breast cancer

1. Breast Cancer (BC)
Dr. Alghazali

2. Learning Objectives
✓ Epidemiology
✓ Risk Factors
✓ The endocrine factors in breast cancer
✓ Genetic factors
✓ Intrinsic types of BC
✓ Pathophysiology and types
✓ Diagnosis
✓ Drug therapy plans
✓ Monitoring and evaluation

3. Epidemiology
❑Breast cancer is the most common type of cancer and second to lung cancer as a cause of cancer death in
American women.
❑Even the frequently is more in white women than any other ethnic group, the mortality rate is highest among
African Americans.
❑Tumor size of most breast cancers at diagnosis is usually small (< 2 cm), however, African American women have
proportionally more cases of advanced disease compared with white women

4. Factors associated with risk of developing the BC
The intrinsic components
➢Age
➢Gender
➢The endocrine factor
➢Family history
-A first degree relative (ie, mother or sister) with breast cancer is associated with a threefold
increase in risk.
-A second degree relative with breast cancer is associated with a 1.5fold increase in risk.
➢Genetic factors

5. The endocrine factors in breast cancer
✓Early menarche
✓Late menopause
✓Long term use of hormone replacement therapy appear to contribute to
breast cancer risk.
✓The endocrine factor most closely linked to breast cancer is estrogen

6. Genetic factors
➢Breast cancer genes (BRCA1 and BRCA2 )are
tumor suppressor genes
➢Women who carry mutations of BRCA1 or 2 have
a lifetime risk of breast cancer between 65% and
90%

7. Intrinsic types of BC
Subtype Tumor feature Treatment
Luminal A ER and PR both are positive, HER2
is negative, and low Ki67 (spread
sign)
Endocrine therapy
Luminal B (HER2 negative) ER is positive, PR is negative,
HER2 is negative, and high is Ki67
Endocrine + chemotherapy
Luminal B (HER2 positive) ER is positive, HER2 is positive Endocrine + targeted and
chemotherapy
HER2 amplified or overexpressed
(nonluminal)
HER2 is positive Targeted and chemotherapy
Basal (triple-negative) ER, PR, and HER2 are all negative Chemotherapy
Ki-67 score of 5% or less is considered low, and greater than 30% is considered high

8. Factors associated with risk of developing the BC
Extrinsic Components
➢Diet high in calories, fat, and cooked meats.
➢Obesity
➢Alcohol
➢Radiation

9. • Obesity in postmenopausal women and distribution
of body fat around the abdominal region also appear
to increase the risk of breast cancer
• A recent review provides compelling evidence of the
negative effect of obesity on overall survival (OS) in
patients.

10. Contralateral breast cancer
• It is the second tumor of breast which was diagnosed after 6 months of
the first cancer
• What is contralateral mastectomy

11. Breast anatomy
• Fatty tissues
• Lobes (lobules)
• Ducts
• Lymph nodes
• Lymph vessels
• Connective tissues

12. Pathophysiology
• Most of BC are genetic disease.
• Start by damaging of DNA which cause abnormal cell growth.
Results in:
➢The cell multiplies faster than normal
➢They don’t dies normally
➢Uncontrolled cells multiplying
➢Theses cells has the ability to spread out though the blood and lymphatic system

13. Types of BC
• Non-invasive
-Ductal Carcinoma
-Lobular Carcinoma
• Invasive
-Invasive ductal carcinoma
-Invasive lobular carcinoma
• Inflammatory breast cancer
• Paget’s breast disease
• Recurrent
• Metastatic

15. Clinical Presentation
Common early signs and symptoms include:
Painless lump (90% of cases) that is:
• Solitary (single)
• Unilateral
• Solid
• Irregular
• Non-tender

16. Uncommon early signs and symptoms include:
❖Nipple discharge (3% of women and 20% of men)
❖Eczema appearance of the nipple (Paget carcinoma)
❖Skin edema, redness, warmth, and induration of the underlying tissue
(inflammatory carcinoma)

17. The symptoms of metastases
❖Bone pain
❖Difficulty breathing
❖Jaundice
❖Mental status changes

18. Diagnosis
✓Physical examination of the breast
✓Three-dimensional mammography
✓Magnetic resonance imaging
✓A breast biopsy is indicated for a mammographic abnormality that
suggests malignancy

19. Stages of BC

20. Clinical Staging
% OF 5 YEAS SURVIVAL (DFS)
Stage I 70-90
Stage II 50-70
Stage III 20-30
Stage IV 0-10

21. Drug Therapy
❑Adjuvant therapy
❑Anti HER2 Therapy
❑Endocrine Therapy

22. Types of surgery:
• Mastectomy
Removal of the entire breast
• Lumpectomy
• It is a beast conserving surgery that used to remove cancer tissues in breast

23. Adjuvant therapy
➢Chemotherapy is usually initiated within 2 to 6 weeks from the surgical procedure
➢The efficacy of systemic therapy decreases if delayed more than 12 weeks following surgery.
➢Currently, four to eight cycles of chemotherapy is administered for 12 to 24 weeks.
➢Dose reduction for standard chemotherapy regimens should be avoided in the absence of severe
acute toxicity because of the negative impact on disease free survival (DFS) and overall survival
(OS)

24. Adjuvant therapy
The most cytotoxic drugs (adjuvant therapy) used in breast cancer are:
❖Alkylating agents: Cyclophosphamide
Side effects:
• Myelosuppression, hemorrhagic cystitis, alopecia, stomatitis, amenorrhea, aspermia
❖Anthracyclines (Daunorubicin, doxorubicin, epirubicin)
Side effects:
• Myelosuppression, cardiomyopathy, alopecia, nausea, vomiting, stomatitis, ulceration, red colored urine,
radiation recall effect and necrosis with extravasation

25. ❖Antimetabolities: Capecitabine, Gemcitabine, Fluorouracil, Methotrexate
Side effects:
• Diarrhea, palmar plantar erythrodysesthesia (hand–foot syndrome),
myelosuppression, stomatitis, nausea, vomiting
❖Vinca alkaloids : Vinorelbine
Side effects:
Neutropenia, Fatigue, nausea, vomiting, ulceration, and necrosis with extravasation

27. ❖Taxanes: Paclitaxel , docetaxel
Side effects:
• Myelosuppression,, alopecia, fatigue, stomatitis, nausea, vomiting, diarrhea,
peripheral neuropathy, nail disorder, skin reactions, hypersensitivity
reactions

28. Adjuvant Chemotherapy Regimens
Paclitaxel
Paclitaxel 175 mg/m2 IV over 3 hours. Repeat cycles every 21 days
or
Paclitaxel 80 mg/m2/week IV over 1 hour. Repeat dose every 7 days
Vinorelbine
Vinorelbine 30 mg/m2 IV, days 1 and 8. Repeat cycles every 21 days
or
Vinorelbine 25–30 mg/m2/week IV. Repeat cycles every 7 days
Liposomal Doxorubicin
Liposomal doxorubicin 30–50 mg/m2 IV over 90 minutes. Repeat cycles every 21–28 days

29. Adjuvant Chemotherapy Regimens
AC :
• Doxorubicin 60 mg/m2 IV for 1 day
• Cyclophosphamide 600 mg/m2 IV for 1 day
Repeat the cycles every 21 days for 4 cycles
FAC:
• Fluorouracil 500 mg/m2 IV, for 1 and 4 days
• Doxorubicin 50 mg/m2 IV continuous infusion over 72 hours
• Cyclophosphamide 500 mg/m2 IV for 1 day
Repeat the cycles every 21–28 days for 6 cycles
CAF:
• Cyclophosphamide 600 mg/m2 IV for 1 day
• Doxorubicin 60 mg/m2 IV bolus for 1 day
• Fluorouracil 600 mg/m2 IV for 1 day
Repeat the cycles every 21–28 days for 6 cycles

30. Adjuvant Chemotherapy Regimens
FEC:
• Fluorouracil 500 mg/m2 IV for 1 day
• Epirubicin 100 mg/m2 IV bolus for 1 day
• Cyclophosphamide 500 mg/m2 IV for 1 day
Repeat the cycle every 21 days for 6 cycles
Paclitaxel → FAC:
• Paclitaxel 80 mg/m2 /week IV over 1 hour every week for 12 weeks Followed by:
• Fluorouracil 500 mg/m2 IV for 1and 4 days
• Doxorubicin 50 mg/m2 IV continuous infusion over 72 hours
• Cyclophosphamide 500 mg/m2 IV for 1 day
Repeat the cycles every 21–28 days for 4 cycles
AC → Paclitaxel:
• Doxorubicin 60 mg/m2 IV for 1 day
• Cyclophosphamide 600 mg/m2 IV for 1 day
Repeat the cycles every 21 days for 4 cycles
• Paclitaxel 175 mg/m2 on 1 day

31. Anti HER2 Therapy
Trastuzumab, lapatinib, pertuzumab
➢It indicated in tumors greater than or equal to 0.5 cm in size.
➢Trastuzumab is given either following completion of the anthracycline or
concurrently with the taxane.
➢The duration of trastuzumab therapy is 12 months
➢All HER2 targeted therapy are cardiotoxic with 5% incidence of heart failure

32. Endocrine Therapy
Hormonal therapy consist of two classes:
➢Antiestrogens
➢Aromatase Inhibitors
➢ Estrogen receptors (ERs) and progesterone receptors (PRs) are cytoplasmic proteins that bind to nuclear DNA and function
as transcription factors.
➢ Approximately 50% to 70% of patients with primary and metastatic breast cancer have hormone receptor–positive tumors.

33. Hormonal therapies
Antiestrogens
• SERMs (Tamoxife, Toremifene)
Side effects:
Hot flashes, arthralgias, myalgias, headaches, diarrhea, mild nausea
• SERDs (Fulvestrant)
Side effects:
Hot flashes, injection site reactions, possibly thromboembolism

34. • LHRH Analogues (Goserelin, Leuprolide, Triptorelin)
Side effects:
Hot flashes, amenorrhea, menopausal symptoms, injection site
reactions
• Progestins (Megestrol acetate, Medroxyprogesterone)
Side effects:
• Weight gain, hot flashes, vaginal bleeding, edema,
thromboembolism

35. • Androgens (Fluoxymesterone)
Side effects:
Deepening voice, alopecia, facial or truncal acne, fluid retention, menstrual
irregularities, cholestatic jaundice

36. • Aromatase inhibitors
• Nonsteroidal: Anastrozole, Letrozole
• Steroidal: Exemestane
Side Effects:
• Hot flashes, arthralgias, myalgias, headaches, diarrhea, mild nausea

37. Monitoring and evaluation process
Physical examination to detect
breast cancer recurrence
Annual mammography
Pain evaluation
Mental status or other neurologic
findings
Laboratory tests
Liver function tests
Complete blood count
Calcium, electrolytes