Artifacts in Nuclear Medicine with Identifying and resolving artifacts.
Updates in the management of ibc educational
1. Updates in the
Management of
Inflammatory Breast
Cancer
AinShamsUniversity
Faculty of
Medicine
General
Surgery
Department
Mohamed El-Shinawi, MD,FACS
Professor of General Surgery
2. Disclosure
I have no commercial associations
that might pose a conflict of
interest in connection with the
following presentation.
3. Contents
• Breast Cancer in Egypt
• Diagnosis of IBC
• Markers for IBC
• HCMV and IBC
• Treatment
• Conclusions and Future Directions
12. Egypt
• Breast Cancer is the most common malignancy in
Egyptian women
• 49.6 per 100,000 population.
Breast
37.6%
Lymphoma
Leukemia
Bladder
Colorectal
Liver
Ovary
Cervix
Thyroid
Bladder
Liver
Lymphoma
Leukemia
Lung
Colorectal
Skin
Larynx
www.nci.edu.eg
13. Breast Cancer among Females in Egypt
http://www.nci.edu.eg/PathologyBook.htm
Studies showing that the rate of breast cancer increased
from 29% in 2002 to 38% in 2013 in Egypt.”NCI-2013”
14. • DISCOVERY OF INFLAMMATORY BREAST CANCER:
• The first description of inflammatory breast
cancer (IBC) was published in 1814 by Sir
Charles Bell, who observed that a purple color
on the skin over the breast tumor and shooting
pains (Bell, 1814).
• The term “inflammatory breast cancer” was first
suggested in 1924 by Lee and Tannebanm as a
type of cancer associated with inflammation of
the breast (Lee and Tannenbaum, 1924).
15. • In 1938, two clinical varieties of IBC
namely: primary IBC and secondary IBC
were described by Taylor and Meltzer
(Taylor and Meltzer, 1938). The term
“primary IBC” is defined as the de novo
development in a previously normal breast
whereas “secondary IBC” describes the
changes of the breast resulting from non-
IBC or breast cancer recurrence (Robertson
et al., 2010).
16. IBC Worldwide
• In the U.S., incidence is -5-8% of all breast cancers, accounts
for 10-15 or possibly 20% of yearly deaths
• Under-diagnosed and under-reported
• 30% of patients have distant metastases at the time of
diagnosis
• Most common in women under 40 yrs of age
• Pregnancy associated breast cancer (25% of IBC)
• Three times more frequent during lactation
• Mean time of survival is 2.5 years
• Common, unifying finding
for IBC is the rapid
infiltration of lymphatics by
cancer cells
18. The minimum criteria required for the
diagnosis of IBC include the following:
• Rapid onset of breast erythema, edema and/or
peau d’orange, and/or warm breast, with or
without an underlying palpable mass.
• History of flattening, crusting, or retraction of
the nipple may be present.
• Patients may have a history of being diagnosed
with mastitis not responding to at least 1 week
of antibiotics.
19. • Duration of history of no more than 6 months.
• Clinical examination revealing erythema
occupying at least one-third of the breast.
• Clinical examination may reveal underlying
palpable mass with or without palpable loco
regional lymph nodes with or without nipple
abnormalities.
• Pathological confirmation of invasive carcinoma
from a core biopsy of the breast.
22. Pathological
• Rapid invasion into blood and
lymphatic vessels where forming
tumor emboli
• Tumor emboli: tumor cells
strongly bound together and
retracted away from surrounding
endothelial lining
IBC tumor emboli provided
by
Akram M. Nouh, Pathologist
23. Based on the Current Knowledge , evidence
suggest that IBC differs from non-IBC locally
advanced disease.
Translational research efforts based should be
directed to clarify the etiology and biology of this
aggressive disease.
29. Cytokines detected and Human
Cytomegalo Virus (HCMV) Infection
NYU Dr. Schneider’s lab, preliminary results
suggested an involvement of (HCMV), a herpes-
virus that infects macrophages and tissue
fibroblasts in the etiology of IBC development.
IL-6 and IL-10 found to be associated with HCMV
infection ( Zedtwitz-Liebenstein, et al., 2009).
“HCMV expresses several homologues of
human interleukin 10 (hIL-10) possessing
immunomodulatory properties..” (Jaworowski, et
al., 2009)
30. HCMV Serological Diagnosis
• IgG and IgM detected IgG and IgM detected with chemilumensence
technique for 14 IBC patients (14 peripheral plasma and 12 central plasma),
18 NIBC patients and 6 controls. IgG was positive in all plasma samples of
IBC and NIBC, and IgM was negative in all plasma samples of IBC and
non-IBC and control group
31. HCMV screening of IBC and Non-IBC
Carcinoma Tissues
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
NIBC IBC
Negativ
e
SamplePercentage
HCMV Nested-PCR of Non-IBC tissue samples HCMV nested-PCR of IBC tissue samples
*
38. Other Markers
A number of other markers have been studied in IBC
p53 mutations have been shown to occur in IBC and is
associated with decreased response to chemotherapy and
poor survival Outcomes
Chemokine receptors CXCR4 and CCR7
expression in IBC tumors have been shown to be
associated
with poor prognostic outcome.
E-cadherin, and lympho angiogenic factors [(e.g.
vascular endothelial growth factor (VEGF)-C, VEGF-D,
VEGFR-3,Prox-1, lymphatic vessel endothelial
receptor1] have been shown to be increased in IBC
tumors compared with non-IBC
tumors .
39. RhoC guanosine triphosphatase
(GTPase),
a breast-specific oncogene, has been
shown to be overexpressed in 90% of IBC
tumors compared with 38% of non-IBC
tumors and is associated with high histologic
grade, advanced
stage, and poor prognostic outcome
41. LINES OF TREATMENT
• Primary systemic therapy
• Surgery
• Radiation Therapy
• Hormonal Therapy
• Novel Systemic Therapies
a. Therapy Targeting HER2
b. Therapy Targeting Vasculolymphatic Pathways-
Angiogenesis, Lymphangiogenesis, and
Vasculogenesis
c. Therapy Targeting Overexpression of RhoC
GTPase and Loss of WISP3
45. Conclusions
• Inflammatory breast cancer disease
biology is complex and has several
different characteristics that determine
the aggressive biology of this disease.
• Since the consistent use of
Neoadjuvant chemotherapy with
Locoregional therapies overall
survival increased.
.
46. Future Directions
• Investigations showed that cytokines,
proteases, and viral infection were
found to play a crucial role in IBC
disease progression
• Therefore our future directions should
be focusing on new and additional
agents to improve the standard
treatment since it remains a disease
with a dismal prognosis.
