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‫الرحيم‬ ‫الرحمن‬ ‫هللا‬ ‫بسم‬
NOTES ON:
BREAST CANCER
Dr.Mostafa Hegazay
Background
 Excluding cancers of the skin, breast cancer is
the most common type of cancer in women in
the United States.
 Accounts for one of every three cancer diagnoses.
 An estimated 174,480 new invasive cases of
breast cancer were expected to occur among
women in the United States during 2007.
 About 2,030 new male cases of breast cancer
were expected in 2007.
Background
 The incidence of breast cancer rises after age
40.
 highest incidence (approximately 80% of invasive
cases) occurs in women over age 50.
 62,030 new cases of in situ breast cancer were
expected to occur among women during
2007.
 Approximately 88% will be classified as ductal
carcinoma in situ (DCIS).
Background
 2007 - estimated 40,910 deaths (40,460
women, 450 men)
 Ranks second among cancer deaths in
women.
 Mortality rates steadily decreased since 1990
 Larger decrease in women under 50
 Due to combination of earlier detection &
improved treatment
Five-Year Survival Rates
Stage 0 100%
Stage I 100%
Stage IIA 92%
Stage IIB 81%
Stage IIA 67%
Stage IIIB 54%
Stage IV 20%
Risk Factors
 Age—more prevalent in older women
 Exposure to natural estrogens
 First childbirth after age 30
 Age at menopause
 Obesity—estrogens stored in body fat
 Affluence
 High-fat diet
 Alcohol consumption
 Genetics/family history
Reducing Risk
 Having children at early age
 Breast feeding
 Healthy body weight
 Exercise
 Anti-estrogens
Symptoms
 New lump or mass
 painless, hard, uneven edges
 sometimes tender, soft, or rounded
 Swelling
 Skin irritation or dimpling
 Nipple pain or nipple turning inward
 Redness or scaliness of the nipple or breast skin
 Nipple discharge (other than milk)
 A lump in the underarm area
Breast Anatomy
 Breast
 Made up of milk-producing glands
 Supported and attached to the chest wall by ligaments
 Rests on pectoralis major muscle
 No muscle tissue
 Layer of fat surrounds the glands and extends
throughout breast
 Three major hormones affect the breast
 Estrogen, progesterone, and prolactin
Breast Anatomy
Breast Anatomy
 Breast contains 15–20 lobes
 Fat covers the lobes and shapes the breast
 Lobules fill each lobe
 Sacs at the end of
lobules produce milk
 Ducts deliver milk to the
nipple
Anatomy – the lymphatic
system
 Important to know if cancer has spread to the
lymph nodes
 The more nodes involved, the more likely it is
that the cancer may involve other organs.
 Affects treatment plan.
Anatomy – the lymphatic
system
Most lymphatic vessels
in the breast connect to
lymph nodes under the
arm (axillary)
•Also internal mammary
nodes
•Supraclavicular or
infraclavicular nodes
Types of Breast Cancer
 The earliest form of the disease is ductal
carcinoma in situ,
 comprises about 15-20% of all breast cancers and
develops solely in the milk ducts.
 Invasive ductal carcinoma,
 develops from ductal carcinoma in situ,
 spreads through the duct walls, and
 invades the breast tissue.
 Most common – 70-80% of cases
Types of Breast Cancer
cont’d.
 Cancer that begins in the lobes or lobules is
called lobular carcinoma.
 more likely to be found in both breasts.
 accounts for 10–15% of invasive breast
cancers.
 Both ductal and lobular carcinomas can be
either in situ, or self-contained; or infiltrating,
meaning penetrating the wall of the duct or
lobe and spreading to adjacent tissue.
Types of Breast Cancer
cont’d.
Less common types of breast cancer include the following:
 Inflammatory
 Medullary carcinoma (originates in central breast tissue)
 Mucinous carcinoma (invasive; usually occurs in
postmenopausal women)
 Paget disease of the nipple
 Phyllodes tumor (tumor with a leaf-like appearance that
extends into the ducts; rarely metastasizes) and
 Tubular carcinoma (small tumor that is often undetectable
by palpation)
Inflammatory Carcinoma
 frequently involves entire breast
 characterized by reddened skin
and edema caused by tumor
spread to lymphatic channels of
skin of breast
 usually without an underlying
palpable mass
 Is a clinical diagnosis verified by
biopsy of the tumor and
overlying skin.
 Key words: lymphatic
involvement of skin, peau
d'orange, orange-peel skin, en
cuirasse
Paget’s disease
 Crusty tumor of nipple
and areola, which may
be associated with
underlying tumor of
the ducts.
DCIS
 In Situ: Abnormal cells that have not escaped the
part of the body where they developed
 For Breast – abnormal cells in the lining of a milk
duct that have not invaded surrounding breast
tissue
 Appearance of being precancerous when viewed
under a microscope, but
 No ability to spread as cancer cells would
 After DCIS, increased risk of invasive breast
cancer from 2 to more than 8 times higher than
the risk found in general population
Grade (differentiation)
 Assigned by pathologist
 How close does the bx resemble normal
tissue
 Helps predict prognosis
 Lower number indicates slower-growing
cancer that is less likely to spread
 Higher number indicates a faster-growing
cancer that is more likely to spread
Grades
Grade 1 (well differentiated) cancers have
relatively normal-looking cells that do not
appear to be growing rapidly and are
arranged in small tubules.
Grade 2 (moderately differentiated) cancers
have features between grades 1 and 3.
Grade 3 (poorly differentiated) cancers, the
highest grade, lack normal features and tend
to grow and spread more aggressively
Grade: Bloom-Richardson
 Bloom-Richardson (BR) Score
 Frequency of cell mitosis
 Tubule formation
 Nuclear pleomorphism
 Bloom-Richardson Grade
 Low grade = BR score 3–5 = grade 1
 Intermediate grade = BR score 6, 7 = grade 2
 High grade = BR score 8, 9 = grade 3
Diagnosing Breast Cancer
 Mammogram
 MRI
 Ultrasound
 Biopsy
 Fine Needle Aspiration
 Core Needle Biopsy (stereotactic and other)
 Excisional biopsy (sometimes with wire localization)
 Lymph node dissection and Sentinel lymph node
biopsy
Sentinel Lymph Node Biopsy
.
Breast Cancer Staging (TNM)
Stage Tumor (T) Node (N) Metastasis (M)
Stage 0 Tis N0 M0
Stage 1 T1 N0 M0
Stage IIA T0 N1 M0
T1 N1 M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T0 N2 M0
T1 N2 M0
T2 N2 M0
T3 N1, N2 M0
Stage IIIB T4 any N M0
any T N3 M0
Stage IV any T any N M1
Treatment
 Surgery
 Mastectomy
 Lumpectomy
 Removal of axillary lymph nodes (for invasive cancers)
 Sentinel node biopsy
 Axillary dissection
 Radiation
 Usually after surgery
 Chemotherapy
 Combinations of drugs
 Hormone therapy
 Tamoxifen, others
Estrogen & Progesterone
Receptor Status
 Proteins on the surface of cells that can attach to
substances such as hormones, that circulate in
the blood.
 Normal breast cells & some breast cancer cells
have receptors that attach to estrogen and
progesterone.
 Play a role in the growth and treatment of breast
cancer.
 ER-positive tumors have a better prognosis and
are more likely to respond to hormone therapy
 About 2/3 breast ca contain at least one of these
 Higher percentage in older women
Premenopausal: Tamoxifen
 Ovaries produce estrogen, sent through
bloodstream directly to the breast
 Tamoxifen mimics estrogen
 Attached to receptors, keeping real
hormones out
Postmenopausal: Aromatase
inhibitors
 Produce most of their estrogen outside the
ovaries
 Generated through androgen hormones store
in fatty tissue and adrenal glands
 In a biochemical process started by the
enzyme aromatase, androgen is converted
into estrogen, into bloodstream and to breast
 Aromatase inhibitors “block” the process
Aromatase Inhibitors (AIs)
Steroidal AIs
Aromasin (exemestane)
Nonsteroidal AIs
Arimidex (anastrazole)
Femara (letrozole)
Many clinical trials showing significant results in
both reduced breast cancer relapse, as well as
reduced rates of metastatic disease
Now being studied in various scenarios with
Tamoxifen
HER2/neu Status
 human epidermal growth factor receptor 2
 A protein involved in normal cell growth
 Important in the control of abnormal or
defective cells that could become cancerous
 HER2/neu positive cancers have an excessive
amount of the HER2/neu cancer gene protein
in and around their cells.
Herceptin
 Considered a targeted therapy or an immune
treatment
 Given IV, once every 2-3 weeks
 Targets the HER2 protein production
 Helps stop the growth of the HER2 positive
cancer cells
 Helps prevent recurrence
Tests for HER2 Breast Cancer
IHC: ImmunoHistoChemistry – measures the
production of the protein by the tumor.
Ranked as 0, 1+, 2+ or 3+
3+ = HER2 positive cancer
FISH: Fluorescence In Situ Hybridization –
probes to look at the number of HER2 gene
copies in the tumor cell.
Treatment Options are
changing
 Intraductal (in situ) – no longer recommend total
mastectomy (recent)
 Treatment options may vary with age
 Brachytherapy (mammosite)
 Patients >45 or >50
 Node negative
 Small tumors
 Combinations of tamoxifen/AIs
 Avastin – new class of drug
 Blocks formation of blood vessels that supply tumors
THANK
YOU

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Breast cancer hegazy

  • 3. Background  Excluding cancers of the skin, breast cancer is the most common type of cancer in women in the United States.  Accounts for one of every three cancer diagnoses.  An estimated 174,480 new invasive cases of breast cancer were expected to occur among women in the United States during 2007.  About 2,030 new male cases of breast cancer were expected in 2007.
  • 4. Background  The incidence of breast cancer rises after age 40.  highest incidence (approximately 80% of invasive cases) occurs in women over age 50.  62,030 new cases of in situ breast cancer were expected to occur among women during 2007.  Approximately 88% will be classified as ductal carcinoma in situ (DCIS).
  • 5. Background  2007 - estimated 40,910 deaths (40,460 women, 450 men)  Ranks second among cancer deaths in women.  Mortality rates steadily decreased since 1990  Larger decrease in women under 50  Due to combination of earlier detection & improved treatment
  • 6. Five-Year Survival Rates Stage 0 100% Stage I 100% Stage IIA 92% Stage IIB 81% Stage IIA 67% Stage IIIB 54% Stage IV 20%
  • 7. Risk Factors  Age—more prevalent in older women  Exposure to natural estrogens  First childbirth after age 30  Age at menopause  Obesity—estrogens stored in body fat  Affluence  High-fat diet  Alcohol consumption  Genetics/family history
  • 8. Reducing Risk  Having children at early age  Breast feeding  Healthy body weight  Exercise  Anti-estrogens
  • 9. Symptoms  New lump or mass  painless, hard, uneven edges  sometimes tender, soft, or rounded  Swelling  Skin irritation or dimpling  Nipple pain or nipple turning inward  Redness or scaliness of the nipple or breast skin  Nipple discharge (other than milk)  A lump in the underarm area
  • 10. Breast Anatomy  Breast  Made up of milk-producing glands  Supported and attached to the chest wall by ligaments  Rests on pectoralis major muscle  No muscle tissue  Layer of fat surrounds the glands and extends throughout breast  Three major hormones affect the breast  Estrogen, progesterone, and prolactin
  • 12. Breast Anatomy  Breast contains 15–20 lobes  Fat covers the lobes and shapes the breast  Lobules fill each lobe  Sacs at the end of lobules produce milk  Ducts deliver milk to the nipple
  • 13. Anatomy – the lymphatic system  Important to know if cancer has spread to the lymph nodes  The more nodes involved, the more likely it is that the cancer may involve other organs.  Affects treatment plan.
  • 14. Anatomy – the lymphatic system Most lymphatic vessels in the breast connect to lymph nodes under the arm (axillary) •Also internal mammary nodes •Supraclavicular or infraclavicular nodes
  • 15. Types of Breast Cancer  The earliest form of the disease is ductal carcinoma in situ,  comprises about 15-20% of all breast cancers and develops solely in the milk ducts.  Invasive ductal carcinoma,  develops from ductal carcinoma in situ,  spreads through the duct walls, and  invades the breast tissue.  Most common – 70-80% of cases
  • 16. Types of Breast Cancer cont’d.  Cancer that begins in the lobes or lobules is called lobular carcinoma.  more likely to be found in both breasts.  accounts for 10–15% of invasive breast cancers.  Both ductal and lobular carcinomas can be either in situ, or self-contained; or infiltrating, meaning penetrating the wall of the duct or lobe and spreading to adjacent tissue.
  • 17. Types of Breast Cancer cont’d. Less common types of breast cancer include the following:  Inflammatory  Medullary carcinoma (originates in central breast tissue)  Mucinous carcinoma (invasive; usually occurs in postmenopausal women)  Paget disease of the nipple  Phyllodes tumor (tumor with a leaf-like appearance that extends into the ducts; rarely metastasizes) and  Tubular carcinoma (small tumor that is often undetectable by palpation)
  • 18. Inflammatory Carcinoma  frequently involves entire breast  characterized by reddened skin and edema caused by tumor spread to lymphatic channels of skin of breast  usually without an underlying palpable mass  Is a clinical diagnosis verified by biopsy of the tumor and overlying skin.  Key words: lymphatic involvement of skin, peau d'orange, orange-peel skin, en cuirasse
  • 19. Paget’s disease  Crusty tumor of nipple and areola, which may be associated with underlying tumor of the ducts.
  • 20. DCIS  In Situ: Abnormal cells that have not escaped the part of the body where they developed  For Breast – abnormal cells in the lining of a milk duct that have not invaded surrounding breast tissue  Appearance of being precancerous when viewed under a microscope, but  No ability to spread as cancer cells would  After DCIS, increased risk of invasive breast cancer from 2 to more than 8 times higher than the risk found in general population
  • 21. Grade (differentiation)  Assigned by pathologist  How close does the bx resemble normal tissue  Helps predict prognosis  Lower number indicates slower-growing cancer that is less likely to spread  Higher number indicates a faster-growing cancer that is more likely to spread
  • 22. Grades Grade 1 (well differentiated) cancers have relatively normal-looking cells that do not appear to be growing rapidly and are arranged in small tubules. Grade 2 (moderately differentiated) cancers have features between grades 1 and 3. Grade 3 (poorly differentiated) cancers, the highest grade, lack normal features and tend to grow and spread more aggressively
  • 23. Grade: Bloom-Richardson  Bloom-Richardson (BR) Score  Frequency of cell mitosis  Tubule formation  Nuclear pleomorphism  Bloom-Richardson Grade  Low grade = BR score 3–5 = grade 1  Intermediate grade = BR score 6, 7 = grade 2  High grade = BR score 8, 9 = grade 3
  • 24. Diagnosing Breast Cancer  Mammogram  MRI  Ultrasound  Biopsy  Fine Needle Aspiration  Core Needle Biopsy (stereotactic and other)  Excisional biopsy (sometimes with wire localization)  Lymph node dissection and Sentinel lymph node biopsy
  • 26. Breast Cancer Staging (TNM) Stage Tumor (T) Node (N) Metastasis (M) Stage 0 Tis N0 M0 Stage 1 T1 N0 M0 Stage IIA T0 N1 M0 T1 N1 M0 T2 N0 M0 Stage IIB T2 N1 M0 T3 N0 M0 Stage IIIA T0 N2 M0 T1 N2 M0 T2 N2 M0 T3 N1, N2 M0 Stage IIIB T4 any N M0 any T N3 M0 Stage IV any T any N M1
  • 27. Treatment  Surgery  Mastectomy  Lumpectomy  Removal of axillary lymph nodes (for invasive cancers)  Sentinel node biopsy  Axillary dissection  Radiation  Usually after surgery  Chemotherapy  Combinations of drugs  Hormone therapy  Tamoxifen, others
  • 28. Estrogen & Progesterone Receptor Status  Proteins on the surface of cells that can attach to substances such as hormones, that circulate in the blood.  Normal breast cells & some breast cancer cells have receptors that attach to estrogen and progesterone.  Play a role in the growth and treatment of breast cancer.  ER-positive tumors have a better prognosis and are more likely to respond to hormone therapy  About 2/3 breast ca contain at least one of these  Higher percentage in older women
  • 29. Premenopausal: Tamoxifen  Ovaries produce estrogen, sent through bloodstream directly to the breast  Tamoxifen mimics estrogen  Attached to receptors, keeping real hormones out
  • 30. Postmenopausal: Aromatase inhibitors  Produce most of their estrogen outside the ovaries  Generated through androgen hormones store in fatty tissue and adrenal glands  In a biochemical process started by the enzyme aromatase, androgen is converted into estrogen, into bloodstream and to breast  Aromatase inhibitors “block” the process
  • 31. Aromatase Inhibitors (AIs) Steroidal AIs Aromasin (exemestane) Nonsteroidal AIs Arimidex (anastrazole) Femara (letrozole) Many clinical trials showing significant results in both reduced breast cancer relapse, as well as reduced rates of metastatic disease Now being studied in various scenarios with Tamoxifen
  • 32. HER2/neu Status  human epidermal growth factor receptor 2  A protein involved in normal cell growth  Important in the control of abnormal or defective cells that could become cancerous  HER2/neu positive cancers have an excessive amount of the HER2/neu cancer gene protein in and around their cells.
  • 33. Herceptin  Considered a targeted therapy or an immune treatment  Given IV, once every 2-3 weeks  Targets the HER2 protein production  Helps stop the growth of the HER2 positive cancer cells  Helps prevent recurrence
  • 34. Tests for HER2 Breast Cancer IHC: ImmunoHistoChemistry – measures the production of the protein by the tumor. Ranked as 0, 1+, 2+ or 3+ 3+ = HER2 positive cancer FISH: Fluorescence In Situ Hybridization – probes to look at the number of HER2 gene copies in the tumor cell.
  • 35. Treatment Options are changing  Intraductal (in situ) – no longer recommend total mastectomy (recent)  Treatment options may vary with age  Brachytherapy (mammosite)  Patients >45 or >50  Node negative  Small tumors  Combinations of tamoxifen/AIs  Avastin – new class of drug  Blocks formation of blood vessels that supply tumors