• BRCA-related hereditary breast and ovarian CA syndromes
  • BRCA: highly penetrant germline mutations in BRCA1 or BRCA2 (autosomal dominant) 
  • ~20% of patients with a hereditary breast and ovarian cancer syndrome have a mutation in BRCA 1 or 2
  • Also confer higher risk of second breast CA (often contralateral breast), MALE breast CA, fallopian tube CA, primary peritoneal CA, pancreatic CA, melanoma, endometrial CA
  • Unaffected BRCA carriers?
    • Clinical breast exams every 6 to 12 months beginning at age 25
    • Annual breast magnetic resonance imaging (MRI) from ages 25 to 29 years
    • Annual mammogram and breast MRI from ages 30 to 75
    • Consideration of chemoprevention and risk-reducing mastectomy
  
  

  Posted 11/22/16 09:12:47 AM by Matthew Cummings

• Classic Chemotherapy/Onc Drug Toxicities
  • Gemcitabine/mitomycin --> TTP
  • Bleomycin/MTX --> ILD (pulmonary fibrosis)
  • 5-FU --> mucositis
  • Tacrolimus/cyclosporine/s/p BMT --> PRES
  • Alkylating agents (cyclophosphamide, busulfan) --> myelodysplasia
  • Thalidomide/lenalidomide --> VTE (DVT/PE)
  • Rasburicase/dapsone/sulfa (less likely) --> hemolysis in G6PD deficiency
  • Anthracyclines (doxorubicin), trastuzumab --> cardiomyopathy
  • Cyclophosphamide/ifosfamide --> hemorrhagic cystitis
  • Peripheral neuropathy --> vincristine
  
  
  
  

  Posted 11/22/16 09:38:51 AM by Matthew Cummings

• Cardiac Tumors -- Clinical Manifestations
  • Embolization (usually systemic, can be pulmonic, embolic risk highest w/ LA tumors)
  • CHF via valvular/outflow obstruction or valvular regurgitation
  • Direct invasion of the myocardium (decreased LV function arrhythmias, heart block, pericardial effusion)
  • Invasion of adjacent lung -- cough, SOB
  • Constitutional symptoms
  Cardiac Sarcomas
  • Incredibly rare
  • Imaging crucial to plan diagnostic/therapeutic approach (surgery vs no surgery) --> TTE, CT, MRI
    • Angiosarcoma, rhabdomyosarcoma, fibrosarcoma, leiomyosarcoma
  
  

  Posted 11/22/16 09:44:39 AM by Matthew Cummings

• Olaratumab for soft-tissue sarcoma
  • Standard therapy had long been doxorubicin +/- ifosphamide
  • Lancet 2016 (Dr. Schwartz senior author): data supporting olaratumab (human anti-platelet derived growth factor MAB) + doxorubicin as preferred therapy for soft-tissue sarcoma
  
  

  Posted 11/22/16 09:52:14 AM by Matthew Cummings

• For further reading...

  Classic Chemotherapy-related Toxicities
  Olaratumab and doxorubicin vs. doxorubicin alone for soft tissue sarcoma (Lancet 2016)
  
  
  
  

  Posted 11/22/16 09:55:21 AM by Matthew Cummings

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