Elshami M. Elamin, MDMedical Oncologist
Central Care Cancer Centerwww.cccancer.comWichita, KS - USA
4% Melanoma of skin
4% Thyroid
27% Breast
15% Lung & bronchus
3% Kidney & renal pelvis
10% Colon & rectum
3% Ovary
6% Uterus
4% Non-Hodgkin’s lymphoma
3% Leukemia
23% All other sites
2% Brain
26% Lung & bronchus
15% Breast
6% Pancreas
9% Colon & rectum
5% Ovary
3% Uterus
4% Non-Hodgkin’s lymphoma
3% Leukemia
2% Liver & intrahepatic bile duct
25% All other sites
192,370 New Cases 40,170 Deaths
American Cancer Society. Cancer Facts & Figures 2009. Atlanta, GA: American Cancer Society; 2009.
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: R.T. Hormonal therapy Chemotherapy Anti-her2 therapy Surgery
Prolong 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)
Breast ca: Any T, any N, M1 = 317 pts (300 pts included in the study)
Compare mortality risks from breast ca between pts who had surgery of primary breast tumor to those had not.
population-based observational study
Not a randomized study
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Local surgery No. of pts %
No surgery 173 58
Surg: -ve margins
61 20
Surg; +ve margins
33 11
Surg: margins unknown
33 11
Total 300 10010
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
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 progression-free 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 dissection13
Women with metastatic breast cancer at diagnosis, primary tumor removal with negative margins significantly improves survival, especially in patients with only bone metastases.
Well-designed prospective studies are needed to re-evaluate 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
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 Time to Duration of
Rate % Response Response
Endocrine 30-40 2-3 mth 12-16 mth
Combination 50-70 1.5-2 mth 8-12 mth
Chemo
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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
Fulvestrant (Faslodex) Pure anti-estrogen (downregulates ER in breast
cancer cells)20
Premenopausal: Cause polycystic ovary (contraindicated)
Postmenopausal: Aromatization of adrenal androgens Estrogens ……
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
04/19/23 23
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
04/19/23 24
ER and/or PR +ve, Her2-neu +ve, Postmenopausal: Adding Trastuzumab or Lapatinib to A.Is.
Improves PFS
Anti-estrogen Fulvestrant is an option for: Postmenopausal after Tamoxifen or A.Is.
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ER/PR negative Symptomatic visceral mets Receptor +ve refractory to endocrine
therapy
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Paclitaxel (Taxol) T+Adria interfere with Adria metabolism
Cardiac toxicity High antitumor activity
ABRAXANE (Alb-bound Paclitaxel) (Cremophor-free)
Docetaxel (Taxotere/Adria) Improvement in RR/OS Febrile neutropenia
Navelbine, Capecitabine, Gemcitabine IXEMPRA (ixabepilone) Halaven (Eribulin):
anti-microtubules extracted from sea sponge
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Predictive response 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 Higher ORR Longer TTP Increased toxicity Little survival benefit
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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 40-65% CR 10-15% Median Duration 10 months
2nd-line : RR < 30% CR < 10% Duration of response < 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? ?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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Med OS mth CHF AC 25 7% AC + Herceptin 33 27% T 18 1% T + Herceptin 22 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 ER/PR +ve:
Trastuzumab with endocrine therapy Progression on Trastuzumzab:
Continue Trastuzumab Lapatinib +/- Capecitabine Lapatinib +/- Trastuzumab
Pertuzumab Trastuzumab-DM1
04/19/23 37
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
FDA revoked its indication
04/19/23 39
Locoregional
Systemic
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Depends on: Type and extent of local/regional failure
Includes: 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
Common sites of recurrence: If MRM and adj chemo without RT:
Chest wall and supraclavicular LN
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After Mastectomy: Resection + IFRT if possible
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
Small isolated in scar/skin flap Excision with 2-3 cm margin
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NCCN:After lumpectomy/SLN:
•Mastectomy + level I/II ALND (preferred)•Consider SLN if prior axill staging done by SLN biopsy only
Axilla Resection if possible + RT
SCV RT
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]
04/19/23 46
Consider addition of hyperthermia to irradiation for local recurrence
No survival benefit
04/19/23 47
Treat as metastatic
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Bisphosphonates (Pamidronate, Zoledronic acid)
Denosumab (XGEVA) Expected survival >3 months Adequate renal function Optimal duration not established Dental exam Calcium + Vit-D
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