Triple negative breast cancer: Early stages management and evolution, a two years experience at the department of breast cancer of CHSF

During our study period, triple-negative breast cancers accounted for 10% of our population. The most aff ected age group ranges from 50 to 60. The majority of patients in our sample are pauciparous. In the group of patients who received hormone therapy, it was mainly HRT for 4 to 6 years. 96.77% of patients consulted a health worker within 3 months of the discovery of the signs. Adenopathies are frequently present at the time of diagnosis. 93.54% of the cases have an invasive ductal carcinoma. Triple negative cancers are essentially poorly diff erentiated. Triplenegative cancer has a high rate of cell renewal. In our study, neoadjuvant chemotherapy is mostly indicated for triple-negative breast cancers ≥ 30 mm at diagnosis and a delayed lumpectomy is then performed in 23.52% of the patients. For tumors of < 30 mm size, a lumpectomy is performed immediately in 76.47% of the patients, followed by adjuvant chemotherapy.


Introduction
Breast cancer is a malignant tumor that develops with no preservation of the different anatomical and functional structures of the breast. There are different types of breast cancer depending on their initial cells of origin from which they develop. The most common breast cancers (95%) are adenocarcinomas, that develop from the epithelial cells (= carcinoma) of the mammary gland (= adeno). There are also other rare types of breast cancer. Adenocarcinomas most often arise from the cells of the ducts and more rarely from the cells of the lobules of the mammary gland. A distinction is made between cancers in situ and invasive cancers. [1][2][3][4][5].
With approximately 54,000 new cases and 12,000 deaths per year estimated in 2015, breast cancer ranks second among cancers and third among cancer deaths worldwide. However, it is the most common cancer among women in France and represents a major public health problem. The incidence of breast cancer has increased signi icantly in the last decades [2].
The main risk factors are age, genetic predisposition, a personal history of breast disease and a personal history of high dose chest radiation. Other risk factors are suspected, such as the endogenous hormonal exposures (puberty age, number of children, age at irst pregnancy, breastfeeding, overweight/obesity) and the exogenous ones (hormone replacement therapy).
Breast cancer can be discovered at an early stage through the mammography screening. In several countries, there is an organized screening program offered to all women aged between 50 and 74. The incidence of this cancer is, therefore, in luenced by the evolution of screening practices [2]. However, there are several subtypes of breast cancer [6,7]. Recent diagnostic advances have made it possible to distinguish the most frequent, hormone-dependent breast cancers, which express estrogen and/or progesterone receptors on their membranes, and are associated with a good response to hormone therapy, and "HER +" cancers "characterized by an overproduction of the HER2 protein. For the latter group, there are today very effective targeted therapies [7]. But 15% of patients have the so-called "triple negative" breast cancer, that is without any known marker on the surface of cancer cells. They have the following characteristics in common [4,6,9].
-Affect younger women. -Progress quickly, it is often a cancer of interval (discovered between two tests of control) -Occur in women not yet concerned by the screening -Are more often detected at large sizes. The neoadjuvant chemotherapy is therefore more often used. Triple negative breast cancers are a priority in research, because up to date, there is no effective targeted therapy to treat women suffering from this form of cancer.
We thus initiated this work based on the following hypotheses: -Triple negative breast cancer has a low frequency and mainly concerns the young population -It would be associated with a group of population at risk -Its prognostic criteria would be severe -The therapeutic means would be limited to chemotherapy, surgery, and radiotherapy.
-Mutations of oncogenes are frequent The general objective of our study is to establish the pro ile and the management of patients with triple negative breast cancer over a period of 2 years, operated in the gynecologyobstetrics department of the Center Hospitalier Sud francilien, France.
Our speci ic objectives are as follow: -To bring out the socio-demographic characteristics of the patients -To identify the clinical and paraclinical aspects of triple negative breast cancer -To describe their histo-prognostic speci icities -To present the treatment modalities

Method
Our study was done over the period from January 1, 2017 to December 31, 2018, spanning a 2-year period.
Type of study: This is a descriptive retrospective study.

The population
This study involved a total of thirty-one patients with triple negative breast cancer followed and operated at the gynecology department of the Centre Hospitalier Sud Francilien during the determined period over the study period.

Inclusion criteria
-Patients with triple negative breast cancer operated during the determined period -Patients whose record was completed including the various studied parameters -Patients in the non-metastatic stage

Non-inclusion criteria
-Patients with another type of breast cancer -Patients with incomplete records -Patients with metastatic cancer

Sampling technique
We conducted a comprehensive census of all patient records operated on for triple-negative C.H.S.F. breast cancer over our study period.

Data collection
Collection technique: Our data collection was based on the records of the genecology department, the oncology department, and the pathology department.

Data collection tool:
To collect our data, we established a fact sheet that was tested corrected and validated.  Chemotherapy and tumor size, lumpectomy by tumor size, sentinel lymph node and adenopathies, indications of axillary Lymph node dissection and mastectomy, breast reconstruction, radiotherapy, oncogenetics investigation.
The evaluation of estrogen and progesterone receptors was carried out by an immunohistochemistry technique, with a threshold of positivity established above 10%. Thus, estrogen and/or progesterone receptors are considered negative when their levels are less than 10%.
The expression of HER 2 protein was detected by two complementary methods: immunohistochemistry (IHC), luorescent in situ hybridization (FISH). A tumor is considered HER 2 negative when immunohistochemistry returns with a scale of 0 or 1+; however, for a result of 2+, the tumor is considered HER 2 negative if FISH is negative.
The sentinel node technique was also performed by two additional methods: colorimetric detection by patent blue injection, and isotopic by injection of a radioactive isotope (Technetium 99), followed by a lymphoscintigraphy, and then intraoperative detection via a probe of the gamma rays that are emitted by the sentinel node. Oncogenetic surveys were conducted by an oncogeneticist, and positive results were con irmed on a second blood sample.
The data was scanned in THE EXCELL software and then interpreted in THE EPI-INFO 7 software. They were represented in as frequency tables, percentages (n/∑n x 100 with ∑ = the sum of the numbers), and igures.
However, the data were collected and analysed in strict compliance with ethical considerations.

Frequency
The following table shows the frequency of triple-negative cancers in the studied population.
Triple negative breast cancers account for 10% of our population (Table 1).

Sex:
The entire population studied was female. Note that three cases of male breast Cancer were managed at our department during the considered period: two in 2017 and one case in 2018. None of them were triple negative. Table 2 shows patients by age at the time of diagnosis of breast cancer.

Age at diagnosis
The most affected age group ranges from 50 to 60, with an average age of 56.68 years, and extremes from 28 to 80 years. However, 29.01% of patients with triple negative cancer less than 50.

Body Mass Index
The following table shows the distribution of patients according to their body mass index (BMI).
The body mass index was calculated by the weight formula (kg) divided by the square of size (meter) and interpreted as follows: -  (Table 3) Out of 31 patients, 19 have a normal BMI, the equivalent of 61.29% of our sample. Table 4 shows the repartition of patients with triplenegative breast cancer based on the age of their menarche.

Age of menarche
58.06% of patients had their menarche between the age of 10 and 13.

Menopause
The following table presents patients according to their menopausal status.
70.96% of patients are in the postmenopausal period at diagnosis (Table 5).

Parity
The following table shows the parity of the studied patients. A nulliparous patient is considered to have no parity, while the patients that are primiparous, pauciparous, and multiparous have respectively one, two to three, and more than three parities. 48.38% of patients with triple negative breast cancer are pauciparous ( Table 6).

Age at the birth of fi rst child
The following table shows the distribution of patients by the age of irst motherhood.
42.85% of patients had their irst delivery between the age of 25 and 30, then 35.71% of them between the age of 20 and 25 (Table 7).       Breastfeeding and its total duration Tables 8 and 9 show the proportion of breastfeeding patients, as well as its duration in months respectively. 20 out of 31 patients were breast-feeding, the equivalent of 64.51%.
30% of the patients breastfed over a period between 9 and 12 months, followed by 25% beyond 24 months.

Hormonal treatments
The following table shows the repartition of patients based on the use of hormonal treatments (contraceptives, Hormone Replacement Therapy HRT) and the total duration of treatment, in years.
64.51% of patients with triple negative breast cancer did not receive hormone therapy. In the group of patients who received hormonal treatments, it consists mainly of HRT (19.35%) for 4 to 6 years. Hormonal contraceptives accounts for 16.12% over a period of 2 to 4 years (Table 10).

Tobacco and alcohol consumption
61.12% of patients do not consume alcohol and tobacco. In the group of patients who use it, it is mainly tobacco at 22.58% (Table 11).

Personal history of malignant tumors
The following table 12 divides patients according to the personal history of malignant tumor.
2 out of 31 patients have a personal history of malignant tumors, or 6.45%. It is a controlling breast cancer, and ENT cancer. Table 13 shows the history of benign breast injury in our patients. 16.12% of patients with triple-negative breast cancer initially developed benign breast lesions. It is essentially the ibroadenomas. Table 14 shows the types of cancer in the patient's family: irst and second degree.

Family history of 1 st and 2 nd degree cancer
67.74% of patients with triple-negative cancer have a family history of cancer at the level of irst-and second-degree relatives. Mainly, it is breast cancer, colorectal cancer, gastric cancer, endometrial cancer.

Time between discovery and consultation
We present in the table 15 the time elapsed between the       discovery of a breast abnormality and the consultation of the patient (Table 15).

Initial tumor size
The following table shows the size of the tumor at the time of diagnosis.
At the time of diagnosis, the majority of patients have a tumor larger than 30 mm. The majority of sizes range from 30 to 40 mm (29.03%) and from 50 to 60 mm (22.58%) ( Table  16).

Tumor site
In table 17, we present the seat of tumors according to the different quadrants of the breast.
The upper-outer quadrant of the breast is the most affected by the tumor (38.70%) followed by the union of external quadrants (22.58%) ( Table 17).

Adenopathies
We present in the following table the association of adenopathies with triple negative cancers at diagnosis, as well as the conclusion of pathology.
Adenopathies are frequently associated with triple negative cancer (58.06%) at the time of diagnosis; with a lymph node invasion (n = 14) (Table 18). Table 19 presents the imaging methods used to explore patients.

Type of imaging:
All patients in our sample received the following imaging methods: mammography, ultrasound, MRI, PET-Scan.

ACR Grade:
We detail in the table below the grades of lesions found at mammography, according to the classi ication of the American College of Radiology. ACR 5, were mainly found (77.41%), followed by ACR 4 (22.58%) ( Table 20).

Preoperative histology
Histological type: The following table shows the type of tumor found on pathological anatomy examination of preoperative sampling.

Histo-prognostic grade:
We present the histo-prognostic pro ile of triple negative breast cancers in the following table 22.         Triple-negative cancer has a high rate of cell renewal, ranging from 80% to 100% (38.70%) 60% -80% (34.37%) ( Table 23). Table 24 shows the type of chemotherapy that was indicated based on the size of the tumor at the time of diagnosis.

Initial tumor size and chemotherapy
Neoadjuvant chemotherapy is mostly indicated for triplenegative breast cancers of size -30 mm at diagnosis. Table 25 shows the indicated immediate and delayed lumpectomies, depending on the size of the tumor.

Tumorectomy and tumor size
The lumpectomy is performed immediately in 76.47%, when the size of the tumor is 30 mm; it is deferred in 23.52% for sizes ≥ 30 mm. Table 26 shows the indications of the sentinel node technique based on the presence of satellite adenopathies.

Sentinel lymph node indications according to adenopathies
The sentinel node technique was indicated in 45.16%, in the absence of adenopathies. It was recused in 54.83% in the presence of adenopathies.
Indications of the Axillary lymph node dissection: The following table 27 lists the indications of axillary lymph node dissection.
Axillary lymph node dissection is performed in 18 patients (58.06%); and mainly indicated for invaded adenopathies on ine needle biopsy (77.77%). Table 28 shows the different indications of mastectomy in our patients.

Mastectomy indications
Mastectomy is indicated in 14 patients; it is essentially done in the case of large tumor size associated with a small breast volume (35.71%), followed by multifocal breast tumors (28.57%).

Breast reconstruction
In table 29, we present the frequency of breast reconstructions and their timing in the patient care.
14 patients had a mastectomy. 21.42% had an immediate breast reconstruction (n = 2), deferred (n = 1). Table 30 shows the different indications of radiotherapy, as well as its timing in relation to the surgical procedure Radiation therapy is indicated in the majority of patients (96.66%), postoperatively (n = 30). Table 31 shows the indications of oncogenetic consultations in patients with triple-negative breast cancer.       11 patients received the proposition for an oncogenetic investigation based on the Manchester criteria (Table 32); Indicated mainly in front of a young age and a family history of cancer.

Oncogenetic survey results and impact in management
The following table presents the results of the oncogenes mutation research, as well as its contribution in the management of the concerned patients.
The therapeutic intake is directed towards a prophylactic bilateral mastectomy and adnexectomy in the case of mutation.

Immunotherapy
The experience of immunotherapy in oncology in our department started a year ago. The patients are screened for immunotherapy. In our series, two patients had presented triple negative recurrences of their already treated breast cancer; irst case PDL1 positive PD-L1 ≥ 1% treated with immunotherapy combined with chemotherapy (atezolizumab/abraxane) while the second and second PDL1 negative treated with chemotherapy alone.  [4] ind respectively frequencies estimated at 20.3%, 25%, and 27.9% of their studied population; This consists the double of the results achieved in European countries. These data suggest that triple negative breast cancers are more common in Asia, with a peak of frequency in India.

Sex
In our study, the entire population studied was female. This result is corroborated by Gueye M in Senegal [25], and James, et al. in New Zealand [7] who found in a population of 1390 patients, a 100% female.

Age at diagnosis
The most affected age group ranges from 50 to 60, with an average age of 56.68 years, and extremes that are from 28 to 80 years. Similar results are found in the city of Tours and in several countries in Europe and America. Indeed, Redondoet al in Spain [20], Wojcinski, et al. in Germany [21], Stead, et al. in the USA [27] ind average ages of 54.7 years, 55.9 years, and 58 years, respectively in their populations. In England, Jack, et    However, it should be noted that a high BMI in nonmenopausal women is associated with a signi icant increase in the risk of triple negative tumors (OR = 1.18, IC 95% (0.86-1.64), p = 0.003), while an increase in BMI appears to be a protective factor for Luminal A and B and HER2 tumors in non-menopausal women. Obesity in non-menopausal women decreases exposure to estrogen due to frequent associated anovulation. This would explain the protective effect of obesity on hormone-dependent tumors in comparison to triple negative tumors [3].

Index cases of Cancers AND 1 st -2 nd degree relatives Number (A) Points (B) A x B
However, despite an increase in the frequency of larger and more advanced TNM Tumors, obesity is not associated with a decrease in survival with non-recurrence. This is con irmed by the study of Ademuyiwa, et al. who followed 418 women treated for breast cancer and found no relationship between obesity and overall survival or survival with non-recurrence [34].

Age of menarche
58.06% of patients had their menarche between the age of 10 and 13.
Note that increased age of menarches would be associated with a decreased risk of triple negative tumor in comparison to other types of tumors. This is shown by Yang, et [25] reported rates of 63.8%, 60%, 59.1%, respectively.

Parity and age of fi rst motherhood
The majority of patients in our sample are pauciparous (43.38%) with a parity of between 2 and 3. 42.85% of patients had their irst delivery between the age of 25 and 30. In Senegal, Gueye, et al. returned to an average parity of 3.6.
Many studies suggest that high parity is associated with an increased risk of triple-negative tumors unlike Luminal A tumors of which multiparity decreases the risk [36].  [39].

Breastfeeding and total duration
20 out of 31 patients were breast-feeding, which consists the equivalent of 64.51%. Among them, 30% of patients breastfed over a period between 9 and 12 months, then 25% above 24 months.
The "Collaborative group on hormonal risk factors in breast cancer" has determined that breastfeeding has a protective effect on all types of breast cancer (reduced cancer risk by 4.3% for any year of breastfeeding) [40]. The mechanisms involved in the effect of lactation on gene expression and breast epithelial cells differentiation are not fully understood. They could include the complete differentiation of breast epithelial cells during breastfeeding and the decrease in the duration of estrogen exposure associated with secondary breastfeeding amenorrhea [39]. Barnard, et al. in 2014, conducted a literature review in order to study the associations between known risk factors for breast cancer (especially the hormonal ones) and different molecular subtypes. In their meta-analysis https://doi.org/10.29328/journal.cjog.1001052 of 38 studies of 27629 patients, including 4981 triple-negative patients, an increase in breastfeeding duration was associated with a decrease in the risk of triple negative breast cancer (as well as Luminal A and B cancers while this association was not found for Her2 positive tumors) [36].

Hormonal treatments
64.51% of patients with triple negative breast cancer did not receive hormone therapy. In the group of patients who received it, it was mainly HRT (19.35%) for 4 to 6 years. Hormonal contraceptives account for 16.12% and were used mainly over a 2 to 4-year period. According to the literature, there is a relationship between the development of triple negative breast cancers and exposure to hormonal treatments.
Indeed, Dolle, et al. reported an increase in the risk of triple negative tumors of 4.7 in women under the age of 40 years and who had used oral contraception for more than one year (OR: 4.2; IC 95% 1.9-9.3, p < 0.001). The risk was 6.4 times for the women who had started contraception before the age of 18 in comparison with those who had never used contraception [42]. Similarly, Ma, et al. inds an increased risk of triple negative tumors associated with oral contraceptive use, but only in women aged 45-64 who started oral contraception before the age of 18 [41].
In addition, the "Collaborative group on hormonal risk factors in breast cancer" con irms that the risk of breast cancer is increased in women using hormone replacement therapy and would be exacerbated with its duration. However, the risk disappears after 5 years of usage. In addition, the study indicates that the relative risk of breast cancer among recent users is higher in thin women than those who are high weight. This analysis studied breast cancers as a whole, without the molecular subtype repartition.
Few studies have studied the association between HRT and triple negative tumor [36].

Tobacco and alcohol consumption
61.12% of patients do not consume alcohol and tobacco. In the group of patients who use it, it is mainly tobacco at 22.58%.
The literature points to a link between tobacco and/or alcohol use and the occurrence of breast cancer in general. Alcohol consumption is a well-established risk factor. For each additional intake of 10 grams of alcohol per day the risk of breast cancer increases by 7%. For tobacco the risk is signi icantly increased in women who started smoking at a young age or more than 5 years of duration before their irst pregnancy at term [36].
However, for the speci ic case of triple negative cancers, Geoffrey, et al. in the USA studied this relationship among 146,985 women enrolled in the Women's Health Initiative. It included 300 cases of triple negative cancer and 2,479 cases of hormone-sensitive cancer over 8 years. It appearsed that smoking and alcohol consumption are not associated with an increased risk of triple-negative breast cancer, but may be modestly associated with an increased risk of breast cancer expressing hormone receptors [43].

Personal history of malignant tumor and/or benign breast lesions
2 out of 31 patients have a personal history of malignant tumors, which is the equivalent of 6.45%. It consists of a controlateral breast cancer, and ENT cancer. 16.12% of patients with triple-negative breast cancer initially developed atypical breast lesions. It was essentially adeno ibromas.
A patient with this type of lesions on a surgical biopsy has an increased risk of developing breast cancer within at least 15 years of diagnosis. Cancer occurs in 40% of cases in the controlateral breast. In the case of atypical ductal hyperplasia, the relative risk is multiplied by 4-5 or even more in cases of mixed atypical hyperplasia (ductal and lobular, RR of 5-6) and lobular carcinoma in situ diagnosed in a woman with a young age and a family history of breast cancer [44].
Family history of 1st and 2 nd degree cancer 67.74% of patients with triple-negative cancer have a family history of irst-and second-degree cancer. This is primarily breast, colorectal, stomach, and endometrial cancer.
In a comparative study, Khalil, et al. in Morocco found a family history in 17.4% of cases of triple negative cancers versus 57.6% of non-triple-negative cancers [6]. This difference could be explained by the small size of the triple negative breast cancer sample.
Women with a family history of breast cancer, whether in the maternal or paternal branch, have an increased risk of developing it. For example, a history of irst-degree breast cancer (mother, sister, and daughter) increases the relative risk to 2.
Two irst-degree history confers a relative risk of 3, and if there is more than 3 (same parental branch, irst and second degree) the relative risk is at least greater than 4 and makes the underlying genetic problem to be considered [44]. while Samain in Nantes has an average of 18 mm. These results would be strongly in luenced by the time elapsed between the appearance of the tumor and the consultation, as well as the various factors of tumor proliferation [5,7,15,45].

Tumor site
The upper-external quadrant of the breast is the most affected by the tumor (38.70%). Secondly, comes the junction of external quadrants (22.58%).
Boisserie, et al. con irm this high frequency in the upperexternal quadrant with 46.6%, followed by the upper-inner quadrant with 17.8% [14].

Adenopathies
Adenopathies are frequently present (58.06%) at the time of diagnosis of triple negative cancer with a histological invasion of lymph nodes (n = 14).
Similar results are reported by Rosalind, et al. in the USA and James, et al. in New Zealand, 51% and 40% respectively [5,7]. Samain in Nantes describes a lower percentage: 23%, while Gueye, et al. in Dakar reported higher value of 68.1% [25,45]. These differences could be explained by the delay between the appearance of the tumor and the consultation, the histological peculiarities and different factors of cell proliferation.
Woodwork, et al. report in their studied population the following results: ACR 1 and 2 in 6.4% of cases, ACR 3 in 4.8%, ACR 4 in 58.7%, ACR 5 in 30.2% [14]. Thus, triple negative breast cancers present on imaging in their severe forms.

Cell Renewal Rate (Ki-67)
Triple-negative cancer has a high rate of cell renewal, ranging from 80% to 100% (38.70% of the cases) and 60% to 80% (34.37% of the cases). This result is corroborated by Rosalind in the USA, which inds a high Ki-67 index in its population in 79% of the patients with triple negative breast cancer [5].

Chemotherapy and lumpectomy by initial tumor size
In our study, neoadjuvant chemotherapy is mostly indicated for triple-negative breast cancers ≥ 30 mm at diagnosis (51.61%) and a delayed lumpectomy is then performed in 23.52% of the patients. On the other hand, for tumors of < 30 mm size, a lumpectomy is performed immediately in 76.47% of the patients, followed by adjuvant chemotherapy (48.38%).
In the Gueye, et al. series in Dakar, neoadjuvant chemotherapy is indicated in 59% of patients. This high rate can be justi ied by the high percentage of tumours ≥ 30 mm at diagnosis, also by the average time for consultation which is 11.1 months in its series [25]. Samain in Nantes reports a lower frequency of neoadjuvant chemotherapy in its series: 34.6% in comparison to 65.4% for adjuvant chemotherapy [45].

Indications of mastectomy and breast reconstruction
Mastectomy was performed in 45.16% of patients; it was mainly indicated in front of a large tumor size associated with a small breast volume (35.71%), then multifocal breast tumors (28.57%). Breast reconstruction was performed in 21.42% of mastectomy patients.
James, et al. in New Zealand, reports in his series a higher frequency of mastectomy: 55% with breast reconstruction performed in 19% of them [7].

Radiotherapy indications
Radiation therapy is indicated in the majority of patients (96.66%), postoperatively (n = 30). This result is corroborated by Samin in Nantes which had a frequency of 91%, and by James in New Zealand which reported a frequency of 66% [7,45].

Oncogenetic survey indications
In our population, 10 patients bene ited from an oncogenetic survey; it was mainly indicated in front of a young age and a family history of cancer. Our results are similar to the recommendations of the Curie and Gustave Roussy Institute [15]  However, there are urgent indications, especially if it can in luence the choice of treatment (surgical: mastectomy + immediate breast reconstruction rather than conservative treatment).

Oncogenetic survey results
The oncogenetic survey was proposed in 11 patients. There are two BRCA 1 mutations (18%), one BRCA 2 mutation (10%), and four cases of absence of mutation (36%). The therapeutic intake in case of a mutation is directed towards a prophylactic bilateral mastectomy and adnexectomy, proposed at the age of 40.
According to the National Cancer Institute [46], patients with a BRCA 1, BRCA 2 gene mutation have a risk of developing breast and ovarian cancer. Thus, depending on the age and the parental project, breast monitoring is proposed starting from 20 years of age based on: clinical examination every 6 months.
Starting from the age of 30, MRI + mammogram/ultrasound if dense breasts every year. Note that MRI is recommended irst, to guide other examinations if an abnormality is suspected. The maximum time of 2 months is recommended between examinations, to be carried out if possible in the same structure for optimal synthesis and comparison.
On the other hand, the alternative to breast monitoring is a prophylactic mastectomy with maximum bene it if performed before the age of 40. A time for re lection is essential and its indication is made in the Meeting of Pluridisciplinary Concertation, and the care of the patient is done by a multidisciplinary team.
Concerning the ovarian risk, monitoring is initiated starting from the age of 35 using an annual pelvic trasnsvsaginal ultrasound. Starting from the age of 40 or as soon as the parental project is completed, a prophylactic adnexectomy is proposed after validation in the Meeting of Pluridisciplinary Concertation.

Immunotherapy
In general 25% of patients suffer from recurrent regional or distant recurrence with a mortality rate that can reach up to 75%. This issue can be explained by the absence of targeted therapies [46]. Immunotherapy had shown good results not only in improving survival rates but also in maintaining adequate tumor response and had recently obtained approval from the US Food and Drug Administration [47]. Most studies speak about the effect of immunotherapy through cases and controls in the context of an initial treatment for triple negative breast cancer and not treatment of its recurrence. According to Schmid, et al, survival progression-free was prolonged by immunotherapy by 7.4 months compared to 4.8 months for those who had not received it in combination with chemotherapy in advanced triple negative breast cancer [48].
Currently more than 50 clinical trials evaluate pembrolizumab, durvalumab, ipilimuma, nivolumab, tremelimumab as well as azolizumab. Immunotherapy, particularly with drugs that inhibit PD1 and PDL1 (and therefore likely to restore the person's anti-tumor immunity), seems promising in patients with metastatic triple negative breast cancer. The combination of atzolizumab (anti PD-L1) with paclitaxel has given very promising results justifying to evaluate its real effectiveness, compared to standard treatment [49].
Tumors that present a high mutational charge seem to be more immunogenic. Based on this, these tumors would be good candidates for immunotherapy. For patients that present BRCA1 and BRCA2 mutations, anti-parp can be prescribed. Olaparib (Lymparza) was approved at the European level for breast cancers (HER2 negative with BRCA mutation) in patients treated with some meds or when medications are not adapted.

Conclusion
Breast cancer is the most common cancer in women and is a major public health problem. It is divided into several subtypes, including triple negatives. The subject of our study entitled "Triple Negative Breast Cancer: Early Stages Management And Evolution, A Two Years Experience At The Department Of Obstetrics And Gynecology Of CHSF" has speci ic objectives to highlight the socio-demographic characteristics of patients, to identify the clinical and paraclinical aspects of triple negative breast cancers, to describe their histo-prognostic speci icities and to present the modalities of management.