Presentation on theme: "Clinical Pharmacology breast cancer"— Presentation transcript:
1Clinical Pharmacology breast cancer byDr.Waleed ElnahasLecturer of surgical oncologyHosam ElghadbanAssistant Lecturer of surgery
2Incidence ** Age:- 40-50 yr NO age is immune after puberty ** Sex:- ♀:♂= 99:1 (the commonest tumor in female)** Side:-Left > rightBilateral-----» Simultaneous 1%-----» Metachronous 5%** Site:-Upper outer quadrant 60% -----» most of mammary tissue** Geographic:-West > eastDeveloped > developing
3Etiology (predisposing factors) 1-Genetic:A-Young age < 30 yrb- Mostly Bilateralc- Multiple relatives with cancer breast (>3)-Hereditary breast cancer :5–10%BRCA-1: Long arm of chromosome 17qBRCA-2: Long arm of chromosome 13qLi-Fraumeni syndrome :P53, Short arm chromosome 17p
42- Endocrinal (Hormonal): - Not married, null Para, elderly primigravida (> 35 yr) and non-lactating female.- Early menarche or late menopause due to prolonged exposure to estrogen.3- Exposure to radiation:- Nuclear war.- Medical purposes (diagnostic or therapeutic being greater for exposures in childhood and adolescence than after age of 40 years).4-drugs : estrogen , contraceptive pills more than 10 years (uncertain)
5pathologyWorld Health Organization Classification of Carcinoma of the BreastNoninvasive carcinoma-Ductal carcinoma in situ Lobular carcinoma in situInvasive carcinoma-Invasive ductal carcinoma %-Invasive lobular carcinoma – 10%-Mucinous carcinoma -- 2%-Medullary carcinoma – 5%-Papillary carcinoma -- 1%-Tubular carcinoma – 1%-Adenoid cystic carcinoma-Secretory (juvenile) carcinoma-Apocrine carcinoma-Carcinoma with metaplasia (metaplastic carcinoma)-Inflammatory carcinoma-Other : sarcoma, lymphoma and melanomaPaget's disease of the nipple
6SpreadDirect spread:- 1. Intrinsic: to surrounding breast tissue 2. Extrinsic: ** To the skin causing ulceration & fungation . ** To deep structures: Pectoral fascia, pectoral muscles & chest wall Lymphatic spread:- Haematogenous spread:- Transcoelomic spread:-
7Clinical picture ** Symptoms: A- Asymptomatic:- discovered accidentally during screening programsB- Symptomatic:-1. Mass (commonest presentation)2. Pain: (Very Rare 10%)3. Nipple discharge: - Bloody discharge in duct carcinoma4. Skin & nipple manifestations5. Manifestations of metastasis:-
8Signs: A) General examinations: 1 ** Signs: A) General examinations: 1. Chest: signs of pleural effusion or mediastinal L.N. 2. Abdominal examination: - Hepatomegaly - Ascites. 3. P/R or P/V: nodules in the Douglas’ pouch or Krukenberg’s tumor. 4. Bone: for tenderness, swelling & pathological fracture
9B) Local examination:1- inspection** Breast: compared to healthy side** Nipple & areola: may show** the skin:1) Skin dimpling, Tethering & Puckering2) ulceration & fungation:3) Peau d’orange (Pitted edema):4) Cancerous satellite nodules (late sign):5) Cancer en cuirasse** The mass: ** the axilla ** The arm
102- palpationpalpate breasts with both the flat of your hand and fingers.with flat fingers compress breast tissuefollow systematically, in a circular pattern around the nipple or along the radial lines (simulate a clock) or vertical segments and feel the entire breast, including the tail near the axilla.Examine criteria of the mass : site, size, shape, consistencyExamine axillary lymph nodes
11TX :Primary tumor cannot be assessed T0 :No evidence of primary tumor American Joint Committee on Cancer TNM Staging System for Breast CancerPrimary Tumor (T)TX :Primary tumor cannot be assessedT0 :No evidence of primary tumorTis: Carcinoma in situNote: Paget's disease associated with a tumor is classified according to the size of the tumor.T1: Tumor 2 cm or less in greatest dimensionT1mic :Microinvasion 0.1 cm or less in greatest dimensionT1a :Tumor more than 0.1 cm but not more than 0.5 cm in greatest dimensionT1b :Tumor more than 0.5 cm but not more than 1 cm in greatest dimensionT1c :Tumor more than 1 cm but not more than 2 cm in greatest dimensionT2 :Tumor more than 2 cm but not more than 5 cm in greatest dimensionT3 :Tumor more than 5 cm in greatest dimensionT4a :Extension to chest wall not including pectoralis muscleT4b: Edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breastT4c :Both T4a and T4bT4d :Inflammatory carcinoma
12NX: Regional lymph nodes cannot be assessed (e.g., previously removed) Regional Lymph Nodes (N) NX: Regional lymph nodes cannot be assessed (e.g., previously removed)N0 :No regional lymph node metastasisN1: Metastasis to movable ipsilateral axillary lymph node(s)N2 :N2a :Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structuresN2b :Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasisN3N3a :Metastasis in ipsilateral infraclavicular lymph node(s)N3b :Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)N3c :Metastasis in ipsilateral supraclavicular lymph node(s)
13M ( METASTASIS)MX : metastasis can no be assessedM0 : no metastasisM1 : metastasis
14American Cancer Society Screening Recommendations Annual mammograms, starting at age 40Clinical breast examsevery year starting at age 40every 3 years for women age20-39Self-breast exams monthly, starting at age 20
15Breast Self-Exam – Step 1 Begin by looking at your breasts in the mirror with your shoulders straight and yourarms on your hips.Here's what you should look for:Breasts that are their usual size, shape, and color.--Breasts that are evenly shaped without visible distortion or swelling.If you see any of the following changes, bring them to your doctor's attention:--Dimpling, puckering, or bulging of the skin.--A nipple that has changed position or become inverted (pushed inward instead ofsticking out).--Redness, soreness, rash, or swelling.
16Breast Self-Exam – Step 2 Raise your arms and look for the samechanges.
17Breast Self-Exam – Step 3 Feel your breasts while lying down, using your right hand to feel your left breast and then your left hand to feel your right breast. Use a firm, smooth touch with the first few fingers of your hand, keeping the fingersflat and together.Cover the entire breast from top to bottom, side to side—from your collarbone to the top of your abdomen, and from your armpit to your cleavage
18Breast Self-Exam – Step 4 Finally, feel your breasts while you are standing or sitting. Many women find that the easiest way to feel their breasts is when their skin is wet and slippery, so they like to do this step in the shower. Cover your entire breast, using the same hand movements described in Step 3.
19Investigations: Mammography (con’t) Standard mammography: depends on density of the tissue and its ability to stop xraybeam from exposing film placed on the other side of the breast.Digital mammography works on the same principle, but there is also some ability to manipulate the image by computer. Main advantage is storage of the films.
20Ultrasound Since solid tissue and collections of fluid look the same on mammography,ultrasound is very useful intelling whether a mass issolid or fluid, and, if solid, ifcharacteristics aresuspicious.Cyst
21MRI MRI relies on completely different type of wave energy: a strong magnet that affects the charge inthe nuclei. As magnetic force is applied and thenreleased, different types of tissue send back different types of radio waves.MRI can be extremely useful in very densebreasts, hereditary cases
22Fine Needle Aspiration Fine needle aspiration of a palpable mass Fine needle aspiration takes individual cells out ofmass. Can be done for palpable or non-palpablemasses. Does not show architecture, especially wallof duct, so best used to confirm strong suspicions.C0 No epithelial cellsC1 InadequateC2 BenignC3 AtypiaC4 SuspiciousC5 Malignant
23Core Biopsy done on palpable and non palpable Core biopsy can also bedone on palpable and non palpableabnormalities, and on microcalcifications.B1 Normal tissue / unsatisfactoryB2 BenignB3 Lesion uncertain malignant potentialB4 Suspicion of malignancyB5a In situ malignancyB5b Invasive malignancy
24Investigations for metastasis 1- abdominal ultrasound 2- chest x ray or CT 3- bone survey or bone scan
26Lumpectomy with breast irradiation Mastectomy TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCERObjective OptionsLocal control LumpectomyLumpectomy with breast irradiationMastectomyRegional control Axillary lymph node dissectionRegional irradiationControl of occult Chemotherapymicrometastatic disease Hormone therapyImproved function and cosmesis Breast-conserving therapyReconstruction (immediate or delayed)
27Localized breast cancer Surgery is mainstayHalsted, 1882, radical mastectomyJohn HopkinsMetastatic breast cancerSystemic treatment
28Radical mastectomyA. Entire breast and a chest wall muscle is removed.LNs in the level 1 (B) and level 2 (C ), and even sometimes more distant lymph node groups (D, E and F) were also removed.
29Modified radical mastectomy (MRM) A. Entire breast is removedClassically some lymph nodes in the level 1 (B) and level 2 (C ) were removed, called an axillary lymph node dissection.MRM = simple mastectomy + ALND
30Breast conserving surgery Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsyRT should be followed
32Adjuvant chemotherapy CMF, first generation, 1970sCyclophosphamideMethotrexate5-FUBenefit inDistant recurrenceSurvival
33Adjuvant chemotherapy CAF or CEF, 2nd generation, 1980sCyclophophamideAdramycin(or Epirubicin)5-FUMore toxic than CMFCAF better than CMF in high-risk groupAxilla LN+LN-, but tumor large or other risk factor
34Adjuvant chemotherapy Incorporate TaxaneTAC, 3rd generation, mid-1990sTaxotereAdriamycinCyclophosphamideMore toxic than CAFBetter than CAF in high-risk groupNeed more time to observe
35Adjuvant Herceptin Effective in Her2+ pts (HER-2 (Human Epidermal growth factor Receptor 2) also known as proto-oncogene Neu Over expression of this gene is correlated with higher aggressiveness in breast cancer.HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation).Effective in Her2+ ptsICH3+FISH+Herceptin + adjuvant chemotherapyOptimal role to be definedConcurrent or sequential?Maintenance ? Duration
36Adjuvant hormone therapy In premenopausal womanOophorectomy could control metastatic diseaseTamoxifenSelective estrogen receptor antagonistEffective in pre- and post-menopausalEffective in adjuvant setting
37Adjuvant hormone therapy Aromatase inhibitorEffective in post-menopausal stateAromatase, in fat tissue,Convert androgen to estrogenMain estrogen source in post-menopausalExemestane : AromasinLetrozole: FemaraAnastrozole: ArimidexMore effective than Tamoxifen
38Adjuvant ovarian suppression Effective in pre-menopausal stateTypeSurgical ablationRT ablationGnRH analogue: Goserelin, LeuprideExact role to be definedCombination with chemotherapy?Combination with AI or TAM?
39Radiation therapy Radiation kills the cancer cells left after surgery. Radiation therapy doesn't make you radio active.Radiation is painless when it’s delivered, but it will become more painful over time.Treatments will be given up to 5-7 weeks, 5 days a week.Treatments only take ½ hour so you can keep your routine.Your hair won’t fall out unless you are also taking chemotherapy.Your skin in the area may become red and easily irritated.You may feel tired even after its over.Radiation after surgery reduces the chances of the cancer reoccurring.
40Treatment of metastatic dz Usual sites: bone, lung, liver, brainIncurableGoal: live with dz for longest timeSystemic treatment is mainstayChemotherapyHormone therapyPalliative local therapyRadiotherapyPalliative surgery