Retrospective Analysis for the Impact of Adjuvant Chemotherapy Initiation Timing On The outcome of Non Metastatic Breast Cancer at Ain Shams Hospitals

Abstract

SUMMARY AND CONCLUSION B reast cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in women worldwide, accounting for 23% of total cancer cases and 14% of all cancer related mortalities (McGuire et al., 2015). This study is a retrospective analysis conducted over 300 female patients diagnosed with invasive non metastatic breast cancer presented to Clinical oncology department at Ain-Shams University hospitals. All patient's records in the period from January 2007 to December 2011 were reviewed allowing five years overall survival and disease free survival follow up, all these data were collected through chart analysis. Patient characteristics, clinical picture and pathological data were thoroughly collected. In the current study, many of the parameters addressed were almost similar to worldwide incidences with little variations. Mean age at diagnosis was 50 years. Stage II was the most prevalent stage, IDC was the most common pathological subtype, and the hormone receptor positive was the most common molecular subtype. Positive family history represented 15% of the total population at least one first or second degree relative. Most of the patients were urban habitat accounting for 77% while rural population was only 23%. The median time to begin chemotherapy is 5 weeks (SD= 2.8), ranging from 1-12 weeks. The patients were classified into 4 strata, a total of 36% of patients started chemotherapy in less than 4 weeks, 44.7% waited 4 - 8 weeks, and 14% initiated their chemotherapy within 8 - 12 weeks while only 5% were delayed more than 12 weeks to start their adjuvant chemotherapy. Sociodemographic problems and long residential distance to institution represented the most common cause of chemotherapy delay, while the second cause was system related as late referral and prolonged time needed to get governmental insurance support. Postmenopausal (elderly) patients were the most common to experience delayed chemotherapy initiation with significant P value =0.01 mainly because of multiple comorbidities and long post-operative recovery. Stage I were less likely to have delays in chemotherapy administration and also patients with hormone positive (ER and PR) were less likely to have delays compared with hormone negative ones (P=0.01 and P=0.006 respectively). On analysis of different prognostic factors, we found that better OS was noticed with only premenopausal patients. But the OS correlation according to the breast cancer molecular subtypes yielded non-significant effect. As regards the type of surgery neither breast conserving therapy nor mastectomy affected the OS outcome Survival analysis using Kaplan- Meier method for overall survival (OS) according to TTC demonstrated, the 5 year overall survival estimate was 91%, 87.7%, 77.7%, 86.7% among patients who received chemotherapy < 4 weeks, 4 – < 8 weeks, 8 - < 12 weeks and 12 weeks or more after surgery, respectively indicating Non-significant association with P-value 0.67 between timing of adjuvant chemotherapy initiation and overall survival. The analyses have also been performed for DFS, that the 5 year follow up resulted in Disease free survival rates 82 %, 81%, 90 %, and 83 % (log-rank P = 0.94) for groups 1 to 4, respectively. The DFS curves expressed the same insignificant pattern as the OS curves regardless the TTC categories. As expected, worse DFS was associated with large tumor size (T3, T4b), greater lymph node involvement and locally advanced stage III (B and C) with a significant P value (0.03, 0.01, and 0.0001 respectively). Superior DFS was noticed in patients underwent mastectomy as a definitive operation rather than conservative surgery with a significant P value (0.02) and also patients whose hormonal status is positive and received endocrine treatment (Tamoxifen) were better than those who didn’t but this association was not similarly found on HER2 status evaluation. Correlation between the molecular subtypes with DFS resulted in a highly significant worse outcome with HER2 and triple negative subtypes with significant P value 0.04 and 0.002, respectively, While hormone positive subtype demonstrated a better DFS (P= 0.01). When assessed the DFS in patients with grade III tumors against other grades as it is an important prognostic factor, as expected it was associated with inferior DFS with p value 0.07. In a subgroup multivariate analysis between breast cancer molecular subtypes and the OS along the TTC categories, no overall survival impact for chemotherapy initiation up to 12 weeks postoperative for all breast cancer subtypes even triple negative patients with non-significant P value. The same correlation was made as regard the DFS and yielded the same lack of significance. To sum up, breast cancer is one of the most important worldwide encountered disease burdens to which many international guidelines for diagnosis and management have been recommended. Yet there is a wide discrepancy in the allowed time between surgery and chemotherapy initiation with no adverse effect on the patient's survival outcomes. Hopefully this study is the first step to answer this question and soon we will be able to tailor our own guidelines for the sake of the best patients' benefit.