1. Clinical Pharmacology breast cancerby
Dr.Waleed Elnahas
Lecturer of surgical oncology
Hosam Elghadban
Assistant Lecturer of surgery

2. Incidence ** Age:- 40-50 yr NO age is immune after puberty ** Sex:-
♀:♂= 99:1 (the commonest tumor in female)
** Side:-
Left > right
Bilateral-----» Simultaneous 1%
-----» Metachronous 5%
** Site:-
Upper outer quadrant 60% -----» most of mammary tissue
** Geographic:-
West > east
Developed > developing

3. Etiology (predisposing factors)
1-Genetic:
A-Young age < 30 yr
b- Mostly Bilateral
c- Multiple relatives with cancer breast (>3)
-Hereditary breast cancer :5–10%
BRCA-1: Long arm of chromosome 17q
BRCA-2: Long arm of chromosome 13q
Li-Fraumeni syndrome :P53, Short arm chromosome 17p

4. 2- 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)

5. pathology
World Health Organization Classification of Carcinoma of the Breast
Noninvasive carcinoma
-Ductal carcinoma in situ Lobular carcinoma in situ
Invasive 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 melanoma
Paget's disease of the nipple

6. Spread
Direct 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:-

7. Clinical picture ** Symptoms:
A- Asymptomatic:- discovered accidentally during screening programs
B- Symptomatic:-
1. Mass (commonest presentation)
2. Pain: (Very Rare 10%)
3. Nipple discharge: - Bloody discharge in duct carcinoma
4. Skin & nipple manifestations
5. Manifestations of metastasis:-

8. Signs: 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

9. B) Local examination:
1- inspection
** Breast: compared to healthy side
** Nipple & areola: may show
** the skin:
1) Skin dimpling, Tethering & Puckering
2) ulceration & fungation:
3) Peau d’orange (Pitted edema):
4) Cancerous satellite nodules (late sign):
5) Cancer en cuirasse
** The mass: ** the axilla ** The arm

10. 2- palpation
palpate breasts with both the flat of your hand and fingers.
with flat fingers compress breast tissue
follow 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, consistency
Examine axillary lymph nodes

11. TX :Primary tumor cannot be assessed T0 :No evidence of primary tumor
American Joint Committee on Cancer TNM Staging System for Breast Cancer
Primary Tumor (T)
TX :Primary tumor cannot be assessed
T0 :No evidence of primary tumor
Tis: Carcinoma in situ
Note: Paget's disease associated with a tumor is classified according to the size of the tumor.
T1: Tumor 2 cm or less in greatest dimension
T1mic :Microinvasion 0.1 cm or less in greatest dimension
T1a :Tumor more than 0.1 cm but not more than 0.5 cm in greatest dimension
T1b :Tumor more than 0.5 cm but not more than 1 cm in greatest dimension
T1c :Tumor more than 1 cm but not more than 2 cm in greatest dimension
T2 :Tumor more than 2 cm but not more than 5 cm in greatest dimension
T3 :Tumor more than 5 cm in greatest dimension
T4a :Extension to chest wall not including pectoralis muscle
T4b: Edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast
T4c :Both T4a and T4b
T4d :Inflammatory carcinoma

12. NX: 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 metastasis
N1: Metastasis to movable ipsilateral axillary lymph node(s)
N2 :
N2a :Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures
N2b :Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis N3
N3a :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)

13. M ( METASTASIS)
MX : metastasis can no be assessed
M0 : no metastasis
M1 : metastasis

14. American Cancer Society Screening Recommendations
Annual mammograms, starting at age 40
Clinical breast exams
every year starting at age 40
every 3 years for women age
20-39
Self-breast exams monthly, starting at age 20

15. Breast Self-Exam – Step 1
Begin by looking at your breasts in the mirror with your shoulders straight and your
arms 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 of
sticking out).
--Redness, soreness, rash, or swelling.

16. Breast Self-Exam – Step 2
Raise your arms and look for the same
changes.

17. Breast 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 fingers
flat 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

18. Breast 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.

19. Investigations: Mammography (con’t)
􀁺 Standard mammography: depends on density of the tissue and its ability to stop xray
beam 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.

20. Ultrasound Since solid tissue and collections of fluid look the
same on mammography,
ultrasound is very useful in
telling whether a mass is
solid or fluid, and, if solid, if
characteristics are
suspicious.
Cyst

21. MRI MRI relies on completely different type of wave
energy: a strong magnet that affects the charge in
the nuclei. As magnetic force is applied and then
released, different types of tissue send back different types of radio waves.
MRI can be extremely useful in very dense
breasts, hereditary cases

22. Fine Needle Aspiration
Fine needle aspiration of a palpable mass
􀁺 Fine needle aspiration takes individual cells out of
mass. Can be done for palpable or non-palpable
masses. Does not show architecture, especially wall
of duct, so best used to confirm strong suspicions.
C0 No epithelial cells
C1 Inadequate
C2 Benign
C3 Atypia
C4 Suspicious
C5 Malignant

23. Core Biopsy done on palpable and non palpable
􀁺 Core biopsy can also be
done on palpable and non palpable
abnormalities, and on microcalcifications.
B1 Normal tissue / unsatisfactory
B2 Benign
B3 Lesion uncertain malignant potential
B4 Suspicion of malignancy
B5a In situ malignancy
B5b Invasive malignancy

24. Investigations for metastasis
1- abdominal ultrasound 2- chest x ray or CT 3- bone survey or bone scan

25. Established prognostic factors
Nodal status
Tumor size
Lymph node
Grade
ER/PR Status
Age
Lymphatic invasion
Histological tumor type
Perinodular infiltration

26. Lumpectomy with breast irradiation Mastectomy
TREATMENT OPTIONS FOR PRIMARY OPERABLE BREAST CANCER
Objective Options
Local control Lumpectomy
Lumpectomy with breast irradiation
Mastectomy
Regional control Axillary lymph node dissection
Regional irradiation
Control of occult Chemotherapy
micrometastatic disease Hormone therapy
Improved function and cosmesis Breast-conserving therapy
Reconstruction (immediate or delayed)

27. Localized breast cancer
Surgery is mainstay
Halsted, 1882, radical mastectomy
John Hopkins
Metastatic breast cancer
Systemic treatment

28. Radical mastectomy
A. 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.

29. Modified radical mastectomy (MRM)
A. Entire breast is removed
Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed, called an axillary lymph node dissection.
MRM = simple mastectomy + ALND

30. Breast conserving surgery
Also called lumpectomy with safety margin with axillary clearance or sentinel lymph node biopsy
RT should be followed

31. Adjuvant systemic treatment
Hypothesis:
Eradicate micrometastasis
From effective treatment for overt (macro) metastasis
Chemotherapy
Hormone therapy

32. Adjuvant chemotherapy
CMF, first generation, 1970s
Cyclophosphamide
Methotrexate
5-FU
Benefit in
Distant recurrence
Survival

33. Adjuvant chemotherapy
CAF or CEF, 2nd generation, 1980s
Cyclophophamide
Adramycin(or Epirubicin)
5-FU
More toxic than CMF
CAF better than CMF in high-risk group
Axilla LN+
LN-, but tumor large or other risk factor

34. Adjuvant chemotherapy
Incorporate Taxane
TAC, 3rd generation, mid-1990s
Taxotere
Adriamycin
Cyclophosphamide
More toxic than CAF
Better than CAF in high-risk group
Need more time to observe

35. Adjuvant 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+ pts
ICH3+
FISH+
Herceptin + adjuvant chemotherapy
Optimal role to be defined
Concurrent or sequential?
Maintenance ? Duration

36. Adjuvant hormone therapy
In premenopausal woman
Oophorectomy could control metastatic disease
Tamoxifen
Selective estrogen receptor antagonist
Effective in pre- and post-menopausal
Effective in adjuvant setting

37. Adjuvant hormone therapy
Aromatase inhibitor
Effective in post-menopausal state
Aromatase, in fat tissue,
Convert androgen to estrogen
Main estrogen source in post-menopausal
Exemestane : Aromasin
Letrozole: Femara
Anastrozole: Arimidex
More effective than Tamoxifen

38. Adjuvant ovarian suppression
Effective in pre-menopausal state
Type
Surgical ablation
RT ablation
GnRH analogue: Goserelin, Leupride
Exact role to be defined
Combination with chemotherapy?
Combination with AI or TAM?

39. Radiation 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.

40. Treatment of metastatic dz
Usual sites: bone, lung, liver, brain
Incurable
Goal: live with dz for longest time
Systemic treatment is mainstay
Chemotherapy
Hormone therapy
Palliative local therapy
Radiotherapy
Palliative surgery

41. Thanks