SAMO FoROMe Post-ESMO 2013 – Breast Cancer

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SAMO FoROMe Post-ESMO 2013 – Breast Cancer
Dr. med. Manuela Rabaglio
Klinik und Poliklinik für Medizinische Onkologie
Breast Cancer Track
• 300 Abstracts
• 142 Poster
• 11 Proffered paper
• 4 late breaking news
• 1 best abstract (Presidential section)
• Debate/Special Sections/Teaching Sections
SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio
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Outline
• Adjuvant endocrine treatment
• Local treatment (surgery/radiotherapy)
• Bisphosphonate
• Targeted treatment
• Miscellaneus
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Adjuvant endocrine treatment
• aTTom trial: A randomised comparison of continuing
adjuvant tamoxifen to 10 years compared to stopping after
5 years in 6953 women with ER positive or ER untested
early breast cancer
• aTTom confirms the findings of the complementary ATLAS
study that, continuing tamoxifen to year 10 rather than
just to year 5 produces further reductions in recurrence
and breast cancer deaths.
• The proportional reduction in recurrence was unaffected by
age or nodal status. Benefits from continuing tamoxifen
treatment beyond year 5 emerge only after 7 years from
start of treatment for recurrence and 10 years for mortality.
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Adjuvant endocrine treatment after 5 years
• Patient wish and acceptance
• Side effects
• Premenopausal women (at diagnosis)
– Still premenopausal : consider continuing TAM (5 y)
– Postmenopausal: consider switching to AI (5y)
• Postmenopausal women
– After 5 years TAM switch to AI for 5 years
– After TAM/AI, complete 5 years AI
– After 5 years AI - ?
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Radiotherapy/Local Therapy
BEST ABSTRACT: Irradiation of the internal mammary
and medial supraclavicular lymph nodes in stage I to III
breast cancer: 10 years results of the EORTC Radiation
Oncology and Breast Cancer Groups phase III trial
22922/10925
• 82.3 vs. 80.7% OS (HR=0.87 (95%CI: 0.76, 1.00), Logrank
p=0.056); 72.1 vs. 69.1% DFS (HR=0.89 (95%CI: 0.80,
1.00), Logrank p=0.044)
AMAROS trial: Axillary lymph node dissection versus
axillary radiotherapy
• A detailed analysis of morbidity. Surgical complications
were observed in 23% of the patients in the ALND-group
versus 9% in the ART-group (P<0.001).
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• In two independent randomized trials young high risk breast cancer
patients with luminal A tumors had benefit from postmastectomy
radiation therapy (British Columbia Trial and DBCG82b Trial)
• Intrinsic subtypes define using PAM50 criteria
• No difference in OS
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• Can breast IMRT improve patient reported outcome
measures?
• Contrary to clinician assessed outcome, breast IMRT did
not translate in to improved Patient reported outcome
measures (PROMs) in this study. Only a small proportion
of patients reported moderate-severe breast changes post
radiotherapy with most PROMs improving over time.
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This House Believes That Axillary Dissection
Should be Avoided in Patients With Positive
Sentinel Node (Prof M. Gnant)
• ACOSOG-Z0011 is a great clinical trial
• The results are not suitable for defining a new standard of
care, and must not be abused for surgeons marketing
purposes.
• In principle , ALND remains the standard of care for
patients with positive sentinel node
– However it has become easier to waive additional axillary
surgery in „borderline“ cases (age, 2nd procedure,
comorbidity, several micromets, ezc)
• Understanding Z0011 results helps in moving forward the
field of breast cancer from numeric issues to the biology of
the disease.
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Still open questions:
• ALND in patient with positive sentinel node
• Radiation therapy of the axilla
• Postmastectomy RT
• Radiation therapy of the internal mammary and
supraclavicular
• IMRT
• Intraoperative RT
• Partial breast RT
More RT vs less surgery?
Role of systemic therapy?
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Bisphosphonate (Neoadjuvant/ Adjuvant)
• NEOZOTAC randomized study comparing the efficacy of
TAC with or without ZA 4mg i.v. q 3 weeks in patients (pts)
with stage II/III, HER2 neg BC neo-adjuvant
• Treatment with ZA did not make a difference as regards
clinical response nor pCR.
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Adjuvant therapy in early breast cancer with zoledronic
acid (AZURE - BIG 01/04): Final efficacy analysis
• ZOL reduced disease recurrence in bone and, consistent
with other studies, had a favourable effect on both invasive
DFS and OS in postmenopausal women (LM > 5 year)
• However, an excess of events outside bone in all other
women resulted in no overall effect of ZOL on disease
outcomes in the total study population.
• An EBCTCG meta-analysis is in progress to guide
treatment recommendations.
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AZURE - BIG 01/04
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Targeted Treatment:
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Targeted Treatment:
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Targeted Treatment:
Primary results from TH3RESA: a phase 3 study of T-DM1
vs treatment of physician's choice in HER2-positive
metastatic breast cancer (MBC):
• T-DM1 resulted in a statistically significant improvement in
PFS, with fewer grade ≥3 AEs than TPC in pts previously
treated with ≥2 HER2-directed regimens for HER2-positive
MBC.
• OS 14.9 mos for TPC, not reached for T-DM1
• Remaining issues are the optimal sequencing of HER2directed therapies and the best role for T-DM1
(discussant Clifford Hudis)
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Targeted Treatment
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Targeted Treatment
• The LEA study failed to demonstrate a statistically
significant increase in PFS by adding bevacizumab to
ET as first line therapy in metastatic breast cancer
• OS was also not impacted.
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Trastuzumab Resistance
BOLERO-3 trial: Evaluation of everolimus (EVE) in
HER2+ advanced breast cancer (BC) with activated
PI3K/mTOR pathway
• Patient with PI3K/mTOR pathway activation may derive
greater benefit from addition of EVE to trastuzumab and
vinorelbine.
• These observations are consistent with the hypothesis that
mTOR inhibition attenuates trastuzumab resistance
resulting from PI3K/mTOR pathway activation.
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Trastuzumab/Lapatinib Resistance- Role of PI3KCA
PI3KCA mutations and correlation with pCR in the
NeoALTTO trial (BIG 01-06) (Abstr. 1859)
• In patients treated with the combination of lapatinib and
trastuzumab, the pathologic complete response rate was
55.8% in those lacking PIK3CA mutations but only 28.6%
in those with mutant tumors (P = .02)
• The lower pathologic complete response rate in PI3KCAmutant tumors is observed in all treatment arms and
irrespective of estrogen receptor status
• PIK3CA mutations were found in 23% of patients
• Thus, assessment of PIK3CA status might be an
important tool in identifying patients unlikely to derive
substantial benefit from these treatments.
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Lapatinib: Rash and response rate
Pattern of rash, diarrhea, and hepatic toxicities
secondary to neoadjuvant lapatinib and their
association with age and pathological complete
response (pCR) in breast cancer (BC) patients: Analysis
from the NeoALTTO trial (Abstr. 1868)
• Rash is more common in young pts receiving lapatinib
• In addition, early development of rash is associated with
a higher chance of achieving pCR, independent of age,
treatment arm and other clinicopathologic features.
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New strategies
• PARP inhibition with BMN 673 in ovarian and breast
cancer patients with deleterious mutations of BRCA1
and BRCA2
• 18 Breast: CR 1 (6%) PR 9 (50%) SD > 12 weeks 4 (22%)
CBR 14 (78%)
• BMN 673 is well tolerated with high objective and clinical
benefit response rates in heavily pre-treated ovarian and
breast cancer pts with deleterious germ line BRCA
mutations. A phase 3 trial in metastatic breast cancer is
underway.
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Liquid Biopsy
• Circulating tumor cells before and during therapy in
metastatic breast cancer
• “Liquid Biopsy”
• This large pooled analysis has a previously unreached
statistical power and provides level-of-evidence 1 on the
independent prognostic value of CTCs before and during
treatment in MBC.
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Intertumoral and intratumoral heterogeneity
• Histology
• ER, PgR, HER2
• Transcription profiling
• Genome sequencing
• Proteomics
• Luminal A
• Luminal B
• HER2+
• Basal like
– Claudin-low
– Molecular Apocrine
– 6 TNBC subtypes
• Basal-like 1 (BL1)
• Basal-like 2 (BL2)
• Immunomudulatory (IM)
• Mesenchymal (M)
• Mesenchymal stem-like
(MSL)
• Luminal androgen receptor
(LAR)
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Intratumoral heterogeneity
Population based study investigating biopsy verifications of
"breast cancer recurrences" and biomarker changes
• discordance of biomarkers between the primary tumor and
the corresponding relapse in 10–40%.
• Patients with loss of ER or PR in relapse have poorer
survival compared to patients with stable positive
biomarkers.
• Indeed, adjuvant therapy may affect the loss of hormonal
receptors.
• Do we need to perform biopsy of recurrent disease?
• Role of CTC?
• Role of genome sequencing and proteomics?
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Physical activity
• Pre- and postdiagnostic physical activity levels in relation
to breast cancer outcome in postmenopausal breast
cancer patients - results of the TEAM-lifestyle study
• Overall survival was higher in patients who had increased
levels of PA, pre- or postdiagnostically, while no
statistically significant association was observed for BC
recurrence and BC specific survival.
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Thank you
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SAMO FoROMe Post-ESMO 2013 – Breast Cancer

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