5/22/2013. PMHx: Obesity, BMI 40s LE neuropathy (no DM) GERD

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1 Guest speaker Moderator Case presentation Mandeep Mehra, MD, FACC,FACP Alan Kono, MD, FACC Alina Robert, MD, cardiology fellow PMHx: Obesity, BMI 40s LE neuropathy (no DM) GERD Fam Hx: Mother died age 88 of MI 2 brothers with HTN Sister with breast CA Maternal aunts with breast CA Social Married, works a full time and a part time job, no children 3/2010 a R breast mass was found on annual PE Core needle bx poorly differentiated infiltrating ductal carcinoma ER+ 90%/PR+ 50%, Her 2+ MRI 8x6 cm lat R breast, 6x4 cm mid-lat R breast, 3.5 cm R axillary node extensive axillary, subpectoral, supraclavic adenopathy, no distant mets Recommendations for neoadjuvant chemotherapy: Taxol (80 mg/m 2 )+ Trastuzumab (Herceptin) 2 mg/kg FEC + Trastuzumab Fluorouracil, Epirubicin 156 mg, cyclophosphamide Herceptin 2 mg/kg Trastuzumab 6 mg/kg as single agent for 52 weeks Followed by modified radical mastectomy Followed by post-mastectomy regional chest-wall radiation therapy 1

2 Human epidermal growth factor-2 gene encodes a tyrosine kinase receptor which mediates signaling in breast epithelial cells An acquired alteration in the gene results in overexpression or amplification of the receptor 20-25% of breast cancers are Her-2+ Her-2+ breast tumors have aggressive clinical course with early metastasis and decreased survival Trastuzumab is a humanized monoclonal antibody directed against the tyrosine kinase receptor in the treatment of breast tumors which overexpress human epidermal growth factor-2 Trastuzumab added to chemotherapy regimens improves response to treatment, response duration, and recurrence by 50-65% 4-5 fold increase in cardiac dysfunction was reported in studies in which Trastuzumab was added to anthracycline regimens Slamon, et al. N Engl J Med 2011;365: Pretreatment MUGA 3/19/2010: LVEF 65%, nl RV systolic fx C1: Taxol and Herceptin 3/25/2010 Paclitaxel, Herceptin 4/8/2012 C2 Taxol and Herceptin 4/15/2012 (days 1, 8, 15) Taxol hypersensitivity Rxn and neuropathy resulting in 15% dose reduction C3: Taxol, Herceptin 5/6/2010 C4: Taxol and Herceptin 2 mg/kg on days 1, 8, 15 Taxol changed to Docetaxel/taxoterene due to worsening neuropathy MUGA f/u 6/17/2010: LVEF 63%, no RWMAs 2

3 C 5: 7/8/2010 Epirubicin 156 mg Fluorouracil 1150 mg Cyclophosphamide 1150 mg Herceptin 720 mg 7/29/2010 seen in f/u in onc clinic, BLE 2+ edema worse at the end of the day, no SOB/orthopnea, held off diuretics, proceeded with cycle 6 FEC/Herceptin C 6 FEC/herceptin 7/29/2010 C 7 FEC/Herceptin 8/24/2010, recurrent edema C 8 FEC/Herceptin 9/9/2010 Total epirubicin dose ~ 300 mg/m^2 MUGA 10/5/2010: LVEF 57%, not significantly changed, nl RV systolic fx 10/7/2010: R modified radical mastectomy Post mastectomy radiation started 11/16/2010 Continued Herceptin 6 mg/kg as single agent for 52 weeks MUGA 3/3/2011 prior to last 2 cycles of Herceptin LVEF 35% Worsening fatigue, DOE with walking fast or climbing stairs no PND, orthopnea, edema, c/p, lightheadedness, 12 #s wt loss since surgery T 97.3, HR 80s, BP 118/76, RR 18, 99% RA PE remarkable for: lungs CTAB, cardiac RRR, JVP 7 cm H2O, no LE edema Pertinent meds: Motrin 800 mg tid PRN, Claritin, Nexium Labs remarkable for: Hgb 12.2, nl renal function, TnT < 0.03, CK 380, NT-proBNP 219 TTEcho: LVEF 40% (visually estimated), 45% (Simpon s Biplane), diffuse HK 1-2+/4+ MR, otherwise no sig valvular disease, nl size chambers RAP 3 mmhg, PASP could not be assessed 3

4 1. Continue Herceptin 2. Stop Herceptin 3. Work up of new cardiomyopathy 1. Ischemic etiologies 2. Nonischemic etiologies 4. Start cardio-protective medications: ACEI, BB Exercise ST 3/17/2011 4:13 min, 6 METS, stopped 2/2 fatigue 90% MPHR No ECG evidence of ischemia Meds Lisinopril initiated and uptitrated HR 60s, thus BB not initiated HF teaching Followed by the HF clinic care managers q 2 wks by phone, no HF Sxs Last 2 cycles of Herceptin held Improved exercise tolerance, continues to work 2 jobs Remains free of HF symptoms Trace LE edema, JVP ~ 5 cm H2O, lungs CTAB, no murmurs Tolerating lisinopril 10 mg qd TTEcho repeated 6/2/2011 LVEF 55% visual estimate, 62% by Simpson s Biplane, no RWMAs RV size and systolic function normal 1+/4+ MR, no other sig valve disease MUGA 7/19/2011: LVEF 48% Tamoxifen 4/11 through 9/18/2011 4

5 Developed abd pain and diarrhea, thought to be nerve impingement vs constipation vs malignancy vs food intolerance MRI, CT, laparascopy did not reveal significant pathology, underwent hysterectomy. Pathology demonstrated grade 3 undifferentiated endometrial CA with invasion through half of myometrium Seen in HF clinic for preop evaluation Lisinopril had been discontinued temporarily, reinitiated TTEcho preop on 1/4/2012 LVEF 45% by Simpson s biplane with diffuse HK 1+/4+ MR PASP 21 mmhg, RAP 3 mmhg 28 XRT treatments to pelvis, 2/16 3/29/2012 Followed by Taxol and carboplatin Taxol carboplatin initiated 4/2012-7/2012 Complicated by neutropenia, worsening neuropathy, only 5/6 cycles given HF clinic every 3-6 months TTE 7/5/2012: LVEF 53% with diffuse HK, no sig change TTE 10/8/2012: LVEF 58%, no RWMAs, no sig valvular disease She developed cough after Cycle 5 Taxol/carboplatin PET/CT: small thoracic nodes, 5 mm R supraclavicular node ACEI changed to ARB (losartan 25 mg) due to development of persistent cough Follow up PET/CT 2/21/2013 Multiple nodal metastases: bilat supraclavicular, mediastinal, R internal mammary and R subpectoral lymph nodes New hypermetabolic LN deep periumbilical subcutaneous tissue Small hypermetabolic osseous lesion in the sternum Multiple new pulmonary nodules throughout R lung Periumbilical LN bx 3/15/2013 Breast CA metastasis Plan for initiation of Docetaxel/Trastuzumab/Pertuzumab TTE 4/8/2013: LVEF 45-55% by visual or Simpson s Biplane estimation with diffuse HK 5

6 Seen in HF clinic prior to initiation of herceptin Continue ARB Check pro-bnp and troponins following each cycle of herceptin TTEcho prior to 2 nd cycle of Herceptin 4/23/2013: Cycle 1 Docetaxel/Trastuzumab/Pertuzumab TnT < 0.03, ProBNP 51 Seen in f/u in oncology clinic 5/15/2013, doing well HF clinic visit and TTE f/u pending 6