الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer (BC) is now the most common cancer worldwide after surpassing lung cancer in 2020. Although BC used to be considered a disease of postmenopausal patients, recently, there is a surge of BC in young patients (BCY). Early-onset BC is frequently encountered in the LMIC, reaching as high as twenty-five percent in some countries. Unfortunately, there is no standard definition of BCY at the moment. The cut of age for the definition of BCY ranges from 30 to 50 years old. In clinical trials, premenopausal patients are frequently referred to as young patients. Thus, posing a challenge in comparing results across the world.
BCY is associated with aggressive clinicopathological characteristics such as more HER2 positive, TNBC, more luminal B, and less luminal A subtypes. In addition, BCY frequently has a large tumor size at diagnosis, more involved lymph nodes (LN), high tumour grades, higher high Ki-67, and positive LVI. As a result, young patients frequently undergo more mastectomies, treated with chemotherapy and OFS. It should be noted that only young-age at diagnosis does not warrant aggressive management of BCY. Like in older patients, treatment of BCY should be guided by the tumor biology and patient’s preferences after discussing the available options and risks.
Unlike BC in old patients, young patients are unique in that they are still actively working, having not completed their families at the time of diagnosis and longer life expectancy. Thus, long-term outcomes should be considered while managing these patients.
Due to the recent attention given to BCY, there is an unmet need to understand BCY in our local setup. Therefore, we conducted a dedicated study of young patients aged ≤40 to determine their incidence, clinicopathological characteristics, treatment, and outcomes.
This retrospective study was conducted in two centers in Alexandria, Egypt - the Alexandria University Hospital and Ayadi Almostakbal cancer center. It involved young patients (≤40 years) diagnosed with BC between January 2008 and December 2017 and were followed up until December 2019. Patients were categorized into two groups: very young (aged <35) and young (aged 35 to ≤40).
There were 7180 BC patients treated in this period, of which 1227 were young. We excluded 100 patients who were duplicated or had empty files. Hence, the incidence of BCY was 15.7% (1127). Out of the 1127 remaining patients, only 56 (5%) were diagnosed with de novo stage IV, thus excluded from further analysis. Thus, out of the 1127 remaining patients, 400 (37.3%) were very young.
The overall median age at diagnosis was 36 years in the whole cohort, while it was 31 and 38 years in very young and young, respectively. The young patients were significantly more obese than the very young. The family history of BC was present in 22% of the patients and was comparable in the two age groups. Most patients presented to the hospital after an average of 3 months from the onset of signs and symptoms.
The most common histological subtype was IDC. Moreover, most of the patients had high tumor grades, high Ki-67, more positive lymph nodes (LN), and high lymphovascular invasion (LVI). Nevertheless, we found no significant differences in terms of tumour grades (p=0.109), Ki-67 (p=0.621), tumour size (p=0.127), LN status (p=0.655), TNM stage (p=0.644), extracapsular extension – ECE (p=0.322), and LVI (p=0.924) between the young and very young. However, there were significant differences in molecular subtypes. The very young had a lower incidence of luminal subtype (p=0.002) and more frequent triple-negative BC -TNBC (0.014) than the young. The HER2 enriched subtype equally occurred in the two groups.
With regards to treatment, mastectomies were frequently performed in both groups. Similarly, adjuvant chemotherapy was more often used than neoadjuvant chemotherapy – mostly was the anthracycline-based chemotherapy. The majority of the patients were irradiated in both groups. Hypofractionated radiotherapy (HFRT) was often used than the conventional schedule in both groups. Among the hormone-receptor-positive patients, adjuvant tamoxifen was given in the majority of the patients. However, ovarian function suppression (OFS) was highly utilized in the very young (10.2%) than the young (5.2%), p=0.055. Out of the one hundred and nineteen HER2-positive patients, 63% received trastuzumab (57% of the very young vs. 66.2% of the young, p=0.57).
After a median follow-up of 41 months, 346 (36.4%) patients their disease relapsed. There was a trend of higher disease recurrence in the very young (39.6%) than the young (34.6%), p=0.071. Nevertheless, the disease-free survival (DFS) was similar in the young and the very young (p=0.419). In univariate analysis, the tumor size, LN status, type of surgery, and ECE were significantly associated with the DFS. However, in multivariate Cox regression analysis, only the tumor size and LN status were independent predictors of DFS.
Regarding the recurrence patterns, there were significantly more distant recurrence rates (DRR) than locoregional recurrence rates (LRR), 73% vs. 27%, respectively, p=0.001. The very young patients had more LRR, while the young had more DRR. Young age, ECE, >4 LN involvement, stage III disease, and MRM were associated with DRR. In contrast, LRR was associated with very young age, BCS, negative ECE, ≤3 positive LN, and stage I-II disease.
73 (7.7%) patients in the young and 34 (9.9%) in the very young died after a median of 41 months follow-up, p=0.06. However, according to the molecular subtypes, the OS was similar between the two age groups (Log-rank p=0.177). Furthermore, univariate analysis showed that tumor size, LN status, and type of surgery are predictors of survival, but only tumor size remained an independent factor in Cox regression.
Among the patients who were treated by chemotherapy, chemotherapy-induced premature ovarian failure (POF) was higher in the young (12.1%) than very young (7.7%) patients, p=0.028. Patients who attained POF had better DFS than those who didn’t, but it failed to translate to better OS in either group.
Unlike most previous studies, we failed to show a significant difference in most clinicopathological and survival between the young and very young. Although the very young had a trend of more relapses and deaths than the very young, their DFS and OS were similar.
Limitations:
Dispite this work being one of the largest and most comprehensive data of breast cancer in young ever conducted in Alexandria, our main limitation is being a retrospective study, thus may have some bias. Besides, some patients had incomplete data which even made us not able to analyse the the stage IV disease patients.