Management of Breast Cancer

Management of Breast Cancer

Dr. Khdair El-Rawaq

Frame

Breast anatomy
Epidemiology
Risk factors
Staging
Diagnostic Work-up
PROGNOSTIC FACTORS
Management
Management of Early stages
Management of Late stages
Palliative Management

Br LymphaticsA :PM muscleB : level IC : level IID : level IIIE :SCVF: IMN

EpidemiologyIncidence (In the year of 2008)
Breast cancer is the second most common cause of death for women .
the most common cause of death for women aged 45 to 55..
it is predicted that 215,990 American women will be diagnosed with breast cancer and that 40,110 women will die from this disease


Incidence per 100,000 in USA

Epidemiology

Breast cancer incidence has long varied in different regions of the world. Incidence is highest in Northern Europe and North America and lowest in Asia and Africa .
Mortality rates declined by 1.4% per year from 1989 to 1995 and thereafter by 3.2% per year. This is thought to be due in part to increased use of mammography, resulting in earlier diagnosis, and the use of effective treatments.

Risk factors

Age >50
Personal or family Hx
Nulliparity
First child > 30 yrs
Jewish- black
Lactation (longer time) (Lancet 2002:360:187-195)
Early menarche- late menopause
Exposure to ionizing radiation
Alcohol increases risk of breast cancer

Risk factors

The relationship between high BMI and ↑ BC risk is seen for postmenopausal F Due to ↑ levels of estrogens, particularly free estradiol (Trentham-Dietz A; Cancer Causes Control 2000 Jul;11(6):533-42.)

Risk factors

Oral contraceptive agents More than 10 yrs : risk x2 in >55 yrs (Van Hoften et al. Int J Cancer 2000)A large meta-analysis → a small but significant increase in relative risk of breast cancer (RR =1.24) in current OCP users Lancet 1996 Jun 22;347(9017):1713-27.


Staging
changes in the AJCC staging criteria from 1988 to 2002 affect stage-specific outcomes.

It has been demonstrated that reclassification will result in improved outcomes.

Staging
A recent study examined overall stage-specific survival using both staging systems for a total of 1350 patients.
It was noted that only 55% of patients who were classified as having stage II disease according to the 1988 system had stage II according to the 2002 system. However, in direct comparison, the number of patients with stage III disease increased by 114%.

Diagnostic Work-up for Carcinoma of the Breast

History
Physical examination
Biopsy
Radiologic studies
Laboratory studies

History

with emphasis on
presenting symptoms (Br. lump, nipple retraction),
menstrual status,
parity,
family history of cancer,
other risk factors.


Physical examination
with emphasis on
breast, (Lt>Rt, 5 yrs to reach palpable size)
axilla(10-40% of T1,T2 have pathologic +ve LNs)
supraclavicular area,
abdomen

Biopsy

core biopsy directed by physical examination, ultrasound, or mammography as indicated, or needle localization.
Complete agreement between the core biopsy and subsequent histologic sections was reached in 89.7% of lesions and partial agreement in 9.2%

Radiologic studies

Laboratory studies
Complete blood cell count, blood chemistryUrinalysisOther studies Hormone receptor status (ER, PR) HER2/neu status,Tumor marker level (CD 153 preop level , in bone mets)Consider genetic counseling/BRCA testing in selected cases, mutated P53

PROGNOSTIC FACTORS

Intrinsic factors

PROGNOSTIC FACTORS

The only accepted prognostic markers that provide critical information necessary for treatment decisions are
TNM stage
axillary LN status
tumor size
grade
lymphatic or blood vessel invasion
hormone receptor status
HER-2 neu oncogene


PROGNOSTIC FACTORS Extensive intraductal carcinoma
>25% of the primary tumorAssociated with higher incidence of breast recurrence in some studiesDoes not affect DFS or OAS if –ve margins (Hurd et al. Ann Surg Oncol 1997)

PROGNOSTIC FACTORS Involvement of axillary LN

Direct relation bet + axillary LNs and chest wall recurrence and survival
(Haagensen. IJROBP 1977)

PROGNOSTIC FACTORS

Data are insufficient to recommend use of
p53 measurements
cathepsin D measurements
estimates of DNA content or S phase in breast tissue

PROGNOSTIC FACTORS

Extrinsic factors
Age (<45 V >45)
Race (black V white)

CHEMOPREVENTIONBreast Cancer Prevention

An ASCO working group published an assessment of tamoxifen use in the setting of breast cancer risk reduction.
All women older than 35 years of age with a Gail model risk of > 1.66% (or the risk equivalent to that of women 60 years of age) should be considered candidates for Breast Cancer Prevention therapy


Management of Early stages  Breast Cancer
early-stage breast cancer, ie, stages 0 ,I andII disease.Stage 0 breast cancer includes noninvasive breast cancer—lobular carcinoma in situ (LCIS) ductal carcinoma in situ (DCIS)Paget’s disease of the nipple when there is no associated invasive disease.

DCIS DEFINITION

Confined to the ductal system of the breast
No evidence of invasion:
No disruption of BM
No involvement of surrounding breast stroma
No risk of mets
ALN +(0-5%) ?focus of invasive ca

MANAGEMENT

BREAST CONSERVATION +/- RT
Metaanalysis Local RR at 5 yrs 22.5% vs 8.9%

Greatest improvement in local control with RT

Necrosis
high grade features
comedo subtype
Boyages and colleagues, Cancer 1999
Other option is mastectomy
Tamoxifen


Stage I and II disease
Multiple studies have demonstrated that patients with stage II breast cancer who are treated with either
breast-conservation therapy (lumpectomy and radiation therapy) or
modified radical mastectomy
have similar disease-free and overall survival rates.

Management of Late stages  Breast Cancer

This addresses the management of locally advanced, locally recurrent, and metastatic breast cancer, ie,
stages IIIB,C and IV disease.
Rates of locoregional recurrence may vary from < 10% to > 50%, depending on initial disease stage and treatment.

Management of Late stages  Breast Cancer

Neoadjuvant systemic therapy
can downstage locally advanced disease and render it operable
may allow breast-conservation surgery to be
Performed.
The majority of patients receiving neoadjuvant chemotherapy, treated with either breast conservation or mastectomy will require radiation therapy following surgery.

Metastatic disease

Metastatic disease is found at presentation in 5% to 10% of patients with breast cancer.
The most common sites of distant metastasis are the lungs, liver, and bone.


Low-risk patients, (elderly)
Low-risk patients, elderly whose tumor is hormone receptor-positive (ie, estrogen receptor-positive and/or progesterone receptor-positive), may be treated with a trial of Hormone therapy
First-line hormonal therapy consists of an aromatase inhibitor
tamoxifen

Hormone-refractory disease can be treated with

Cytotoxic agents systemic cytotoxic therapy.
FAC, paclitaxel, TAC (Taxotere[docetaxel], Adriamycin [doxorubicin], cyclophosphamide), or docetaxel may be used in this situation

Intermediate- or high-risk patients

include those with rapidly progressive disease or visceral involvement, as well as those with disease shown to be refractory to hormonal manipulation by a prior therapeutic trial. Those treated by:
Cytotoxic agents systemic cytotoxic therapy
Monoclonal antibody therapy(Trastuzumab ,Lapatinib) and
targeted agents (Avastine)

High-dose chemotherapy Patients who present with or subsequently develop distant metastasis.
Adjunctive bisphosphonate therapy
Use of these agents results in a significant reduction in skeleton-related events, including pathologic fracture, bone pain, and the need for radiation therapy to bone. Pamidronate and zoledronic acid (Zometa)

ROLE OF RADIATION THERAPY IN METASTATIC DISEASE

bone metastases are the most commonly treated metastatic sites in patients with breast cancer,
brain metastases, spinal cord compression, choroidal metastases, endobronchial lung metastases, and metastatic lesions in other visceral sites can be effectively palliated with irradiation