breast cancer introduction and management

1. FULCHAN A
4TH PHARM D
FAROOQIA COLLEGE OF
PHARMACY, MYSORE-21

2. BREAST CANCER
 Malignancy originating from breast tissue
 Second most common cancer among women after skin
cancer.
 Commonly seen in women over 60 years old aged
people.
 Rarely seen in men, but their risk increases as the age
advances.
2

3. I. Breast Cancer Statistics
 Breast cancer is the second most commonly
diagnosed cancer among American women, after
skin cancer.
 Breast cancer is also the second leading cause of
cancer death among U.S. women, after lung cancer

4. Breast Cancer and Age
 Breast cancer incidence and mortality rates increase
with age.
 Between 1998 and 2002, 95% of all new cases and 97%
of breast cancer deaths occurred in women age 40 and
older.
 During this period, the median age at the time of
diagnosis of breast cancer was 61 years.

5. Epidemiology - Incidence
 One in three women will develop cancer in their
lifetime (living to 85)
 Breast cancer makes up one third of all cancers in
women

6. Mortality
 Breast Cancer is a “good prognosis” tumor
 Five year disease free survival is 81%
 Lifetime overall survival is 66%

7. Etiology/Risk factors of Breast
Cancer
 Family History of Breast Cancer.
 Puberty in very early age.
 Menopause occurred at later age.
 History of infertility.
 Those who had their first child after 40 years have an
increased risk of developing Breast Cancer.
 Estrogen therapy during post-menopausal period (5.2yrs).
 Obese women
 Women who drink more than moderate amounts of
alcohol.

8. SYMPTOMS OF BREAST CANCER
 Earliest symptom is often a lump or thickening in the
breast or under the arm.
 In the early stages the lump may move freely beneath
the skin when it is pushed with the fingers.
 During advanced stages the lump may adhere to the
chest wall or to the skin over it & cannot be moved.
 A change in the size, shape or contour of the breast or
in the appearance of the skin of the breast or nipple
can be a symptom of breast cancer.
 Sometimes the skin may appear puckered or dimpled.

9. SYMPTOMS OF BREAST CANCER
 The lump may be painful, but pain is an uncommon &
unreliable sign.
 A discharge from the nipple may occur.
 Sometimes the breast becomes red & swollen.
 Sometimes the breast feels normal, but the lymph
nodes in the underarm feel like hard small lumps &
may be slightly tender.

10. SCREENING OF BREAST CANCER
Experts recommend that all older women be
screened regularly for breast cancer.
Women are encouraged to examine their
breasts each month.
Experts recommend that women over 40
years have an annual breast examination.

11. SCREENING TESTS OF BREAST CANCER
Mammogram
Magnetic resonance imaging.

12. MERITS OF MAMMOGRAM
 It detects many cancers that are too small to feel.
 Mammography is designed to be sensitive enough to
detect the possibility of breast cancer at an early stage,
it may identify a suspected cancer when none is
present .
 If the mammogram is not completely normal, MRI
may be done.
 MRI is sometimes more sensitive for identifying small
cancers.
 However , MRI is even more likely to produce false –
positive results.

13. Prognosis Depends On:
1) Nodal Status
 The cancer spreads out to the lymph nodes
 Once it gets out of the breast it goes to other parts of
the body
 You want the cancer to be found before it spreads

14. Prognosis Depends On:
2) Size
 A cancer can be felt at about 2 cm, just under an inch
 Once it gets bigger than 2 cm it seems to become more
aggressive and more likely to spread

15. Prognosis Depends On
3) Grade
 Grade describes how aggressive the tumor is
 Low, intermediate and high grade
 The pathologist makes the determination by what is
seen under the microscope

16. Prognosis depends on
 Genetics
 Overexpression of erb-B2 oncogene, angiogenic growth
factors
 Mutations in tumour suppressor p53 gene

17. Abnormal Breast Development
 Excessive formation of breasts and nipples can occur
along the mammary ridges that extend along an
anterior line from the armpits to the thighs.
 Significant uneven development of the breasts may
occur.
 Hypertrophy of the breasts results in fibrous
overgrowth which can cause discomfort because of the
breasts’ excessive weight.
 Gynecomastia is the formation of a distinct nodule of
breast tissue under the nipple of pubescent males
because of the effects of female hormones. The tissue
may be surgically removed.

18. PATHOPHYSIOLOGY OF BREAST
CANCER
 The development of breast cancer occurs when breast
cells lose their differentiation and proliferation
controls.
 Various hormones, oncogenes & growth factors
influence the proliferation of these abnormal or tumor
cells.
 There is strong evidence to suggest that estrogen
directly & indirectly stimulates the growth of tumor
cells.

19. PATHOPHYSIOLOGY OF BREAST
CANCER
 Furthermore, numerous growth factors that also play a
role in tumor development are secreted by the breast
cancer themselves.
 These factors can be classified as either autocrine(if
they stimulate their own growth) or paracrine (if they
have an effect on other cells).
 Examples of the autocrine growth factors include
transforming growth factor alpha & insulin like growth
factors I & II (IGF-I & IGF-II).

20. PATHOPHYSIOLOGY OF BREAST
CANCER
 Transforming growth factor beta, platelet –derived
growth factor (PDGF) are all paracrine growth factors.
 The exact mechanism of tumor development is not
completely understood.
 The mechanism of action of several of the hormonal
agents used for the treatment of breast cancer involves
the alteration of the growth factors involved in tumor
development.

21. Staging
 Early breast cancer
 Stage 0 – carcinoma in situ or disease not invaded basement
membrane
 Stage I – small primary tumour without lymph node
involvement
 Stage II- Metastasis to ipsilateral axillary lymph nodes
 Locally advanced breast cancer
 Stage III – large tumour with extensive nodal involvement
where node is fixed to chest wall, inflammatory breast cancer
that is rapidly progressive
 Advanced or metastatic breast cancer
 Stage IV – Metastases to organs distant from the primary
tumour

22. Goals of therapy
 For early & locally advanced breast cancer
 Cure
 Metastatic breast cancer
 Improve symptoms
 Improve quality of life
 Prolong survival

23. Treatment
 Early breast cancer
 Local-regional therapy
 Systemic adjuvant therapy
 Adjuvant chemotherapy
 Adjuvant endocrine therapy
 Locally advanced breast cancer
 Primary/neoadjuvant/chemotherapy
 Metastatic breast cancer
 Endocrine therapy
 Chemotherapy

24. Early breast cancer – local
therapy
 Surgery alone can cure patients with in situ cancers
and half of those with Stage II cancers
 Breast conservation therapy preferable to radical
mastectomy
 Primary systemic or neoadjuvant therapy gaining
favour
 Axillary lymph node sampling or sentinel lymph node
biopsy for staging and prognostic information.

25. Systemic adjuvant therapy
 Administration of systemic therapy following surgery,
radiation or both.
 Preferable in all women with stage I & II, but absolute
benefit greater in premenopausal women
 Choice between chemotherapy, endocrine therapy or
both depends on patient factors
 Generally chemotherapy to be used in all women
irrespective of menopausal status, additional
endocrine therapy in women with receptor-positive
disease. (NCCN)

26. ADJUVANT CHEMOTHERAPY OF
BREAST CANCER
 Combination regimens derived from those that
produce highest response in advanced disease
 Doxorubicin containing regimens popular as they are
superior to CMF regimens and require only 4 cycles
 Taxanes –newer class with activity against metastatic
BC; in combination increase disease free survival in
node positive BC
 Chemo initiated within 3 weeks of surgical removal,
optimal duration of treatment – 12-24 weeks
 Short term toxicities of chemo countered by serotonin-
antagonists and CSF

27. CAF/FAC
 Cyclophosphamide 600 or 500mg/m2 IV day 1
 Doxorubicin 60 (or 50)mg/m2 IV day 1 (over 72 hr)
 Fluorouracil 600mg/m2 IV day 1 (or 500mg/m2 days
1,4)
 Repeat cycle every 21-28 days.

28. CMF
 Cyclophosphamide 100mg/m2 PO days 1-14 (or
600mg/m2 IV, day 1)
 Methotrexate 40mg/m2 IV days 1,8 (or day 1 only)
 Flurouracil 600mg/m2 IV days 1,8.
 Repeat cycle every 28 days.

29. AC regimen
 Doxorubicin 60mg/m2 IV day 1
 Cyclophosphamide 400-600mg/m2 IV day 1
 Repeat cycle every 21 days.

30. CEC /FEC
 Cyclophosphamide 75mg/m2 PO, days 1-14
(600mg/m2IV, day 1)
 Epirubicin 60 (or 100)mg/m2 IV, days 1, 8
 Fluorouracil 600 (or 500) mg/m2 IV, days 1,8
 Repeat cycle every 21 days

31. Adjuvant endocrine therapy
 Tamoxifen – gold standard due to extensive trial
experience showing decreased recurrence & mortality.
Beneficial effects on lipids & bone density
 20mg soon after chemo, continuing for 5 years.
 Other endocrine therapies have insufficient follow-ups
to assess impact on survival.
 Toremifene –alternative to tamoxifen, goserelin
(LHRH) for premenopausal women, aromatase
inhibitors for post menopausal women

32. Locally advanced breast cancer
 Surgery, radiation or both is insufficient to cure in this
stage.
 Neoadjuvant – initial treatment of choice
 Benefits include rendering inoperable tumours
resectable and increasing rate of breast-conserving
surgery.
 Combination chemotherapy similar to adjuvant
therapy, generally include anthracycline and taxane

33. Metastatic Breast cancer
 Choice of endocrine or chemotherapy based on
 Site of disease involvement
 Presence or absence of certain characteristics

34. Endocrine therapy
 Treatment of choice for patients who have hormone
receptor – positive metastase in soft tissue, bone or
pleura
 Sequentially treated with endocrine therapy until
rapidly growing metastatic disease, at which time
chemo is given
 Ovarian ablation (oophorectomy)- therapy of choice
in premenopausal women, similar response rates as
tamoxifen.
 Aromatase inhibitors block peripheral conversion of
androgens to estrogens, preferred in post menopausal
women

35. Endocrine therapies in metastatic
breast cancer

36. Chemotherapy
 Preferred in women with
 Hormone receptor – negative tumours
 Rapidly progressive lung, liver or bone marrow
involvement
 Failure or endocrine therapy
 Combinations produce complete response in < 10% of
patients
 Single agents associated with lower response rates with
similar time to progression & overall survival and are
better tolerated.

37. Targeted therapy
Trastuzumab, monoclonal antibody – binds to Her-2
protein- produces response rates of 15-20% as single
agent.
Prolongs survival when combined with chemo

38. Thank You