This study conducted at the national institute of oncology in morocco analyzed the epidemiological, clinical, and therapeutic characteristics of TNBC. Only one recent report has evaluated the demographics and clinical presentations of this subtype in Moroccan population . The current study represents a large retrospective review of 152 patients with a diagnosis of TNBC in our institution over 2-year period (2007–2008) and is to our knowledge the largest series in our context focusing on this particular population. Most of demographic and clinical features of our study group are in accordance with previous findings in the literature.
Of nine hundred eighty breast cancer patients, diagnosed between 2007 and 2008, with available immunostaining data, 16,5% were assessed as TNBC. In the US, approximately 15-20% of breast cancers are TNBC [6, 7]. However, some studies have suggested that its prevalence differs between races with a higher prevalence reported among African-American women and Hispanic [8, 9].
TNBC are associated with a younger age at presentation, having a mean age of 53 years old, compared to 58 years old for other subgroups in a study reported by Dent and al . However, until now, there is still no final conclusion about whether age is a risk factor of TNBC, and there are still inconsistent findings in previous clinical studies. In our study population, the median age at diagnosis (46 years) was younger than the average age mostly reported in the United States [6, 7] but may be comparable to the median age in Hispanic triple negative breast cancer patients [8, 9]. Additionally, thirty two (17, 7%) patients had an age ≤ 35 years old suggesting that there might be factors that may predispose them to development of this disease. Given that the early age at onset is generally considered an indicator of genetic susceptibility to breast cancer and the fact that triple negative entity most often presents at a young age, an important part of future progress will be the identification of subgroups who may have a higher personal or familial risk of developing TNBC.
From an epidemiologic perspective, the known risk factors for triple-negative disease are modest, suggesting few clear interventions. Race appears to be a risk factor, as TNBC is more frequent in premenopausal patients of African-American heritage [6, 10]. There is also some suggestion that TNBC are more prevalent among women who reside at a lower socioeconomic level and/or lack access to healthcare [11, 12]. In the current study, no racial or socioeconomic specificity have been identified.
What is less well known is whether anthropometrics, demographics, and reproductive history are independently associated with TNBC. Previous population-based work has observed that younger age at menarche or younger age at first pregnancy, higher parity, shorter duration of breast feeding, higher body mass index (BMI) or higher waist to-hip ratio (WHR) were all associated with basal-like tumors versus luminal A tumors (tumors characterized by positive ER and PR and negative HER2) . Oral contraceptive use for more than one year was associated with a 2.5-fold increase in the incidence of TNBC [16, 17]. It has been proposed that the mechanism through which oral contraceptives use impacts the risk of breast cancer among young women is that estrogen promotes the growth of breast cancer-enhancing angiogenesis and stromal cell recruitment . In the current series, oral contraception was found in 23% of our patients.
This study found less than 10% of family history of breast cancer. Unfortunately, the research of a BRCA1/2 gene mutation was not performed due to its non availability in the time of study period.
Recently, the association between BRCA1 mutations and the development of TNBC is well established . In a recent report, Gonzalez – Angulo and al found a 19.5% incidence of BRCA mutations . Review of the spectrum of breast cancer tumor subtypes, which include basal-like, triple-negative and BRCA1-positive tumors, suggest that they have overlapping clinical, pathologic and molecular features, which are different from endocrine responsive breast cancers. Gene-profiling studies of this heterogeneous subset have lead to a better understanding of the molecular pathology of these aggressive tumors and the identification of possible therapeutic targets . More recently, poly (ADP-ribose) polymerase PARP inhibitors appear to take advantage of the concept of synergic lethality, or dual pathway inhibition, in attacking triple-negative and BRCA-associated tumors [22, 23]. The current study found less than 10% of family history of breast cancer. Unfortunately, the research of a BRCA1/2 gene mutation was not performed due to its non availability in the time of study period.
Reviews data from others cases series show that a lower proportion of triple-negative breast cancers are discovered by mammography, which is possibly related to the age distribution of these patients [6, 10]. In our study, the triple-negative breast cancers were more likely to be detected through clinical exam than through imaging, such as mammography and ultrasound. This may reflect a more rapid growth rate and the probable necessity of mammography screening in younger patient < 50 in our country.
Clinically, TNBC Patients had relatively large tumors (two thirds were >2 cm) and a high rate of node positivity (48%). Other reports have observed that patients with TNBC generally present at a similar stage compared to other tumors [7, 8, 16], but appear to have an inferior outcome [7, 8, 16, 19]. This inferior prognosis has been found to be independent of several other factors such as tumor grade, size and nodal status .
Histologically, TNBC are associated with a higher histological grade, marked cellular pleomorphism, increase mitotic activity and atypical mitotic figures [25, 26]. Similarly, in our series, TNBCs are characterized by a frequent ductal histology, high grade in two third of patient, and high proliferation and mitotic rates.
Triple negative breast cancer in the studied patients was more frequently diagnosed at advanced stage. Consequently, the majority of patients received radical mastectomy. Only 23% of our patients with local disease received conservative surgery. Haftty et all demonstrates in a previous report that there was no evidence that TNBC patients are at higher risk for local relapse after conservative surgery and radiation although triple negative have a poor prognosis .
Dent and al reports that the pattern of distant recurrence was strikingly different between cancer subgroups. In patients with triple negative breast cancer, the risk of any recurrence rose sharply from date of diagnosis, peaked 1 to 3 years, and dropped quickly thereafter. The patients outcomes (OS and DFS) in our series are in accordance with other previous reports [7, 27].
TNBC clearly represents an important clinical challenge. This is due to poor disease-free intervals in the adjuvant and neoadjuvant setting, shortened progression-free survival associated to a more aggressive clinical course in the metastatic setting, and the lack of targeted therapy . Most recent studies in triple-negative disease are directed to better identify effective treatment options and improve outcomes in these patients. Chemotherapy is known to be effective in triple-negative disease, and advances in chemotherapy have particularly benefited this patient group. However, there is not a clear, proven effective single agent that targets a driving vulnerability in triple-negative breast cancer.
Although response to chemotherapy is high in the neoadjuvant setting, the overall prognosis of this subset of tumors remains poor. Liedtke and al demonstrates in a previous report that patients with TNBC have increased pathologic complete response (pCR) rates compared with non-TNBC, and also had better survival compared to TNBC patients who don’t achieve pCR.