therapy options Course Objectives. Identify the treatment options available to treat the following subtypes of breast cancer

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Breast Cancer: Updates in systemic therapy options

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  1. Breast Cancer: Updates in systemic therapy options Hope Qamoos, NP Breast Oncology Stanford Hospital and Clinics

  2. Breast Cancer: Updates in systemic therapy optionsCourse Objectives • Identify the treatment options available to treat the following subtypes of breast cancer • Hormone receptor positive • Her2 positive • Triple Negative • BRCA ½ mutated • Identify specific side effects and risks associated with each treatment modality

  3. Breast Cancer • Statistics: Second leading cause of cancer death 1 in 8 women will be diagnosed with breast cancer in their lifetime. • Incidence increases with age with most breast cancers occurring after the age of 50. Incidence drops again after the age of 80. • Approximately 80% of breast cancers are hormone receptor positive • Approximately 15-20% of breast cancers are triple negative • Approximately 15-20% of breast cancers are HER2 positive

  4. Breast Cancer • Stages I-IIIB are treated with curative intent • T-size of in breast tumor • N-nodal involvement • M-distant metastasis outside of the local-regional area • Stage IV is considered incurable, treatment is focused on palliation. • Patient considerations • Early stage or curable disease could consider more aggressive treatment with multi-agent chemotherapy in order to create higher chance of cure • Metastatic breast cancer, typically treated with targeted and single-agent chemotherapy with focus on palliation and quality of life.

  5. Breast Cancer • Systemic Therapy choices based on Stage and characteristics of tumor type. • Hormone receptor positive breast cancer • Any ER or PR positivity • Her2 testing • IHC and FISH • Triple Negative • BRCA1/2 mutations

  6. Hormone Receptor Positive • Neo-adjuvant vs Adjuvant therapy • Oncotype 70 gene assay • Node negative ER/PR positive, Her 2 negative • Low, intermediate, high risk of recurrence • Stage I-III • Chemotherapy: Gold standard regimens • DDAC-T or TC • Anti-hormone therapy

  7. Hormone Receptor Positive Endocrine Therapy: Stages I-IIIB • Tamoxifen 5 vs 10 years • ATLAS trial: 6846 women randomized to an additional 5 years of tamoxifen vs placebo. Benefit in tamoxifen group, overall survival benefit of 2.8% at 15 years. • ATTOM trial: • Aromatase Inhibitors with Ovarian Suppression • SOFT and TEXT trials

  8. Hormone Receptor Positive • Stage IV: Metastatic Breast Cancer • SERM • Tamoxifen • Toremifene • Aromatase Inhibitor • Anastrozole • Letrozole • Exemestane • Estrogen receptor modulator • Fulvestrant • MTOR inhibitors • BOLERO trials: Added everolimus with exemestane was seen to prolong progression free survival

  9. Hormone Receptor Positive Treatment Side effects • SERM (Tamoxifen, Toremifene) • Hot flashes • Vaginal dryness • Decreased libido • DVT • Uterine Cancer • Cataract development • Aromatase Inhibitors (anastrozole, letrozole, exemestane) • Joint pain • Hot flashes • Vaginal dryness • Decreased libido • Bone loss/osteopenia

  10. Hormone Receptor Positive Treatment Side effects • Estrogen receptor modulator (fulvestrant) • Pain at injection site • Hot flashes • Fatigue • Insomnia • Vaginal dryness • Decreased libido • MTOR inhibitor (everolimus) • Mucositis/stomatitis • Bone marrow suppression • Rash • Pneumonitis

  11. Her2 positive • Stage I-III • 1998 FDA approval of Herceptin in metastatic disease • HERA and PHARE trials 6m, 1 year, 2 years • NEOSPHERE and TRYPHENA study: Consider neo-adjuvant secondary to FDA approval of pertuzumab • Regimens DDAC-TH+P or TCH+P • Herceptin continues for one full year, Pertuzumab ends with surgery. • NEO-ALLTO and ALLTO trials • KATHERINE TRIAL (NSABP-B50): evaluating the use of TDM-1 in the adjuvant setting

  12. Her2 positive • Stage IV-Metastatic Breast Cancer • Herceptin with chemotherapy single agents • Lapatinib with Xeloda • Approved by the FDA 2007 • Lapatinib 1250 mg daily, Xeloda 1000 mg/m2 BID 14 days on 7 days off

  13. Her2 positive • Dual blockade of Her2 with combination Her 2 targeted therapy • CLEOPATRA: Phase III trial of Pertuzumab with Herceptin and Taxotere • Approved by the FDA 2012

  14. Her2 positive • TDM-1 • (ado emtansine trastuzumab) • Drug conjugate • EMILIA trial: February 2013 FDA approved for the use as a single agent in metastatic setting after progression while on trastuzumab • TH3RESA trial: June 2014 TDM-1 vs physician choice. • MARIANNE trial: ongoing, closed to recruitment. Testing combination of TDM-1 with pertuzumab • http://www.doctissimo.fr/html/dossiers/cancer_sein/articles/15253-t-dm1-cancer-sein.htm

  15. HER2 positive treatment side effects • Targeted therapy: • Trastuzumb and pertuzumab: • Decrease in LVEF: echo every three months • DO NOT NEED LAB WORK • Flu-like syndrome • TDM-1 • Elevated LFT’s • Thrombocytopenia • Bloody nose, easy bruising, bleeding gums, bleeding with BM • Flu-like syndrome • Mild nausea • Fatigue

  16. Triple Negative • Estrogen and Progesterone negative, Her 2 negative. • Treatment with chemotherapy Stages I-III • Neo-adjuvant or Adjuvant • DDAC-T or TC, • GeparSixto Trial: consideration of platinum based therapy • Residual Cancer Burden (RCB) score • Calculation from MD Anderson assess cellularity, amount of tumor bed, nodal involvement, percentage of DCIS • RCB 0-1 low risk of recurrence • RCB II, III intermediate risk • RCB IV high risk of recurrence • Tool can help inform the oncology team in terms of likelihood of recurrence and indication for additional chemotherapy in the adjuvant setting or with chemo-sensitizing agent

  17. Triple Negative • Stage IV Metastatic Breast cancer • Chemotherapy single agents • Consideration for single agent platinum therapy • Androgen receptor testing (AR) • Clinical trials

  18. BRCA 1/2 mutations • Platinum based therapy: DNA damaging

  19. BRCA 1/2 mutations • PARP inhibitors: veliparib, iniparib, olaparib, BMN 673 (BROCADE trial) • http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies/breastcancer_htmlcourse/page5

  20. BRCA 1/2 side effects of PARP inhibitors • Overall well tolerated as a single agent, side effects were more likely to be related to concurrent chemotherapy use • Fatigue • Nausea • Bone marrow suppression: neutropenia and anemia

  21. Future is bright • PARP inhibitors • CDK 4/6 inhibitors • SRC inhibitors • SMAC inhibitors • Mutant Her2 testing

  22. References • Andre F, O'Regan R, Ozguroglu M, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2014; 15: 580-591. • Baselga J, Cortes J, Kim S-B, et al: Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109-111, 2012 • Baselga, J., Campone, M., Piccart, M. et al. Everolimus in Postmenopausal Hormone Receptor positive Advanced Breast Cancer.New England Jounal of Medicine 2012;366:520-9. • Gelber RD, Goldhirsch A, Piccart M, et al: HERA trial: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow up. 2012 ESMO Congress. Abstract LBA6. Presented October 1, 2012. • Krop, I.E., Kim, S.B, Gonzalez-Martin, A, et al. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial.Lancet Oncology 2014;15:7 689-699. • Kummar S, Chen A, Parchment RE, et al. Advances in using PARP inhibitor to treat cancer. BMC Med. 2012;10:25. doi: 10.1186/1741-7015-10-25. - See more at: http://www.onclive.com/publications/oncology-live/2013/august-2013/new-life-for-parp-inhibitors-emerging-agents-leave-mark-at-asco/4#sthash.21DyDVeb.dpuf • Pivot X, Romieu G, Bonnefoi H, et al: PHARE trial results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. 2012 ESMO Congress. Abstract LBA5. Presented October 1, 2012. • Swain SM, Kim S-B, Cortes J, et al: Confirmatory overall survival analysis of CLEOPATRA: A randomized, double-blind, placebo-controlled Phase III study with pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive first-line metastatic breast cancer. 2012 San Antonio Breast Cancer Symposium. Abstract P5-18-26. Presented December 7, 2012. • Swain, S.M, Kim, S.B., Cortes, J. et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study Lancet Oncology 2013;14:6 461-471. • Gianni L, Pienkowski T, Im YH, et al: Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomisedmulticentre, open-label, phase 2 trial. Lancet Oncol 13:25–32, 2012. • VermaS, Miles D, Gianni L: Updated overall survival results from EMILIA, a phase 3 study of trastuzumab emtansine (T-DM1) vs capecitabine and lapatinib in HER2-positive locally advanced or metastatic breast cancer. 2012 ESMO Congress. Abstract LBA12. Presented October 1, 2012.

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