Title: The profile and challenges of managing breast cancer in developing countries
1The profile and challenges of managing breast
cancer in developing countries
- Dana Lucia Stanculeanu ,MD,PhD
- Romania
-
2ROMANIAin SE of Europe
3Present
- - In Romania are only two Oncology Institutes -
Bucharest and Cluj- Napoca (south-east and west
regions of the country). - Each of the 42 counties has an oncology network
with Oncology offices and Oncology departments ,
depending on economical potential of the region. - In 1998 it was created the National Insurance
House supposed to support all expenses related
by citizens health. - A National Oncology Program for prevention,
diagnoses and treatment was validated by
government .
4Problem 1
- National Cancer Registry
- - existed till 1989
- - since 1989 statistic data was collected
through 2 sources National Statistic Center and
Statistic Center of MoH - - there are many differences between the
reality and the registered data
5Problem 2
- Romania a developing country ,with financial
problems including the health system - The decrease of active population that can pay
health insurance - Lack of consistent private alternative health
insurance which can be in competition with
National Insurance House thus resulting in a
dysfunctional health system in Romania
6Effects
- Not enough funds for health and for Oncology
Program because of - Economic alternatives
- Under financing of real need of resources because
errors in registration data for Oncology thus
resulting in - Physicians being forced to focus on treatment of
existing cases, most in advanced stages and
diminishing possibility on early diagnosis and
prevention
7Breast cancer in Romaniaepidemiology
- Cancer the second death cause after
cardiovascular diseases - Breast cancer in Romania first death caused
through cancer at women - Increasing incidence from 1981- 24,61/ooo
inhabitants to 41,29ooo inhabitants in 1999. - In Romania most of cases are diagnosed in
advanced stages - stage III - 41,32 stage IV - 17,16
- In The Oncology Institute of Bucharest in 1998
stage III was at 68,85 and stage IV was at
8,48 - The breast cancer mortality has grown in 1999
being of 25,31ooo inhabitants in comparison
with standard world mortality for breast cancer (
11,52ooo inhabitants )and European standard
mortality for breast cancer (16,00ooo
inhabitants)
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12Patient at first visit in Oncology Institute
Bucharest
13Patient at first visit in Oncology Institute
Bucharest
14Patient at first visit in Oncology Institute
Bucharest
15Patient at first visit in Oncology Institute
Bucharest
16Patient at first visit in Oncology Institute
Bucharest
17Why in this stage?
- Lack of educational programs for population
- Difficult access to information
- Lack of support from media channels in promoting
screening programs with free access and promoting
witch-doctors, healers - Errors in the health system operations
- Low socio-economic level
18Despite of these, patients are treated !
- In Romania, therapeutic judgment is established
by The Committee of therapeutic indication
(Surgeon, Medical Oncologist , Radiotherapist,
Pathologist) - The treatment choice is made in accordance with
therapeutic guidelines , individualized for each
patient. - The therapeutic guidelines are inspired by
European guidelines (ESMO guidelines) - The main difficulty is created by an under
financed program that may create the
impossibility to make a treatment according with
therapeutic guidelines.
19The evolution of surgical treatment for breast
cancer
Conservative treatment
Modify radical mastectomy
Radical mastectomy (Halsted)
2001
20The surgery of breast cancer today
- The conservative treatment
- Sentinel lymph node biopsy
- Techniques of modify radical mastectomy
- Breast reconstruction
- Laparoscopic ovarian ablation
21The conservative treatment in I and II stage
Limited surgery ? Radiotherapy
? Systemic treatment
or Radiotherapy ? Systemic treatment
or Systemic treatment ? Radiotherapy ? Limited
surgery
22Because the most cases are advanced stage at
diagnosis in Romania ? mastectomy
- Radical mastectomies( Halsted surgery) are
not indicated and are replaced with modified
radical mastectomy - Madden technique
- Patey technique
- Professor Chiricutas technique
- IOB technique (Trestioreanu, Balanescu, Pitaru)
23Radiotherapy after surgery
- Radiotherapy after limited surgical resection
gives additional problems for Radiotherapist
compared with radiotherapy after radical
mastectomy . - It is more difficult in case of radiotherapy
after limited surgical resection because of young
patients with small tumours , without lymph nodes
who choose a more esthetic operation and this
result must not be affected through irradiation.
- The risk of local recurrence ,of excessive
irradiation, of critical organs (heart, lung) and
the risk of survival reduction is real when the
the irradiation is not homogenous, under right
dose or not appropriate to the clinical stage of
the disease
24Objectives followed
- Identify the patients with high risk of heart
toxicity(patients with left breast tumor) - Development of techniques which allow the
improvement of local control through Radiotherapy
and reducing side effects - Reducing risk of excessive irradiation of the
heart through an homogenous and correct
irradiation of the breast
25Reason for using new irradiation technique
-advantages
- The heart and lung irradiated volumes are reduces
through - Three-dimensional planning usage, CT assisted
- The calculation of absorbed dose in the volume
not in plan, which provides an accurate image of
the irradiation of critical organs
26New irradiation techniques used in Romania
- Radiotherapy modulated by intensity
- - allows the tumour irradiation with a high and
homogenous dose without irradiation of healthy
organs near the tumour - Three-dimensional new method of stimulating the
treatment plan (surface, CT assisted) - With CT assistance we can have the possibility
to reconstruct a three-dimensional image starting
from multiple two dimensional images -
27New irradiation techniques used in Romania
- RT three-dimensional conformational
- Which now allow Romanian Radiotherapists to use
a bigger number of fascicules, fields with forms
in accordance with target volume, fascicules
which are not in the same plan.
28RT an useful treatment way in association with
limited resection in early stage of the breast
cancer
- RT- decreases the risk of mortality related to
breast cancer (influenced by age and prognostic
factors) overall benefit 0,8- 4,1 (EBCTCG) - - but increases with 0,8- 5,6 the risk of
mortality by cardiologic cause -
29- Using RMI ,the dose at heart level is
significantly reduced ,without affecting the
planned tumor volume . - Through RMI, the dose of collateral breast level
can be maintained at an acceptable level . - Selection of cases which allow the reduction of
dose at heart level in the moment of making
treatment plan, depending on tumor localization,
and the establishment of an accurate criteria
for the application of this method . - These techniques are successfully used in The
Oncology Institute of Bucharest .
30The systemic treatment of breast cancer in
Romania
- New treatment options with curative intention
were identified, even for local advanced breast
cancer. - The systemic therapy , neoadjuvant and adjuvant,
with statistically proofs in favour of cure,
free-disease survival and an overall survival are
also used in Romania. - The systemic therapy is individualized for each
patient depending on the prognostic factors.
31A. Chemotherapy
- Historic
- 1950 first clinical trial (not utilized )
- 1960 first modern clinical trial clinic
- 1969 Cooper regime (CMFVP), first utilization
with results in breast cancer resistant at
hormonal therapy. - 1970 adjuvant chemotherapy become standard
treatment in metastasis in breast cancer (MBC),
N - 1976 Bonadonna regime recognized as standard for
MBC, N - 1980 It is extended in breast cancer N-
treatment - 1980 antracyclines introduced in the treatment
regime - 1990 taxanes and vinorelbine start to be used
- 1999 new molecules (Capecitabina, Trastuzumab)
- 2000 very promising novel targeted therapy
(e.g.Iressa)
32- Adjuvant chemotherapy in Romania
- These regimes that used anthracyclines produced a
significant improvement - of overall survival and decreasing of overall
mortality especially at patients N (20-25
reduction of mortality ) - Most utilized regimens were CAF/CEF
- Intensified dose and chemotherapy with high doses
- Epirubicin seems to be the most appropriate
anthracyclinic antibiotic for intensification
and increasing dose . - Increasing dose of epiubicin permits the
improvement of overall survival . - Chemotherapy with high doses and with stem cell
support is exclusively reserved to clinical
trials (not used yet in Romania).
33- Adjuvant chemotherapy
- Taxanes use
- Existent clinical data does not permit the
establishment of final recommendation regarding
their place in the improvement of survival at
patients with breast cancer N. - For cases with breast cancer N- ,the taxanes
are utilized only in clinical trials. - New direction in chemotherapy
- The modality of integration of taxanes in
adjuvant treatment. - Integration of the new drugs has shown efficacy
in treatment of advanced breast cancer
(Trastuzumab, Capecitabin)
34Neoadjuvant Chemotherapy
- Utilized at least with the same efficacy results
as adjuvant chemotherapy , regarding overall
survival and free-disease survival. - Main advantage potential reduction of size of
primary tumour and increasing numbers of
conservative treatments. - Can be a test of chemo-sensitivity in
vivoallowing the individualization of the
chemotherapy regimes after surgery. - The usage of taxanes in neoadjuvant treatment is
under evaluation
35Chemotherapy in metastatic breast cancer treatment
- Even if it was introduced since 1950 ,
chemotherapy in metastatic breast cancer
treatment is a disputed subject in Romania as is
in other countries. - There is a consensus regarding the modest value
of this in increasing survival efficacy of
salvation chemotherapy (2nd and 3rd lines)is low
(RR 20, means overall survival lt10 months
6-12 months). - For the most of the patients, the usage of more
than 3 therapeutic lines is made with minimal
benefits. - A whole serie of chemotherapy salvation regimes,
in cases which resisted antrhaclynes, were tried,
but none of them proved superior except the
taxanes, especially Docetaxel
365. New molecules
- Trastuzumab (Herceptin), first monoclonal
antibody humanized recombined anti HER-2,proved a
targeted action on the receptors HER-2,for
HER2/neu, overexpressed in 25-36 of breast
cancer . - It is under evaluation the combination
TRASTUZUMAB TAXOTERE possible as adjuvant
therapy for patients ER, HER2/neu (trial NSABP
B31) - The effect of long term administration (1-2
years) of TRASTUZUMAB after primary treatment
(surgery and adjuvant chimiohormonotherapy ) is
under evaluation -trial HERA - CAPECITABIN which has indication for breast
cancer treatment chemo-resistant at taxanes and
antracyclines - Expecting with maxim interest the clinical
trials with a EGFR-TK inhibitor (IRESSA) ,knowing
that EGFR are over expressed also in breast
cancer tumours.
37Romanian experience
- In local advanced stages are used standard
regimes, FEC/EC. - In selected cases are used regimes, with taxanes
which in the majority of the cases lead to
downstaging tumour and allow the surgery. - At patients with metastasis,especially hepatic
metastasis, usage of taxanes represents first
option when the budget allows this. - In Oncology Institut from Bucharest,only a small
number of patients that fulfil the administration
criteria beneficiated by Transtuzumab treatment
,with similar results reported by oncologycal
publication. - Often , the Romanian Oncologist obtain incredible
therapeutic results, taking into account that he
can not assure constantly the same therapeutic
regimes because of the budget limitations.
38B. Hormonal therapy in Romania
- Most utilized as first line therapy
antiestrogens Tamoxifen, accessible from
financial point of view, with good results - For patients with ER breast cancer,administratio
n of this treatment is not depending by age or
menopausal status,lymph nodes invasion , size of
tumour. - Patients with ER- tumours dont beneficiate by
this treatment,in this case they are not
protected against risk of collateral breast
cancer treatment. - For a more small number of postmenopausal
patients with advanced breast cancer are used
aromatase inhibitors as first line therapy
(e.g.Anastrozole, Letrozol ),this being only
financial restricted
39Hormonal therapy in Romania
- Postmenopausal patients with locally advance or
metastatic breast cancer, ER receptor - - For an more small number of
postmenopausal patients with advanced breast
cancer are used non-steroidal aromatase
inhibitors as first line therapy
(e.g.Anastrozole, Letrozol),this being only
financial restricted. - - For second line hormonal treatment first
option are also the aromatase inhibitors
(e.g.Anastrozole, Letrozole, Exemestane)
40Ovarian ablation
- Significant improvement of survival in
premenopausal patients with breast cancer,
independent of lymph node affecting status . - Ovarian suppression with LHRH analog (Goserelin)
at premenopausal patients ER has similar
benefits with chemotherapy in patients with not
sever prognostic factors. In addition, this
option if treatment is not associated with severe
side effects of chemotherapy (alopecia, nausea,
infection ) - It is used at this type of patients in
combination LHRHa Tamoxifen, with good results. - The clasic ovarian ablation has associated some
disadvantages for patients - - Oophorectomy is associated with
increased morbidity .The procedure is
irreversible, even if the patient does or does
not obtain any clinical benefit.It can be made
laparoscopic with better results as classical
techniques -
41- New direction in hormonal therapy of breast
cancer - Will be adopted and utilized in Romania also
based on latest evidence data of important
clinical trials for evaluation of - a) Adjuvant treatment
- ATAC Anastrozole vs Tx vs Anastrozole Tx
- FEMTA Femara vs Tx
- TEAM Exemestane vs Tx
- b)replacement of Tamoxifen
- ARNO Tx 2 years 3 years Anastrozole vs Tx 5
years - IBCSG 1898 2years Tx 3 years Letrozole vs 2
years Letrozole 3years Tx - c)secvential treatment after 5 years of Tamoxifen
treatment - USI 5 years Tx 5 years Letrozole vs placebo
5 years - NSABP B-33
42The most difficult problem in Romania in the
treatment of breast cancer hormonal therapy
- -Often, for Oncologist, the testing of ER status
is a real problem and the hormonal choice is
forced limited only at Tamoxifen. - The economic barriers do not always allow to
assure the continuity of the best option
treatment . - For this reason , the clinician can be forced
sometime to use some less efficient option (e.g.
aminogluthetimide, progestatives)
43 Conclusions
- The systemic therapy, neoadjuvant and adjuvant,
individualized for each patient offer benefits
regarding the overall survival. - Expected evaluation of new molecules , new
associations - Hormonal therapy remains the key treatment of
breast cancer.
44Conclusions
- Romanias integration in clinical trials can
offer benefits for patients with breast cancer - The according of consultancy in prevention and
screening will be helpful for the implication of
non-government organizations - The possibility of Romanias including in UE can
be a chance for economic re-launch and for a
solid and efficient health system