Updates in the Treatment of Breast cancer Mohammad Jahanzeb, MD, FACP Professor of Clinical...
Transcript of Updates in the Treatment of Breast cancer Mohammad Jahanzeb, MD, FACP Professor of Clinical...
Updates in the Treatment of Breast cancer
Mohammad Jahanzeb, MD, FACPProfessor of Clinical Medicine, Hematology-Oncology
Director, UM Sylvester Deerfield CampusAssociate Center Director for Community Outreach
Sylvester Comprehensive Cancer CenterUniversity of Miami, Miller School of Medicine
Clinical Breast Cancer Subsets defined by IHC
All Breast Cancers
ER+65-75%
HER2+15-20%
Triple negative
15%
H Burstein and A Goldhirsch St Gallen 2007
HER2 Positive Disease
Milestones of HER2/anti-HER2 therapies in BC
EGFR discovery
Cohen
neu oncogene discovery Weinberg
EGFR MoAb inhibited growth
Mendelsohn
FDA approves trastuzumab in
adjuvant setting
1982 19851978 1984 1998 2006 2007 2010
Her2 amplification in breast cancer
Aaronson
FDA approves trastuzumab
alone for 2nd line and in with
paclitaxel for 1st line MBC
FDA approves lapatinib +
letrozole for MBC
FDA approves lapatinib +
capecitabine for MBC
1987
Her2/neu amplification
correlates with shorter survival
Slamon
MBC : metastatic breast cancer; MoAb : monoclonal antibody
Her2 cloned Ullrich and Coussens
1983 2012
FDA approves pertuzumab + trastuzumab + docetaxel for
MBC
2013
FDA approves trastuzumab
emtansine for MBC
Accelerated approval of pertuuzmab/
trastzumab as neoadjuvant
therapy
Expanding Options in HER2 Targeting
· Block heterodimerization
– Add pertuzumab
· Antibody-toxin conjugate
– TDM1
· Downstream pathway inhibition
– Block MTOR/PI3K?
· Oral panHER TKI
– Lapatinib, neratinib
· Alternate antibody-drug conjugate
– MM302
Optimal HER-2 Directed Therapy Sequencing for HER-2+ Advanced Breast Cancer
Verma S et al. The Oncologist 2013;18:1153-1166©2013 by AlphaMed Press
First results from the phase III ALTTO trial (BIG 02-06; NCCTG 063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (TL) or their combination (L + T) in the adjuvant treatment of HER2-positive <br />early breast cancer (EBC)
Presented By Martine Piccart-Gebhart at 2014 ASCO Annual Meeting
Adjuvant Lapatinib (ALTTO) Scheman=8381 total/6281 analyzed
HER2+ESBC
+ Trastuzumab X 1 year
+ Lapatinib X 1 year
+ Trastuzumab+ Lapatinib X 1 year
+ Trastuzumab X 3 months → Lapatinib X 9 months
Chemotherapy
Piccart et al, ASCO 2014
Different treatment approaches
• Sequential anti-HER2 therapy after all chemo (N= 4,613)
• Concurrent anti-HER2 therapy after anthracycline-based chemo (N=3,337)
• Concurrent anti-HER2 therapy with non-anthracycline chemo (N=431)
DISEASE-FREE SURVIVAL (DFS) ANALYSIS
Presented By Martine Piccart-Gebhart at 2014 ASCO Annual Meeting
OVERALL SURVIVAL (OS) ANALYSIS
Presented By Martine Piccart-Gebhart at 2014 ASCO Annual Meeting
Take Home Message from ALTTO
· While there was doubling of pCR in the NEOALTTO study, it did not translate into improved survival outcomes in ALTTO at 4.5 years follow up
· There was increased toxicity noted with lapatinib: diarrhea, rash or erythema
12
APHINITY ADJUVANT TRIAL
N=4805TCa x 6
TCa x 6
TCa = 6 cycles of docetaxel and carboplatin
Completed recruitment on 31-Aug-2013
I-SPY 2 Trial Neratinib Arm HER2(+) Subset (n = 66 v 22 control)
Park et al AACR 2014
Signature Estimated pCR rate Probability Neratinib is Superior to
Control
Predicted Probability of
Success in Phase 3Neratinib Concurrent
Controls
HER2+/HR- 56% 33% 95% 79%
HER2+/HR+ 30% 17% 91% 65%Neratinib is an oral dual HER2 and EGFR tyrosine kinase inhibitor
Phase III Trials· Neratinib
– Extending adjuvant therapy – Nala trial
· Neratinib/capecitabine vs lapatinib/capecitabine
· > 2 lines of HER2 targeted regimens for MBC
– ISPY3· Neoadjuvant trial to follow ISPY2
· Afatinib– Lux trial
· Vinorelbine/afatinib vs vinorelbine/trastuzumab· Progression on one line of trastuzumab rx
Can HER2 PET Predict Response to Anti-HER2 therapy?
THE ZEPHIR TRIAL
Presented By Geraldine Gebhart at 2014 ASCO Annual Meeting
Slide 9
Presented By Geraldine Gebhart at 2014 ASCO Annual Meeting
Conclusions· Absence of HER2 target per HER2 PET predicts
treatment failure
· Imaging early treatment response with FDG PET predicts treatment success
· Combining both imaging modalities improves predictive accuracy – HER PET+/FDG decline – 100% PPV– HER2 PET-/No FDG decline- 100% NPV
Hormone Receptor Positive Disease
Current Standard Options for Adjuvant Endocrine Therapy
Menopausal Status at Diagnosis
Initial Therapy Extended Therapy
Pre / peri-menopausal
Tamoxifen5 Tamoxifen5
Tamoxifen5 AI5 (*if post-menopausal)
Postmenopausal AI5
Tamoxifen2-3 AI2-3
Tamoxifen5 AI5
Tamoxifen5 Tamoxifen5
Adapted from ASCO Guidelines 2014. Available at: www.asco.org
What about ovarian suppression?
What about AI + OFS in premenopausal women?
There are insufficient data currently to recommend AI for > 5 years
SOFT/TEXT· SOFT: SUPPRESSION OF OVARIAN FUNCTION TRIAL · TEXT: TAMOXIFEN AND EXEMESTANE TRIAL (at NYU)· Both Phase III Trials; Exemestane Plus gonadotrophin-releasing hormone
(GnRH) Analogue as adjuvant therapy for premenopausal women with hormone receptor positive breast cancer
· Question: is temporary ovarian function suppression with GnRH analogues (ovarian ablation permanent with surgery or radiation) useful when combined with AI or TAM.
· Goserelin (zoladex 3.6 sc monthly), leuprorelin (lupron 3.75 im monthly), buserelin, triptorelin (3.75 im monthly)
· DFS event rate much lower than anticipated combined analysis (4690 patients)
TEXT & SOFTTamoxifen + OFS vs. Exemestane + OFS
Tamoxifen 20 mg/day+ OFS* (n = 1338)Premenopausal, HR+ BC
≤ 12 wks after surgery
N = 2672
Stratified by trial, use of chemotherapy, nodal status
*OFS TEXT: triptorelin 3.75 mg IM every 28 days for 6-8 weeks prior to initiation of
HT or concurrently with chemotherapy. SOFT: triptorelin, bilateral oophorectomy or Ovarian irradiation
TEXT
Exemestane 25 mg/day+ OFS* (n = 1021)
Tamoxifen 20 mg/day
• Premenopausal HR+ BC≤ 12 wks after surgery
(if no chemo) or
• ≤ 8 mos after chemo if
premen status confirmed
• N = 3066
SOFT
Tamoxifen + OFS*
Tamoxifen 20 mg/day+ OFS* (n = 1024)
N = 2346
Exemestane 25 mg/day+ OFS* (n = 1334)
Joint Analysis
Median follow up: 68 months
42% N+
Neo/Adjuvant chemotherapy: 58%
Pagani O, et al. NEJM July 2014.
N = 2344
Exemestane+ OFS*
SOFT/TEXT: Exemestane + OFS better DFS
Median f/u 5.7 years
SOFT/TEXT: selected AEs
QOL not differentEarly cessation of treatment 16 vs 11%
SOFT/TEXT: take home message
Low event rates
Exemestane with ovarian function suppression is a new evidence based treatment option for premenopausal women with HR+ early breast cancer
Important question from SOFT (tamoxifen+OFS vs tamoxifen) will be answered end of 2014
Some premenopausal women diagnosed with HR+ breast cancer have an excellent prognosis with highly-effective endocrine therapy alone (>97% BC free at 5 yrs)
Need longer f/u, esp OS
ABCSG-12: Study Design· Key endpoints
– Primary: DFS at 5 yrs– Secondary: relapse-free survival, OS, BMD, safety
TAM 20 mg/day
ANA 1 mg/day
1803 premenopausal pts with stage I/II BC
• 80% > 40 yrs• N+ 30%
• OFS: Goserelin Q 28 days• OFS started concurrently
with endocrine therapy • Only 5% received
Chemotherapy
Treatment 3 yrs(median follow-up: 62 mos)
TAM + ZA 4 mg q6m
ANA + ZA 4 mg q6m
R
Long-term monitoring for 5 yrs
for recurrence
and survival
(DFS, OS)
3-yrBMD
5-yrBMD
Gnant M, et al. N Engl J Med. 2009, Lancet 2011
DFS
ABCSG-12 (84 Months)ET + Zometa Vs ET
100
80
60
40
20
0
DF
S (
%)
0 12 24 36 48 60 72 84 96 108
Mos Since RandomizationPatients at Risk, nNo ZAZA
903900
858862
833841
807822
758788
653674
521544
405419
191208
OS100
80
60
40
20
0
OS
(%
)
0 12 24 36 48 60 72 84 96 108
Mos Since RandomizationPatients at Risk, nNo ZAZA
903900
864868
856858
839849
811818
706708
576587
456454
215232
Gnant M, et al. Lancet 2011.
88% vs 92 % p=0.009 95% vs 97% p=0.09
ABCSG-12 (84 Months): DFSTamoxifen vs AI
Conclusions· Highly effective endocrine therapy alone offers
excellent prognosis for some premenopausal women with HR+ BC– 95% 5 year OS in all three studies.
· Role of OFS: Await data on Tam vs Tam + OFS · Side effects of OFS should not be
underestimated. · I am not ready to use AI + OFS in
premenopausal women yet.
Targeted Therapies for ER+ MBC· CDK 4/6 regulates
cell cycle progression
• Palbociclib is an oral, potent inhibitor of CDK4/6
• PALOMA-1:– Palbo + Letrozole is superior
to Letrozole in 1st line ER+ MBC (median PFS 20.2 vs. 10.2 mo, HR 0.49, p=0.0004)
CDK4/6 inhibitor summary· Palbociclib improves PFS with letrozole
– Confirmatory phase III trials ongoing– Watch for maturing data in combination with fulvestrant or paclitaxel
· Several other CDK4/6 inhibitors in development, such as abemaciclib and LEE011
· Many remaining questions:– Is there an optimal endocrine, chemotherapy or targeted therapy
partner?– How do we sequence these relative to everolimus?– What are mechanisms of resistance?
Presented by: Tiffany A. Traina, MD
Next?
· Palbociclib: accelerated FDA submission expected
· PALOMA 2 (Letrozole +/-)· PALOMA 3 (Faslodex +/-)· Novartis: Monaleesa (Let +/-)· Lilly: RTC · Others?
Triple Negative Disease
TNBC patients have a worse prognosis
NTN stage I
TN stage INon TN stage II
TN stage II
Non TN stage III
TN stage III
Bauer et al Cancer May 2007
Triple-negative phenotype and molecular sybtypes.
Carey L A The Oncologist 2010;15:49-56
TNBC Shares Clinical and Pathologic Features With BRCA1-Related Breast
CancersCharacteristics Hereditary BRCA1 Triple Negative/Basal-like[1-3]
ER/PR/HER2 status Negative Negative
TP53 status Mutant Mutant
BRCA1 status Mutational inactivation* Diminished expression*
Gene-expression pattern Basal-like Basal-like
Tumor histologyPoorly differentiated
(high grade)Poorly differentiated
(high grade)
Chemosensitivity to DNA-damaging agents
Highly sensitive Highly sensitive
*BRCA1 dysfunction due to germline mutations, promoter methylation, or overexpression of HMG or ID4 [4]
1. Perou CM, et al. Nature. 2000; 406:747-752.2. Cleator S, et al. Lancet Oncol. 2007;8:235-44.3. Sorlie T, et al. Proc Natl Acad Sci U S A. 2001;98:10869-10874.4. Miyoshi Y, et al. Int J Clin Oncol. 2008;13:395-400.
Platinum Agents in TNBC
Trial Population Results
Control arm BALI-1 (CDDP) Sporadic TNBC 10% RR
Control arm phase III iniparib (gem/carbo) Sporadic TNBC 30% RR
TBCRC 001 (cetuximab/carbo) Sporadic TNBC 17% RR
14-pt trials neoadj CDDP (Byrski + Silver) BRCA1+ 86% pCR
24-pt trial neoadjuvant CDDP (Silver) Sporadic TNBC 15% pCR
Baselga J, et al. Ann Oncol. 2010;21(Suppl 8). Abstract 274O. O’Shaughnessy J, et al. J Clin Oncol. 2011;29(Suppl). Abstract 1007. Carey L, et al. 2008;26(Suppl). Abstract 1009. Byrski T, et al. J Clin Oncol. 2010;28:375-379. Silver DP, et al. J Clin Oncol. 2010;28:1145-1153.
Good preclinical rationale, particularly in BRCA-associatedClinical data:
Clinical role of platinums less clear: promising in BRCA+
CALGB 40603 and other trials designed to clarify
Neoadjuvant Carboplatin for TNBC
von Minckwitz, Lancet Oncol 2014; 15: 747–56; Sikov, SABCS 2013; Rugo SABCS 2013; Alba, BCRT, 2012 (136)
Summary of recent randomized trials
Study Design NpCR
Control Platinum
GeparSixto nplDox/Pac/Bev+/- wCb (AUC1.5) X 18 wks
315 42.7% 53.2%
ALLIANCE 406032x2 design
wPac +/- Cb (AUC 6) +/- bev AC X 4
433 41% 54%
GEICAM/2006-03 ECX4D +/-Cb AUC6 X 4 94 30% 30%
ISPY2 wPac+/-Cb/veliparib ACx4 71 26%(est) 52%(est)
Both GeparSixto and CALGB 40603 included Bev along with Cb and I spy included PARPi
Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide /
epirubicin / 5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer.
Kenji Tamura, Jun Hashimoto, Hitoshi Tsuda, Masayuki Yoshida, Hideko Yamauchi, Kenjiro Aogi, Satoru Shimizu, Hiroji Iwata, Norikazu Masuda, Naohito
Yamamoto, Kenichi Inoue, Shinji Ohno, Katsumasa Kuroi, Tamie Sukigara, Yasuhiro Fujiwara, Masashi Andoh
Abstract 1017
Aims• Compare pCR in HER2 Negative tumors with
paclitaxel +/- carbo followed by CEF (note: ER+ and TNBC combined)
• Evaluate pretreatment biomarkers Ki-67, EGFR, Cytokeratin (CK) 5/6, BRCA1, vimentin, ERCC1 and ZEB1 by IHC
Study Schema
CarboplatinAUC5
q3wks x 4
Paclitaxel 80 mg/m2 qwk x 12
CP-CEF
P-CEF
HER2 (-) BCStage II/IIIA18-70 years
PS 0/1Good Organ
functionWritten IC
S U
R G
E R
Y
CEF 500/100/500 mg/m2
q3wks x 4
R
CEF 500/100/500 mg/m2
q3wks x 4
Paclitaxel 80 mg/m2 qwk x 12
Enrolled 181 ptsN= 75 for TNBC56% Node positive
pCR rates
CP-CEF P-CEF0
20
40
60
80
100
32%17%
All patients
pC
R r
ate
(%)
CP-CEF P-CEF0
20
40
60
80
100
62%
26%
TNBC patients
pC
R r
ate
(%)
Primary Endpoint
P =0.04
pCR rates by EGFR
expression
EGFR- EGFR+
p=0.010
(%)
0All AllCP CPP P
11.518.2
6.7
45.0
63.6
22.220
40
60
80
p=0.040
p= N.S.
pC
R r
ate
Results
Mechanisms of Synthetic Lethality-PARP-1
42Image from: Iglehart JD, Silver DP. Synthetic Lethality-A new direction in cancer-drug development. NEJM 2009; 361 (2) ; 189-191. 2009 Massachusetts Medical Society.
All rights reserved. Permission requested.
Paclitaxel + Trastuzumab* +
New Agent A
Paclitaxel + New Agent C
Patient is on Study
Paclitaxel+ Trastuzumab
Paclitaxel + Trastuzumab* +
New Agent B
Paclitaxel
Paclitaxel + New Agent E
AC
ACHER 2 (+)
HER 2(–)
Randomize
Randomize
Surgery
Surgery
Learn and adapt from each patient as
we go along
Paclitaxel + New Agent F
Paclitaxel + Trastuzumab* +
New Agent C
Paclitaxel + New Agent DPaclitaxel +
New Agent GH
Paclitaxel + Trastuzumab* +
New Agent F
MRI
Residual
Disease
(Pathology)
Key
43
I-SPY 2 TRIAL:
Learn, Drop, Graduate, and Replace Agents Over Time
The I-SPY 2 Bayesian model estimates the probability distribution
of pCR rates in each signature
Actual pCR rates are biased by the adaptive randomization and are
not calculated
Rugo et. al. SABCS 2013
Veliparib/Carboplatin GRADUATES
in the Triple Negative Signature
SIGNATURE
Estimated pCR Rate(95% probability interval) Probability
Veliparib +Carbo is
Superior to Control
Predictive Probability of
Success in Phase 3
Veliparib/Carbo
ConcurrentControl
All HER2- 33% (22-43%)
22% (10-35%)
92% 55%
HR+/HER2- 14% (4-27%)
19% (6-35%)
28% 9%
HR-/HER2- 52% (35-69%)
26% (11-40%) 99% 90%
Rugo et. al. SABCS 2013
PARP Inhibitors in Development
• Olaparib (Astra Zeneca) PO• Veliparib (ABT888 - Abbvie) PO• BMN-673 (Biomarin) PO• Niraparib (MK-4827) PO• CEP 9722 (Cephalon) PO• GPI 21016 (MGI Pharma) PO• Iniparib (BSI 201 – Sanofi-Aventis) IV• Rucaparib aka AGO 14699 (Pfizer) IV• INO 1001 (Inotek – Genentech/Roche) IV
• Others?
TNBC: potential therapeutic targets
Mayer I A et al. Clin Cancer Res 2014;20:782-790
©2014 by American Association for Cancer Research
Novel Agents in Development for TNBC
· Met inhibitor: ARQ197, onartuzumab (Metmab), foretinib
· PI3K and/or inhibitor: BKM 120, temsirolimus (+ neratinib)
· HDAC inhibitors: entinostat, vorinosat· Demethylating agents: azacitidine
(+ entinostat)· PARP inhibitors: ABT-888, E7449,
Biomarin-BMN673, AZD2281, rucaparib
· Olaparib+ BKM120; · Angiogenesis inhibitor: cediranib
(+ olaparib), ramicurumab, IMC18F1, foretenib, sorafenib
· Hsp90 inhibitors: ganetespib · Aurora kinase inhibitors: ENMD 2076· Androgen Receptor Blockers:
enzalutamide
· EGF inhibitors: erlotinib (+ metformin), apatanib
· Lucitanib (FGFR+VEGF inhibitor)· Masitinib (C-Kit inhibitor)· MEK inhibitors: GSK1120212· Wnt inhibitor: LGK974· CDK inhibitor: dinaciclib, P276-00· FMS-Kit inhibitor: PLX3397 · Apoptosis inducer: LCL161
(deactivating inhibitor of apoptosis proteins)
· Immunotherapy: MUC1 vaccine, adoptive cellular therapy (DC-CIK)
· Cytotoxics: SN38 -NK012, AEZS-108 (LHRH-dox);
· Checkpoint inhibitors (anti PD-1, anti PDL-1)
Biologics in Breast Cancer: Bevacizumab
Antibody designed to normalizing the tumor blood vessels (antiangiogenic) and aid delivery of chemotherapy: Avastin (Bevacizumab)
E5103: addition of Bev to standard AC-T in women with high risk breast cancer· LN+ · LN – (TN>1cm, HR+ >5 cm or <5 cm with oncotype >11)
Bev at 15mg/kg given concurrently with chemo and +/- maintenance
In 2010 FDA rescinded Bev approval for metast BC
E5103: Bevacizumab2986 patients
No benefit from addition of Bev
Bevacizumab: take home message
No role for bevacizumab in breast cancer (FDA approval rescinded for metastatic disease and no benefit shown in earlier stages, including E5103)
Biospecimen bank with be utilized for predictors of toxicity and late relapse
SWOG Proposed Study
R
TNBC Post NAC PT1C or N+
N=400
Placebo x 1 year
MK3475 x 1 yearAnti-PD1 antibody
Primary endpoint:
DFS
A randomized, phase III trial to evaluate the efficacy and safety of MK-3475 as adjuvant therapy for triple receptor-negative breast cancer with >1 cm residual invasive cancer or any positive lymph nodes
(>pN1mic) after neoadjuvant chemotherapy
Slide 28
Presented By Melinda Telli at 2014 ASCO Annual Meeting
EA 1131A
RTNBC
Post NAC PT1C or N+
Placebo
Carboplatin X 4 cycles
Primary endpoint:
DFS
EA 1131A : A randomized, phase III trial to evaluate the efficacy of adjuvant carboplatin for triple receptor-negative breast cancer with
residual invasive cancer
427 Enrolled 407 MBC Bx 299 Genomics
195 Druggable Lesions55 Genomic-driven Rx
SAFIR 01 Molecular-Driven Study Flow
(13%)
Andre F, et al. Lancet Oncol 2014
Most Activating Mutations are Rare
SAFIR 01 Study
Outcomes
Andre F, et al. Lancet Oncol 2014
Targets addressed:
• PI3KCA mutation
• EGFR amplification
• AKT mutation
• FGFR amplification
• IGF-1R amplificationOverall Benefit Rate:12/407 (3%)Response Rate: 4/407 (1%)
17 Targeted Regimens
PREVENTION, SUPPORTIVE CARE & SURVIVORSHIP
Prevention of Early Menopause Study<br />(POEMS)-S0230<br /> Phase III trial of LHRH analog during chemotherapy to reduce ovarian failure in early stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance)
Presented By Halle Moore at 2014 ASCO Annual Meeting
Background
Presented By Halle Moore at 2014 ASCO Annual Meeting
POEMS/S0230 Schema
Presented By Halle Moore at 2014 ASCO Annual Meeting
Results· Ovarian failure at 2 years
– Standard chemotherapy: 15/69- 22%
– Standard chemotherapy + Goserelin: 5/66- 8%
· More women attempted and achieved successful pregnancies in the goserelin arm compared to the chemotherapy alone arm– 12/113 (12%) vs 22/105: (21%)
· Total number of babies: 12 vs 18
· Increased menopausal symptoms during treatment
· No negative impact on cancer outcomes
Take Home Message· Fertility preservation is an important issue
for young patients
· Current Options:- Ovarian Stimulation and embryo cryopreservation- Oocyte cryopreservation- Ovarian tissue cryopreservation (Experimental)- GnRH agonist during chemotherapy?
Vitamin d and breast cancer<br />Background
Presented By Ana Elisa Lohmann at 2014 ASCO Annual Meeting
PROGNOSTIC ASSOCIATIONS OF 25OH VITAMIN D <br /> IN NCIC CTG MA.21 <br />A PHASE III ADJUVANT RANDOMIZED CLINICAL TRIAL <br />OF THREE CHEMOTHERAPY REGIMENS<br /> (CEF, EC/T, AC/T) IN HIGH RISK BREAST CANCER <br /> <br /><br />
Presented By Ana Elisa Lohmann at 2014 ASCO Annual Meeting
Results· Sample size
– MA.21: N = 2104 patients
– Vit D sub-study: N = 934 patients
· Low VIT D level was not associated with recurrence free survival, breast cancer free survival or overall survival
· However,– Most patients had adequate VIT D levels at study entry (mean VIT D
level 27.9ng/ml), only 20% were deficient– One time point– Lack of data on VIT D supplementation– Analysis of a subset of patients not fully representative of the entire
population– Restrictive study population (white, young and with high risk BC)
Take Home Message· Link between VIT D and breast cancer
outcomes remains inconclusive
· Randomized trial desirable but not feasible
– Common use of VIT D and better VIT D levels– Patients with low level might not want to get
randomized to placebo
Effect of obesity in premenopausal ER+ early breast cancer:
· EΒCΤCG data on 80,000 patients in 70 trials· Independent prognostic factor (regardless of surgery type, tumor size,
grade, LN status, chemo, hormonal therapy)· Dose response: increasing BMI increasing BC mortality
Pan et. al.PASCO2014 abst # 503
Obesity confers worse outcomes in premenopausal ER+ BC
Pan et. al. PASCO2014 abst # 503
THANK YOU!