Metastatic Breast Cancer What is new? Subtypes and variation? Anne Blaes, MD, MS University of Minnesota, Division of Hematology/Oncology Director, Adult Cancer Survivor Program Current estimates for metastatic breast cancer Approximately 6 10% of newly diagnosed breast cancers are stage IV at diagnosis It is estimated that 20 30% of all early breast cancer cases will become metastatic >155,000 people are living with metastatic breast cancer in the U.S. Median survival after a diagnosis of Stage IV breast cancer is 3 years; this has doubled since 1970 5 year survival rate = 22% www.mbcn.org
Goals of Therapy Prolong overall survival without diminishing quality of life Reduce the symptoms caused by the tumor Strategy: Treat until disease progression or toxicity, then change therapy. *Consider biopsying metastatic disease there is up to a 20% discrepancy in receptor status between the primary breast tumor and distant disease. Not all breast cancer is the same Carey JAMA 2006;295:2492 2502.
ER positive 75% HER2 + 15% Triple Negative 15% Carey JAMA 2006;295:2492 2502. Estrogen receptor positive metastatic breast cancer
Krop, Ian Harvard Medical School Krop, Ian Harvard Medical School
Krop, Ian Harvard Medical School Tamoxifen Aromatase Inhibitors Fulvestrant Estradiol Estrogen receptor Tamoxifen
Premenopausal First Line: Ovarian suppression or oophorectomy Tamoxifen Aromatase Inhibitor Palbociclib + Letrozole OR OR Ribociclib + Letrozole Postmenopausal First Line: Palbociclib + Letrozole Anastrozole Letrozole Exemestane Ribociclib + Letrozole Fulvestrant Tamoxifen
Cyclin Dependent Kinase (CDK) Inhibitors 2013 Nature Education Cyclin Dependent Kinase (CDK) Inhibitors Palbociclib Ribociclib Abemaciclib 2013 Nature Education
PALOMA-1 Finn RS. Lancet Oncol 2015;16:25 35 PALOMA-1 Median Progression -free Survival P + L = 20.2 mos L = 10.2 mos Finn RS. Lancet Oncol 2015;16:25 35
Abemaciclib + fulvestrant September, 2017 PFS: 22.4 months vs 10.2 months Ribociclib April, 2017 Sledge JCO 2017; 35(25):2875 2884. Endocrine Resistance Cell Growth Krop, Ian Harvard Medical School
Overcoming Endocrine resistance Everolimus motility Estrogen Receptor PI3K Akt mtor proliferation survival Overcoming Endocrine resistance Everolimus Everolimus Estrogen Receptor PI3K Akt mtor motility proliferation survival
BOLERO-2 Baselga J. NEJM 2012;366:520 9. BOLERO-2 Median Progressionfree Survival Ev + Ex = 10.6 mos Ex = 4.1 mos Baselga J. NEJM 2012;366:520 9.
Side effects of Anti Estrogen Therapy Hot Flashes Vaginal discharge/dryness Muscle and joint aches and pains (AI) Mood disturbances Weight gain Thinning of the bones (AI) Blood clots (TAM) HER2 Positive Metastatic breast Cancer
HER2 amplification www.aboutcancer.com HER2 targeted therapy Trastuzumab (Herceptin) November, 2006 Pertuzumab (Perjeta) June, 2012 Ado trastuzumab emtansine (Kadcyla) February, 2013 Lapatinib (Tykerb) March, 2007 Neratinib (Nerlynx) July 2017 for adjuvant treatment
CLEOPATRA Median overall survival with pertuzumab 56.5 months vs 40.8 months in the control arm Baselga NEJM 2012; 366(2):109 19. KADCYLA (ado trastuzumab emtansine, T DMI) Genentech, USA Inc 2017
EMILIA Median OS on T DM1 was 29.9 months vs 25.9 months on capecitabine and lapatinib Verma NEJM 2012; 367(19):1783 91. Summary HER2 therapy for metastatic breast cancer Herceptin, pertuzumab, taxane Herceptin, pertuzumab, endocrine Adotrastuzumab emtansine Capecitabine + Lapatinib Herceptin + Lapatinib Herceptin, everolimus, vinorelbine Herceptin + chemotherapy
Side effects HER2 targeted therapy Congestive Heart Failure (fatigue, shortness of breath, leg swelling) Diarrhea (more severe with lapatinib and neratinib) Hand foot syndrome (lapatinib) Rash Triple Negative and hormone refractory Metastatic breast Cancer
Breast Care Center of Miami Smorgasbord of treatment options Doxorubicin Paclitaxel Docetaxel Abraxane Xeloda Vinorelbine Carboplatin Pembrolizumab PARP inhibitors Gemcitabine Eribulin Ixabepilone Doxil
Immune therapy in triple negative breast cancer PD L1 Immune Cell Cancer Cell Immune Cell Cancer Cell Blockade of PD-1 or CTLA-4 Signaling in Tumor Immunotherapy. Ribas A. N Engl J Med 2012;366:2517-2519.
Pembrolizumab Immune therapy in triple negative breast cancer ORR = 18.5% Mediation duration of response not reached. Nanda et al. 2016; 34(21): 2460 67
Summary Triple Negative or Hormone Refractory Taxane Xeloda Anthracycline Eribulin Ixempra Vinorelbine Gemcitabine Abraxane Doxil Pembrolizumab Carboplatin Olaparib
Summary Prognosis and sites of metastases vary by breast cancer subtype Breast cancer subtypes help guide treatments Treatments and treatment related side effects vary by breast cancer subtype No two breast cancers are the same. The search for new subtypes is ongoing Supportive Care and Survivorship As we all know, there are a number of side effects from treatments but also from breast cancer With > 65% of individuals living > 5 years with their cancer diagnosis, addressing symptoms, psychological support, financial/job support, etc is essential
Thank You 13th Annual Cancer Survivorship Conference Date: May 5, 2018 Time: 8 a.m. 1:30 p.m. Location: McNamara Alumni Center, 200 Oak Street SE, Minneapolis, MN Details: Save the date for this free educational conference focused on questions and issues survivors and their families often face after cancer treatment Registration: https://www.cancer.umn.edu/newsevents/events/save date annual cancersurvivorship conference