Transcript Breast Cancer

Breast Cancer
Dr. Padma Poddutoori,
PG-Y3, I.M.
Dr.Sohail Chaudhry,
Attending Physician, Hemoncology.
Clinical case presentation

CC: lump in the left breast
 HOPI: A 47 yr old premenopausal woman
who was doing well until 8 months back
when she first noticed a lump in the left
breast at 2 ‘O’ clock position. A diagnostic
mammogram showed 2 nodular densities in
the left upper quadrant, close to the palpable
abnormality. U/S showed a cluster of cysts
in between the 12 and 1 ‘O’ clock position
and a thick walled cyst, in between 11 and
12 ‘O’ clock position, 1.8 cm from which
greenish black fluid was aspirated.
Clinical case presentation contd…
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An U/S which was done 3 wks later, which showed a
suspicious solid mass.
Core needle biopsy done showed grade 2 invasive ductal
carcinoma in 4 of 4 cores, ER and PR positive, no over
expression of HER2/neu.
Menstrual and gynecologic history:
She was nulliparous with menarche at 13, was exposed to
DES, no h/o OCP use and had undergone routine
gynecologic screening
Vaginal biopsy 23 yrs back showed adenosis with no
evidence of cancer
Clinical case presentation contd…

Allergies: stinging insects
 PMH: no h/o DM, HTN or CAD
 Social history: lives with her husband, non
smoker, drinks fewer than 5 alcoholic
beverages a wk.
 Family history: no h/o breast or ovarian
cancer
 Medications: none
Clinical case presentation contd…

Vitals: normal
 On examination:
Breast: breasts were symmetric, no skin changes,
nipple discharge or erosions. A flat mass 5x 5 cms
was palpated in the upper outer quadrant left
breast, not mobile, not attached to overlying skin,
no lymphadenopathy, no mass in the right breast.
Rest of the examination was normal
Imaging
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Radionuclide bone scan showed a focus of increased uptake in
the right aspect of the T6 vertebral body, which suggested the
possibility of a metastasis.
Mammography revealed an ill defined mass in the upper outer
quadrant of the left breast.
A targeted ultrasonography of the left breast revealed an illdefined, hypoechoic, lobulated mass, 3.5 cm by 2.7 cm x 2.0
cm, at 2 o’clock position.
MRI of the breasts revealed an ill-defined, lobulated, enhancing
mass, 2.9 cm x 2.7 cm x 2.5 cm, in the upper outer quadrant of
left breast, corresponding to the mammographic and
ultrasonographic findings.
CT of the thoracic spine, performed revealed a lytic destructive
lesion, 1.8 cm x 1.6 cm x 1.5 cm, in the right side of T6
vertebral body. A small, soft-tissue component extended into the
right anterior lateral epidural space, without central canal
stenosis.
Needle biopsy of the T6 vertebral lesion was performed under
Breast Imaging Studies
Gradishar W et al. N Engl J Med 2008;359:1382-1391
Spine Lesion Imaging Study
Gradishar W et al. N Engl J Med 2008;359:1382-1391
Pathology

All four tissue cores had involvement by
both infiltrating ductal Ca and ductal
CIS, with focally abundant extracellular
mucin.

Immunohistochemical staining showed
the expression of both ER and PR.
Breast cancer incidence

It is the most common malignancy in women-31% of all
female cancers, 15% of cancer deaths-no 2 cause of cancer
deaths
 178,480 new invasive breast cancer cases were diagnosed
in women in U.S in 2007
 Epidemiology:
Gender: female:male =100:1; BRCA mutations are
associated with increased risk for br.cancer in men
Age: 0.8% in women <30 yrs old, 6.5% in women 30-40
yrs old
Race: Caucasians > African Americans
Geography: north america highest rate in the world
SES: higher in higher SES
Disease site: left >right and higher in the UOQ and in
retroareolar area
Basic principles of treatment
of breast cancer

Local and Regional Treatment
Early breast cancer: lumpectomy with RT.
Axillary Lymph-Node Dissection:
recurrence is higher in women with positive
axillary LN. Sentinel LN mapping can be
done, which has 100% PPV and 95% NPV
Radiotherapy: RT is an integral part of
breast-conserving treatment.
Postmastectomy RT reduces the incidence of
local and regional recurrences by 50 to 75%.
Basic principles of treatment
of breast cancer
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Systemic Hormone Therapy or Chemotherapy: For adjuvant
therapy, combination CT is more effective than single-drug therapy,
reducing the annual risk of death by 20%. The benefit is greater when
tamoxifen is given for 5 yrs, and with ER positive tumors.
Preoperative Chemotherapy: 90% of primary operable tumors
decrease in size by >50% after CT, thus making lumpectomy a
possibility for women who would otherwise have required a
mastectomy. No survival benefit of pre-op CT over post-op CT
Duration of Chemotherapy: 4-6 M. The combinations used most often
are fluorouracil, doxorubicin, and cyclophosphamide (FAC); fluorouracil,
epirubicin, and cyclophosphamide (FEC); doxorubicin and
cyclophosphamide (AC); and cyclophosphamide, methotrexate, and
fluorouracil (CMF). These combinations are given at intervals of 3-4
wks. 6 cycles of FAC or FEC (18 to 24 wks), 6 cycles of CMF (18 to 24
wks), or 4 cycles of AC (12 to 16 wks) are considered standard therapy.
In premenopausal women, ovarian ablation has a benefit, equal to that
of combn CT or tamoxifen.
Combination CT and Hormonal Therapy: more effective than either
alone. Recommended for women with a high risk of recurrent disease.
Metastatic Breast Cancer: optimal palliation and prolongation of life
are the main goals of treatment.
INDICATIONS FOR ADJUVANT SYSTEMIC THERAPY AFTER
SURGERY IN WOMEN
WITH OPERABLE BREAST CANCER.
TYPE OF DISEASE
Breast cancer without evidence of invasion
Noninvasive breast cancer (ductal or lobular carcinoma in situ)
Breast cancer with evidence of invasion, but -ve axillary LN
Microinvasive breast cancer (<1 mm in largest diameter)
Invasive ductal or lobular carcinoma <1 cm in largest diameter
Invasive carcinoma <3 cm in largest diameter with favorable
histologic findings (pure tubular, mucinous, or papillary)
Invasive ductal or lobular carcinoma »1 cm in largest
diameter
Invasive carcinoma »3 cm in largest diameter with favorable
histologic findings (pure tubular, mucinous, or papillary)
Invasive breast cancer with positive axillary lymph nodes
All tumors, regardless of size or histologic findings
ADJUVANT
THERAPY INDICATED
None
None
None
None
Chemotherapy,
hormonal
therapy, or both
Chemotherapy,
hormonal
therapy, or both
Chemotherapy,
hormonal
therapy, or both
SELECTION OF ADJUVANT SYSTEMIC THERAPY FOR WOMEN WITH
OPERABLE PRIMARY BREAST CANCER AND INDICATIONS FOR ADJUVANT
TREATMENT
CHARACTERISTICS OF
PATIENT AND TUMOR
LEVEL OF RISK
ADJUVANT SYSTEMIC
THERAPY*
.
LEVEL OF RISK
ADJUVANT SYSTEMIC THERAPY
<50 yr
Negative
Positive
Any
Low
Positive
Moderate or high
Chemotherapy
Hormonal therapy
Or Chemotherapy or Chemotherapy and
hormonal therapy
Chemotherapy and hormonal therapy or
Investigational therapies
Unknown
»50 yr
Negative
Positive
Positive
Any
Chemotherapy and hormonal therapy
Any
Low
Moderate or high
Chemotherapy
Tamoxifen Or Chemotherapy and
hormonal therapy
Chemotherapy and hormonal therapy or
Investigational therapies
Unknown
Any
AGE
ESTROGEN-RECEPTOR
STATUS
Chemotherapy and hormonal therapy
TEN-YEAR CANCER-FREE SURVIVAL AND OVERALL
SURVIVAL AMONG WOMEN TREATED WITH CHEMOTHERAPY
WITH OR WITHOUT RADIOTHERAPY AFTER MASTECTOMY
STUDYAND
OUTCOME
NO. OF
SUBJECTS
PERCENT
SURVIVING
P
VALUE
CHEMOTHERAPY
CHEMOTHERAPY
AND
RADIOTHERAPY
British
Columbia
Cancer-free
survival
Overall
survival
Danish Breast
Cancer
Cooperative
Group
Cancer-free
survival
Overall
318
41
54
56
64
1708
34
45
48
54
0.007
0.07
<0.001
<0.001
.
Optimal Palliative Therapy for Women with Metastatic Breast Cancer
Hortobagyi G. N Engl J Med 1998;339:974-984
Hormonal therapy

Pre-menopausal women:
Tamoxifen x 5 yrs
AI[Arimidex or Famara] with LHRH agonist +/- zometa ?
A study was conducted in premenopausal women- 2 groups
enrolled:
Tamoxifen +LHRH agonist +/- Zometa
vs
AI + LHRH agonist +/- Zometa
Post menopausal women:
Tamoxifen x 5 yrs
AI[Arimidex or Famara] x 5 yrs
Tamoxifen x 5 yrs Famara x 5 yrs
Tamoxifen x 2.5 yrs Aromasin [Exemestane]
HORMONAL THERAPIES FOR WOMEN WITH
METASTATIC BREAST CANCER
ORDER OF
THERAPY
PREMENOPAUSAL WOMEN
POSTMENOPAUSAL
WOMEN
First line
Antiestrogens or ovarian ablation
(chemical, surgical, or
postradiation)
Antiestrogens
Second line
Ovarian ablation after
antiestrogens;
antiestrogens after ovarian
ablation
Aromatase inhibitors
Third line
Progestins
Progestins
Fourth line
Androgens
Androgens or estrogens
Newer modalities of treatment

Bevacizumab (Avastin, Genentech) is a
humanized monoclonal antibody directed
against all isoforms of VEGF-A.
 Trastuzumab, a monoclonal antibody
targeting the extracellular domain of the
HER2 protein, was approved in 1998 as a
first-line treatment in combination with
paclitaxel for HER2-positive metastatic breast
cancer.
 Exemestane[Aromasin] inhibits aromatization
in vivo by about 98 %. Exemestane therapy
after 2-3 yrs of tamoxifen therapy significantly
improved disease-free survival as compared
with the standard 5 yrs of tamoxifen
Analyses of Toxic Effects and Efficacy
Demographic and Disease Characteristics of Eligible Patients
Miller K et al. N Engl J Med 2007;357:2666-2676
Survival Analyses
Miller K et al. N Engl J Med 2007;357:2666-2676
Enrollment, Patients, and the Timing of Chemotherapy and Trastuzumab in Trial B-31 and
Trial N9831
Romond E et al. N Engl J Med 2005;353:1673-1684
Kaplan-Meier Estimates of Disease-free Survival (Panel A) and Overall Survival (Panel B)
Romond E et al. N Engl J Med 2005;353:1673-1684
What can be
done in this patient?
THANK YOU!