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Breast Cancer

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Lauren Kuta

on 24 March 2015

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Transcript of Breast Cancer

Breast
Cancer

Lauren Kuta, PharmD Candidate 2015
Rosalind Franklin University of Medicine & Science
Statistics:
seers
Types of Breast Cancer
Non-Invasive:
Lobular
Ductal
Invasive:
Lobular
Ductal
How to Diagnose
Mammogram
Ultrasound
Biopsy
Chest X-ray/CT scan
Pathology review
Staging
T N M
0-4
Size
0-3
Nodes
0 or 1
Mets
Stage 1:
Early-small primary tumor, N=0
Stage 2:
Early-small primary tumor, regional node involvement
Stage 3:

Locally advanced-Large size, extensive node involvement
Stage 4:
Advanced, M=1
CURE
CURE
CURE
POSSIBLE
PALLIATION

In 2011, 220,097 women and 2,078 men in the U.S. were diagnosed with breast cancer.

In 2011, 40,931 women and 443 men in the U.S. died from breast cancer
About 11% of all new cases of breast cancer in the U.S. are found in women younger than 45 years of age.
From 2001 to 2010 in the U.S., incidence of breast cancer has remained level among women.
FAST FACTS:
From 2001 to 2010 in the U.S., deaths from breast cancer have decreased significantly by 2.0% per year among women.
ER/PR +
Types of Breast Cancer
ER/PR -
HER2 +

HER2 -

HER2 +

HER2 -

Endocrine therapy
Trastuzumab
Chemotherapy
Endocrine therapy
Chemotherapy
Chemotherapy
Trastuzumab
Chemotherapy
Interventions
Used Other Than Medications
Surgical
Mastectomy
Breast conservation


Radiation
Meet LS:
Diagnosed stageII
ER+/PR+, HER2-
'02
'15
stage IV
mets to liver,
brain, bone & lung
adjuvant chemo
with AC x4 cycles
+
tamoxifen
no radiation
remission
accomplished
relapse occurs
pathology shows:
ER+/PR+, HER2+
numerous chemotherapy tried
taxotere
goserelin
abraxane
HER+:
trastzumab
pertuzumab
Due to disease progression
and medication therapies, pt
developed:
Cardiomyopathy
Osteonecrosis of the jaw
ER/PR+
anastrozole
megestrol
fulvestrant
age: 40
age: 53
Options are limited...
Now What?
METHOTREXATE
References
Parise CA, Caggiano V. Breast Cancer Survival Defined by the ER/PR/HER2
Subtypes and a Surrogate Classification according to Tumor Grade and
Immunohistochemical Biomarkers. J Cancer Epidemiol. 2014;2014:469251. doi:
10.1155/2014/469251. Epub 2014 May 26.

Treon SP, Chabner BA. Concepts in use of high-dose methotrexate therapy. Clin
Chem. 1996 Aug;42(8 Pt 2):1322-9.

Up to Date Database, "Methotrexate". Topic 9630 Version 151.0. Accessed on March 23, 2015. https://www-uptodate-com.ezproxy.rosalindfranklin.edu/contents/methotrexate-drug-information?source=search_result&search=methotrexate&selectedTitle=1~150#references
Methotrexate:
Discovered in the late 1940s
Tumor regression rates are between 10-30% if used as a single agent
Used mostly in RA
MOA:
MTX
Folate pathway
polyglutamation
slows purine synthesis
(guanosine & adenosine)
= LESS MATERIAL TO PRODUCE CELLS & CYTOTOXIC
ADVERSE EFFECTS
Acute renal failure
Bone marrow suppression
CNS effects: May cause neurotoxicity including seizures
Dermatologic toxicity: SJS, severe skin sloughing
Fertility: May cause impairment of fertility, oligospermia, and menstrual dysfunction (Category X)
Gastrointestinal toxicity: diarrhea and ulcerative stomatitis
Hepatotoxicity: acute or potentially fatal chronic fibrosis or cirrhosis
PRIOR TO ADMINISTRATION...
Drug Interactions:
any hepatotoxic agents
nephrotoxic chemo agents
PPIs & NSAIDS cannot be used-increase of MTX serum levels
Dose adjustment:
CrCl 10 to 50 mL/minute: 50% of dose
CrCl <10 mL/minute: Avoid use
Serum creatinine <1.5 mg/dL: No dosage adjustment necessary
Serum creatinine 1.5 to 2 mg/dL: Administer 75% of dose
Serum creatinine >2 mg/dL: Administer 50% of dose
Bilirubin 3.1 to 5 mg/dL or transaminases >3 times ULN: Administer 75% of dose
Bilirubin >5 mg/dL: Avoid use
Dose
Advantages
Toxicity
Observed
Precautions
3-15g/m2 over 6-24 hours
*500mg/m2 show
inadequate concentration
in cerebrospinal fluid
MTX has a "rescue" agent
Uses passive diffusion
Great for brain mets due to ability to go into CSF
neutropenia can be easily treated with antibiotics
bumps in LFTs are benign and reversible
chance of poor outcomes are increased with age
High Urine Flow
transient bumps in CrCl can delay MTX excretion

24 hours of additional hydration can combat these bumps

80% of MTX appears in the urine unchanged within 12 hours of administration
Alkaline
Urine pH
more acidic urine=
decrease in drug solubility

prevents precipitation of MTX in the urine

use bicarbonate to make urine
basic

***more important than
urine flow!
Drug
Concentrations
measured after 24-48 hours to ensure MTX is being cleared from plasma
Right Patients
patients should have a minimum 60ml/min CrCl

preview patient medications to decrease interactions

drainage of all third-space fluids before MTX
Rescue Agents
Leucovorin:
competes with MTX using folate pathway to enter cell

should be administered as a 10 fold excess of MTX
Back Up Rescue to Leucovorin:

Glucarpidase: bacterial enzyme which hydrolyzes MTX thus allowing another means for excretion
Weight based: 50 units/ kg
1 vial= 1,000 units
$109,000
Was LS a good
candidate for MTX?
CrCl= 80ml/min

Meds: amoxicillin
carvedilol
gabapentin
ramipril
levothyroxine

53 years old
non-pregnant female
Clinical Take Away
Breast cancer treatment is dependent of drug targets and staging
What Questions Do You Have?
?
?
?
?
As if that wasn't enough...

BRCA1/BRCA2
tumor suppressor genes
if mutated, increased chance of breast/ovarian cancer
Always re-biopsy with breast cancer recurrence
Not every patient is a candidate for MTX
MTX is useful for mets-especially if brain is involved

Chemotherapy is almost always an option for every type breast cancer
LS presented to her primary care oncologist with the following symptoms:

Sudden onset of memory loss
Constant falling
Has to use a walker now to get around
Full transcript