management of carcinoma breast
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CA Breast: Is our patient receiving adequate treatment?
Dr. Asghar H. Asghar, FCPSOncologist, KIRAN, Karachi
Breast Cancer
It is the most common cancer in female
Second leading cause of cancer death after CA lung
Worldwide incidence more than one million per year
90,000 in Pakistan 40,000 expire in Pakistan
Incidence with age
Age 20-29: 1 in 2,000 Age 30-39: 1 in 229 Age 40-49: 1 in 68 Age 50-59: 1 in 37 Age 60-69: 1 in 26 Ever: 1 in 8
Source: American Cancer Society Breast Cancer Facts & Figures, 2005-2006.
Breast Cancer
Incidence in Asia is highest in Pakistan
In 70%, cause is unknown Certain risk factors are there Most of the cases are diagnosed in
stage III and IV People don’t want to consult doctors
due to certain stigma
Risk Factors
Old Age Early menarche Late menopause First child birth
(>30 years) Nulliparous Personal history of
breast cancer
Family history in 1st degree relatives
Post-menopausal HRT
Previous suspicious breast biopsy
Hereditary syndromes (BRCA-1 & 2)
4 “F” for CA Breast
Familial Fifty Female Fatty Acids (saturated) Fortune
Hormones Affecting the Breast
Survival Rate of Breast Cancer
stage 5-year survival rate
0 93%I 88%IIA 81%IIB 74%IIIA 67%IIIB 49%IIIC 41%IV 15%
Triple Assessment
Clinical Evaluation – Lump and regional nodes
Imaging (ultrasound <35 years old or mammography >35 years old)
Cytology or Histology
Triple Assessment
Clinical Evaluation – Lump and regional nodes
Imaging (ultrasound <35 years old or mammography >35 years old)
Cytology or Histology
Performing a BSE (Inspection)
Best done a week after the period, when breasts are not tender or retaining fluid
Stand in front of a mirror with hands on hips
Look for signs of dimpling, swelling, soreness on palpation, or redness
Repeat this with arms over head
Palpation in BSE
Palpate breast in quadrants or in a circular motion
Repeat palpation exam when lying down
Check axillary tail of each breast for enlarged lymph glands
Check nipples and area just beneath to it
Gently squeeze nipples to detect any discharge
Malignant masses
Hard, irregular and painless Malignant masses are painful in
only 10-15% of patients. Skin dimpling Nipple retraction Bloody or watery discharge Possibly fixed to the skin or chest
wall
Mammogram
X-ray of breast for detection of tumors too small to be palpated
First (baseline) between ages 35-40 years.
Annually after age 40.
Mammography Machine Highly sensitive
test Sensitivity is
reduced in young women due to the presence of high glandular tissue
Mammography Procedure
Mammographic Findings
Mammographic Findings
BI-RADS
Breast Ultrasound
Differentiate solid vs cystic lesions
Sensitivity 75%
Specificity 97%
Fine Needle Aspiration Cytology (FNAC)
•Simple
•Easy to perform
•Cheap
•Not time consuming
•Negative FNAC doesn’t exclude cancer
Tru-Cut Biopsy
• It is needed when FNAC is negative
•Also simple
•Done on OPD basis
•No operation
•Mild local anesthesia
•More reliable than FNAC
Risk Assessment Tool
ER Positive ER Negative
Proportion of patient
75% 25%
Mean age (Years)
63 57
<50 years 20% 35%
≥50 Years 80% 65%
>2 cm 29% 41%
≤2 cm 65% 50%
Anderson WF et al. Breast Cancer Res Treat 2002; 76: 27–36
Breast cancer demographics (n=82,488)
TNM Staging
Carcinoma Breast Management
Detailed clinical history Thorough physical examination Diagnostic workup Treatment
Surgical Chemotherapy Radiotherapy Hormonal Therapy Targeted Therapy
Investigations
Routine blood examination CXR, USG abdomen or CT Chest and
abdomen FNAC, Core needle biopsy Bone scan ER/PR and HER-2 neu status Ki-67, CA-15-3 Echocardiography/MUGA scan p53, BRCA-1 and BRCA-2
Aims of Treatment
To cure the disease and improve the survival
Relief of symptoms To minimize the risk of recurrence Return to a quality of life as before
diagnosis To minimize cosmetic issues
Management of Early Stage Breast Cancer(stage 0, I, II)
Ductal Carcinoma in Situ (DCIS)
DCIS may never invade but long term data shows that 30-50% do invade in 10 years if left untreated .
Total Mastectomy (TM) or Lumpectomy (L) with or without radiation.
Radiotherapy should be considered for women with DCIS where conservation is desired.
Axillary lymph node dissection is not necessary in the management of most patients with DCIS.
Lobular Carcinoma in Situ (LCIS) 20-25% LCIS invade in 10-20 years. Annual physical examination &
annual bilateral mammography appears to be the best management option
Lumpectomy or total mastectomy with or without contra-lateral prophylactic mastectomy
Close follow-up in the key point
Invasive Ductal Carcinoma (IDC) Treatment depends on following
factors: Clinical extent Pathological characteristics Prognostic factors Patient age (menopausal status) Patients preference and the
psychological profile
Invasive Ductal Carcinoma (IDC)
Two surgical options: Breast conservation Surgery (BCS) Modified Radical Mastectomy (MRM).
MRM should be considered in: Patient preference, no cosmetic problem. Large tumor in small breast. High risk for local recurrence. Diffuse micro-calcification or multi-
centric disease. Unreliable for further follow0up.
Axillary Level
Pre-requisites for Neoadjuvant
Pre-treatment of Tru-Cut biopsy Tumor localization with surgical clips Sentinel Lymph Node (SLN) biopsy
for clinically negative axilla Tru-cut or FNAC or SLN biopsy for
clinically positive axilla
Recommendation after SLN
If SLN negative before neoadjuvant: omit axillary clearance
If SLN positive before neoadjuvant: axillary clearance required
If SLN not done before neoadjuvant: axillary clearance required
Neoadjuvant Chemotherapy
pCR (26%) was observed more in patients who completed Neoadjuvant chemotherapy (NSABP-27)
If neoadjuvant is not complete then will be completed in adjuvant setting
No role of further chemotherapy if completed neoadjuvant
NSABP-B-18 Trial
BCS rate higher after neoadjuvant However, no disease specific survival
advantage as compared to adjuvant chemotherapy in stage-II
NSABP-27 (n=2411)
Response
Both clinical and pathological response (26%) was higher in AC-T arm as compared to AC (14%) arm
Docetaxel was not superior to AC in DFS and OS
HER-2 Positive patients
Paclitaxel x4 F/B FECx4 Paclitaxel x 4 + Trastuzumab x 24
weekly F/B FEC x 4 No. of patients 42 All were treated in neoadjuvant setting
J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28
Results
pCR more in favor of Trastuzumab 26% vs 65%
Neoadjuvant Hormone Therapy
Many trials have been done in post-menopausal ER positive patients
Improved clinical response and higher rate of BCS in patients who used AIs as compared to SERMs
Letrozole and Anastrozole has superior results
IDC: Adjuvant Chemotherapy Pre-meno. Node +ve and ER –ve pts:
FAC, AC-T, TC, CMF for 4-6 months. Pre-meno. Node +ve and ER +ve pts:
Chemo + HT (Goserline/Ovarian Ablation, Tamoxifen, Anastrazole)
Pre-meno. Node –ve & ER +ve pts: Chemo + HT
Post-meno. Node +ve and ER -ve pts: Chemo only. No HT
Post-meno. Node –ve & ER +ve pts: Chemotherapy + HT
IDC: Post-Op Irradiation
Mandatory in breast conservational surgery
Mandatory after MRM if >5 cm, node positive, close margin,
Irradiation to Axilla
It is indicated in the following: Three or more metastatic lymph node.
Any lymph node > 2.5 cm
Involvement of apex of axilla
< 10 lymph node removed??
Gross extra-capsular tumor extension.
When to radiate after conservation surgery?
If not giving chemo, then best to start within 4-6 weeks.
If chemo is being given then should be started within 4-6 weeks after completion of chemo.
Complication of conservation surgery and irradiation
Arm or breast edema Breast fibrosis Painful mastitis or myositis Pneumonitis. Apical pulmonary fibrosis Rib fracture (rare)
Management of Late Stage Breast Tumors.(stage III and IV)
Treatment Options
Chemo, irradiation, surgery and hormonal therapy are the options
MRM is the best option for all resectable tumors.
Neoadjuvant chemotherapy with or without hormone therapy is also another good option.
Indications for post-mastectomy Irradiation
Lesion > 5 cm Any skin, fascial or skeletal muscle
involvement Poorly differentiated tumors?? Positive or close surgical margins (<1 mm). Lymphatic permeation, matted L.N or > 3
LN involved. < 10 LN removed Gross extracapsular tumor extension
Poor Prognostic factors
Increasing tumor size Higher histological grade Presence and number of lymph node
metastases Estrogen-receptor negative Progesterone-receptor negative HER-2-neu positive
Tamoxifen x 5 years
Tamoxifen x 5 years
ER(-)PR(-)ER(-)PR(-)ER(+) or PR(+)ER(+) or PR(+)
no further treatmentno further treatment
surgery +/- radiation +/- chemotherapysurgery +/- radiation +/- chemotherapy
Tamoxifen contraindicated and
postmenopausal
Tamoxifen contraindicated and
postmenopausal
Adjuvant TreatmentAdjuvant Treatment
AIsx 5 years
AIsx 5 years
AIsx ? years
AIsx ? years
High RiskHigh RiskLow RiskLow Risk
no further treatmentno further treatment
Adjuvant Tamoxifen
Reduced the risk of recurrence annually by 39%
Reduces the risk of annual mortality by 31%
MA-17 trial showed the survival advantage with extended use of Letrozole (Femara) compared with placebo
Another good options in AIs now available is Aromasin (Exemestane)
Algorithm for hormone therapy
Cystosarcoma Phyllodes
Mastectomy is the best option. Irradiation to chest wall only ? Due to low nodal metastasis,
irradiation to axilla is not advocated.
Take Home Message
Our patient needs detailed counseling that surgery is not the only treatment
Surgery if done well in time will be the turning point for success
Multidisciplinary team approach is the key point in this management
Without this, we can say that our patient may not be receiving adequate treatment
