MANAGEMENT OF LUMINAL BREAST CANCER

1. Management of luminal breast
cancers
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2. The different intrinsic breast cancer subtypes in relation to
mammary differentiation.
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4. NEED FOR MOLECULAR SIGNATURES
• Improve the clinicopathological diagnosis –
tumours with similar clinical and pathological
presentations may have different behaviours
• Predict recurrence
• Select therapies
By risk stratification and ensure highest benefit
and least toxicity
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5. • In 2013, St. Gallen international breast
conference reported that –
“ Breast cancer should not be treated as single
disease but should be defined by molecular
subtypes using genetic array testing or by IHC.
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6. Luminal A breast cancers
• Most common subtype – 50 to 60 %
• Low histological grade
• Low degree of nuclear pleomorphism, low mitotic
activity
• Include special histological subtypes ( tubular,
invasive, cribriform, mucinous and lobular)
• Good prognosis
• Relapse rate lower
• Recurrence is common in bone whereas liver lung
and CNS metastases occur in less than 10 %
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7. Luminal B
• 15 to 20 %
• Aggressive phenotype, higher grade and
proliferative index
• Worse prognosis
• High recurrence rate
• Lower survival rates after relapse
• Relatively insensitive to hormonal therapy and to
paciltaxel and doxorubicin containing
chemotherapy
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8. Hormone receptor testing
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10. ER + low subgroup
• benefit of endocrine therapy for tumors with ER
1%‐10% expression, termed “ER‐low positive
• accounts for 3% to 9% of all patients
• moderate benefit from tamoxifen
• While comparing the ER‐low tumors with
ER‐negative ones, most studies showed no
significant difference in terms of recurrence‐free
survival, DFS, overall survival, and time to
recurrence
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12. Adjuvant systemic therapy for luminal
breast cancers
• Chemotherapy
• Endocrine therapy
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13. Adjuvant chemotherapy
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17. Adjuvant chemotherapy
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18. CAN CHEMOTHERAPY BE BE AVOIDED IN
HORMONE RECEPTOR POSITIVE EARLY BREAST
CANCERS?
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19. Multigene assays to select
chemotherapy
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22. MAMMAPRINT GENES
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23. VALIDATION OF GENOMIC ASSAYS
ONCOTYPE Dx
TAILORx TRIAL
Rx PONDER TRIAL
MAMMAPRINT MINDACT
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27. Results of TAILORx trial
• After following 10,273 patients for at least 5 years—
with a median of 7.5 years—the TAILORx trial
established that
chemotherapy may safely be spared in patients with
estrogen receptor–positive, HER2-negative, and lymph
node–negative breast cancer with a 21-gene
recurrence score of 0 to 25, who were postmenopausal
or older than 50 years at diagnosis
OR
Premenopausal 50 years or less
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32. MAMMAPRINT AND MINDACT TRIAL
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34. Secondary end point
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35. The primary DMFS endpoint at 5 years continues to be met in CT untreated C-
High / G-Low risk women, confirming MINDACT as a positive de-escalation study.
With longer follow-up and in line with the natural history of luminal breast
cancer, more distant relapses do occur but the estimated gain of 2.6% for CT
administration in C-High / G-Low patients remains small in light of CT harmful
effects.
The level IA evidence for the clinical utility of the 70-gene signature for adjuvant
CT decision making is maintained.
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37. ADJUVANT RADIATION
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38. Adjuvant radiation
• Indication following total mastectomy with
axillary lymph node dissection
NCCN GUIDELINES
negative axillary nodes
tumour < 5cm
no RT
negative axillary nodes
tumour < 5 cm
negative margins but <1mm
consider RT to chest wall
consider regional nodal irradiation in women
with high risk features
( central tumours, T< 2cm, , < 10 axillary
nodes removed and atleast one of the
following- ER –ve, Grade 3, LVI)
Negative axillary nodes and tumour > 5cm Consider RT to chest wall +/- nodal
irradiation
1-3 postive nodes Strongly consider RT
> 4 positive nodes RT recommended
Margins positive Re- excision to negative margins is preferred ,
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39. Adjuvant RT following BCS and axillary staging
negative axillary nodes WBRT +/- boost to tumour bed + consider
nodal irradiation in patients with high risk
features
or
Consider APBI ( accelerated partial breast
irradiation in select low –risk patients)
or
Consider omitting breast irradiation in age
> 70 yrs with ER +ve, cNO , pT! tumours
who receive adjuvant endocrine therapy)
1-3 positive nodes
( cT1- T2, cN0,
1-2 positive sentinel nodes
No preoperative chemotherapy)
WBRT +/- boost
> 4 positive axillary nodes WBRT +/- boost to tumour bed + nodal
irradiation
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40. Adjuvant endocrine therapy
• Tamoxifen
• Aromatase inhibitors
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41. Duration of adjuvant hormonal
therapy
• Tamoxifen for 5 years
41% reduction in annual reccurence rate
34 % reduction in death rate
irrespective of age, menopausal status ,
chemotherapy status
Extended tamoxifen therapy > 5years in patients
with no evidence of tumor recurrence –
no improvement in DFS or OS
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42. Extended adjuvant endocrine therapy
• Late recurrences outnumber early recurrences
• Risk factors –
stage
High grade
Biological featurs of tumour
Longer duration of treatment - advantages
Decrease risk of metastatic cancer recurrence
Prevent in-breast recurrence
Prevent second primary
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43. • ATLAS TRIAL
10 years of tamoxifen reduce recurrence
compared to 5 years
MA17 R trial
extended aromatase inhibitor therapy
following initial 5 years of AI + tamxofen
Increased DFS Not OS in longer treatment arm
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44. Aromatase inhibitors
• In postmenopausal who have baseline
aromatase inhibitor activity , inhibit esrogen
production by 90 %
• Not appropriate for premenopausal patients
as residual ovarian function can lead to
enhanced production of aomatase and over
come effects of aromatase inhibitors
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47. Ovarian suppression as adjuvant
therapy
• Role in addition to tamoxifen or
chemotherapy in premenopausal
• Multiple RCTs have demonstrated
effectiveness
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48. • TEXT and SOFT TRIALS demonstrated that ovarian
suppression does contribute improved long term
survival outcomes in younger women.
• Patients included
age < 40 years, HR +, higher stage
premenopausal with or without chemotherapy
But patients with
node negative
age > 40 years
no chemotherapy
No benefit with ovarian suppression
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49. • Based on the results of the SOFT and TEXT
trials, the NCCN Panel
• has included ovarian suppression plus an
aromatase inhibitor for 5 years as an adjuvant
endocrine therapy option for premenopausal
patients with hormone-receptor–positive
breast cancer at higher risk of recurrence (eg,
young age, high-grade tumor, lymph-node
involvement).
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50. • Ovarian suppression – GnRh agonist therapy
Goserelin,triptorelin, leuprolide
• Side effects –
hot flashes
arthralgias
greater sexual dysfunction
premature osteoporosis
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51. Neoadjuvant endocrine therapy
• Two randomized clinical trials that
investigated preoperative endocrine therapy
among premenopausal women with operable
HR-positive/HER2-negative breast cancer.1
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52. STAGE trial
• The Study of Tamoxifen or Arimidex, combined with Goserelin
acetate, to compare Efficacy and safety (STAGE)
• Arm 1- neoadjuvant tamoxifen plus goserelin
• Arm 2- neoadjuvant anastrozole plus goserelin
• Results : 69 of 98 (70.4%) patients had a complete or partial
response compared with 50 of 99 (50.5%) patients in the group that
received tamoxifen plus goserelin
(estimated difference between groups 19.9%
• However, adjuvant trials report that ovarian function suppression
with endocrine therapy is associated with more toxicity with
prolonged use than tamoxifen alone.
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53. • In a randomized phase III study, Kim et al compared 24
weeks of neoadjuvant chemotherapy with neoadjuvant
endocrine therapy using tamoxifen and goserelin.
• The primary end point of the study was clinical
response rate as determined by caliper measurement
and MRI.
• The final analysis included 174 patients.
• Result :Response rate was significantly higher in
patients who received chemotherapy using both
caliper measurement (83.9% v 71.3%, P = .046) and
MRI (83.7% v 52.9%, P < .001).
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54. • Neoadjuvant Endocrine therapy without
intent for surgery has typically been reserved
for patients who are poor surgical candidates
and medically unfit for chemotherapy
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