Early Stage Breast Cancer
Clinical Pharmacology
Bleeding Disorders
Disorders of Platelets
Miscellaneous
100
Oncotype Dx score above which adjuvant chemotherapy is warranted in postmenopausal F with node positive HR+ invasive breast cancer
RS 26+ indicates high recurrence risk and adjuvant chemo w/ TCx4 or ddAC-T would be indicated.
100
Name at least 3 HER-2 targeted therapies
trastuzumab, pertuzumab, ado-trastuzumab, famtrastuzumab deruxtecan, lapatinib, Neratinib
100
Inheritance pattern of Hemophilia A and B
(X-linked) recessive)
100
Pt presents with thrombocytopenia and on peripheral smear you notice platelet clumping?
What is the diagnosis? Test tube used? New test tube needed to correct the problem?
Pseudothrombocytopenia
- EDTA causes platelet clumping, seen on PS
- Use citrate (blue top) instead
100
Antibody associated with Heparin induced thrombocytopenia?
Heparin molecules bind to platelet-factor 4 (PF4)
This complex activates platelets, which then further releases more PF4 from the platelets
200
Which of the 5 molecular subtypes of breast cancer is associated with the best prognosis?
200
Treatment/Antidote for an Anthracycline extravasation from a port
200
Type of von willebrand disease characterized by thrombocytopenia and low vWF
type IIB: mutation in A1 domain of vWF—>increases vWF binding to GP1b
◦ thrombocytopenia and low vWF —> absence of large vWF multimers
◦ low FVIII:C, very low vWF:ristocetin cofactor, low/normal vWF antigen and increased ristocetin-induced platelet agglutination
◦ can be confused w/ platelet-type vWD: GP1b mutation
◦ DDAVP can worsen bleeding—>do NOT give
◦ tx w/ vWF concentrate replacement
200
Name the 4 components of the 4T score in a pt suspected of HIT?
The '4T' scoring system is widely used to predict the risk that an individual with Thrombocytopenia may have HIT.
The 4Ts in the 4T score are:
- Thrombocytopaenia
- Timing
- Thrombosis
- Other causes of Thrombocytopaenia are not evident.
200
56-year-old woman presents to the physician with complaint of redness and itching in her left nipple. She says she has noticed that her areola has felt "rough and bumpy" and that there is occasional oozing of yellow pus from the skin around the nipple. Physical examination shows the finding seen in the image.
Paget’s (Nipple-areola complex)
Treatment: Mastectomy and axilla dissection (can hide tumor)
300
Preferred therapy for T2N0M0 HER2+ breast cancer
Neoadjuvant treatment with TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) followed by definitive breast surgery
300
Which CDK 4/5 inhibitor is most associated with neutropenia?
Palbociclib
- PALOMA-1 showed improved PFS when added to letrozole in ER+ metastatic BrCa (20 vs 10 months)
- First dose reduction 100mg daily, dc after 75mg, hold for ANC<500
300
Name 2 bypass agents for hemophilia if an inhibitor is present or severe bleeding (unknown inhibitor status).
Novo 7 (activated recombinant factor VII): Activates the extrinsic pathway to bypass the need for factors VIII or IX
FEIBA (factor eight inhibitor bypassing agent): Activated prothrombin complex concentrate (FIIa, VIIa, Xa)
Emicizumab (FVIII-mimetic therapeutic antibody that bridges factors 9 and 10)
Alternatives: DDAVP (SE: tachyphylaxis), TXA
300
Name the standard 1st, 2nd, 3rd and 4th line treatment options for treatment of ITP?
Treatment ITP
- 1st: steroids (pred 1mg/kg or Dex 40 mg x4-more rapid response)
- 2nd: IVIG (safe during preg)
- 3rd: Splenectomy or rituximab
- 4th: Eltrombopag, romiplostim, Avatrombopag or fostamatinib
- ITP in children tends to be self-limited, Observe as 80% of cases resolve in 6 mo
300
Name the score used to predict ADAMTS13 deficiency in suspected thrombotic thrombocytopenic purpura (TTP) with high discrimination and 3 of its components?
Plasmic score
Platelet count <30 x 109/L
Hemolysis -Reticulocyte count >2.5%, haptoglobin undetectable, or indirect bilirubin >2.0 mg/dL (34.2 µmol/L)
Active cancer
History of solid-organ or stem-cell transplant
MCV <9.0 x 10-14 L (<90 fL)
INR <1.5
Creatinine <2.0 mg/dL (176.8 μmol/L)
400
What is the preferred adjuvant treatment for localized medullary breast cancer?
Medullary
- High nuclear grade, lymphocytic infiltration
- Favorable prognosis
- Treat same as invasive ductal
- Breast conserving therapy followed by adjuvant XRT
- 2mm margins are considered negative and reduce ipsilateral recurrence
- Consider 5 years of tamoxifen or AI for ER+ DCIS when residual tissue present (for prevention)
400
Name 3 drugs that can cause a drug induced TTP
Drug-associated TTP
- Clopidogrel (normal ADAMTS)
- Ticlopidine (reduced ADAMTS)
- CycloSPORine A
- Mitomycin
- Gemcitabine
- Quinine
- Tacrolimus
400
Type of Von Willebrand disease that is characterized by very low levels of factor 8 often making is tough to differentiate from hemophilia?
type IIN: also known as “pseudo hemophilia”
◦ very low FVIII:C, low/normal vWF:antigen
◦ low F8 levels but still ~5-15% w/ high/normal PTT
◦ autosomal recessive (vs hemophilia: x linked). Hemarthrosis and Muscle hematoma in a Female.
◦ may have normal vWF antigen, ristocetin cofactor and vWF multimer patterns
◦ missense mutation in the FVIII:C binding site on vWF—>F8 unable to bind to vWF—>F8 easily degraded
◦ tx: vWF and F8 prior to surgery and for bleeding
400
Which platelet disorder has the following features: LARGE platelets
Abnormal aggregation to ristocetin but normal to collagen/ADP
Decrease in Gp1b receptor?
Bernard-Soulier
- Absent GpIb/V/IX
- No ristocetin aggregation
- Associated with Luekocyte adhesion deficiency III
- Autosomal recessive
- Giant Platelets
- Mucosal bleeding and mild TCP
- If refractory to plts can give Novoseven
- platelets do not agglutinate or aggregate in response to ristocetin on aggregation studies.
400
HER2 Testing on IHC and FISH that is considered HER2 "low"
HER2 Testing
- IHC score 0 = negative
- IHC 1-2 (with with low FISH <6.0 copies) = low
- IHC 2+ and IHC FISH or 3+ IHC = High
- HER2 ISH copy number >6.0 signals to be positive in HER 2+ IHC
500
The indications for adjuvant abemaciclib
What is HR+ HER2-, node positive breast cancer at high risk of recurrence and Ki-67 >20%?
Adjuvant CDK 4/6 in Localized Breast Cancer
- MonarchE trial: high-risk HR positive breast cancer to receive 2 years of abemaciclib
- IDFS improved 3.5%
- Abemiciclib approved as adjuvant therapy for patients with HR positive, HER2 negative high-risk disease:
- >4 nodes
- Or 1-3 nodes with Ki67 >20%
- Or >5 cm tumor
500
What is the mechanism of action of Caplacizumab (Caplivi) in treatment of TTP?
Target = A1 domain of the ultra-large von Willebrand factor which
Inhibits interaction with the glycoprotein Ib-IX-V receptor in the platelets.
Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific. The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.
500
In patients with acquired hemophilia A, what factor VIII activity level and inhibitor titer predicts a higher likelihood of response to corticosteroids alone as an immune-suppressing therapy (IST).
pretreatment factor VIII (FVIII) activity =1% and inhibitor titer <20 BU
500
Name the syndrome:
X-linked
Thrombocytopenia w/ microthrombocytes
Decreased Immunity
Eczema
Bloody Diarrhea
Wiskott-Aldrich (WAS gene mutation)
500
Genetic mutation associated with breast, uterine, and thyroid cancer, hamartomas and macrocephaly
What is PTEN mutation? (Cowden's Syndrome)