الفهرس 
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Abstract
SUMMARY
Despite advances in screening, locoregional treatment and systemic adjuvant therapy for breast cancer, metastatic relapse is still common. Metanalysis of adjuvant breast cancer trials indicated that after adjuvant polychemotherapy, 40% of patient had a recurrence many with distant metastases.
Metastatic breast cancer is rarely curable and the administration of chemotherapy is mainly palliative.
Definition of the clinical benefit induced by palliative Chemotherapy is difficult to assess. One must take into account not only chemotherapy’s response rate but duration of response and patient’s quality of life.
The aim of this study was to determine the benefit of chemotherapy beyond the second line in patients with a metastatic breast cancer; then, if a benefit was established, to identify patients who better benefit from the treatment.
A total of 420 female patients with metastatic breast cancer were diagnosed in NEMROCK between 2005 and 2010, of whom originally 52 female patients, later reduced to 24 female patients, and further reduced to 9 female patients received a third, fourth and fifth lines of chemotherapy, respectively. Files of these 52 patients were studied for patient clinico-epidemiological characteristics, disease outcome and treatment related toxicity.
The evaluation of benefit in each chemotherapy lines was based on time to disease progression ( PFS ) wich is defined as time between the date of the beginning of treatment and the date of progression of disease or death.
The results of our study lead to main conclusion, the duration of PFS significantly decreases with the succession of chemotherapy lines (P <0.0001), with 40.4% of patients in third line, 37.5% in fourth line and 22.2% of patients in fifth line achieving a clinical benefit according to our criterion of PFS duration longer than 6 months.
Median duration of PFS in third line of chemotherapy (PFS 3) was 5 months [range: 1-21]. Factors favorably linked to a longer duration of PFS were:
Age at initial diagnosis (> 50-years-old) (P=0.323), adjuvant hormonal therapy exposure (P=0.368), no visceral metastasis (P=0.250) and duration of PFS achieved by previous chemotherapy line 2 longer than 6 months (P=0.153).
Median duration of PFS in fourth line of chemotherapy (PFS 4) was 4 months [range: 2-10]. Factors favorably linked to a longer duration of PFS 4 were:
Age at diagnosis (< 50-years-old) (P=0.5), duration of PFS achieved by previous chemotherapy line 3 longer than 6 months (P=0.5). ) and disease free survival (DFS) duration more than 2 years (P=0.260).
Median duration of PFS in fifth line of chemotherapy (PFS 5) was 2 months [range: 1-10]. Factors favorably linked to a longer duration of PFS 5 were:
Age at diagnosis (> 50-years-old) (P=0.417), duration of PFS achieved by previous chemotherapy line 4 longer than 6months (P=0.232) and disease free survival (DFS) duration more than 2 years (P=0.322).
None of these factors shows statistically significant difference.
The overall response rate of the third line was 28.8%, the response rate of the forth line was 20.8% and the response rate of the fifth line was zero.
from the study the response rate is decreasing by using more chemotherapy lines and this mean that more resistant tumor cell lines prevailed.
The median overall survival from initial diagnosis of the 52 patients treated by third, fourth and fifth lines of chemotherapy was 40.5 months [range: 15–87months]. The median survival benefit from start of 3rd line of chemotherapy was only 11 months.
Evaluation of the different prognostic factors in our study showed that pathological type IDC vs ILC and DFS >2 years vs <2years significantly affecting survival (P value=0,002); table (4).
The main toxicities in this study were anemia and granulocytopenia. In the 5th line it was recorded in (100 %) of patients and in the 4th line in70.8 % of patients, while in the 3rd line the incidence of hematological toxicity was only (31.75%).
Delay of chemotherapy cycles for 1-3 weeks was performed for 47/155 (30%) cycles of chemotherapy. 8/52 (15.4%) patients received blood transfusion. Colony stimulating factor was given for 10/52 (19.2%) patients who developed grade 3 granulocytopenia.
Cardiotoxicity and peripheral sensory neuropathy grade 1/2 in the 5th line were (33.3%). Nausea and vomiting grade 2/3 in the 5th line (100%) .
The toxicity was increased by using more chemotherapy lines and this mean that the effect of chemotherapy on toxicity is cumulative.
from the study we can conclude that a prolonged PFS duration in previous line, the response rate and toxicity had a major impact on prescription of an additional chemotherapy line.
Other conclusion is that using of chemotherapy beyond second-line in selected cases is reasonable; however, more randomised trials are needed to consolidate this finding.