Breast cancer

Mahmoud El-Gantiry
Prof. of Radiation Oncology
National Cancer Institute
Cairo University
 Breast Cancer (BC)
Epidemiology:
A. Incidence:
Breast cancer is the most common lethal
neoplasm in women.
The incidence varies among different populations
1 out of 8 women will have BC in her life-time.
~ 25 percent of women with cancer have BC.
The incidence of male breast cancer is about 1 %
of all breast cancer cases occur in men.
 Clinical Presentation
The majority of carcinoma in situ, T1, or T2:
– Painless or slightly tender breast mass or have an
abnormal screening mammogram.
Patients with more advanced tumors:
– breast tenderness, skin changes, bloody nipple
discharge, or occasionally change in the shape and
size of the breast.
Rarely patients may present with axillary
lymphadenopathy (which occasionally may be
painful) or
distant metastasis.
FIGURE 50-7. Clinical staging of carcinoma of the
breast. Stages, in part, reflect curability by surgery
and radiation therapy (locoregional modes).
TABLE 50-3. Diagnostic workup
 Treatment
Operable (T1-3,N1?2,M0)
Curative intent.
Locoregional treatment
– Mastectomy + PORT
– OR conservative surgery + Radical RT.
Adjuvant systemic therapy:
– CTh + Hormonal therapy.
 Treatment (cont.)
Locally advanced (T+3-4,N?2-3,M0)
? Curative intent.
Neoadjuvant CTh.
(according to the response)
– Locoregional treatment
Mastectomy + PORT
OR RT alone.
Systemic therapy:
– CTh + Hormonal therapy.
 Treatment (cont.)
Advanced metastatic disease:
(any T, any N, M1)
Palliative intent.
Factors affecting treatment decision:
– Menstrual states.
– Site of metastases (vital organs).
– Extent of the disease.
– Performance status and age.
Treatment:
– Systemic therapy, RT, Surgery, trials of new therapy
and supportive treatment.
Role of RT in Breast Cancer
Preoperative RT.

Post-mastectomy RT.

Conservative surgery + RT.

Palliative RT.
Role of RT in Breast Cancer
Preoperative RT.

Post-mastectomy RT.

Conservative surgery + RT.

Preoperative RT
Locally advanced disease.

Aim: ??? Convert to Operable.

Rarely used now.

Role of RT in Breast Cancer
Preoperative RT.

Post-mastectomy RT.

Conservative surgery + RT.

Palliative RT.
PORT
Rational:
Minimal tumor bulk after surgery, better
controlled by moderate dose.
Accurate mapping of the volume after the
operative and pathology reports.
Minimal effect on wound healing.
No delay of surgery; the definitive treatment.
Isolated local recurrences with or without post-mastectomy radiotherapy:
2/3 proportional reduction in local recurrence in all studies, old and new.
PORT
Indications:
Patients with T3 and T4 tumors.

> 4 Positive axillary lymph nodes.

Residual disease.
PORT
Technique:
Comprehensive PORT is generally used to
irradiate the chest wall and peripheral
lymphatics using megavoltage beam.

Optimal technique is used to minimize the

dose to the underlying lung and heart.
PORT
Advantages:

PORT decreases local recurrence from

10-40% (according to extent of surgery)
to less than 5%.

PORT improves disease-free survival

(DFS) and overall survival (OS).
PORT
Complications:
Acute: general malaise, nausea and
skin desquamation.
Late: lung, heart, skin and soft tissues.
– Sub-optimal RT techniques in the past
resulted in excess cardiac deaths.
– Modern radiation techniques reduced heart
dose which decreased cardiac deaths and
improvement of OS.
Role of RT in Breast Cancer
Preoperative RT.

Post-mastectomy RT.

Conservative surgery + RT.

Palliative RT.
Conservative breast therapy (CBT)
Surgery (? Lumpectomy + ? axillary LN)
+ Radical RT.
+ Adjuvant Systemic therapy.
CBT (cont.)
Absolute contraindications:
First or second trimester of pregnancy.
Previous radiotherapy to the breast.
Two or more gross tumors in two different
quadrants.
Diffuse malignant appearing
microcacifications.
CBT (cont.)
Relative contraindications:
Large tumor / breast ratio.
Central tumors.
Large pendulous breast.
Collagen vascular (connective tissue)
diseases.
Age.
Extensive In-Situ Carcinoma (EIS).
The extent of the safety margin
Overall survival in EORTC trial comparing
breast-conserving with MRM in early stage

100
90
80
Overall survival %

70
60
50
40
30
20 Overall log-rank test: P =0.1119
10
0 (years)
0 2 4 6 8 10 12 14 16 18
O N Number of patients at risk : Treatment
165 420 401 366 329 289 266 194 82 14 Mastectomy
208 448 420 389 347 316 282 215 96 17 BCT
BCT
Role of RT
I- Is RT essential?
II- The RT volume.
III- The RT dose.
IV- The RT boost.
BCT
RT (cont.)
I- Is RT essential?

FIGURE 50-10B. Event-free survival of women treated by lumpectomy

(open circles) or lumpectomy and radiation therapy (closed circles).
(Fisher B, Costantino J, Redmond C, et al: Lumpectomy compared with
lumpectomy and radiation therapy for the treatment of intraductal
breast cancer. N Engl J Med 328:1581-1586, 1993)
Cumulative incidence of noninvasive and invasive
ipsilateral breast cancers in women treated by
lumpectomy (open circles) or lumpectomy and
radiation therapy (solid circles).

lumpectomy
lumpectomy

Lumpectomy + RT Lumpectomy + RT
BCT
RT (cont.)
II- The RT volume:
The treatment portal for the breast only, in patients with < 3 + ve LN who
receive adjuvant chemotherapy.
BCT
RT (cont.)
II- The RT volume (cont.).
(A and B) Examples of localization films of tangential
breast portals demonstrating the amount of lung to
be included in the field.
Irradiation of the breast. Field configurations and isodose lines for 6-MV
photons. (A) "Standard tangents" technique.
(B) Deep tangents technique.
(C) En face internal mammary field (IMF) technique.
(D) Twenty-degree IMF technique.
BCT
RT (cont.)
III- The RT dose.
Whole breast + Peripheral lymphatics:
5000 cGy / 25 fractions / 5 weeks
Or its biological equivalent dose.
BCT
RT (cont.)
IV- The RT boost.
Patients after Bt RT (n = 5318) were
randomised between a boost of 15-16 Gy
or no boost.
Age: The most important prognostic factor.
– Patients < 41: Local failure rate was reduced
at 5 years from 19.5 to 10.2%.
– Patients > 50: limited benefit of boost.
Role of RT in Breast Cancer
Preoperative RT.

Post-mastectomy RT.

Conservative surgery + RT.

Palliative RT.
Palliative RT:
Definition: It is treatment of symptomatic
manifestations of incurable disease.

Aims:
1. Control troubling symptoms.
2. Improve quality of life and
3. Occasional improvement of survival.
Palliative RT (cont.):
Indications
Advanced loco-regional disease:
- control of bleeding, pain and infection.
Distant metastases:
- Bone.
- Brain.
- Others e.g. choroid mets., soft tissues.
Ovarian castration:
Palliative RT (cont.):
Conclusions:
Palliative RT in advanced breast cancer is:
Effective,
Convenient,
Cost effective,
with Tolerable side effects.
 Local control in EORTC trial 22881 evaluating the boost in breast-conserving
therapy in early stage breast cancer .
At 5 years local control without boost is 93.2% (92.2 - 94.3) and with a boost of
15-16 Gy 95.7% (94.8 - 96.6 %)

100
90

CR No Boost
CR15 Gy

(years)
0 2 4 6 8 10 12
Breast Cancer (BC)
Etiology:
The variation of incidence among
different populations:
? Environmental factors: e.g. high
consumption of dietary fat, sugar.

? Genetic factors especially in younger

women.
BC etiology: (cont)
Environmental factors:
The best established etiologic agent is
exposure to radiation:
(especially at 10-14 years –Dose: 10 -100 rem)
– Pulmonary TB.
– RT to HD patients.
– RT to postpartum mastalgia.
Diet: high content of fat and sugar.
Hormones: Higher incidence in nullipara,
early menarche, late menopause and first
pregnancy after 30 years.
? A viral etiology
BC; Etiology (cont)
Hereditary Factors:
Familial aggregations of breast cancer occur
in ~ 18 % of cases, but only ~ 5 % are familial
based on extended pedigree analysis.
Mutations in the tumor-suppressor gene p53
The highest risk is among positive BRCA1 and
BRCA2 (+++Jewish women).
The disease occurs at an earlier age and ??
bilateral in patients with familial breast cancer.
It may be associated with carcinomas in other
sites (especially the colon, ovary, or uterus).
Other risk factors:
Gross cystic disease, atypical hyperplasia
and multiple papillomatosis,
- Most forms of benign breast disease
do not predispose BC

Lobular carcinoma in situ carries a 30

percent risk of invasive cancer.
Factors known to decrease risk:
Asian ancestry.

Term pregnancy before age 18 years.

Early menopause , Surgical castration

before the age of 37 years.
Factors having no effect on risk
(previously thought to be risk factors):

Multiparty.

Lactation.

Breast feeding.
TABLE 50-6. American Joint Committee
histopathologic classification of breast tumors.
(NOS, not otherwise specified).
 Statements of evidence
I Ia Evidence obtained from meta-analysis of randomized controlled trials.
Ib Evidence obtained from at least one randomized controlled trial.
II IIa Evidence obtained from at least one well-designed controlled study without
randomization.
IIb Evidence obtained from at least one other type of well-designed quasi-
experimental study.
III Evidence obtained from well-designed non-experimental descriptive studies,
such as comparative studies, correlation studies and case studies.
IV Evidence obtained from expert committee reports or opinions and/or clinical
experiences of respected authorities.
Grades of Recommendations
A. Systemic Review and Randomised controlled trial. (Evidence levels I)
B. Well conducted non-randomized studies (levels II and III)
C. Expert committee reports or opinions and/or clinical experiences of
respected authorities. (Evidence level IV)
Role of RT in Breast Cancer
Post-mastectomy RT.

Conservative surgery + RT.

Palliative RT.

Preoperative RT.
PORT
CONTROVERSIES:
I- Improved Loco-regional control BUT No
improvement of overall survival.
II- The role of PORT in stage T1-2, M 0 with
+ve 1-3 LN.
III- Timing of RT (radical or PORT) and
adjuvant CTh.
PORT
CONTROVERSIES:
I- Improved Loco-regional control BUT No
improvement of overall survival.
II- The role of PORT in stage T1-2, M 0 with
+ve 1-3 LN.
III- Timing of RT (radical or PORT) and
adjuvant CTh.
PORT
Evidence-Based:
Two recent large randomized trials:
– The Danish Cooperative Breast
Group, 1997.
– British Columbia study, 1997.
– Meta-analysis of all previous chest
wall irradiation studies, 2000.
All showed improvement in DFS
and OS.
PORT
Why earlier studies have failed to
pick up a survival advantage?
Older RT techniques (before 1975):
– Significant increase of non-malignant
mortality i.e. cardiac mortality.
Modern RT techniques:
– lower doses to the heart.
– lower cardiac mortality.
– higher overall survival rate.
PORT
Conclusions:
PORT improves DFS and OS.

To obtain the maximum benefit we

should:
1- Treat the high risk patients.
2- Use the optimal RT technique.
PORT
CONTROVERSIES:
I- Improved Loco-regional control BUT No
improvement of overall survival.
II- Role of PORT in stage T1-2, M0 with
+ve 1-3 LN.
III- Timing of RT (radical or PORT) and
adjuvant CTh.
II- Role of PORT in stage T1-2, M0 with + ve 1-3 LN.

Controversial results.
Individualized.
Needs randomized trials.
PORT
CONTROVERSIES:
I- Improved Loco-regional control BUT No
improvement of overall survival.
II- The role of PORT in stage T1-2, M 0 with +
1-3 LN.
III- Timing of RT (radical or PORT) and
adjuvant CTh.
PORT
CONTROVERSIES:
III- Timing of RT (radical or PORT) and adjuvant CTh.

Controversial.

Adjuvant chemotherapy is to be given

first for 12 weeks (4 cycles).

Radiotherapy.

Rest of chemotherapy.