LETROZOLE- AN ANTILETROZOLE- AN ANTI

BREAST CANCER DRUG BREAST CANCER DRUG

LOC HUA

CHEMISTRY 12B- SEMINAR

# 11

AN OVERVIEW OF BREAST AN OVERVIEW OF BREAST CANCERCANCER

1.1. What is breast cancer?What is breast cancer? A single cell in a tissue undergoes A single cell in a tissue undergoes transformation transformation which converts a normal cell to a cancer which converts a normal cell to a cancer

cell.cell. The cell evades destruction, it proliferates to form a The cell evades destruction, it proliferates to form a tumortumor, a mass of abnormal cells within , a mass of abnormal cells within

otherwise normal tissue.otherwise normal tissue. If the abnormal cell remain at the original site, the lump is called a begin tumor.If the abnormal cell remain at the original site, the lump is called a begin tumor. A malignant tumor becomes invasive enough to impair the functions of one or more organs. At A malignant tumor becomes invasive enough to impair the functions of one or more organs. At

this point the tumor is cancer.this point the tumor is cancer.

AN OVERVIEW OF BREAST AN OVERVIEW OF BREAST CANCERCANCER

2.2. What factors can cause breast cancer?What factors can cause breast cancer? Women over 40 have higher risks of breast cancerWomen over 40 have higher risks of breast cancer Native Americans, Hispanics, and Asians have lower rates of breast cancer than Native Americans, Hispanics, and Asians have lower rates of breast cancer than

Caucasians and African Americans Caucasians and African Americans Genetic factor and family historyGenetic factor and family history Because growth of breast tissue is highly sensitive to estrogens, the more a women Because growth of breast tissue is highly sensitive to estrogens, the more a women

is exposed to estrogen over her lifetime, the higher the risk for breast cancer is exposed to estrogen over her lifetime, the higher the risk for breast cancer Pregnancy appears to Pregnancy appears to increaseincrease the risk of breast cancer for up to 15 years following the risk of breast cancer for up to 15 years following

the first birth, particularly in older women the first birth, particularly in older women

AN OVERVIEW OF BREAST AN OVERVIEW OF BREAST CANCERCANCER

3.3. Stages of Breast CancerStages of Breast Cancer Stage 0:Stage 0: This means that paitient either have DCIS which is an early age of breast This means that paitient either have DCIS which is an early age of breast

cancer or LCIS which is not a cancer but increase the chance to have breast cancer.cancer or LCIS which is not a cancer but increase the chance to have breast cancer. Stage I:Stage I: cancer is less than 1 inch across. The cancer is only in the breast and has cancer is less than 1 inch across. The cancer is only in the breast and has

not spread out.not spread out. Stage II:Stage II: cancer is about 1 to 2 inches or larger and has spread to the lymph nodes cancer is about 1 to 2 inches or larger and has spread to the lymph nodes

under armunder arm Stage III: Stage III: cancer has spread to tissues near the breast (skin or chest wall, including cancer has spread to tissues near the breast (skin or chest wall, including

the ribs and the muscles in the chest). cancer has spread to lymph nodes inside the the ribs and the muscles in the chest). cancer has spread to lymph nodes inside the chest wall along the breast bone. chest wall along the breast bone.

Stage IV: Stage IV: This stage is defined by either of the following: the cancer has spread to This stage is defined by either of the following: the cancer has spread to other organs of the body, most often the bones, lungs, liver, or brain. the tumor has other organs of the body, most often the bones, lungs, liver, or brain. the tumor has spread locally to the skin and lymph nodes inside the neck, near the collarbone. spread locally to the skin and lymph nodes inside the neck, near the collarbone.

Recurrent: Recurrent: In this stage, the cancer has come back (recurred) after treatment. It may In this stage, the cancer has come back (recurred) after treatment. It may come back in the breast, in the soft tissues of the chest (the chest wall), or in another come back in the breast, in the soft tissues of the chest (the chest wall), or in another part of the body.part of the body.

AN OVERVIEW OF BREAST AN OVERVIEW OF BREAST CANCERCANCER

4.4. Statistics of Breast CancerStatistics of Breast Cancer

Structure and Synthesis Structure and Synthesis LetrozoleLetrozole

1.1. Pharmacology of LetrozolePharmacology of Letrozole A type of drug called an aromatase inhibitor which work by limiting the ability A type of drug called an aromatase inhibitor which work by limiting the ability

of an enzyme called aromatase to create estrogen. of an enzyme called aromatase to create estrogen. Letrozole comes in pill form and is taken once a day. It’s also called Femara.Letrozole comes in pill form and is taken once a day. It’s also called Femara. Letrozole is a drug for patients that have been taking Tamoxifen for five Letrozole is a drug for patients that have been taking Tamoxifen for five

years.years.

Structure and Synthesis Structure and Synthesis LetrozoleLetrozole2.2. Synthesis LetrolzoleSynthesis Letrolzole

Structure and Synthesis Structure and Synthesis LetrozoleLetrozole

structurestructure

Structure and Synthesis Structure and Synthesis LetrozoleLetrozole

FT -IR of LetrozoleFT -IR of Letrozole

Show the amine group

Show the nitriles group

Show the aromatic ring

Structure and Synthesis Structure and Synthesis LetrozoleLetrozole1H NMR1H NMR

13C NMR

Carbon Chemical Shift (ppm) Proton Chemical Shift (ppm) Atom Number and Notes

66.36 6.81 (singlet) 1 (alkyl methine)

113.29   1,1' (benzene rings)

117.82   19, 21 (benzene rings)

128.9 7.70, 7.72 (doublet) 3, 5, 3', 5' (benzene rings)

132.91 7.28, 7.30 (doublet) 2, 6, 2', 6' (benzene rings)

141.76   4, 4' (benzene rings)

143.68 8.09 (singlet) 5 (triazole ring)

153.05 8.07 (singlet) 3 (triazole ring)

Structure and Synthesis Structure and Synthesis LetrozoleLetrozole

Comparison between Tamoxifen and LetrozoleComparison between Tamoxifen and Letrozole

TamoxifenTamoxifen LetrozoleLetrozole

1. Long term 1. Long term workingworking

After 5 years the drug becomes After 5 years the drug becomes ineffectiveineffective

Continue after 5 years treatmentContinue after 5 years treatment

2. Effect 2. Effect no effect on the production of estrogen no effect on the production of estrogen A very powerful aromatase A very powerful aromatase inhibitor, suppresses the production inhibitor, suppresses the production of estrogen of estrogen

3. Physical effect 3. Physical effect Effect on women sexual function, Effect on women sexual function, memory loss, strokememory loss, stroke

hot flashes, sweating, edema, hot flashes, sweating, edema, sore muscles and fatigue sore muscles and fatigue

4. Pregnancy 4. Pregnancy affect on the fetusaffect on the fetus cause fetal harm when cause fetal harm when

administered to pregnant womenadministered to pregnant women

Reference Reference http://www.cancer.gov/newscenter/pressreleases/letrozoleQandhttp://www.cancer.gov/newscenter/pressreleases/letrozoleQand

AA http://www.drugs.com/pdr/Femara_Tablets.htmlhttp://www.drugs.com/pdr/Femara_Tablets.html

http://www.usdoj.gov/dea/programs/forensicsci/microgram/http://www.usdoj.gov/dea/programs/forensicsci/microgram/journal071203/mj071203_pg6.htmljournal071203/mj071203_pg6.html

http://www.fda.gov/cder/foi/label/http://www.fda.gov/cder/foi/label/2003/20726se8008_Femara_lbl.pdf#search='synthesis2003/20726se8008_Femara_lbl.pdf#search='synthesis%20letrozole‘%20letrozole‘

http://www.sante.univnantes.fr/pharma/biocit/publispdf/p34.pdfhttp://www.sante.univnantes.fr/pharma/biocit/publispdf/p34.pdf

http://www.reutershealth.com/wellconnected/doc06.htmlhttp://www.reutershealth.com/wellconnected/doc06.html