breast cancer, diagnosis of breast cancer , aetiology of breast cancer, pathophysiologyy of breast cancers, drugs for the treatment of breast cancers, counselling points for breast cancers and education , surgical inyerventions in breast cancer, types of surgical intervention , chemotherapy in breast cancers,

1. BREAST CANCER Afra A. Y. Agyapong
1

2. OUTLINE
Introduction
Epidemiology
Causes/risk factors
Pathophysiology
Clinical Presentation
Management
Conclusion
2

3. INTRODUCTION
Breast cancer is the most frequently diagnosed life threatening
cancer in women, worldwide.
It arises from the tissues of the breast usually the ducts and
lobules
If diagnosed early, it is curable.
3

4. ANATOMY OF THE BREAST
Breast is the tissue overlying the pectoral muscles
Specialized tissues that produce milk
The amount of fat determines the size of the breast
Milk producing part of the breast is organized into 15-20 sections called
lobes
Within each lobe, there are smaller structures called lobules, where milk is
produced.
Connective tissue and ligaments provide support to the breast and give it its
shape
4

5. 5

6. EPIDEMIOLOGY
Occurs in both men and women
One in eight women are expected to develop the disease over
the course of their lifetime.
Incidence rates have declined from 1994 due to decreased use
of hormone replacement therapy
6

7. RISK FACTORS
Gender: Female> Male
Personal history of breast cancer
Family history of breast cancer
Early menarche (<12yrs)
Late menopause (>55yrs)
Late first pregnancy (>30yrs)
Long term use of hormone replacement therapy (estrogen)
Inherited gene BRCA 1 and BRCA 2
Oral contraceptives???
7

8. PATHOPHYSIOLOGY
Cancers arise through a series of molecular alterations at the
cell level
Discrete breast tumor subtypes with distinct etiopathogenesis
and clinical behavior
Exact number of subtypes and molecular alterations are not
known but involve the presence or absence of
• estrogen and progesterone receptors
• human epidermal growth factor 2 receptors
8

9. BREAST TUMOR SUBTYPES
9
Cancer subtype Hormonal receptor HER-2 receptor Distinct characteristics
Luminal A ER and/or PR positive HER-2 negative Low grade, tend to
grow slowly, has the
best prognosis
Luminal B ER and/or PR positive HER-2 negative Grow faster than
Luminal A because of
high levels of protein
ki-67
Triple negative Breast
cancer
ER and PR negative HER-2 negative Grows and spreads
fast. Common in
younger women and
people with BRCA1
gene mutation
HER-2 positive ER and PR negative HER-2 positive Grow faster than
luminal cancers.
Usually has the worst

10. TYPES OF BREAST CANCER
ACCORDING TO % OCCURRENCE
Invasive
•Invasive ductal carcinoma: most common type
•Invasive lobular carcinoma
Non invasive
•Ductal carcinoma in situ
•Lobular carcinoma in situ
Inflammatory breast cancer
10

11. DIAGNOSIS
Patient history
Physical examination
Imaging (Mammogram & Ultrasound)
Biopsy
11

12. CLINICAL PRESENTATION
Identification of painless lump in the breast
Nipple discharge or retraction
Skin changes in the breast (peau d’orange?)
Metastatic disease (10% pf patients)
12

13. STAGING OF BREAST CANCER
Done to evaluate the extent of the disease and determine best
treatment course
Stage I- small tumors (< 2cm) with no lymph node involvement
Stage II- small tumors with lymph node involvement or larger
tumors (>2cm and < 5 cm)
Stage III- Larger tumors (>5cm) with lymph node involvement
Stage IV-Metastasized to other organs.
13

14. PROGNOSTIC FACTORS
Larger tumor size
Presence of disease in lymph nodes
Estrogen and progesterone receptor negative tumors
HER-2 positive tumors
14

15. MANAGEMENT
1. Surgery: lumpectomy, mastectomy
2. Radiotherapy
3. Neoadjuvant therapy and Adjuvant therapy
• Hormonal therapy: SERM, LHRH agonists, aromatase inhibitors,
anti-estrogens
• Chemotherapy: Doxorubicin, Docetaxel, cyclophosphamide,
fluorouracil
• Targeted therapy: Trastuzumab, Neratinib, Pertuzumab
15

16. MANAGEMENT (CHEMOTHERAPY)
16
DRUGS MOA DOSAGE SIDE EFFECTS
Doroxucibin Anthracyclines:
inhibits
topoisomerase II
function
45-60mg/m2 IV 3
wks
Not to exceed
cumulative dose
of 450-500
mg/m2
Cardiotoxicity due
to formation of
oxygen free
radicals, alopecia,
leukopenia
Paclitaxel Taxanes: Binds to
beta subunit of
microtubules,
inhibit mitosis
80mg/m2/ wks IV Nausea vomiting,
myelosuppression
, neuropathy,
hypersensitivity
Cyclophasphamid
e
Inhibits DNA
synthesis by
forming cross
links with DNA
600mg/m2 IV Leukopenia,
alopecia,
vomiting,
myelosuppression

17. MANAGEMENT(TARGETED THERAPY)
Given to target HER-2 positive breast cancers
17
Medication MOA Dosage Side effects
Trastuzumab Monoclonal
antibody
5.4mg/ kg IV
3 wks
Fever,
neutropenia
Pertuzumab Monoclonal
antibody
840 mg IV
loading dose,
then 420 mg
3wks
Fever, allergic
reaction,
Neratinib
(Cancer
growth
blocker)
Block
signaling
process
cancers use to
240mg PO
daily for a
year
UTIs, Nose
bleed
diarrhea

18. MANAGEMENT (HORMONAL THERAPY)
DRUG dosage Side effects MOA
LHRH agonists
Leuprolide
Goserelin
7.5mg IM depot
28days
30mg IM 4 mths
3.6mg SC depot 28
days,
10.8 mg SC 3mths
Bone mineral density
depletion
Used in pre-
menopause
Inhibit pituitary
release of LH and FSH
Aromatase inhibitors
Anastrozole
Letrozole
Exemestane
1mg PO daily
2.5mg PO daily
25mg PO daily
Alopecia, decreased
appetite, diarrhea, hot
flash, joint disorders
Used only in post-
menopause. Inhibit
enzyme aromatase
SERM
Tamoxifen
Raloxifen
20mg PO daily 5 yrs
60mg PO daily 5 yrs
Hot flashes, vaginal
discharge, embolism
Vasodilation, leg
cramps
Used in both pre &
post menopause.
Blocks estrogen from
binding to receptor.
Anti-estrogen drug 500mg IM on days Nausea vomiting, hot Binds to estrogen
18

19. PREVENTION
Prophylactic Mastectomy
SERM: Tamoxifen and raloxifene
Raloxifen is considered as effective as tamoxifen in prevention
with less toxicity such as thromboembolic events and uterine
cancer
19

20. REFERENCES
Koda Kimble, Mary A and Loyd Y (2012).Applied therapeutics: the clinical use
of drugs. 10th edition. Baltimore Md. Lippincott Williams & Wilkin pp. Page
2201-2209
Pathak M., Dwivedi S. N., (2018). Neoadjuvant chemotherapy regimens in
treatment of breast cancer: a systematic review and network meta-analysis
protocol. Syst Rev. 2018; 7: 89. doi: 10.1186/s13643-018-0754-1
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of
chemotherapy and hormonal therapy for early breast cancer on recurrence
and 15-year survival: an overview of the randomized trials. Lancet.
2005;365:1687
Kuchenbaecker K. B et al. (2017) Risks of breast, ovarian and contralateral
breast cancer for BRCA 1 andBRCA2 mutation carriers. JAMA 2017; 317(23):
2402-2416.
The British National Formulary (2020), 80th Edition, the pharmaceutical Press.
20

21. American Society of Clinical Oncology (2020). Selection ofOptimal
Adjuvant Chemotherapy and Targeted Therapy for Early Breast
Cancer: ASCO Guideliine Update. J Clin Oncol 38.
ascopubs.org/journal/jco. Doi:
https://doi.org/10.1200/JCO.20.02510
21

22. 22