DO YOUNG AGE AND TRIPLE NEGATIVE MOLECULAR SUBTYPE HAVE A NEGATIVE EFFECT ON SURVIVAL IN PATIENTS WITH EARLY STAGE BREAST CANCER?

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1 DO YOUNG AGE AND TRIPLE NEGATIVE MOLECULAR SUBTYPE HAVE A NEGATIVE EFFECT ON SURVIVAL IN PATIENTS WITH EARLY STAGE BREAST CANCER? Çetin Ordu, Atilla Bozdoğan, Gül Alço, Kezban N. Pilancı, Derya Selamoğlu, Zeynep Erdoğan, Filiz Ağaçayak, Serkan İlgün, Filiz Elbüken, Şefik İğdem, Sait Okkan, Vahit Özmen Florence Nightingale Breast center Purpose: The aim of this study is to analyze the association between prognostic factors, molecular sub-types and surgical treatment on survival in young women ( 40 years) with early breast cancer. Method: In this prospective database review at the Florence Nightingale Breast Center, we included 332 consecutive patients aged 40 years with clinical stages I to II invasive breast cancer who underwent surgery at a single institution from January 1, 1998, through January 1, Results: Most of the patients (64.2%) were treated with BCS. The mean age and median follow-up were ± 3.61 years, and 72 months (range, ), respectively. In multivariate analysis, multicentricity/multifocality (MC/MF) and young age (<35 years) were independent prognostic factors for both disease free survival (DFS) and overall survival (OS). The patients aged 35 to 40 years had significantly higher rates of locoregional recurrence free survival (LRFS) and DFS than the patients aged <35 years in the mastectomy group (p=0.007 and p=0.039 respectively). The patients with triple negative breast cancer (TNBC) had significantly lower OS rate compared with patients with luminal A subtype (p=0.042). Additionally, TNBC patients with BCS had significanly higher OS rate than patients with TNBC and mastectomy (p=0.015). Conclusion: This trial revealed that age under 35 years was an independent prognostic risk factor for OS and DFS when compared with age 40 years. There were no difference regarding DFS, molecular subtypes, and only OS was significantly lower in patients with TNBC (p=0.003). In addition, BCS could be performed in young patients with TNBC. Keywords: young age, breast cancer, overall survival, disease free survival, breast conserving surgery, molecular sub-types,

2 Figure 1a. LRFS for patients aged years at 5 years was significanly higher than patients aged < 35 years (local recurrence free survival-month-) Figure 1b. Patients under 35 years age had significantly lower DFS compared with patients aged years.(disease free survival- month-) Figure 2. Kaplan meier curves of survival analysis according to molecular subtypes

3 Table 1:Patients and tumor characteristics properties BCS(n=213) Mastectomy(n=119) n % n % Total p a Mean age 35.34± ± ± < Median Tm diameter (mm) 20(1-65) 30(2-110) 20(1-110) <0.001* pt Stage <0.001* pn Stage <0.001* pn pn p Stage (TNM) <0.001* Histology IDC Others Tumor focality <0.001* Unifocal MC/MF Histologic grade I-II III LVI <0.001* Positive Negative EIC 0.006* Positive Negative ER Negative Positive PR Negative Positive Her-2** Negative Positive Median Ki-67 % 30(2-95) 25(5-80) 30(2-95) Chemotherapy 0.028* Yes None Radiotherapy <0.001* Yes None Hormonal therapy Yes None *=p<0.01;a=chi-square Test;Independent Samples t Test Mann-Whitney U Test, ** Her2 Non-available in 4 patients.mc/mf:multicentricity/multifocality, IDC: Invasive ductal carcinoma, LVI: Lympho vascular invation;eic: Extensive intra-ductal component Cetin Ordu :14 Formatted: Space After: 0 pt, Line spacing: single, Not Bold, Not Bold, Not Bold, Not Italic, Not Bold

4 Table 2: Survival association between age and surgery method LRFS(%5 years) BCS Mastectomy * LogRank Test p eker :37 Deleted: e, Not Bold DFS(%5 years) BCS Mastectomy * LogRank Test p OS( % 5years) BCS * Mastectomy LogRank Test p * LRFS:Local recurrence free survival DFS:Disease free survival OS:Overall survival *=p<0.05 Cetin Ordu :25

5 Table 3. Comparing survivals of luminal subtypes LRFS:Local recurrence free survival DFS:Disease free survival OS:Overall survival *=p<0.05 LRFS 5 years DFS 5 years OS 5 years Luminal subtype p /HR(95%CI) p /HR(95%CI) p /HR(95%CI) Luminal A vs Luminal B NS NS NS Luminal A vs Her2 Group NS NS NS Luminal A vs TNBC NS 0.071/2.125( ) 0.003/11.342( ) eker :37 Deleted: between Cetin Ordu :26