Breast Cancer Breast Cancer and and

Strategic TreatmentStrategic Treatment

Presented by:Presented by: Komal PadhariyaKomal Padhariya

(T.Y.B.Pharm)(T.Y.B.Pharm) Guided by:Guided by:

Mrs. Sugandha Mrs. Sugandha C. C.

Anatomy of breastAnatomy of breast Breast profile:Breast profile: A DuctsA Ducts B LobulesB Lobules C Dilated section of duct to C Dilated section of duct to

hold milk hold milk D NippleD Nipple E FatE Fat F Pectoralis major muscleF Pectoralis major muscle G Chest wall/rib cageG Chest wall/rib cage Enlargement:Enlargement: A Normal duct cellsA Normal duct cells B Basement membraneB Basement membrane C Lumen (center of duct)C Lumen (center of duct)

Interior of breastInterior of breast

The breast is The breast is composed of glandular composed of glandular and adipose tissue in and adipose tissue in varying proportions. varying proportions. The glandular tissue The glandular tissue consists of 15–20 consists of 15–20 lobes containing lobes containing numerous lobules, numerous lobules, linked by ductules. linked by ductules. The latter combine to The latter combine to form the lactiferous form the lactiferous ductsducts

Blood supply to breastBlood supply to breast

Anatomy of the breast, showing Anatomy of the breast, showing lymph nodes lymph nodes

Each breast also has Each breast also has blood vesselsblood vessels and and lymph vesselslymph vessels. Lymph . Lymph vessels lead to vessels lead to organsorgans called called lymph nodeslymph nodes. . Lymph node filters Lymph node filters substances in lymph substances in lymph and helps fight and helps fight infectioninfection and disease. and disease.

Breast cancer:Breast cancer:

Breast cancer is a disease in which mBreast cancer is a disease in which malignant (cancer) cells form in the alignant (cancer) cells form in the tissues of the breast. tissues of the breast.

Age and health history can affect the Age and health history can affect the risk of developing breast cancer.risk of developing breast cancer.

Breast cancer is sometimes caused Breast cancer is sometimes caused by inherited gene mutations by inherited gene mutations (changes). (changes).

Certain factors affect prognosis Certain factors affect prognosis (chance of recovery) and treatment (chance of recovery) and treatment options.options.

TYPES OF BREAST CANCERTYPES OF BREAST CANCER

BREAST CANCER

NON INVASIVE & INVASIVE

DCIS & LCIS

VASCULAR & LYMPHATIC INVASION

1. DUCTAL CARCINOMA

INSITU

2. LOBULAR CARCINOMA

INSITU

NON INVASIVE CELL GROWTH

3. INVASIVE DUCTAL

CARCINOMA

4. INVASIVE LOBULAR

CARCINOMA

1. SOLID 2. CRIBIFORM

3. PAPILLARY 4. COMEDO

NON INVASIVE & INVASIVE DCIS & LCISNON INVASIVE & INVASIVE DCIS & LCIS

A normal lobular cells

B lobular cancer cells

C basement membrane

A normal duct cellsB ductal cancer

cellsC basement membrane

D lumen (center of duct)

A normal cellsB lobular

cancer cells breaking

through the basement membraneC basement membrane

A normal duct cells

B ductal cancer cells

breaking through the basement membrane

C basement

Invasive Ductal Carcinoma (IDC)

Lobular Carcinoma in situ (LCIS)

Ductal Carcinoma in situ (DCIS)

Invasive Lobular Carcinoma (ILC)

NON INVASIVE CELL GROWTHNON INVASIVE CELL GROWTH

AA cancer cells cancer cellsBB basement basement membranemembrane

A cancer cellsB basement membraneC lumen (center of duct)

AA cancer cells cancer cellsBB basement basement membranemembraneCC lumen lumen (center of duct)(center of duct)

AA living cancer cells living cancer cellsBB dying cancer cells dying cancer cellsCC cell debris cell debris (necrosis)(necrosis)DD basement basement membranemembrane

ComedoPapillaryCribiformSolid

Symptoms of breast Symptoms of breast cancer:cancer:

Breast lumpBreast lump Lump or mass in the armpitLump or mass in the armpit A discharge from the nipple area – any bleeding or A discharge from the nipple area – any bleeding or

weepingweeping Hardening of the skin in the nipple areaHardening of the skin in the nipple area Inversion of the nipple – turning inward or at an unusual Inversion of the nipple – turning inward or at an unusual

angleangle Change in the sensation of the nippleChange in the sensation of the nipple Breast painBreast pain Weight lossWeight loss Bone painBone pain Breast enlargement only on one sideBreast enlargement only on one side Changes in the areolaChanges in the areola

RISK FACTORS OF BREAST CANCERRISK FACTORS OF BREAST CANCER

There are two categories of risk factors for breast cancer-There are two categories of risk factors for breast cancer-those we have control over (modifiable) and those we do those we have control over (modifiable) and those we do not (non-modifiable)not (non-modifiable)

BEYOND YOUR CONTROLBEYOND YOUR CONTROL GenderGender AgeAge GeneticsGenetics RaceRace Family HistoryFamily History Late pregnanciesLate pregnancies

WITHIN YOUR CONTROLWITHIN YOUR CONTROL SMOKINGSMOKING ALCOHOLALCOHOL Radiation ExposureRadiation Exposure LifestyleLifestyle

Diagnosis of breast Diagnosis of breast cancer:cancer:

Breast self-examBreast self-exam Breast physical exam, done by a Breast physical exam, done by a

doctordoctor Mammography Mammography

Tests that examine the breasts are Tests that examine the breasts are used to detect (find) and diagnose used to detect (find) and diagnose

breast cancer.breast cancer. MammogramMammogram BiopsyBiopsy

i.i. Excisional biopsyExcisional biopsy

ii.ii. Incisional biopsyIncisional biopsy

iii.iii. Core biopsyCore biopsy

iv.iv. Needle biopsyNeedle biopsy

v.v. EstrogenEstrogen & &progesterone receprogesterone receptor testptor test

STAGES OF BREAST CANCERSTAGES OF BREAST CANCER Staging is the process physicians use to asses the size and Staging is the process physicians use to asses the size and

location of patients cancerlocation of patients cancer To stage cancer, cancer are designated the letter T(Tumor To stage cancer, cancer are designated the letter T(Tumor

size),N(Palpable nodes) and M(metastatissize),N(Palpable nodes) and M(metastatis))

Numerical Stages of Breast Cancer

The stage of a breast cancer describes its size and the extent to which it. has spread. The staging system ranges from Stage 0 to Stage IV

Staging Breast CancerStaging Breast Cancer

StageStage Tumor SizeTumor Size Lymph Node Lymph Node InvolvementInvolvement

Metastasis Metastasis (Spread)(Spread)

IIIIIIIIIIIIIVIV

Less than 2 cmLess than 2 cmBetween 2-5 cmBetween 2-5 cmMore than 5 cmMore than 5 cmNot applicableNot applicable

NoNoNo or in same side of breastNo or in same side of breastYes, on same side of breastYes, on same side of breastNot applicableNot applicable

NoNoNoNoNoNoYesYes

StageStage Definition Definition Stage 0Stage 0 Cancer cells remain inside the breast duct, Cancer cells remain inside the breast duct,

without invasion into normal adjacent breast without invasion into normal adjacent breast tissue tissue

Stage I Stage I Cancer is 2 centimeters or less and is confined Cancer is 2 centimeters or less and is confined to the breast (lymph nodes are clear) to the breast (lymph nodes are clear)

Stage II Stage II The tumor is over 2 centimeters but no larger The tumor is over 2 centimeters but no larger than 5 centimetersthan 5 centimetersOrOrThere is spread to the lymph nodes under the There is spread to the lymph nodes under the arm arm

Stage III (includes Stage III (includes substages IIIA & substages IIIA & IIIB) IIIB)

Also called locally advanced cancer. The tumor Also called locally advanced cancer. The tumor is more than 5 centimeters acrossis more than 5 centimeters acrossOrOrThe cancer is extensive in the underarm lymph The cancer is extensive in the underarm lymph nodesnodesOrOrIt has spread to other lymph nodes or tissues It has spread to other lymph nodes or tissues near the breast near the breast

Stage IV Stage IV The cancer has spread—or metastasized—to The cancer has spread—or metastasized—to other parts of the body. other parts of the body.

Additional staging Additional staging information:information:

Early stage:Early stage: Stage 0 Stage 0 Stage I Stage I Stage II Stage II Later stage:Later stage: Stage II if there are many lymph nodes Stage II if there are many lymph nodes

involved involved Stage III (IIIA, IIIB) Stage III (IIIA, IIIB) Advanced stage:Advanced stage: Stage IVStage IV

Strategic treatment of Strategic treatment of breast cancer:breast cancer:

Four types of standard treatment are Four types of standard treatment are used:used:

Surgery Surgery Radiation therapy Radiation therapy Chemotherapy Chemotherapy Hormone therapy Hormone therapy New types of treatmentNew types of treatmentSentinel lymph node biopsy followed by Sentinel lymph node biopsy followed by

surgerysurgeryHigh-dose chemotherapy with stem cell High-dose chemotherapy with stem cell

transplanttransplantMonoclonal antibodies as adjuvant therapyMonoclonal antibodies as adjuvant therapy

SurgerySurgery

Breast-conservingBreast-conserving surgery surgery

1.1. LumpectomyLumpectomy

2.2. Partial Partial mastectomymastectomy

Breast-conserving surgery. Dotted lines show area containing the tumor that is removed and some of the lymph nodes that may be removed.

Other types of surgery Other types of surgery include the following:include the following:

Total mastectomy:Total mastectomy: Total mastectomy. Dotted Total mastectomy. Dotted

line shows entire breast is line shows entire breast is removed. Some lymph removed. Some lymph nodes under the arm may nodes under the arm may also be removed.also be removed.

Modified radical Modified radical mastectomy:mastectomy:

Modified radical Modified radical mastectomy. Dotted line mastectomy. Dotted line shows entire breast and shows entire breast and some lymph nodes are some lymph nodes are removed. Part of the chest removed. Part of the chest wall muscle may also be wall muscle may also be removed. removed.

Radical mastectomy:Radical mastectomy:

  

Woman in position for radiation treatment, from the front. Middle radiation Woman in position for radiation treatment, from the front. Middle radiation beam is shown.beam is shown.

AA Bright yellow: breast being treated Bright yellow: breast being treatedBB Light yellow: beam in air, not touching woman Light yellow: beam in air, not touching womanCC Opening of the linear accelerator Opening of the linear acceleratorDD Arm holder supports woman's right arm Arm holder supports woman's right arm

   Woman in position for radiation treatment, from the side. Side radiation Woman in position for radiation treatment, from the side. Side radiation treatment beam is showntreatment beam is shown

AA Bright yellow: breast being treated Bright yellow: breast being treatedBB Light yellow: beam in air, not touching woman Light yellow: beam in air, not touching womanCC Opening of the linear accelerator Opening of the linear acceleratorDD Arm holder Arm holder

   Cross-sectional view of a woman receiving radiation to the breast areaCross-sectional view of a woman receiving radiation to the breast area

AA Middle radiation beam Middle radiation beamBB Side radiation beam Side radiation beamCC Bright yellow: place where radiation is given to the breast Bright yellow: place where radiation is given to the breast

DD Rib cage/chest wal Rib cage/chest wal

llEE Heart Heart

FF Lungs Lungs

GG Backbone Backbone

HH Sternum/breast bone Sternum/breast bone

Radiation therapyRadiation therapy

ChemotherapyChemotherapy

Systemic chemotherapy Systemic chemotherapy Regional chemotherapy Regional chemotherapy Classes of Drugs:Classes of Drugs: Alkylators Alkylators Antimetabolites Antimetabolites Antibiotics Antibiotics Antimiotic agents Antimiotic agents Antimicrotubule Antimicrotubule

Chemotherapy combinations Chemotherapy combinations for non-metastatic breast for non-metastatic breast

cancer:cancer: AC ± T – Adriamycin (chemical name: doxorubicin) AC ± T – Adriamycin (chemical name: doxorubicin)

with cyclophosphamide (brand name: Cytoxan), with cyclophosphamide (brand name: Cytoxan), with or without Taxol (chemical name: paclitaxel) with or without Taxol (chemical name: paclitaxel) or Taxotere (chemical name: docetaxol)or Taxotere (chemical name: docetaxol)

CMF – cyclophosphamide, methotrexate, and CMF – cyclophosphamide, methotrexate, and fluorouracil ("5-FU" or 5-fluorouracil)fluorouracil ("5-FU" or 5-fluorouracil)

CAF – cyclophosphamide, Adriamycin, and CAF – cyclophosphamide, Adriamycin, and fluorouracil ("5-FU" or 5-fluorouracil)fluorouracil ("5-FU" or 5-fluorouracil)

CEF – cyclophosphamide, Epirubicin (similar to CEF – cyclophosphamide, Epirubicin (similar to Adriamycin), and fluorouracil ("5-FU" or 5-Adriamycin), and fluorouracil ("5-FU" or 5-fluorouracil)fluorouracil)

FAC – fluorouracil ("5-FU" or 5-fluorouracil), FAC – fluorouracil ("5-FU" or 5-fluorouracil), Adriamycin, and cyclophosphamide.Adriamycin, and cyclophosphamide.

Hormone therapyHormone therapy

Role of estrogenRole of estrogen

Selective estrogen-Selective estrogen-receptor modulator receptor modulator (SERM) (SERM)

eg.eg.Tamoxifen,Tamoxifen, RaloxifeneRaloxifene, ,

ToremifeneToremifene

Aromatase inhibitors• Arimidex • Aromasin • Femara

The only estrogen-receptor down regulator (ERD)

Eg. Faslodex

Ovarian shutdown and removal

Side effectsSide effects Side Effects Common to All Treatments:Side Effects Common to All Treatments: Mood swingsMood swings DepressionDepression Weight gainWeight gain Hot flashesHot flashes Vaginal drynessVaginal dryness BloatingBloating Early start of menopause (may be reversed)Early start of menopause (may be reversed) "Flare reaction" or burning pain in bones "Flare reaction" or burning pain in bones

(metastatic cancer only)(metastatic cancer only)

New types of treatment are New types of treatment are being tested in clinical trials.being tested in clinical trials. Sentinel lymph node biopsy Sentinel lymph node biopsy

followed by surgeryfollowed by surgery

•High-dose chemotherapy with stem cell transplant

•Monoclonal antibodies as adjuvant therapy•Herceptin (chemical name: trastuzumab) is a very effective treatment against HER2-positive breast cancer in women with stage II, III, and IV disease (medium to large cancers or cancers with lymph nodes involved or metastatic disease.

HOW HERCEPTIN WORKS ?HOW HERCEPTIN WORKS ?

1. BLOCKING OF THE 1. BLOCKING OF THE TUMOR CELL GROWTHTUMOR CELL GROWTH

2.SIGNALING OF 2.SIGNALING OF THE IMMUNE THE IMMUNE

SYSTEMSYSTEM

3. WORKING WITH3. WORKING WITH CHEMOTHERAPYCHEMOTHERAPY

MECHANISM OF ACTIONMECHANISM OF ACTION

Two tests are used to figure out if the Two tests are used to figure out if the cancer is likely to respond to Herceptincancer is likely to respond to Herceptin

FISH (Fluorescence In Situ Hybridization)FISH (Fluorescence In Situ Hybridization) IHC (ImmunoHistoChemistry)IHC (ImmunoHistoChemistry)

1.1. FISH (Fluorescence In Situ Hybridization)FISH (Fluorescence In Situ Hybridization) Tests shows how many copies of HER 2 gene are in Tests shows how many copies of HER 2 gene are in

tumor cellstumor cells Gives scores of either “positive” or “negative”Gives scores of either “positive” or “negative” If tumor “FISH positive” it will probably respond well to If tumor “FISH positive” it will probably respond well to

herceptinherceptin

HER 2 amplification by single color FISH (red signals)

2. IHC (Immuno Histo Chemistry)

• Test used to see if a tumor has too much of the HER 2 receptor protein on the surface of the cancer cells

• Gives a score of 0 to 3+ that indicates the amount of HER 2 receptor protein in the tumors

• If the tumor scores 0 to 1+ called “HER 2 negative”. • If the tumor scores 2+ or 3+ called “HER 2 positive”• Women with IHC positive respond favourably to herceptin• Drug is not considered effective for tumors with IHC scores of 0and 1+

HER 2 overexpression (3+) shown by IHC

DOSAGEDOSAGE The dose is calculated by the weight of the patient The dose is calculated by the weight of the patient

4mg/kg on the first day then 2mg/kg once a week .4mg/kg on the first day then 2mg/kg once a week .

Convert patient weight in to kg – 2.2 pounds=1kg .Convert patient weight in to kg – 2.2 pounds=1kg . patients weight in pounds/2.2 = patient weight in kgpatients weight in pounds/2.2 = patient weight in kg

Insert patient weight in kg in to dosage equation using Insert patient weight in kg in to dosage equation using either 4 or 2 mg/kg as multipliereither 4 or 2 mg/kg as multiplier

FORMULA :FORMULA :

patient weight in kg x = ml of Herceptin reconstituted patient weight in kg x = ml of Herceptin reconstituted solution solution

multiplier/21 mg/kgmultiplier/21 mg/kg

ADMINISTRATIONADMINISTRATION

Given intravenously Given intravenously Given once a week or once every three Given once a week or once every three

weeksweeks 4mg/kg loading dose administered over a 4mg/kg loading dose administered over a

90 min infusion 90 min infusion 2 mg/kg maintaince dose administered 2 mg/kg maintaince dose administered

as a 30 min infusion as a 30 min infusion DO NOT ADMINISTER as IV PUSH OR DO NOT ADMINISTER as IV PUSH OR

BOLUSBOLUS Herceptin should not mixed or diluted Herceptin should not mixed or diluted

with other drugswith other drugs

SIDE EFFECTS OF HERCEPTINSIDE EFFECTS OF HERCEPTINEARLY EFFECTSEARLY EFFECTS Fever and sweatingFever and sweating ChillsChills Skin flushing – rednessSkin flushing – redness Discomfort in the throatDiscomfort in the throat Difficulty in breathingDifficulty in breathing

ONGOING EFFECTSONGOING EFFECTS Weakness , tirednessWeakness , tiredness HeadacheHeadache Sore eyesSore eyes Joint painJoint pain DiarrheaDiarrhea

LATE SIDE EFFECTSLATE SIDE EFFECTS Heart problemsHeart problems Allergic like reactionsAllergic like reactions Lung reactionsLung reactions

HERCEPTIN AND CHEMOTHERAPYHERCEPTIN AND CHEMOTHERAPY

Herceptin is often given in combination with Herceptin is often given in combination with other cancer drugs.other cancer drugs.

Some of the chemotherapy drugs that has Some of the chemotherapy drugs that has been given with Herceptin includesbeen given with Herceptin includes

TaxolTaxol NavelbineNavelbine XelodaXeloda ParaplatinParaplatin Chemotherapy drugs are given intravenously Chemotherapy drugs are given intravenously

on the same weekly schedule as Herceptinon the same weekly schedule as Herceptin Studies revealed that , women with metastatic Studies revealed that , women with metastatic

disease got better results when they took disease got better results when they took Herceptin with chemotherapy drugsHerceptin with chemotherapy drugs

CONCLUSION:CONCLUSION:

A survey says that every one in 875 A survey says that every one in 875 women and every one in 10,000 men women and every one in 10,000 men suffer from breast cancer worldwide. In suffer from breast cancer worldwide. In many cases it is found as small tumor many cases it is found as small tumor while in some the cancer spreads which while in some the cancer spreads which could be fatal. could be fatal.

Early detection can help us to avoid Early detection can help us to avoid serious damages caused by proliferation. serious damages caused by proliferation. This can be possible by self examination This can be possible by self examination and with the help of the physician.and with the help of the physician.

The treatments for curing breast The treatments for curing breast cancer are very expensive so cancer are very expensive so spendingspending

““5 minutes for self examination 5 minutes for self examination OR 5 weeks in hospital”OR 5 weeks in hospital”

The choice is yours!!!The choice is yours!!!

THANK YOUTHANK YOU