Patients included in this study illustrate interesting characteristics where 33.2% are young (≤ 40 years) and 66.8% are pre-menopausal. While the median age at presentation is around 63 years in the United States and Western Europe, the median age at presentation in this study is 45 years. The young age of patients in this study is attributed to the overall age distribution in the KSA, where 50% of the population is less than 15 years of age and only 3% are older than 65 years. These patients' characteristics are in sharp contrast with those reported in the West.
Gajdos et al
] reported that patients diagnosed with breast cancer before age 36 differ from older patients in several respects. The younger age group presents more often with more advanced and aggressive cancer. In spite of aggressive treatment (mastectomy and chemotherapy) in the younger age group, local and distant failure rates are higher than for patients 36 and older. The higher rate of local recurrence in patients less than 36 years reflects an excess number of local recurrences in patients treated with breast conservation. In the present study, we have found that patients ≤ 40 years were treated more often with breast-conserving surgery compared to mastectomy (48.6% versus 36.5%, p
= 0.0006), adjuvant chemotherapy (87.9% versus 65.6%, p
< 0.0001), and less often with tamoxifen (p
< 0.0001). Our current findings are in agreement with what have been reported by Gajdos et al
investigating breast cancer in young women [25
]. It is important to mention that similar protocols for the treatment of breast cancer patients were used in both USA and KSA and this may reflect the similarity of both studies.
Our results show that young age is a critical prognostic factor in women with breast cancer in Saudi Arabia. Among all studied prognostic factors, the distribution of grade, histology, and hormonal receptor status showed a significant difference between the two age groups in our patient population.
The results of the present investigation showed that being young age at diagnosis (≤ 40 years) is an independent prognostic factor for disease-free survival in addition to nodal status, pathological tumor size, stage and hormonal receptor status. We performed subgroup analysis by investigating patients with negative versus positive lymph nodes and had different results. Young age had a significant impact on survival in patients with positive lymph nodes but not in patients with negative lymph nodes.
The present findings support previous reports showing that women diagnosed with breast cancer at younger age have a poorer prognosis compared with their older counterparts [8
]. The extensive heterogeneity of breast cancer complicates the precise assessment of tumor aggressiveness which makes therapeutic decisions difficult and treatment impropriate in some cases [28
]. Therefore, it is very important to understand the interactions between the genetic complexity and the environmental factors which modulate the onset and progression of breast cancer in young women which may help in designing a personalized treatment for this patient population. For example, it has been demonstrated that about 15–30% of western breast cancer women aged less than 35 years are likely to have germ-line BRCA1 or BRCA2 mutations [29
]. Similar results were reported for BRCA1 and BRCA2 mutations in Korean women with breast cancer at a young age (< 40 years) [31
] and also for BRCA1 mutations in a series of Singaporean Chinese women with early onset (cut-off of 40 years) [32
]. Study on BRCA1 and BRCA2 mutations in Saudi women older than 40 years with breast cancer concluded that mutations in these genes are likely to contribute to the pathogenesis of familial breast cancer in the Kingdom of Saudi Arabia [33
]. A recent interesting tissue microarray study by Eerola et al
]demonstrated that tumors of BRCA1 and BRCA2 positive-mutations aged 50 years or more (postmenopausal) differed significantly from those of younger age group (premenopausal) with similar mutations. This difference may reflect diverse biological behavior and pathways of tumor development among the older and the younger BRCA1 and BRCA2 patients, with impact also on prognosis and survival. Overall, there is an emerging picture indicating that breast cancer risk in BRCA1 and BRCA2 positive women are substantially higher than in the general population and the genes are considerably affected by non-genetic, environmental factors and by additional genetic modifiers [35
]. In the light of the high incidence of breast cancer in young Saudi women [2
], mutation study of these genes and gene-expression profile, which is a more powerful predictor of the outcome of disease in young patients with breast cancer [36
], are extremely warranted.