Transcript EARLY BREAST CANCER

Elshami M. Elamin, MD
Medical Oncologist
Central Care Cancer Center
www.cccancer.com
Wichita, KS - USA
192,370 New Cases
40,170 Deaths
4% Melanoma of skin
2% Brain
4% Thyroid
26% Lung & bronchus
27% Breast
15% Breast
15% Lung & bronchus
6% Pancreas
3% Kidney & renal pelvis
9% Colon & rectum
10% Colon & rectum
5% Ovary
3% Ovary
3% Uterus
6% Uterus
4% Non-Hodgkin’s lymphoma
4% Non-Hodgkin’s lymphoma
3% Leukemia
3% Leukemia
2% Liver & intrahepatic bile duct
23% All other sites
25% All other sites
American Cancer Society. Cancer Facts & Figures 2009. Atlanta, GA: American Cancer Society; 2009.
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CBC, Ca+, LFTs
CEA, CA 27-29, CA 15-3
C-x-rays
Bone scan
Chest/Abd/Pelvis CT
PET
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Age, Menopausal status (at time of mets)
ER/PR, Her2 status
Prior therapy and response
Number/Sites of mets (<3, soft tissue/bone vs visceral)
PS
Co-morbidity
Psychosocial
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Palliation:
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R.T.
Hormonal therapy
Chemotherapy
Anti-her2 therapy
Surgery
 Prolong
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survival
Cure
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 Routine
surgerical removal of the
primary tumor usually is not
recommended !!
 Only for local control and complications
 bleeding, ulceration, and infection at the
primary tumor site, "toilette" mastectomy
 Survival is determined by distant mets,
not by local disease
 ? No survival benefit
 ? May stimulate growth of mets
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Elisabetta Rapiti, Helena M. Verkooijen, Georges Vlastos,
Gerald Fioretta, Isabelle Neyroud-Caspar, André
Pascal Sappino, Pierre O. Chappuis, Christine
Bouchardy
J Clin Oncol 24:2743-2749, 2006
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Geneva Cancer Registry (1977-1996)
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Breast ca: Any T, any N, M1 = 317 pts (300 pts
included in the study)
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Compare mortality risks from breast ca between
pts who had surgery of primary breast tumor to
those had not.
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population-based observational study
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Not a randomized study
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Local surgery
No. of pts
%
No surgery
173
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Surg: -ve
margins
Surg; +ve
margins
Surg: margins
unknown
Total
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20
33
11
33
11
300
100
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Surgical removal of breast tumor improves
prognosis of women with met breast cancer.
 40% reduction in breast cancer mortality
 Only in pts with –ve margins
 Sites of mets do not affect outcome.
 Pts with bone mets benefit the most
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No significant survival benefit for axillary
dissection
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224 pts studied: 82 (37%) underwent
mastectomy and 142 (63%) were treated
without surgery. The median follow-up time
was 32.1 months.
 Surgery was associated with a trend toward
improvement in overall survival (P=.12) and a
significant improvement in metastatic progressionfree survival (P=.0007)
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Retrospective study of 16,023 patients.
Surgery of the primary tumor was associated
with a 39% reduction in the risk of death
 3 Yr Survival:
 35% for patients excised to negative margins
 26% for those with positive margins
 17.3% for those not having surgery
 (P < .0001).
 No sig survival benefit for axillary dissection
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Women with metastatic breast cancer at diagnosis,
primary tumor removal with negative margins
significantly improves survival, especially in
patients with only bone metastases.
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Well-designed prospective studies are needed to reevaluate the treatment paradigm "no surgery of
the primary tumor" in breast cancer with
metastases at diagnosis and to determine the
impact of breast surgery on outcome of these
patients.
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New chemotherapy agents (Taxanes).
Biologic agents.
 Ant-Her2 (Herceptin, Tykerb)
 ? Avastin
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Surgical complications are infrequent.
In a multivariate analysis:
 Each more recent year of recurrence was associated
with a 1% per year reduction in the risk of death.
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Response
Rate %
Time to
Response
Duration of
Response
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Endocrine
30-40
2-3 mth
12-16 mth
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Combination
Chemo
50-70
1.5-2 mth
8-12 mth
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ER/PR
Age
Her-2 neu
Sites of mets
 Visceral/Bones
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Tamoxifen (Novadex, Soltamox, Valodex,
Istubal)
 Its metabolite hydoxytamoxifen acts as estrogen
antogonist in the breast
 It acts an estrogen agonist in the endometrium
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Fulvestrant (Faslodex)
 Pure anti-estrogen (downregulates ER in breast
cancer cells)
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Premenopausal:
 Cause polycystic ovary (contraindicated)
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Postmenopausal:
 Aromatization of adrenal androgens  Estrogens ……
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Aminoglutethemide
Anastrozole (Arimidex)
Letrozole (Femara)
Exemestane (Aromasin)
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Ovarian Ablation (Oophorectomy):
 Surgical (immediate)
 RT (2-3 months)
 LH-RH analogues
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ER and/or PR +ve, Postmenopausal :
 Within one yr of antiestrogen:
 A.Is. are preferred
 Antiestrogen naïve or more than 1 yr from
antiestrogen
 A.Is. appear superior compared to Tam
 Recent Cochrane Review suggested small survival
benefits
4/8/2016
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ER and/or PR +ve, Premenopausal:
 Within one yr of antiestrogen:
 Ovarian ablation is preferred + endocrine therapy as
postmenopaual
 Antiestrogen naïve:
 Antiestrogen alone
 LHRH ovarian ablation + endocrine therapy as
postmenopaual
 LHRH ovarian ablation + A.I. is not recommended
4/8/2016
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ER and/or PR +ve, Her2-neu +ve,
Postmenopausal:
 Adding Trastuzumab or Lapatinib to A.Is.
 Improves PFS
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Anti-estrogen Fulvestrant is an option for:
 Postmenopausal after Tamoxifen or A.Is.
4/8/2016
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ER/PR negative
Symptomatic visceral mets
Receptor +ve refractory to endocrine
therapy
4/8/2016
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Paclitaxel (Taxol)
 T+Adria interfere with Adria metabolism
 Cardiac toxicity
 High antitumor activity
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ABRAXANE (Alb-bound Paclitaxel) (Cremophor-free)
Docetaxel (Taxotere/Adria)
 Improvement in RR/OS
 Febrile neutropenia
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Navelbine, Capecitabine, Gemcitabine
IXEMPRA (ixabepilone)
Halaven (Eribulin):
 anti-microtubules extracted from sea sponge
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Predictive response
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Prior adjuvant chemo > 12 months
Her-2 neu
Topoisomerase IIa
? In vitro study
Prolong survival by ~ 20%
 MS : 20 – 30 months
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Combination chemotherapy
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Higher ORR
Longer TTP
Increased toxicity
Little survival benefit
4/8/2016
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Single-Agents (Adriamycin, Taxane, Xeloda, etc)
 Inferior to combination in RR and “survival”
 Recent studies
 Similar survival
 Better QL
 Less toxicity
JCO 16:3720,1998
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First-line (CMF, CAF, AC):
 RR
 CR
 Median Duration
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2nd-line :
 RR
 CR
 Duration of response
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40-65%
10-15%
10 months
< 30%
< 10%
< 6 months
Adriamycin-Regimen:
 Statistically significant RR, Time to treatment failure, Survival
 More toxic (Alopecia, Myelosupression, Cardiotoxicity)
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What is the optimal Duration of Chemo?
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?6 cycles
To maximum response or Stable dz
2-3 cycles beyond CR
Chemo holiday
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Conventional chemo vs High-dose chemo + ASCT
 No improvement in survival
Stadtmauer NEJM:2000
 It is not a practice anymore
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AC
AC + Herceptin
T
T + Herceptin
Med OS mth
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18
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CHF
7%
27%
1%
12%
 Chemo + Herceptin significantly better
Siamon ASCO 1998 #377, Norton ASCO 1999 # 483
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ER/PR –ve:
 Trastuzumab alone or with Taxol +/- Carbo or Doce
or Vinorelbine or Capecitabine
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ER/PR +ve:
 Trastuzumab with endocrine therapy
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Progression on Trastuzumzab:
 Continue Trastuzumab
 Lapatinib +/- Capecitabine
 Lapatinib +/- Trastuzumab
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Pertuzumab
Trastuzumab-DM1
4/8/2016
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Met, advanced BC overexp Her2 s/p anthra,
taxane, herceptin:
 Xeloda (2000mg/m qd)+/-Tykerb 1250mg (5tab) qd:
 TTP 8.4 vs 4.4 m
 Toxiciy;
 diarhea
 PPE
 cardiac 1.6%
 prolong QT
 Dose reduce for;
 low LVEF
 hepatic
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First-line Taxol +/- Avastin
 PFS 11.8 vs 5.9 m (P<0.001)
 No sig diff in OS
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FDA revoked its indication
4/8/2016
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 Locoregional
 Systemic
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Depends on:
 Type and extent of local/regional failure
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Includes:
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RT
Excision
Endocrine therapy
Chemotherapy
Combinations
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Initial treatment; Mastectomy or breast
conservation:
 EORTC 10801 and Danish BCG 82TM trials (stage
I-II):
 No diff in initial events of local recurrences
 No diff in survival after salvage treatment
 50% of both groups were alive at 10 yrs
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Common sites of recurrence:
 If MRM and adj chemo without RT:
 Chest wall and supraclavicular LN
4/8/2016
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After Mastectomy:
 Resection + IFRT if possible
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After Breast conservation:
 Mastectomy and ALND if level I/II not previously done
 Limited data suggest that repeat SLND may be possible
 Accuracy of repeat SLND is unproven
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Small isolated in scar/skin flap
 Excision with 2-3 cm margin
NCCN:
After lumpectomy/SLN:
•Mastectomy + level I/II ALND (preferred)
•Consider SLN if prior axill staging done by SLN biopsy only
4/8/2016
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Axilla
 Resection if possible + RT
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SCV
 RT
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IM Node
 RT
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After local treatment:
 Consider limited duration chemo or endocrine
therapy similar to adj therapy.
 BIG 101/IBCSG 27-02/NSABP B-37 [chemo for
isolated local and/or regional ipsil recurrence
in early stage breast cancer]
4/8/2016
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Consider addition of hyperthermia to
irradiation for local recurrence
 No survival benefit
4/8/2016
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 Treat
as metastatic
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Bisphosphonates (Pamidronate, Zoledronic
acid)
Denosumab (XGEVA)
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Expected survival >3 months
Adequate renal function
Optimal duration not established
Dental exam
Calcium + Vit-D
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