Burkina Faso, management of breast cancer is still challenging due to usually late diagnosis. There are limited therapeutic choices and there are often complications making prognosis poor. The aim of the present was to describe the current clinical situation of breast cancer in women under 40 years old at Yalgado Ouedraogo University Hospital (Burkina Faso).

Materials and methods: Prospective cohort study of 58 cases of breast cancer confirmed by histopathology was conducted at Yalgado Ouedraogo CHU, from August 1st, 2014 to February 29th, 2016.

Results: Mean age of patients was 34.8 years (± 4 years). History of breast cancer was observed in 22.4% of cases. Invasive ductal carcinoma was diagnosed in 94.8% of cases. T3 and T4 tumors accounted for 20.7% and 38.0% respectively. Locally Advanced Carcinomas were found in 34.5% of cases. Fifty-three women had total mastectomy and among them, 34.5% margins of resection were infiltrated. Lymphocytic infiltrate and presence of vascular emboli accounted for 86.2% and 51.7% respectively. Based on Scarff-Bloom-Richardson classification, 38 patients were grade III. Hormone receptors was negative in 27/45 cases. Chemotherapy and radiotherapy were performed respectively in 98.3% and 48.3% of cases. The average survival of patients was 22.7 ± 2.8months.

Conclusion: Despite treatment, the prognosis of breast cancer remains poor for young women in Burkina Faso. Several challenges remain to be addressed including promotion of early screening with genetic counseling, establishment of an effective technical platform and national subsidy for therapeutic care.

• Breast-cancer

• Young-woman

• Treatment

• Reserved prognosis

• Burkina-faso

Marie Ouedraogo NL, Zongo N, Zida M, Sawadogo AY, Sawadogo E, et al. (2018) Breast Cancer in Women Under 40 Years Old at Yalgado Ouedraogo University Hospital (Burkina Faso). JSM Surg Oncol Res 3(1): 1022.

ACR: American College of Radiology; BI-RAD: Breast Imagingreporting And Data System; CERBA: Pietro Annigoni Biomolecular Research Center; CHU.YO: Yalgado Ouedraogo University Hospital Center; CMF: Cyclophosphamide-Methotrexate-5-Fluorouracil; cTNM: Clinical Classification in Tumor-Nodes-Metastasis; LABIOGENE: Laboratory of Molecular Biology and Genetics; MRI: Magnetic Resonance Imaging; pTNM: Pathologic Classification in Tumor-Nodes-Metastasis; SBR: Scarff-Bloom and Richardson.

Breast cancer remains the leading cancer among women and the leading cause of female death worldwide [1]. About 6.6% of breast cancer is diagnosed in women less than or equal to 40 years of age, and this cancer accounts for 40% of all cancers diagnosed in these subjects [2,3]. It has been recognized that breast cancer has a less favorable prognosis when diagnosed in young women. This motivated the promotion not only of screening but also of the early management of this cancer in young people [2]. The many therapeutic challenges to be addressed have certainly been the basis for new therapies over the past two decades. Indeed, these have opened the way to several treatment modalities, offering breast cancer victims a multitude of therapeutic choices, especially for young people, in order to improve the quality of life and survival [1].

For emerging economies however, especially in Africa, many efforts remain to be made due to the lack of an effective and/or efficient technical platform for the diagnosis and comprehensive management of this pathology. In Burkina Faso, breast cancer is considered as the most common cancer among women. The diagnostic and therapeutic challenge limits choices and total mastectomy according to modified Patey, occupies the first place in the surgical treatment. Conservative treatment is limited in young women, given the advanced stage of the tumor at the time of diagnosis in most cases. Thus, the best management of this cancer is closely conditioned to the promotion of early detection and effective improvement of the technical platform. There is no consensus in the definition of the young woman breast cancer victim. According to the studies, a young woman corresponds to a woman under 35, under 40, or even just pre-menopausal [2,3].

This research therefore aimed at describing the current clinical situation of breast cancer in women under 40 years old in Burkina Faso.

This was a prospective cohort study of surgical treatment and prognostic factors of breast cancer confirmed by histopathological analyses in women under 40 at CHU-YO. This study took place from August 1st, 2014 to February 29th, 2016. It was approved by the Ethics Committee for Health Research of Burkina Faso (N° 2014-8-098). After obtaining written informed consent from each patient, clinical, paraclinical and therapeutic data were collected from the General Surgery, Gynecology-Obstetrics, Oncology and Anatomy-Pathology departments of the CHU-YO. Women under 40 years of age with histologically confirmed breast cancer, who gave their free and written consent to participate, were included in the present study.

The parameters studied for each patient were: epidemiological and socio-demographic characteristics (age, sex, occupation, weight, height, level of education, origin); clinical data (antecedents, consultation time, reasons for consultation, symptoms and physical signs). Each patient received assessment such as: breast ultrasound and mammography with the ACR/BIRADS classification, grade, molecular biology; pTNM classification; chemotherapy and radiotherapy, tolerance of treatment, type of surgery, postoperative care, post-treatment complications, and length of hospitals stay. Data collection was possible through interview, physical examination, and investigations. For each patient, the tumor was classified according to the cTNM (clinical classification in Tumor-Nodes-Metastasis) and pTNM (p = pathologic) classification of breast cancers (7th edition 2010), and graded according to Scarff-Bloom and Richardson (SBR) grading system.

Therapeutic management was decided in most cases during a multidisciplinary consultation meeting. The collected data were coded, entered and analyzed on computer media using the Epi info version 7 software; Microsoft Office Excel 2010 and Microsoft Office Word XP 2010 software were used for word processing. The Chi square test (X²) was used to compare the results and p value<0.05 considered it to be statistically significant, Survival was analyzed using the Kaplan-Meier test and the comparison of survival curves with prognostic factors was done according to the Log-Rank test using SPSS version 24. For the purposes of our study, we used the definition considering women under 40 years old.

Fifty-eight women under age 40 were diagnosed and treated for breast cancer at the Yalgado Ouedraogo University Hospital Center from August 1st, 2014 to February 29th, 2016.

Epidemiological data

The mean age of the patients was 34.8 ± 4 years with range of 15 to 39 years. The average consultation time was 2 months, with extremes of 1 week and 6 months. Oral contraception was used in 62% of cases for an average duration of 3 years.

Clinical data

The presence of breast nodule was the main reason for consultation. It was noted in 49 cases (84.5%). Other reasons for consultation were mastodynia (10.3%), breast pruritus (3.4%) and breast nipple discharge (1.7%). In 18.9% of cases the tumor appeared during pregnancy. Family history of tumor and distribution of patients by prognostic factors are shown in Table 1. Breast ultrasound was performed in all cases and was suggestive of diagnosis in 45 patients (77.6% of cases). Axillary adenopathies were visualized in 49 cases. Thirty-three patients received diagnostic mammography. Objective lesions in mammography have been classified according to the American College of Radiology (ACR) and Breast Imagine Reporting and Data System (BI-RAD). In 22.4% (13/58) of cases, the tumor was classified BI-RAD-4 and in 27.5% (16/58) BI-RAD-5. Only one patient benefited from Magnetic Resonance Imaging (MRI).

Tumors T3 and T4 represented respectively 20.7% and 38.0% (p-value= 0.041) and had an inflammatory appearance in 34.5% of cases. In 19% of cases they were in the type of infectious mastopathies. The site of the tumor was the left breast in 36 patients (62% of cases). The palpated axillary lymph nodes were motile in 37 patients (63.8% of cases) and fixed in 15.5% of cases.

Paraclinic data

Germline mutations of BRCA1 and BRCA2 could only be investigated in 15 patients. Two types of pathological mutations were identified. The first type was high-penetration mutated genes identified in 3 cases, including 2 for BRCA1 and one for BRCA2. These 3 patients each had a family history of primary breast cancer. The second type was represented by the moderately penetrated mutated genes, including 2 cases for BRCA1 and 1 case for BRCA2.

The staging work-up showed 3 cases (5.2%) of metastases, including one case at the bone level, one case at the pulmonary level and one case at the hepatic level at the thoraco-abdominal CT scan. All 3 cases showed a high penetrance mutation on the BRCA1/2 genes.

Therapeutic data

Modified Patey mastectomy was performed in 53 cases (91.37%), for all tumors ≥3 cm. Two patients (3.44% of cases) underwent from conservative treatment (superior-internal and infero-internal quadrantectomy) with removal of axillary adenopathies in all cases. In no case could the sentinel lymph node technique be performed.

Palliative mastectomy of metastatic patients was performed in 3 patients. In 57 cases (98.3%), chemotherapy was performed. Thirty-one (54.4% of cases), patients received neoadjuvant chemotherapy. Each patient received 3-6 chemotherapy session, before surgery. Twenty-seven patients (45.6% of cases) received adjuvant chemotherapy within the recommended interval (5-6 weeks after surgery). Pregnant women did not received chemotherapy during pregnancy but three months after delivery.

The protocols adopted were: epirubicin-5-fluorouracil cyclophosphamide (FEC 60 and 100) in 35 cases (61.4%); 5-fluorouracil-adriamycin-cyclophosphamide (FAC 100) in 18 cases (31.6%) and cyclophosphamide-methotrexate-5-fluorouracil (CMF) in 4 cases (7%). Treatment with chemotherapy was complete in 78.9% of cases. Only one patient received tamoxifenonly hormone therapy. In 48.3% of adjuvant cases, external radiotherapy of the tumor bed, the axillary region and the chest wall was prescribed for tumors with lymph node invasion and/ or infiltration of the resection margins. It was performed 6 weeks to 3 months after the surgical treatment according to whether adjuvant chemotherapy will be performed or not. The number of sessions received ranged from 3-4 per week depending on the case, due to one session per day, 3-4 days for 5 weeks. The doses administered varied from 25-45 grays. In no case was the targeted therapy performed.

Histological analysis

At the pathological examination of the operative specimen, infiltrating ductal carcinoma was observed in 94.8% of cases. Margin was involved in 34.5% of the cases (p-value = 0.001). Ganglionic invasion and the presence of vascular emboliaccounted for 86.2% (p-value < 0.001) and 51.7% respectively. In 39 cases (67.2%), more than tree invading lympho-nodes were noted.

The tumor was classified according to SBR, grade II in 29% of cases and grade III in 58.6% of cases (p-value = 0.001). Hormonal receptors could be searched for in 45 patients. This research proved negative in 27/45 cases (RO+ = 12 cases, RP+ = 6 cases, RO- = 15 cases, RP- = 12 cases). The expression of HER2 by the tumor could not be sought.

Post-therapeutic evolution

The mean age of patients in our series was 34.8 years with a standard deviation of 4 years. During the study period, posttherapeutic events were observed: 8 cases of tumor recurrence including 4 cases of bilateralization; distant metastases noted in 13.8% of cases; upper limb lymphedema (12% of cases), a lymphocele (19% of cases), and suppuration of the operative wound (05.2% of cases) was also noted; post-irradiation cardiac and pulmonary involvement (03.4% of cases). The survival rate of patients at 24 months was 68.96%. The average survival of the patients was 22.64 months +/- 2.82. Eighteenth cases of death were recorded (31.3% of cases).

The age of the patients at diagnosis (≤40 years) would be a less favorable prognostic factor because the tumor would tend to be more aggressive and of high grade. In addition, the diagnosis of cancer would be made at a stage most often advanced, which would increase the risk of tumor recurrence [3,4]. A personal history of invasive breast carcinoma was noted in 2 cases. Thirteen patients (22.42% of cases) had a family history of breast cancer including 15.5% of first degree (7 patients’ mothers and 2 patients’ sisters) and 6.9% of second degree (in patients’ aunts). This is a poor prognostic factor with a p-value< 0.001.

Breast cancer has been defined as a genetic disease but only 5-10% is hereditary [5]. In young subjects the occurrence of breast cancer was most often correlated with a family history of breast and/or ovarian cancer with a high risk of mutations of cancer suppressor genes [2,6]. As a result, BRCA1 and/or 2 are the genes most frequently implicated in the mutation that causes breast cancer [1,5,7]. In our series, the genetic study that could only be performed in 15 patients, for lack of financial means, helped to identify 3 cases of high penetration mutations of BRCA1 (2 cases) and BRCA2 (1 CAS). This result reinforces the hypothesis attributing genetic and hereditary origin to breast cancer in young women. However, situations may arise where young women with breast cancer are founding members, being the first in the family to carry a germline mutation of a predisposition gene, particularly BRCA1 [5,7].

The general condition of our patients has deteriorated significantly, from 12.07% at baseline to 29.31% after 7 months. This could be related not only to the advanced stage of the tumor at the time of diagnosis, but also to the importance of cancer aggressiveness in these young women. Indeed, despite the introduction of multidisciplinary care that many of them have benefited from, it did not constitute an intangible barrier to the progression of the disease in these subjects. In literature, the aggressiveness of breast cancer in young women, and even more so in young black women, has been noted by several authors [8-11]. A comparative study conducted in the USA noted higher morbidity and mortality among black young women compared to Caucasian women who have had breast cancer [12]. Black race specific genetic data associated with more aggressive breast cancer are required in Africa. At the time of diagnosis, 29 patients (50% of the patients), had a tumor size T3, 5 patients (8.6% of cases) were classified T4, and 17 (29% of cases) T2 size. The tumors were inflammatory in34.5% of cases. It is important to note that it was statistically significant when tumor size is important with a p-value = 0.001. So locally advanced tumors have therefore characterized our series. The financial problems, the first use of traditional medicine, and the geographical inaccessibility to the care units would partly explain the diagnostic delay in our study environment [11].

In literature, it is correlated with a tumor size ≥5cm, a greater susceptibility to recurrence of the tumor after treatment. Large tumor size is therefore an important prognostic factor [13]. Tumor microenvironment largely orchestrated by inflammatory cells, would play a pivotal role in the development and progression of cancer, and a high level inflammation biomarkers would decrease the chances of survival in breast cancer [13]. Although these markers were not measured in our patients, the inflammatory appearance of the tumor suggests that the level of biological inflammation was high in our series. The inflammatory character of the tumor in the young subject has also been noted by several authors [14-16]. Axillary lymphadenopathies were palpable in 79.3% of cases. In literature lymph node involvement varies between 50 and 75% [9,11,14].

This could be explained in part by the rapid evolution of the tumor (high mitotic index) and the delay in treatment, both diagnostic and therapeutic. Indeed, the rate of division of tumor cells seems to be more accelerated in young subjects, which would also be a pejorative factor [2]. Morphologically, all women underwent breast ultrasound, which was suggestive of diagnosis in 93.1%. Thirty-four patients were eligible for mammography according to WHO recommendations. In 22.4% (13/58) of cases, the tumor was classified BI-RAD-4 and in 27.5% (16/58) BI-RAD-5. It would be of little contribution at a young age given the high density of the breast at this time [17]. Thus, for greater sensitivity, it is recommended to perform an “echomammography” coupling that would give more satisfactory results in young women [6]. Therapeutically, most patients received multidisciplinary treatment. From the surgical aspect, the modified Patey mastectomy was prominent for all tumors ≥3cm. The visibly advanced clinical stages, the fear of a possible recurrence, the low socioeconomic level and the insufficiency of the technical platform have influenced the radical choice in our context. In the literature, mastectomy would also limit the sequelae of the ipsilateral upper limb. Several African authors have also adopted this therapeutic choice [14,15,18]. European and American trends, however, have evolved towards conservative treatment that tends to be the “gold standard” today [1,10]. Indeed, the promotion of early diagnosis and the availability of new technologies have led to the adoption of this technique, which would limit the psychosocial consequences that radical treatment engenders. Only two patients benefited from this treatment in our series. They had a tumor size T1 and T2a and a socio-economic level allowing them a complementary adequate care abroad. On the pathological examination of surgical specimens, infiltrating ductal carcinoma was the dominant histological type (92.7% of cases) in our series. This histological type was in fact most often associated with a high histoprognostic grade and greater insensitivity to hormones (absence of estrogen and progestogen receptors) in young women [14].

Lymphocytic infiltration was positive in 86.2% of cases and in 70.9% of cases more than 3 ganglia were invaded. When compared presence and absence lymphocytic infiltration, we noted that p-value was statistically significant (p-value < 0.001). Lymphocytic infiltration is not a rare phenomenon in young women. It would be even more important in these patients [13]. It has been described as a risk factor for higher recurrence and a less favorable prognosis. The risk of recurrence is even aggravated by the high rate of positive lymph nodes I [1,2,13], n no case was the practice of sentinel lymph node and extemporaneous examination performed for lack of adequate technical platform. It would have allowed a complete surgical excision of the tumor which would increase the chances of survival of the patients. The banks of tumor were infiltrated in 34.48% of cases (20/55) and the presence of vascular emboli in 52.7% of cases. The demonstration of these two elements would reflect an important factor of recurrence of the tumor, and earlier at a young age. A surgical reoperation would be recommended to completely remove the remaining tumor [1,2]. In our series, the search for hormone receptors was performed 45 patients. Of these, 27 had a negative result (RO-: 20 cases, RP-: 7 cases). In the literature, tumors that do not express hormonal receptors have been reported by several authors in young women [2,11,12]. Hormonal receptor negativity has been described as one of the factors of unfavorable prognosis. The classification of the histoprognostic grade was specified in all cases: Seventeen patients were classified (27.59%) grade II and 34 cases (58.62%) grade III (p-value = 0.001, statistically significant). This result confirms the aggressive nature of breast cancer in young women, described by several authors [1,2,13]. Indeed, a high grade (grade III) would be an important criterion of malignancy that would negatively influence the prognosis. In the end, pathology performed the pTNM classification in all cases. T3N + tumors predominated with significant ganglionic invasion (86.2% of cases). The delay in medical consultations and, in turn, the delay in diagnosis, the lack of financial resources and the lack of mass awareness on breast cancer in our country could partly justify this result. Surgery was preceded by chemotherapy in 54.4% of cases.

The importance of tumor size motivated the indication of neoadjuvant chemotherapy to reduce the chances of posttreatment recurrence. Adjuvant chemotherapy was performed in 45.6% of cases. The protocols adopted were: epirubicin-5- fluorouracil cyclophosphamide (FEC 60 or 100) in 35 cases (61.4%); 5-fluoro-uracil-adriamycin-cyclophosphamide (FAC 100) in 18 cases (31.6%) and cyclophosphamide-methotrexate5-fluorouracil (CMF) in 4 cases (7%). The indications of the protocol were made according to the individual prognostic factors. They have been validated by a multidisciplinary staff. Similar treatment regimens have been adopted by several authors [11,14-16]. Chemotherapy plays an important role as a barrier to tumor recurrence [19]. Radiotherapy, regularly performed elsewhere, was only performed in 48.28% of cases in our study. The inability to perform this therapy on site has been an important limiting factor. Indeed, the majority of our patients were of low socio-economic level and thus unable to honor the costs of care abroad. Tamoxifen-only hormone therapy was performed in a single patient. Virtually absent in our series, it is indicated for tumors with hormone-positive receptors [2,8,13]. The evolutionary profile of our patients was marked by post-treatment events, the most important of which was local and distant tumor recurrence, observed in 8 cases, with 4 cases of bilateralization. The young age, the large tumor size, the lymphatic extension of the tumor, the high histo-prognostic grade, the absence of expression of the tumor at the hormonal receptors, have been described, as important factors of tumor recurrence [1,2,13]. The survival rate of patients at 24 months was 68.96%. The average survival of the patients was 22.64 months ± 2.82. Eighteenth cases of death were recorded (31.3% of cases). The presence of a poor prognostic factor in the majority of patients, the absence or insufficiency of a technical platform for effective management has negatively influenced survival in our context. The survival curve showed that the survival of patients who received the surgical treatment associated with adjuvant chemotherapy was better (Figure 1). In fact, patients who had benefited from neoadjuvant chemotherapy had large tumors that did not allow primary surgery, which is a factor in poor prognosis.

Figure 1 Survival curve of patients who underwent mastectomy supervised by chemotherapy.

Table 1: Family history of tumor and distribution of patients by prognostic factors (N = 58).

Our study described the challenges faced by surgeons in Burkina Faso in dealing with the malicious and insidious manifestations of breast cancer. To improve the quality of life and survival rate of breast cancer patients in developing countries, public health ministries in different countries should promote more: the promotion of early screening with genetic counselling, the establishment of an effective technical platform and the national subsidy for therapeutic care.

We thank all the individuals who made this study possible. Our appreciation also goes to the whole team of the CERBA/ LABIOGENE, and Saint Camille Hospital of Ouagadougou. We will also like to thank National Health Ethic Committee and Gynecology, General surgery and Pathology Departments of Yalgado Ouedraogo Hospital.

1. Mascaro A, Farina M, Gigli R, Vitelli CE, Fortunato L. Recent advances in the surgical care of breast cancer patients. World J Surg Oncol. 2010; 8: 5.

2. Narod SA. Breast cancer in young women. Nat Rev Clin Oncol. 2012; 9: 460-470.

3. Brenner DR, Brockton NT, Kotsopoulos J, Cotterchio M, Boucher BA, Courneya KS. Breast cancer survival among young women: a review of the role of modifiable lifestyle factors. Cancer Causes Control. 2016, 27: 459-472.

4. Brandt J, Garne JP, Tengrup I, Manjer J. Age at diagnosis in relation to survival following breast cancer: a cohort study. World J Surg Oncol. 2015; 13: 33.

5. van der Groep P, van der Wall E, van Diest PJ. Pathology of hereditary breast cancer. Cell Oncol (Dordr). 2011; 34: 71-88.

6. Fosse P, Girault S, Capitain O, Valo I, Bouchet F, Vervueren L, et al. FDG-PET in the initial staging of locally advanced breast cancer before neoadjuvant chemotherapy. Médecine Nucléaire. 2012; 36: 69-76.

7. Courtillot C, Touraine P. [Management of families at high risk for hereditary breast-ovarian cancers: the endocrinologist’s point of view]. Ann Endocrinol (Paris). 2008; 69: 193-200.

8. Balekouzou A, Yin P, Pamatika CM, Bishwajit G, Nambei SW, Djeintote M, et al. Epidemiology of breast cancer: retrospective study in the Central African Republic. BMC Public Health. 2016; 16: 1230.

9. Guendouz H, Chetibi W, Abdelouahab A, Bendib A. Cancer du sein de la femme de moins de 35 ans: étude rétrospective à propos de 612 cas. Société française de sénologie et de pathologie mammaire La Lettre du sénologue. 2011; 52.

10. Livaudais JC, Li C, John EM, Terry MB, Daly M, Buys SS, et al. Racial and ethnic differences in adjuvant hormonal therapy use. J Womens Health. 2012; 21: 950-958.

11. Boufettal H, Noun M, Samouh N. [Breast cancer in young patient in Morrocco]. Cancer Radiother. 2010; 14: 698-703.

12. Ademuyiwa FO, Gao F, Hao L, Morgensztern D, Aft RL, Ma CX, et al. US breast cancer mortality trends in young women according to race. Cancer. 2015; 121: 1469-1476.

13. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420: 860-867.

14. Znati K, Bennis S, Abbass F, Akasbi Y, Chbani L, Elfatemi H, et al. [Breast cancer in young patient in Morocco]. Gynecol Obstet Fertil. 2014; 42: 149-154.

15. Elmoukhatari I, Elmoarabit B, Oulmouden N, Khouchani M, Elomrani A, Tahri A. Cancer du sein chez la femme de moins de 40 ans dans la région de Marrakech. Cancer/Radiothérapie. 2011, 15: 578.

16. Espié M, Cottu PH. [Breast cancer in young women: problem and questions]. Pathol Biol (Paris). 2003; 51: 391-392.

17. Johnstone PA, Moore EM, Carrillo R, Goepfert CJ. Yield of mammography in selected patients age < or = 30 years. Cancer. 2001; 91: 1075-1058.

18. Aloulou S, El Mahfoudi A, El Omrani A, Khouchani M1. [Factors related to late diagnosis of breast cancer: experience of CHU Mohammed VI Marrakech]. Pan Afr Med J. 2015; 21: 162.

19. Martinson HA, Lyons TR, Giles ED, Borges VF, Schedin P. Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention. Exp cell Res. 2013, 319: 1671-1678.