Transcript Slide 1

MEDICAL GRANDROUNDS
JYN A. CABAL M.D.
March 15, 2007
OBJECTIVES:
• To present a case of invasive ductal
carcinoma
• To give new updates regarding breast
cancer diagnosis and management
General Data
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L.H.
54 year-old
Female
Single
Nulliparous
First Cycle of Chemotherapy
History of Present Illness
8 weeks PTA
(+) mass on right outer
upper quadrant R breast
on routine x-ray
mammography
Consult done, on P.E.:
(+) 6.5 cm mass on right
outer upper & lower
quadrant in largest
diameter, no skin lesions,
dimpling, nipple discharge
or inversion
6 weeks PTA
4 weeks PTA
MR mammography
breast core needle biopsy:
Invasive Ductal Ca Grade
III
R modified radical
mastectomy
MR MAMMOGRAPHY
Scanty fibroglandular tissue, both breasts
2.4 x 3.6 x 3.7 cm enhancing lobulated
mass on upper outer quadrant of R breast,
highly suspicious of malignancy
0.6cm x 0.6 cm enhancing nodule in 6 o’
clock position of L breast
CORE NEEDLE BIOPSY
• INVASIVE DUCTAL CA, GRADE III
• IMMUNOHISTOCHEMISTRY (IHC)
ER 1+, PR 2+, HER-2/neu 3+
Histopathology
Invasive Ductal Ca
Nuclear Grade III
Histologic Grade III
3.9 cm in widest diameter
Axillary LN Negative (19 LN)
Histopathology - Stanford
• Estrogen receptor 3+, 95%
• Progesterone Receptor 3+, 30%
• HER-2/neu (-) for FISH (Fluorescence In
Situ Hybridization)
ER Assay
PR Assay
IHC – Her-2
DIAGNOSTICS
• CT Scan of whole abdomen – fatty
infiltrating changes in the liver
• Bone Scan – no evidence of metastatic
disease to the bone
DIAGNOSTICS
• CBC
Hgb – 12.8
Hct – 37
WBC – 5300
Segmenters - 53
Lymphocytes - 35
PC – 297 T
Past Medical History
• (+) Hypertension for 4 years on Irbesartan
150 mg OD
• 1993 -- (+) L ovarian cyst excision 
borderline serous papillary tumor
-- (+) TAH-BSO given Premarin as
hormone replacement therapy x 2 years
Personal/Social History
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Single
Nulliparous
Non-smoker
Non-alcoholic beverage drinker
Menstrual History
• Menarche at age 17
• Surgical menopause at age 41
Family History
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(+) Colon Cancer, RCC – mother, 90y/o
(+) Gastric Cancer – father, deceased
(-) Breast Cancer
(+) HPN – maternal side
(-) Diabetes Mellitus
(-) Asthma
Review Of Systems
(-) weight loss
(-) anorexia
(-) headache
(-) fever
(-) dyspnea
(-) cough
(-) chest pain
(-) palpitations
(-) orthopnea
(-) dysphagia
(-) constipation
(-) diarrhea
(-) dysuria
Physical Examination
• General awake, conscious, coherent, not in
cardiopulmonary distress
• BP- 120/70 HR- 70
RR- 36.2 T- 36.5
• Wt- 68 kilos Ht- 167 cms.
BSA- 1.77
• BMI- 24.4 (overweight)
Neck trachea midline, freely movable, thyroid not
palpable; no lymphadenopathy
Breast (+) 15 cm incisional scar on R ant chest wall,
no lymphadenopathy, no skin lesions; L breast: no
mass, skin dimpling, nipple discharge
Chest and Lungs symmetric chest expansion, tactile
fremitus symmetric, resonant percussion
throughout, no crackles, no wheezes
Heart
Apex beat and PMI at 5th
intercostal space, LMCL; S1 heard best at
apex, S2 heard best at base, no murmurs;
regular rhythm
Abdomen full, soft, nontender; liver, spleen,
and kidney not palpable
Lymphatic
no palpable lymph nodes in
neck, supraclavicular, axillary, epitrochlear,
or inguinal areas
Musculoskeletal
muscles appear
symmetric with appropriate and equal
strength bilaterally, full range of active and
passive motion
Salient Features
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54 year old
Female
Single
Nulliparous
History of HRT use
History of family cancer
Admitting Impression
Doxorubicin (Adriamycin) 60 mg/m IV
Cyclophosphamide 600 mg/m IV
INVASIVE DUCTAL
CARCINOMA
RISK FACTORS
• Age
• Current or prior hormone
replacement therapy
• Ethnicity/race
• Family history of breast
cancer
• Early menarche
• Late menopause
• Older age at first live
childbirth
• Atypical
Hyperplasia/LCIS
• Genetic mutations such
as BRCA ½ genes
• Prior thoracic RT
• BMI
• Alcohol consumption
Risk Factor – HRT Use
• Women 50-64 years of age showed an association
between current use of estrogen-only HRT and
increased risk of breast cancer
(Beral V. Lancet. 2003;362:419-427)
• Nurses’ Health Study demonstrated a significantly
increased breast cancer risk after long term use
(20 years or longer) of estrogen alone
(Chen WY, Manson JE, Hankinson SE, et al. Arch Intern Med.
2006;166:1027-1032)
Breast Cancer Work Up
History and P.E.
Breast Imaging:
Mammogram
Breast ultrasound
Magnetic Resonance Imaging
Breast Cancer Work Up
Breast Biopsy
Tumor tests: Estrogen receptors
Progesterone receptors
HER-2/neu/cerb-b2
Other tests: CBC, platelet count, CXR, liver
function tests, CT Scan, PET Scan
MRI in Patients with Breast
Cancer: Current Applications
• Detects cancer that is occult on conventional
imaging such as mammography and
sonography
• In preoperative evaluation, it can detect
multifocal and multicentric disease that was
previously unsuspected which facilitates
accurate staging
• For patients who have undergone
lumpectomy, it can be helpful in assessment
of residual tumor load
• Can be helpful to diagnose recurrence when
conventional imaging and P.E. are nonconfirmatory
• Can assess response to neoadjuvant
chemotherapy for locally advanced breast ca
• Patient selection for preoperative breast
MRI:
• Young patient
• Patient with dense or moderately dense
breasts
• Patients with difficult tumor histologic
findings such as infiltrating lobular
carcinoma and tumors with extensive
intraductal component in which tumor
size assessment is difficult
Tumor Tests
• ESTROGEN and PROGESTERONE RECEPTORS
- are parts of cells that attach to hormones estrogen
and progesterone; serve as “welcome mats”
- Hormone Receptor Assay:
ER (+) and PR (+) – response rate of 70%
ER (+) and PR (-) – response rate of 30%
ER (-) and PR (-) – response rate of 10%
- tumors that lack either or both of these receptors
are more likely to recur than tumors that have them
Tumor Tests
• HER-2/neu/cerb-B2 oncogene
- codes for a surface membrane receptor
that interacts with an unidentified growth
factor and is frequently amplified in human
breast carcinoma
- mapped to chromosome 17
TESTS for HER-2/neu
• IMMUNOHISTOCHEMISTRY
- test that detects HER-2/neu protein on the
surface of the cell by staining the cell with
antibodies
- can be 0, 1+ (negative), 2+ (borderline),
3+ (positive)
- if IHC 2+, have the tissue tested with FISH
test
Tests for HER-2/neu
• FLOURESCENCE IN SITU HYBRIDIZATION (FISH)
- gold standard for confirmatory testing
- measures HER-2 gene abnormality
- “paints” the HER-2 genes inside the cell so
they may be accurately counted
- may be (+) or (-)
** All in all, IHC has been shown to miss 15-20% of
positive specimens compared with less than 5%
with FISH
• Only tests IHC 3+ or FISH (+) respond well
to therapy that work against HER-2
Risk Categories for Node Negative
Breast Cancer (Alberta Breast Cancer Program 2006)
Risk Category
Risk Factors
Low
- < 1 cm, no negative risk factors
- 1 - 2 cm, grade 1, no negative risk factors
High
- 1 - 2 cm with any 2 or more negative risk factors,
- 2 - 3 cm with any one negative risk factor,
- any > 3 cm (regardless of other risk factors)
Intermediate
all other combinations of factors that do not fit into either the low
or high risk criteria above
NEGATIVE RISK
FACTORS
- histologic grade 3
- estrogen receptor negative
- cerbB2 overexpression
- presence of lymph/vascular invasion
- age < 35 years
Surgical Procedures of Breast Ca
• Lumpectomy/Breast Conservation Therapy
• Simple Mastectomy
• Modified Radical Mastectomy
• Radical Mastectomy
Surgical Procedures of Breast Ca
Lumpectomy vs Mastectomy
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Mastectomy with axillary LN dissection or
breast-conserving therapy with lumpectomy,
axillary dissection, & whole breast
irradiation are medically equivalent primary
treatment options in the majority of women
with Stage I and Stage II breast cancers.
(Fisher B, et al.. N Engl J Med October 17, 2002;347:1233-41. )
• Survival outcomes for young women with
breast cancer receiving either breastconserving therapy or mastectomy are
similar
(Kroman N, Holtveg H, Wohlhart J, et al. Effect of
breast conserving therapy vs redical mastectomy on prognosis for
young women with breast ca. Cancer 2004; 100:688-693)
Lumpectomy or breast conservation
therapy is usually not recommended for:
• women who have already had radiation
therapy to the affected breast
• women with 2 or more areas of cancer in the
same breast that are too far apart to be
removed through 1 surgical incision, while
keeping the appearance of the breast
satisfactory
• women whose initial lumpectomy along with
(one or more) re-excision has not completely
removed the cancer
• women with certain serious connective tissue
diseases such as scleroderma, which make them
especially sensitive to the side effects of radiation
therapy
• pregnant women who would require radiation
while still pregnant (risking harm to the fetus)
• women with a tumor larger than 5 cm (2 inches)
that doesn't shrink very much with neoadjuvant
chemotherapy
• women with a cancer that is large relative to her
breast size
Neodjuvant Therapy
• Chemotherapy given before surgery
• Can shrink large cancers so that they are
small enough to be removed by
lumpectomy instead of mastectomy
• Not indicated unless invasive breast cancer
is confirmed
• Indication:
 women with large clinical stage IIA,
stage IIB, and T3N1M0 tumors who meet
the criteria for breast conserving therapy
except for tumor size and who wish to
undergo breast conservation therapy
• Several randomized trials have assessed the
value of neodjuvant chemotherapy in
postmenopausal women with estrogen
receptor positive breast cancer.
• Neodjuvant therapy with an aromatase
inhibitor is an option in the treatment of
postmenopausal women with hormone
receptor-positive disease
• The use of either Anastrozole or Letrozole
provides superior rates of breast conserving
surgery and usually objective response.
(Smith IE. Dowsett M, Ebbs SR, et al. J Clin Oncol. 2005;
23:5108-5116)
Adjuvant Therapy
• A form of therapy added to the primary
treatment to keep cancer from returning
 Radiation
 Chemotherapy
 Hormone Therapy
 Biologic Therapy
Hormonal Therapy
• Indication:
 Patients with invasive breast cancers
that are estrogen and progesterone
receptor positive
Exception: LN (-) cancer < 0.5cm or
0.6cm to 1cm with favorable
prognostic factors
TAMOXIFEN – selective estrogen receptor
modulator
- 1986: received FDA approval
as adjuvant therapy in node-positive
postmenopausal women with breast cancer
- 1990: tamoxifen was approved
for women of any age with node-negative
disease, as long as hormone receptors were
positive or unknown
AROMATASE INHIBITOR (AI) - suppresses
estrogen production indirectly via inhibition
of the aromatase enzyme
Anastrozole
Letrozole
• Switching to Anastrozole after the first 2 to
3 years of Tamoxifen is well tolerated and
significantly improves event-free and
recurrence-free survival in postmenopausal
patients with early breast cancer
J Clin Oncol. 2005 Aug 1;23(22):5138-47.
• Risk of breast cancer recurrence was lower
in women in the letrozole arm relative to
the tamoxifen arm.
(Thurlimann B, et al .N Engl J Med. 2005;353:2747-2757.)
Chemotherapy
• Recommended based on:
 tumor size (> 1cm)
 tumor grade
 presence or absence of LN
involvement
 tumor hormone receptor status
• NCCN Recommendation < 70 y/o
 AC x 4
(doxorubicin/cyclophosphamide) +
sequential paclitaxel x 4, every 2
weekly regimen
 Doxorubicin, followed by CMF
 Cyclophosphamide/epirubicin, and
fluorouracil with or without docetaxel
 Cyclophosphamide, methotrexate and
fluorouracil [CMF]
Doxorubicin and cyclophosphamide [AC]
Doxorubicin and cyclophosphamide
followed by paclitaxel or docetaxel [AC ->T] or docetaxel concurrent with AC
[TAC]
 Cyclophosphamide/Docetaxel (TC)
 Gemcitabine/paclitaxel (GT)
 Epirubicin/cyclophosphamide (EC)
 Cyclophosphamide, doxorubicin, and
fluorouracil [CAF]
Biologic Therapy
• TRASTUZUMAB (Herceptin)
- is a monoclonal antibody with specificity
for the extracellular domain of HER-2/neu
receptor, preventing breast cancer cells to grow
- can shrink some breast cancer metastases
that return after chemotherapy or continue to
grow during chemotherapy
• Adverse
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Effects:
Fever and chills
Weakness
Nausea/Vomiting
Cough
Diarrhea
Headache
Heart problems
• HERA Trial
The use of trastuzumab resulted in a 46%
reduction in the risk of recurrence in
patients following all local therapy & a
variety of standard chemotherapy regimens.
( Piccart-Gebhart MJ Procter M, Leyland-Jones B, et al. N
Engl J Med.2005; 353: 1659-1672)
• There is a 52 % reduction in risk of
recurrence and a 33% reduction in the risk
of death in patients with HER-2 (+),node
(+) breast cancer & node (-) with primary
tumors >1cm if ER/PR (-) or >2cm if ER/PR
(+).
(Joint Analysis of NSABP B-31 & NCCTG N9831 Trial, 2005)
Key Points
• The accuracy of HER-2 assays used in
clinical practice is a major concern since this
could affect patient’s treatment.
• Breast MRI is an adjunct to other breast
imaging and should not be used in lieu of
standard breast imaging.
THANK YOU !