Management of early breast cancer

MANAGEMENT OF EARLY BREAST
CANCER
Dr. Akhil Kapoor
Department of Radiation Oncology
Acharya Tulsi Regional Cancer Treatment &
Research Institute, Bikaner
AcharyaTulsiRegionalCancerCenter,Bikaner

STAGING
AcharyaTulsiRegionalCancerCenter,
Bikaner

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PATHOLOGIC N STAGE
 pN1mi = Micrometastasis ≤ 2mm size
(0.2-2mm)
or, <200 cells
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STAGES INCLUDED IN EARLY BREAST CANCER
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LCIS
 Multicentric in 90% of specimens
 Bilateral in 35-59% cases
 10% Invasive ca has associated LCIS.
Must at diagnosis:
 Bilateral Mammogram
 Pathology Review
Importance of Mammogram:
 LCIS: A marker for increased risk for subsequent
development of invasive (usually ductal carcinoma)
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 Surgical Excision Biopsy is must to proceed for
management.
 Management is done according to associated DCIS
or Invasive Ca disregarding the presence of LCIS.
 If margins are positive for LCIS, additional surgery
to obtain clear margins for LCIS is not required.
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LCIS AS SOLE HISTOLOGIC DX
 Most widely accepted approach: Close observation
with mammographic surveillance
 Patients with highest risk (Young; diffuse high grade
lesion; Family history):
Bilateral Prophylactic Mastectomy
 Tamoxifen alone reduces the risk by 56%.
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PAGET’S DISEASE
 Rare entity: <5% of all Breast Ca cases; In fifth-
sixth decade.
 D/d: Eczema (B/L in Eczema)
 Palpable mass present in 50% cases (Invasive Ca
in 90%).
 If no palpable mass, 66-86% underlying DCIS.
 Prognosis and management according to
underlying disease.
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USUAL MANAGEMENT:
 Complete excision of Nipple Areola Complex with
microscopically clear margins for both Paget’s and
associated malignancy.
Followed by:
 Whole Breast RT
 5 Year Local Recurrence Rate of 5.2% (EORTC
Study)
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DCIS
 Pure DCIS: No indication of Axillary dissection.
 Apparent pure DCIS: Upto 25% cases turn out to
be Invasive Ca in lumpectomy specimen.
 Thus, if Mastectomy is performed: SLNB preferred.
 If lumpectomy includes Axillary tail, SLNB preferred
(as surgery compromises future SLNB in the rare
event of associated Invasive Ca)
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RECURRENCE
 Recurrence is 50% DCIS and 50% Invasive Ca.
 Risk Factors for Recurrence:
1) Age <50yrs
2) Palpable mass
3) Close (<1mm) or involved margins
4) High Grade
5) Diameter >1cm
6) Presence of Comedo Necrosis.
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VAN NUYS INDEX
 Modified VNPI includes AGE as well.
more
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 Whole Breast RT following lumpectomy reduces the
recurrence rate by 50% in DCIS.
 Boost to tumor bed by 10 Gy is recommended in
cases with close margins and age <50yrs.
 MRI may be advised in patients suspected to have
multi centric disease.
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 Patients without any high risk feature: Surgical
Excision alone is sufficient.
 Tamoxifen addition for 5 years (NSABP B-24 trial):
 Reduces the recurrence rate by 3.4% (HR 0.30,
p<0.001) in ipsilateral IBTR.
 Absolute reduction in Contra lateral Breast Ca by
3.2% (HR 0.68, p=0.02).
Thus, Tamoxifen is added in ER+ DCIS after
Lumpectomy and Radiation.
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 Her 2 status in pure DCIS: No significance.
Indications of Simple Mastectomy in DCIS:
 Multicentric Disease
 Diffuse Microcalcifications
 Family History
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WORK UP FOR EARLY BREAST CA
Hematological Tests
 Baseline CBC, RFT, LFT
(as Surgery and Chemotherapy are to be given)
 Serum Alkaline phosphatase: Raised in patients
with Bone Mets
"bone burns, liver lasts" : Heat Unstable ALP in Bone
diseases.
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PATHOLOGY
 Pathology Review
 Determination of ER, PR and Her-2-neu Status
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IMAGING STUDIES
o Bilateral Mammogram ± USG
o Bone Scan:
Indicated in
 Localised bone pain
 Elevated ALP
o Chest CT: If pulmonary symptoms
o Baseline Echo/ MUGA Scan (MultiGated
Acquistion- Tc99m)
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ABDOMINAL ± PELVIC CT:
Indications:
 Abnormal Physical Examination of abdomen or
pelvis
 Abdominal Symptoms
 Abnormal LFT
 Raised ALP
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BREAST MRI
Requirements:
 Expert Breast Imaging Team
 Dedicated Breast Coils
 Facility for MRI guided Needle Sampling or wire
localisation of MRI detected abnormalities.
Indications:
 To evaluate dense breasts (young)
 Breast Ca in Pregnancy
 In patients with Positive Axilla with Occult primary (not
identified with Mammogram).
 To determine Multicentric Disease in I/L Breast
 Screening of C/L Breast in high risk patients
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PET-CT
 Not usually indicated.
 Indicated in situations when standard imaging is
equivocal/suspicious especially in locally
advanced/metastatic breast cancer.
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FOR T3N1MO
Usually Part of the Initial Work up:
 Chest CT
 Abdominal CT
 Bone Scan
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BCS
(in absence of Extensive Intraductal Component-Boost Required)
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PRE OPERATIVE SYSTEMIC THERAPY
 Indicated if patient desires BCS and fulfills the
criteria for BCS except for size.
 Core Biopsy with placement of image-detectable
marker to demarcate the tumor bed for post-CT
surgical management.
 Clinically negative axilla should be checked by
USG, suspicious nodes should be sampled by
FNAC or core needle and clipped with image
detectable marker.
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 Similarly, clinically positive nodes must be sampled
and clipped.
 Clipped Nodes that are positive on histology must
be removed at the time of Surgery.
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 CT regimes are similar in neo-adjuvant and
adjuvant settings.
 Endocrine therapy alone may be considered in
Post-menopausal patients with receptor positive
disease (Aromatase inhibitor).
 Her-2 + disease treated with systemic therapy
along with at least 9 weeks of trastuzumab.
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DEFINITION OF MENOPAUSE
 PM Range: FSH >25 IU/l; E2 <200pmol/l
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HER 2 NEGATIVE
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HER 2 POSITIVE
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MOA PERTUZUMAB
 PERJETA targets a different domain on the HER2
receptor than trastuzumab, allowing the
combination to provide a more comprehensive
blockade of HER2-driven signaling pathways.
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PERTUZUMAB
 The pCR rates were 39.3% in patients who
received pertuzumab plus trastuzumab and
docetaxel
 and 21.5 % in patients who received trastuzumab
plus docetaxel.
 (adjusted p-value = 0.0063).
 The pCR rates and magnitude of improvement with
the addition of pertuzumab were lower in the
subgroup of patients with hormone receptor-
positive tumors compared to patients with hormone
receptor-negative tumors.
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PREOP SYSTEMIC THERAPY
 Confirmed Progressive disease anytime:
Proceed to MRM
 If CR/PR with possible BCS:
Proceed to Lumpectomy
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BASELINE DOCUMENTATION OF “TARGET” AND
“NON-TARGET” LESIONS
 All measurable lesions up to a maximum of five lesions per
organ and 10 lesions in total, representative of all involved
organs should be identified as target lesions and recorded
and measured at baseline.
 Target lesions should be selected on the basis of their size
(lesions with the longest diameter) and their suitability for
accurate repeated measurements (either by imaging
techniques or clinically).
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 A sum of the longest diameter (LD) for all target
lesions will be calculated and reported as the
baseline sum LD. The baseline sum LD will be used
as reference by which to characterize the objective
tumor response.
 All other lesions should be identified as non-target
lesions and should also be recorded at baseline.
Measurements of these lesions are not required,
but the presence or absence of each should be
noted throughout follow-up.
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EVALUATION OF TARGET LESIONS
 Complete Response (CR): Disappearance of all target
lesions
 Partial Response (PR): At least a 30% decrease in the
sum of the LD of target lesions, taking as reference the
baseline sum LD
 Stable Disease (SD): Neither sufficient shrinkage to
qualify for PR nor sufficient increase to qualify for PD,
taking as reference the smallest sum LD since the
treatment started
 Progressive Disease (PD): At least a 20% increase in
the sum of the LD of target lesions, taking as reference
the smallest sum LD recorded since the treatment
started or the appearance of one or more new lesions
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EVALUATION OF NON-TARGET LESIONS
 Complete Response (CR): Disappearance of all
non-target lesions and normalization of tumor
marker level
 Incomplete Response/ Stable Disease (SD):
Persistence of one or more non-target lesion(s)
or/and maintenance of tumor marker level above
the normal limits
 Progressive Disease (PD): Appearance of one or
more new lesions and/or unequivocal progression
of existing non-target lesions
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BCS WITH SURGICAL AXILLARY STAGING
 No Axillary Node: RT to Whole Breast ± Boost
APBI in selected patients
 +ve Axillary Node: RT to whole breast ± Boost
+ Nodal RT ± IMN RT
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TUMOR BED BOOST
 Rationale: 65%-80% of breast recurrences after
BCS + RT occur around the primary tumor site.
 Clark et al. noted in 1,504 patients a greater
incidence of failures at 10 years of 17% in those to
whom no boost was delivered, compared with 11%
in those who received doses of 5 to 15 Gy at the
primary excision site (P = .03)
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Currently, most institutions prefer electron beam
boost because
 of its relative ease in setup,
 outpatient setting,
 lower cost,
 decreased time demands on the physician,
 and excellent results compared with 192Ir implants.
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EORTC TRIAL
 Bartelink et al. after BCS and axillary dissection,
stage I or II, received 50 Gy of radiation to the
whole breast in 2-Gy fractions over a 5-week period
 Randomly assigned to receive either no further
local treatment (2,657 patients) or a boost of 16 Gy,
usually given in 8 fractions by electron beam (2,661
patients).
 The 5-year actuarial rates of local recurrence were
7.3% and 4.3%, respectively (P <.001).
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INTERNATIONAL BREAST CANCER STUDY
GROUP TRIALS
 Premenopausal with 1-3+LN: LRR 19-27% if
G2-3 disease with vascular invasion
but that risk was <15% if they had G1 disease with
no vascular invasion.
 Postmenopausal with 1-3+LN:
G3 disease and T>2 cm LRR 24%
as compared with <15% for those with G1–2
disease with T<2 cm.
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DOSE OF RADIATION
 Dose of 45-50Gy at 1.8-2Gy per fraction given 5
fractions per week.
 Another dose schedule: 42.5 Gy at 2.66Gy per
fraction in 16 fractions
 Boost to tumor bed in patients at high risk (Age<50
years, high grade disease) with 10-16Gy at 2 Gy
per fraction.
 Dose to regional nodes: 50-50.4Gy at 1.8-2Gy per
fraction (±Scar Boost to 60Gy at 2Gy per fraction).
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HYPOFRACTIONATION IN BREAST
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START TRIAL A
 Criteria: Early breast cancer (pT1-3, pN0-1 M0);
BCS or Mastectomy
 50 Gy in 25 fractions over 5 weeks
 41.6 Gy/3.2Gy per fraction in 13 fractions over 5
weeks, or
 39 Gy/3Gy per fraction in 13 fractions over 5 weeks
 The overall treatment time was kept constant in all
three arms
 Allowed treatment of regional lymph nodes
(supraclavicular and axillary), used in 20%.
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RESULTS
 Median follow-up was 9·3 years.
 10-year rates of local-regional relapse:
 50 Gy: 7.4%
 41.6 Gy: 6.3% (p=0.65)
 39 Gy: 8.8% (p=0.41)
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START TRIAL B
 Criteria: Early breast cancer (pT1-3, pN0-1 M0)
 50 Gy/2 Gy per fraction, 25 fractions over 5 wks,
 40 Gy/2.67 Gy per fraction,15 fractions over 3 wks.
 Results:
 10-year rates of local-regional relapse:
 50 Gy: 5.5%
 40 Gy: 4.3% (p=0.21)
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COSMESIS
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COSMESIS
 Breast induration, telangiectasia, and breast
oedema were significantly less common normal
tissue effects in the Hypofractionated group than in
the 50 Gy group.
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DFS IN START A & B
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SUBGROUP ANALYSIS
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 Inclusion Criteria:
Invasive Breast Ca, BCS, Margins clear, N0
 Control group: 50.0 Gy in 25 fractions over a period
of 35 days
 Hypofractionated group: 42.5 Gy in 16 fractions
over a period of 22 days.
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 No Nodal radiation; No Boost
RESULTS
The risk of local recurrence at 10 years:
 6.7% standard irradiation
 6.2% hypofractionated regimen
Good or excellent cosmetic outcome at 10 years:
 71.3% in control group
 69.8% in hypofractionated
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HAZARD RATIO FOR SUBGROUPS
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SELECTION CRITERIA FOR APBI (ASTRO)
 Age>60 yrs
 pT1N0, ER +
 Margins Negative by at least 2mm
 BRCA 1, 2 Negative
 LVSI Absent
 DCIS Absent
 Ext Intraductal Component Absent
 Unicentric
 Unifocal (same quadrant)
 Histology: IDC/Mucinous/Tubular/Colloid
 No previous NACT
 Asso. LCIS allowed
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DOSE IN APBI
 34Gy/3.4Gy per fraction/2 fractions per day 6 hrs
apart for 5 days
 For APBI by EBRT,
38.5Gy/3.85Gy per fraction/2 fractions per day 6 hrs
apart for 5 days
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 The finding comes from a meta-analysis of
individual data for a total of 8135 women
participating in clinical trials who were followed for
an average of 11 years; 1314 of these women
were found to have 1 to 3 positive nodes.
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EBCTCG STUDY
 In women who had 1-3+ nodes, PMRT reduced the
RR by 32% and reduced the breast cancer mortality
rate by 20%.
 The benefit was similar whether women had only
1+ node or whether they had 2 or 3+ nodes.
 For women with ≥4 + nodes (n = 1772), RT reduced
overall recurrence by 21% and breast cancer
mortality by 13%.
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 Woodward et al. found that the risk of LRR after
mastectomy and anthracycline-based
chemotherapy was only 13% for patients with stage
II disease and one to three positive lymph nodes.
 However, at the same institution, patients with
similarly staged disease treated with PMRT had a
LRR risk of only 3%.
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COFACTORS FOR >15% LRR AFTER
MASTECTOMY + CT WITH 1-3 +LN
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CLINICAL CASE
 A 40 year lady with lump in upper outer quadrant of
breast underwent MRM with final HPR as follows:
pT1N0 (T=0.4 cm), Metaplastic histology, ER+, PR-,
Her 2+; other parameters favorable.
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QUESTION
 What next in management?
Ans: Adjuvant endocrine therapy is sufficient.
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DECISION CHART
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QUESTION
 What if the same patient was ER, PR Negative?
Ans: No adjuvant therapy
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CLINICAL CASE
pT1N0 (T=1 cm), Ductal histology, ER+, PR-, Her 2-
; other parameters favorable.
Ques: Next Management?
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ONCOTYPE DX
 Analyzes a panel of 21 genes within a tumor
to determine a Recurrence Score.
 The RS is a number between 0 and 100 that
corresponds to a specific likelihood of
breast cancer recurrence within 10 years of
the initial diagnosis.
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GENES ANALYZED IN ONCOTYPE DX
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USE
Oncotype DX demonstrated both
 Prognostic significance (the capability of predicting
distant recurrence)
 Predictive significance (the capability of the test to
assess the potential benefit of additional adjuvant
chemotherapy).
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Kaplan-Meier plots for distant recurrence comparing treatment with tamoxifen (Tam) alone
versus treatment with tamoxifen plus chemotherapy (Tam + chemo).
Paik S et al. JCO 2006;24:3726-3734
©2006 by American Society of Clinical Oncology
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Relative and absolute risks of chemotherapy (chemo) benefit as a function of recurrence
score (RS) risk category.
Paik S et al. JCO 2006;24:3726-3734
©2006 by American Society of Clinical Oncology
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CLINICAL CASE
pT1N0 (T=0.8 cm), Mucinous histology, ER+, PR-,
other parameters favorable.
Next Management?
Ans: No adjuvant therapy
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FOLLOW UP
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THANKS
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NEXT PRESENTATION
Management of Locally Advanced
Breast Cancer
Dr. Satya Narayan
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Management of early breast cancer

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