Treatment options in breast

cancer management
Presenter Dr Aminu B
Moderator Prof Odigie
 outline
Introduction
Epidemiology
Classification
Investigation
Principles of treatment
Treatment/ Modality options
Complications
Recent advances
Conclusion
 Introduction
Breast cancer(ca) continues to be a big
challenge to surgeon, his patient, relations
and the govt
Breast cancer is the most common malignancy
in women, world wide. It accounts for 31% of
female cancers.
It is responsible for 15% of cancer deaths in
women.
In zaria 1 in 3-5 breast lumps is malignant
 Brief Epidemiology
Gender
Breast ca is relatively uncommon in men
the female-to-male ratio is approximately 100:1.
It accounts for < 1% of all cancer cases in men
The incidence of breast ca in men has remained
relatively stable over the past decades, except in Africa,
where the incidence is now rising and Chronic liver
disease/gynecomastia has been associated in Nigeria.
BRCA mutations are associated with an increased risk
for breast cancer in men.
 epidemiology
Age
Race
Geography
Socioeconomic status
Heredity, family history
Diet, alcohol, cigarette smoking
Exercise, obesity
Proliferative disease
menstrual history
Exogenous hormone use
Parity
Radiation exposure
 classification
1. CELLULAR
2. TNM
3. AJCC
4. PATHOLOGIC
5. MANCHESTER
Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Intraductal carcinoma, lobular carcinoma in situ, or Paget disease of the nipple with no associated invasion of
normal breast tissue
-Tis (DCIS): Ductal carcinoma in situ
-Tis (LCIS): Lobular carcinoma in situ
-Tis (Paget): Paget disease of the nipple with no tumor. T1: Tumor not larger than 2.0 cm in greatest dimension
T1mic: Microinvasion not larger than 0.1 cm in greatest dimension
T1a: Tumor larger than 0.1 cm but not larger than 0.5 cm in greatest dimension
T1b: Tumor larger than 0.5 cm but not larger than 1.0 cm in greatest dimension
T1c: Tumor larger than 1.0 cm but not larger than 2.0 cm in greatest dimension
T2: Tumor larger than 2.0 cm but not larger than 5.0 cm in greatest dimension
T3: Tumor larger than 5.0 cm in greatest dimension
T4: Tumor of any size with direct extension to (a) chest wall or (b) skin
T4a: Extension to chest wall, not including pectoralis muscle
T4b: Edema (including peau dorange) 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
N lymph nodes
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: Metastasis to ipsilateral axillary lymph
node(s) fixed or matted
N2a: Metastasis in ipsilateral axillary lymph nodes fixed to one another 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: Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node
involvement, smetastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or
internal mammary lymph node involvement
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)
M
Mx cannot be assessed
No metastasis
metastasis
 AJCC Stage Groupings
Stage 0
Tis, N0, M0
Stage I
T1s, N0, M0
Stage IIA
T0, N1, M0
T1, N1, M0
T2, N0, M0
Stage IIIA
T0, N2, M0
T1, N2, M0
T2, N2, M0
T3, N1, M0
T3, N2, M0
Stage IIIB
T4, N0, M0
T4, N1, M0
T4, N2, M0
Stage IIIC
Any T, N3, M0
Stage IV
Any T, Any N, M1
 Principles of treatment
1. Curative or palliative
2. Establish a diagnosis
-History
Complaint
Course of illness
Cause of illness
Complications
Current treatment received
-detailed physical examination
Investigations
3. Confirm your diagnosis
4.Extent of disease
-Optimise the patient
-Directs line of mgt
-Prognosis
-outcome
 Breast scan, USS
FNAC/CORE
Incision biopsy & histology,
SLN
receptor status
Mammogram of contra lateral side
Chest Xray
Abdomino pelvic USS
MRI
 Skeletal survey
FBC DIFF, platelet count, clotting profile
U/E LFT
Stool mcs
Treatment is multidisciplinary
The principal treatment modalities are;
Local
- Surgery
- Radiotherapy
Systemic
-Cytotoxic chemotherapy
-Hormonal therapy.
- immunotherapy/targetted therapy, monoclonal antibody

Either of which may be

1. Adjuvant
2. neoadjuvant
 surgery
The aims of local or loco-regional treatment
are:
1. to determine the tumour type and its
extent.
2. to eradicate local or regional breast cancer
and so improve survival.
3. to prevent local recurrence.
4. to reduce tumour burden and so improve
the efficiency of adjuvant therapy.
 The current operative procedures are:
1. Wide local excision (lumpectomy ,
quadrantectomy , segmental mastectomy)
with or without axillary lymph node clearance.
2. Total e.g. simple mastectomy without
axillary lymph node clearance.
4 modified radical mastectomy
 Contra-indications
(i) Tumour > 2cm/ or multifocal.
(ii) Widespread micro calcification
(iii) Adjacent carcinoma-in-situ
(iv) Marked intraductal component
(v) Poor cytological differentiation(vi) Lymphatic
vessel invasion.
(vii) A small breast
(viii) A centrally situated tumour.
(ix) Pregnancy
(X) A history of previous therapeutic irradiation.
 complications

i) The breast may become less attractive with

time.
ii) Fibrosis and gross asymmetry may occur.
iii) Radiation ulcer or necrosis , sarcoma may be
induced.
iv) There may be lymphoedema, nodularity or
firmness
of the skin which makes detection of local
recurrence, even by mammography , difficult.
v) Fear of recurrence
 modifications
Modified radical mastectomy
Patey-preserves p. major , sacrifices p. minor
to clear level i,ii,iii lymph nodes
Scalon divides p .minor to reach level iii
lymph nodes
Auchincloss-retracts p .minor to remove level
i, ii lymph nodes justifying this by the fact that
only 2% actually benefit from clearance of
highest level node
 The indications are:

i) Lack of facilities for radiation.

ii) Tumour > 2cm.
iii) Widespread microcalcification of the breast
on mammography .
iv) Duct carcinoma-in-situ or invasive carcinoma
found at themargin of a tumour mass or in the
tumour bed following wide local excision.
v) Poor cytological differentiation or marked intraductal
component within a tumour even if it is less than 2cm.
vi) Lymphatic vessel invasion even if the tumour is < 2cm.
vii) Toilet procedure for incurable carcinoma.
viii) A history of previous breast conservation with
irradiation.
However, some centres will do a second breast
conservation in selected patients i.e. those with a small
tumour and a breast big enough for a good cosmesis
 Post-operative complications
haemorrhage.
seroma (treated by repeated aspiration),
infection and shoulder stiffness.
Full axillary clearance may cause limb swelling,
and numbness, pain or weakness of the
shoulder, upper arm and axilla due to
severance of the intercostobrachial nerve
To reduce local recurrence(premenopausal)
from the fourth week of the menstrual cycle
to the third day of menstruation
At this time the level of oestrogen which
stimulates local growth factors,
- is low
-the progesterone level is high
- apoptosis is marked
 CHEMOTHERAPY
Neoadjuvant
first-line treatment for larger tumours
downstage the tumour prior to surgery
renders inoperable tumours operable
Adjuvant
chemotherapy following local treatment
reduces the risk of metastatic disease
 Overview of common chemotherapeutic
agents used in Breast cancer
Alkylating agents e.g. Cyclophosphomide
Cell cycle non-specific
Interfere with DNA synthesis
Antimetabolite (Folic acid antagonist) e.g.
5FU, methotrexate.
Inhibitor of nucleic acid biosynthesis
S-phase
 Vinca Alkaloids e.g. vincristine, vinblastine
Inhibit microtubules
M-Phase
Antibiotics e.g. Adriamycin, Epirubicin
Inhibit cell division by interfering with DNA
Taxanes bind to microtubules.
 Side effects
COMMON SPECIFIC
NAUSEA AND VOMITING RENAL TOXICITY

TIREDNESS UROTHELIAL TOXICITY

BONE MARROW SUPPRESSION HEPATIC TOXICITY

MUCOSITIS CARDIAC TOXICITY

DIARRHOEA OR CONSTIPATION PULMONARY FIBROSIS

SKIN PIGMENTATION PERIPHERAL NEUROPATHY

METABOLIC ABNORMALITIES VASCULAR AND HYPERSENSIVITY

REACTIONS
EARLY MENOPAUSE
DEAFNESS
MALE AND FEMALE INFERTILITY
SECOND MALIGNANCIES
 HORMONAL THERAPY
About 60% of ER+ and 80% of PR+ tumours
and their metastases
only 10% of receptor negative tumours
respondto hormonal therapy.
 Anti-oestrogens
Tamoxifen
It is a synthetic, non-steroidal, peripheral anti-
oestrogen
reduces circulating estradiol
binds the oestrogen receptors inhibiting
uptake of the growth-promoting oestrogen by
the tumour cells.
 It reduces oestrogen receptor content of
tumour
Its inhibition of angiogenesis aids its effect on
apoptosis
Tamoxifen has effects even on ER negative
tumours
Side effects nausea, vomiting, pigmentation
of the areola, hot flushes, pruritus vulvae.
Suppression of Adrenal Corticoids
Anastrozole
non-steroidal and inhibits conversion of
androstenedione to oestrone
Inhibits conversion of testosterone to estradiol.
The oestrogen level is thereby markedly reduced
usually by about 90%.
Others are
-aminogluthetimide
-corticosteroids
 Indications for hormonal therapy
Postmenopausal patients with ER' tumours
positive axillary nodes
For palliation patients
Preoperatively to shrink large ER+ tumours
and make them operable
 Factors Affecting Response to
Hormonal Therapy
Oestrogen/Progesterone receptors
Latent interval between treatment of primary
disease and the appearance of metastases
Relation to menopause: Premenopausal
patients respond best and menopausal patients
worst
Response to previous hormone therapy: A
patient
who has responded to the first line of hormone
therapy is likely to respond to the second line if
her tumour is ER+ or PR+.
 immunotherapy
Trastuzumab
Approximately 25% of patients with breast cancer
have tumors that overexpress HER2/neu
Trastuzumab is a humanized monoclonal
antibody
It binds to the HER2/neu receptor.
In patients previously treated with cytotoxic
chemotherapy whose tumors overexpress
HER2/neu, administration of trastuzumab as a
single agent resulted in a response rate of 21%
 RADIOTHERAPY
The indications for radiotherapy are:
After wide local excision and axillary lymph
node clearance for invasive carcinoma
2. Involvement of sampled axillary lymph
node after total mastectomy
(advanced) carcinoma: Radiotherapy for
alleviating pain,for controlling or treating the
local disease or recurrence.
 radiotherapy reduces the incidence of
locoregional metastases in early breast cancer
Down stage tumour
generally improve the overall wellbeing in
inoperable advanced breast ca
Elderly who do not have adequate reserve for
surgery
 radiotherapy
This can be done preoperatively or post
operatively
Main aim of preoperative radiotherapy is;
(1) Down stage a tumour eg fungating, fixed to
chest wall
(2) to make an inoperable tumour operable
(3) Haemostatic dose to control bleeding
(4) palliative
Postoperatively-aim
(1)Loco regional control-
-the higher T the more risk of tumour spill
intra op
-chance of axillary involvement
-supra clavicular involvement
(2)Include axilla, chest, supraclavicular,
internalmammary
 Methods are-external beam or teletherapy or
brachytherapy
EBRT=minimum distance is 80cm
Brachy therapy material is applied to bed via a
drain for breast, probe for cervix
Cobalt 60 machine is used
Principles
Avoid normal tissue
Give tangentially
Less than 2cm of lung field
Give time for normal cells to recover
Minimum of 6 days recovery time
 Total dose 1.2-2.0 grays
1 gry=joule
Conventional fractionation is done
Up to 50 gray is given
2 gry per fraction
For 50 gray =25 fractions
Over 5 weeks excluding weekends
 Some recommended protocols
DCIS TIS, NO, MO
Localized: Wide local excision plus irradiation.
Multifocal: Total mastectomy + axillary
clearance.
LCIS
Localized: Wide local excision plus irradiation.
Multifocal: (i) Total mastectomy + axillary
clearance.
(ii) Observation of contra lateral breast
Invasive Ductal (or Lobular) Carcinoma
A. Without palpable axillary lymph nodes
1. Tumour impalpable (ToNoM0) or palpable but
<2cm(Tl,NoM0)
Localized
(i) Wide local excision + axillary clearance + RT +HT
(ii) Total mastectomy + axillary clearance +HT+CCC
Multifocal:
Total mastectomy + axillary clearance + HT + CCC
Localized
(i) Wide local excision + axillary clearance + RT
+HT
(ii) Total mastectomy + axillary clearance +HT
+RT
Multifocal:
Total mastectomy + axillary clearance + HT +
CCC
B. With palpable axillary lymph nodes (T1a-
3a,N1, M0 ,Stage 2)
1. Neo-adjuvant hormonal chemotherapy
2. Total mastectomy + axillary clearance + CCC
and RT.
Paget's disease.
Total mastectomy + axillary clearance + HT
Advanced Carcinoma
A. Stage 3 (T 1b-3b N1-2, M0)
1. ER-
(i) CCC for 3 months (neo-adjuvant
chemotherapy).
(ii) Total mastectomy + axillary clearance
(iii) CCC for 3 more months
2. ER+
(i) HT (Tamoxifen lOOmg daily for 2 weeks).
(ii) CCC is started after 2 weeks. If there is response
to tamoxifen, it is continued 20mg daily.
(ii) Total mastectomy + axillary clearance.
(iii) HT + CCC depending on response in (i).
(iv) Irradiation of tumours not responding to
hormonal chemotherapy
B. Stage 4( T1-4 N0-2 M1) =As in (A)
Treatment should be individualised
Should meet pt needs
Wholistic overview of patient required
 complications
Surgery
Chemotherapy
Radiotherapy
others
 prognosis
The age and menopausal status of the patient.
The stage of the disease.
The histologic and nuclear grade of the
primary tumor.
The ER and PR status of the tumor.
The measures of proliferative capacity of the
tumor.
HER2/neu gene amplification.
 Recent advances
Laparoscopic surgery
Genetic screening & counselling
Prophylactic mastectomy
Targeted therapy
 conclusion
Incidence of breast cancer is rising
Management is multidisciplinary, mutimodal
and always a challenge
Pronosis is better with early detection