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Background: Latin American (LA) studies on triple-negative breast cancer (TNBC) and their characteristics are scarce. This forces physicians to make clinical decisions based on data obtained from studies that include non-Hispanic patients. Our study sought to obtain local epidemiological data, including risk factors and clinical outcomes from a Chilean BC registry.

The age of the subducting crust becomes progressively younger from north to south along the eastern edge of the Nazca plate, until the newly-formed crust at the actively spreading Chile Rise enters the trench. This location is termed a triple junction since three different tectonic plates meet there.

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The Chile triple junction (CTJ) is the only modern site on Earth where an actively spreading mid-ocean ridge crest is being swallowed by a subduction zone at a continental margin (figure 2). This is a particularly interesting area to study because we can observe two types of plate boundaries and their processes in very close proximity. The Chile Rise continues to spread as it is thrust beneath the continental margin of South America. Because of the angle between the trench and subducting ridge segment, one flank (or side) of the ridge is underneath the continental margin, while the other flank is exposed on the seafloor. Also because of the oblique subduction, the age of subducting crust varies from 0 Million years (Myr) at the triple junction to 25 Myr 900 kilometers/km (560 miles) north of the CTJ.

In 1960, the Chilean subduction zone was host to the largest earthquake ever recorded, a magnitude 9.8 quake that ruptured over a distance of 1,000 km (621 miles) along the Chile margin. This earthquake triggered a powerful tsunami that caused damage to coastal areas throughout the Pacific Ocean as far away as Japan. The earthquake rupture would have continued farther south along the subduction zone and possibly been even more devastating had it not encountered the warm and ductile (malleable, pliant) crust of the subducting Chile Rise at the triple junction. This event is an excellent example of the powerful tectonic forces contained within the subduction zone at the Chile margin area.

The unique triple junction geometry is conducive to the formation of several different types of hydrothermal venting. Hydrothermal venting occurs when seawater penetrates the crust or sediments near the axis of an oceanic spreading center; is heated by the underlying magma (molten rock) or a chemical reaction; and returns to the seafloor as hot (or warm), mineral-rich water (figure 3). Since the Chile Rise is spreading at an intermediate rate of about 60 millimeters/yr (2.4 inches/yr), the amount of magma beneath the ridge is enough that high-temperature "black smoker" type hydrothermal systems with mineral-rich chimneys (figure 3, inset) are likely to be found approximately every 100 km (62 miles) on the ridge near the triple junction.

Also, because the ridge continues to spread beneath the continental margin, seawater in the sediments of the overlying plate could potentially be heated, leading to a cooler, more diffuse hydrothermal system on the landward side of the triple junction.

Taitao Peninsula lies near the triple junction and various geological features, such as the Taitao ophiolite, are related to the dynamics of the triple junction.[5] Ridge and trench collisions are clear indications of the subduction history around the Pacific Ocean and are likely a dominant mechanism of ophiolite positioning. This results in a rapid sinking and spreading along with magmatic activity near the oceanic trench.[4]

This group is heterogeneous, containing histological sub-types with especially good prognosis such as adenoid cystic carcinoma and varieties of greater aggressiveness such as metaplastic carcinoma. The basal-like sub-type defined by PAM50 is the most represented in the triple-negative category, where more than 90% of basal-likes are triple negative, and at the same time, basal-like is the most common sub-type within the triple negatives [23, 24]. Additionally, triple negatives have been subdivided into four more groups on the basis of gene expression, however, up to now, this sub-classification has had no real use in clinical practice [25].

In Latin America, breast cancer is the leading cause of death from tumours in young women. Triple-negative breast cancer is becoming a more common situation in young women, accounting for 20% of deaths due to breast cancer in the 45 years or younger age group, twice as much as the reported rate in developed countries. The reported prevalence of triple-negative disease in Latin America in young women ranges between 18% and 35%, with the highest rates being reported in countries such as Mexico and Peru [33].

Not much data on triple-negative disease has been published in Chile. A retrospective study in a university centre explored the situation of breast cancer at extreme ages (under 41 years of age and over 69) over a period of 16 years. 12% of patients in the registry were under 41 years of age, with Luminal B being the most frequent sub-type (43%), followed by Luminal A (33.2%) and triple-negative disease in third place (17.8%) [34]. Not yet published information from the Oncology Institute, Arturo Lpez Prez Foundation in Santiago, Chile reports that in 20 new cases of triple-negative breast cancer diagnosed during 2017, only 20% of patients were under the age of 40 and the average age of all patients was 49 years old, which shows an epidemiological discrepancy compared with known data from other populations of the same regional area. On the other hand, official data from the Luis Tisn Hospital in Santiago, Chile (flagship hospital for the diagnosis and treatment of breast cancer) reviewed for this work, showed that out of a total of 285 biopsies performed on patients with breast cancer between June 2014 and May 2015, only 8.7% corresponded to the triple-negative sub-type, thus showing a much lower prevalence of this sub-type of breast cancer in a representative sample of Chilean women with breast cancer when compared with other groups in Latin America.

Patients with metastatic disease have a short progression-free survival expectancy following the failure of the first-line chemotherapy with an average of no longer than 4 months, indicating the great need to develop drugs to treat triple-negative breast cancer. With the exception of Olaparib for the treatment of tumours with BRCA germline mutations [42], there are currently no other approved therapies for this group, leaving cytotoxic chemotherapy as a pillar of systemic treatment. On the other hand, the actual prevalence of BRCA mutations is not well known among the various towns and regions of Latin America. There are varying results in different populations within the same country and in populations selected by genetic risk criteria [43, 44].

Various recommendation guidelines for Latin American regarding the management of early and metastatic breast cancer recognise triple-negative breast cancer as a high-risk variety, however, they do not suggest the use of different therapies from those already commonly used for other sub-types (excluding targeted therapies for Luminal HER2), such as treatments based on anthracyclines and taxanes. Triple-negative breast cancer has higher response rates to neoadjuvant chemotherapy in comparison with other sub-types of breast cancer and is known as the triple-negative breast cancer paradox [45]. Advantages of neoadjuvancy include minimising the size of the tumour to allow breast-conserving surgery in selected cases, reducing options for extensive axillary dissection, making an inoperable tumour resectable and allowing an in vivo evaluation of the sensitivity of the tumour to chemotherapy, thereby decreasing the possibilities of metastasis. There is a shortage of public policies and management guidelines on early disease that include studies on BRCA mutations and the use of platinum duplicates in neoadjuvant therapies. In a meta-analysis involving 11,955 patients undergoing neoadjuvant chemotherapy for breast cancer, the pathologic complete response showed a significant correlation with disease-free survival and overall survival [38]. Patients who achieved a pathologic complete response had significantly better results. Recurrence-free survival with an HR of 0.24 and overall survival with an HR of 0.16 indicate that pathologic complete response has a prognostic value in triple-negative breast cancer. The most used adjuvant systemic treatment in Latin America, where neoadjuvancy was not used previously, includes the sequential combination of chemotherapy based on anthracyclines followed by taxanes. Similar confrontation occurs in metastatic disease where, since hormonal therapies cannot be used, the range of options is limited today to systemic therapies which include anthracyclines, taxanes, platinum-based duplicates (e.g. a combination of carboplatin and gemcitabine) and capecitabine, ixabepilone, among other options.

In Israel and Europe, triple-negative breast cancer, like ovarian cancer, has been widely associated with populations having a high prevalence of BRCA gene mutations (BRCA 1 and BRCA 2); a situation occurring in various populations worldwide in women who are carriers of these mutations. In Latin America where the known presence of BRCA mutations is much lower than in the other regions mentioned, the prevalence of triple-negative breast cancer ranges between 8% and 35% according to different reports. However, the prevalence of this problem is not known for certain because little data has been reported on the various sub-types in the country, and we are limited to information published in reports on regional experiences and series, including information presented at scientific events but not published.

This disinformation must be improved in order to consider health policies that focus on the triple-negative disease; a sub-type of breast cancer with its own characteristics such as its aggressiveness, its occurrence mainly in young women, its high rate of metastasis and mortality when compared with other histological sub-types, all of which convert this sub-type into a unique variety with a worse prognosis. e24fc04721