Breast cancer in women younger than 30 years: prevalence rate and imaging findings in a symptomatic population

Introduction To identify the prevalence rate of primary breast cancer in women younger than 30 years of age in a symptomatic population in Riyadh, Kingdom of Saudi Arabia. To analyze the imaging pattern and possible risk factors in cases with cancer. Breast cancer in this age group is generally rare and not clearly understood. Methods At King Abdulaziz Medical City for National Guard, Riyadh, a retrospective 5-year (January 2006 to December 2010) data was collected from the Medical Imaging departmental records on breast imaging. Patients younger than 30 years of age were identified including those with breast cancer. The clinical presentation, risk factors, imaging findings and final outcomes were analyzed in a descriptive way. The total number of patients diagnosed with primary breast cancer was recorded. Results Seventeen out of a total of 4873 patients younger than 30 years examined had primary breast cancer constituting a rate of 3.5 per 1000 symptomatic patients. The age range was 17 to 29 with mean of 27. The total number of patients with primary breast cancer diagnosed during that period was 413 making a percentage of 4.1% (17 out of 413) in those younger than 30 years. First presentation with a palpable mass and imaging findings of unequivocal category 5 of Breast Imaging Reporting and Data System (BI-RADS) occurred in all. Eight patients had stage I and II while nine had stage III and IV cancers. Only 2 of the 17 had first-degree family history. The youngest was 17 years old. Conclusion A prevalence rate of 3.5 per 1000 primary cancer occurred in the symptomatic population studied and 4 in every 100 primary cancer diagnosed in the unit occurred in women younger than 30 years. First presentation, low family trait and typical imaging features of malignancy was found in all cases.


Introduction
Breast cancer is considered rare in young women below 40 years.
About 5 to 6% of total breast cancer occurs in women younger than 40 years [1]. In the epidemiology of breast cancer, young women are said to differ according to race [2]. Although breast cancer is more common in Caucasian women than African Americans, in women under 35, breast cancer is more than twice as common in African American women and is diagnosed at a more advanced stage [2].
In a recent publication [3] from the UK, the incidence of breast cancer in women younger than 35 years was 1.4% and in those younger than 30 years it was 0.43%. This low incidence provides the rationale behind avoiding unnecessary breast biopsy of young patients. A published report [4] on the epidemiology of breast cancer in women in Arab countries reveals that 50% of breast cancers occur in women under 50 years of age, whereas only 25% of breast cancers occur in women under 50 years in the industrialized world. In the United States, approximately 27% of either invasive or noninvasive cancers occur in women under 50 years of age [5].
The major risk factors in breast cancer are: age, genetic predisposition and estrogen exposure. A positive family history has a relative risk of 2.6% while having multiple first-degree relatives (mother, sister, daughter) with premenopausal cancer confers a lifetime risk as high as 50%, much of this risk is associated with a genetic defect in BRCA1 or BRCA2 [6][7][8][9]. Also, increased breast density both increases the chance of missing a breast cancer as well as increasing the absolute risk for breast cancer. Exposure to radiation, e.g., radiation therapy to the chest, is a risk factor for secondary breast cancer in adolescents [10,11]. With the increasing awareness of breast cancer occurrence among the general population which includes the young, our diagnostic clinics are inundated with young patients presenting with all sorts of complaints ranging from breast pain, palpable mass to breast-size asymmetry or knowledge of family friends with breast cancer.
Information on breast cancer in Arab women under 30 years of age who are normally examined with ultrasonography is scanty. We do not know the prevalence rate or proportion in relation to the total breast cancers. We do not know the proportion of missed or interval cancers nor the typical imaging features or associated risk factors. This study therefore aims at indentifying the prevalence rate and proportion of breast cancer that occurs in Arab women younger than 30 years. The imaging characteristics, risk factors, e.g., family history or previous radiation, or breast density will be analyzed in cases with breast cancer.

Methods
Retrospective data was collected from Picture Archiving and Inclusion criteria were all patients who had initial full breast imaging and staging in our unit with pathologically confirmed breast cancer.
Exclusion criteria were patients with breast involvement of generalized lymphoma or leukemia. Furthermore, patients who had breast cancer diagnoses and had surgery elsewhere before coming to us were not included. All cases were also discussed in our regular multidisciplinary breast cancer meetings. Special ethical consent for this study was not needed due to the retrospective nature of the study. Literature search was by MEDLINE and PubMed. A detailed analysis of breast cancer cases occurring in patients younger than 30 years of age at presentation was made. These patients were not stratified. They were imaged as they came from breast surgeons, from the local Primary Care Centre and from elsewhere from other Gulf Countries. They represent the usual population we care for at the King Abdulaziz Medical City for National Guard, Riyadh. Data were analyzed using descriptive statistics.

Imaging
Patients with palpable masses had breast ultrasound examination as the first-line imaging examination while those with clinically obvious cancers such as bulging masses and/or deformed breast outlines had mammography as the first-line imaging examination; however, subsequently all had both ultrasound and mammography. Magnetic resonance imaging (MRI) was performed in some cases to show the extent of tumor spread and possible multifocality or multicentricity Page number not for citation purposes 3 or before neoadjuvant chemotherapy. Computed tomography staging and isotope imaging were also obtained before treatment.

Ultrasound Imaging
This was performed with an UltraMark 9 Philips Medical System, Netherlands using a 12-5 MH2linear array transducer. Real time gray-scale and Doppler images were obtained. The images were interpreted by experienced radiologists using the Breast Imaging-Reporting Data System (BI-RADS) classification [12]. The size of the masses was measured when possible. The disease was assessed as to whole breast involvement, unifocality, multifocality, multicentricity and bilaterality. Axillary nodes were also assessed. Biopsy of the lesions was made with ultrasound guidance.

Mammography
Mammograms were obtained with LORAD MS (Hologic Selenia, United States) equipment. Standard two-view mammography was performed in both breasts in all patients. Additional views including magnification, compression, exaggerated, craniocaudal and axillary tail views were obtained when necessary. The findings were classified according to the BI-RADS Lexicon [12]. Radiographic breast density was also defined according to BI-RADS rating i.e. 1.
Heterogeneously dense and in type; 4. Extremely dense breast. The normal breast of the patient was used for the classification. BI-RADS [12] rating instead of computerized grading has been used because studies using observer ratings have been shown to have similar estimates [13]. MR Imaging: Patients were examined in a prone position with breasts hanging freely in a dedicated breast coil. A 3T (Philips Equipment, Netherlands) was used.
The usual departmental protocol was followed including STIR, T2 and T1 weighted, three-dimensional (3D) fat-suppressed gradient- breast density (Figure 1, Figure 2) while 4 out of 17 had a category 3 breast density (Figure 3 A

Discussion
The study reveals a prevalence rate of 3. Irish young women where patients with primary breast cancer had a low family trait [14].
Only 3 of the 17 patients had breast density of category 3. Due to the limited number of patients involved, it is difficult to draw a conclusion on the effect of density. However, these patients had breast density less than the usual pattern in young females who commonly have dense breasts which obscure findings in mammography [2]. The factors that affect breast density include age, hormone replacement therapy, menstrual cycle phase, parity, body mass index, family, and genetic tendency [6]. Three of the 17 patients (17.6%) were pregnant at presentation.
One of the pregnant patients was in the first trimester and two were in the second trimester. One had metastatic disease while the others had stage 2 and 3 diseases. This is within the reported incidence of 10-20% of breast cancer in women 30 years of age and younger [15]. Two of these patients had modified radical mastectomy and axillary lymph node dissection during pregnancy and are doing well. These two surviving cases support the current reports [14] that gestational breast cancer is not associated with a worse prognosis compared to similar staged non-pregnant breast cancer. The third patient who had metastatic disease at presentation had passed away.
The histological pattern of all except the youngest 17 years old was grade 3 invasive ductal carcinoma. The youngest patient had secretory carcinoma which is described as having a favorable prognosis [16]. It was previously called 'juvenile carcinoma' but now has a descriptive term 'secretory carcinoma' because it has Page number not for citation purposes 5 distinctive features that differ from other types of ductal carcinomas such as the presence of large amounts of intracellular and extracellular secretory material [16]. Recent report has shown that metastasis and death can occur in secretory carcinoma despite the reported indolent nature of the disease and hypothesize that p63 may be a potential marker [17]. This young patient had mastectomy and axillary dissection. Like all retrospective studies, ours has its limitations. A notable limitation is the lack of genetic studies, absence of stratification of the patients in relation to origin.
However, the outcomes of this study are clear. A multicentric detailed prospective study in this age group with breast cancer is suggested.

Conclusion
In conclusion, a prevalence rate of 3.5 per 1000 symptomatic population of women younger than 30 years had primary breast cancer and 4 out of 100 primary breast cancers occurred in this group. The occurrence below 20 years of age remains very rare even in this study. First presentation with a breast mass, low family trait, and typical imaging features of malignancy with BI-RADS 5 category were found. Vigilance and awareness education to breast symptoms is required in this age group. showing dense speculate mass in the breast (arrowed) showing solitary intensely enhancing microlobulated lesion in the right breast. Kinetic pattern also had rapid washout (not shown).
Histopathology revealed secretory carcinoma