Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

[Targeted therapies: towards a new toxicology?]. / Thérapies anticancéreuses ciblées: vers une nouvelle toxicologie?

Targeted therapies (TT) represent since 10 years, an interesting progress in oncology for many cancers in adjuvant, neoadjuvant or palliative situation. The development of this new class of drugs, with an original mechanism of action, their easy administration, mainly per os, and a particular toxicity profile different from "classical" chemotherapy (CT) leads them entering in the therapeutic arsenal of breast, digestive tract, lung and hematologic cancers, in association with CT. Medical oncologists took rapidly the train of TT, managing a new and original skin, digestive, cardiovascular, endocrine and pulmonary toxicity profile, that remains relatively less important than "classical" CT.

Therapeutic results and prognostic factors of stage III NSCLC: a population-based study in Tunisia.

BACKGROUND: Prognostic factors are crucial to guide patient's selection through therapeutic decisions and outcome prediction. AIM: To investigate prognostic factors associated with improved survival in stage III non-small cell lung cancer. PATIENTS AND METHODS: We retrospectively reviewed clinical data of 88 stage III non-small cell lung cancer patients treated between 2010-2017. Multidisciplinary evaluation prior to therapy onset was mandatory. Univariate analyses and multivariate logistic regression were performed to identify factors associated with survival. RESULTS: Median follow-up was 28 months, 56% of patients experienced recurrence. Median overall survival (OS) was 19 months. On univariable analysis, improved OS correlated with younger age (p = 0.011), better performance score (ECOG PS < 2) (p < 0.01), absence of weight loss (p = 0.019) and smaller tumor size (≤ 7 cm) (p = 0.005). OS was improved in patients receiving therapy planned by multidisciplinary meeting compared with those who did not (p < 0.01), in those with resected tumors (p = 0.001), responding to therapy (neoadjuvant chemotherapy (p = 0.034) and concurrent chemoradiation (p = 0.001), as well as those with lower neutrophil-lymphocyte ratio (p = 0.026) and lower platelet-lymphocyte ratio (p = 0.003). Postoperative adjuvant therapy increased OS (64 vs 24, p = 0.025). Longer recurrence-free interval, locoregional failure and better perfomance status at recurrence were good prognostic factors for OS. Multivariate analysis showed that only upfront surgery followed by adjuvant therapy (hazard ratio (HR) = 0.61; 95% confidence interval (CI) 0.38-0.96; p = 0.034), adherence to multidisciplinary team decision (HR = 0.26; 95% CI 0.15-0.47; p < 0.01) and tumor size > 7 cm (HR = 2.31; 95% CI 1.29-4.13; p = 0.005) were independent prognostic factors affecting OS. CONCLUSIONS: Optimal therapeutic strategy and adherence to the decision provided by the multidisciplinary evaluation of patients played an important role in stage III non-small cell lung cancer outcome.

[Diagnostic and therapeutic management of operable bronchopulmonary carcinoid tumours]. / Prise en charge diagnostique et thérapeutique des tumeurs carcinoïdes broncho-pulmonaires opérables.

INTRODUCTION: Bronchial carcinoid tumours (CT), divided into typical carcinoid (TC) or atypical carcinoid (AC), are rare tumours whose therapeutic management remains unspecified. METHODS: Retrospective study collecting cases of bronchial CT operated at the thoracic surgery department of Abderrahmane-Mami hospital of Ariana and recruited from the pneumology departments of Northern Tunisia, during a 12-year period. RESULTS: Ninety patients were collected (74 cases of TC and 16 cases of AC). The mean age was 45 years and the sex ratio H/F=0.5. The chest X-ray was normal in 11 cases, as well as flexible bronchoscopy in seven cases. The tumour was classified: stage IA (10 cases), IIA (28 cases), IIB (31 cases), IIIA (15 cases) and IIIB (six cases). Surgery resulted in a complete resection in 78 patients, an extensive resection in six patients, and a conservative resection in six patients. Adjuvant chemotherapy was given in 10 patients. The survival was 84% at five years and 42% at 10 years. CONCLUSION: The prognosis of CT depends directly on the histological subtype. It is excellent for TC after complete resection, unlike ACs that are similar to well-differentiated bronchial carcinomas.

Objective Clinical and Radiological Response under Sunitinib in a Case of Thigh Hidradenocarcinoma.

A 56-year-old male was treated by local surgery in 1968 and 2005 for a left thigh lesion. A 2nd local relapse occurred in 2015 and was treated by complete macroscopic surgery with histology concluding to a hidradenocarcinoma. A 3rd locoregional relapse occurred in October 2018, with the presence of inflammatory ulcerated lesions. A 2nd histology and immunohistochemistry exam showed a proliferation positive for CK, CK5, and p63 suggesting the diagnosis of hidradenocarcinoma. The patient was treated by 3 lines of chemotherapy, 1st by Adriamycin, 2nd by carboplatin-paclitaxel, and then 3rd by oral capecitabine, leading to a stable clinical disease but without a clinical benefit. A locoregional plus metastatic lung progression was observed in March 2019, with the presence of lung nodules and retroperitoneal lymph nodes, multiple skin left thigh and left inguinal ulcerated lesions. The patient received then in 4th line in April 2019 oral sunitinib at 50 mg daily, with 4 weeks therapy/2 weeks pause. Side effects were represented by mucositis, anorexia, weight loss, and fatigue. We observed since the 1st week of therapy a fast response, with a decrease of the ulcerated lesions, a skin loss, and deep hemorrhagic areas. CT-scan showed after 2 weeks of sunitinib an objective response on both locoregional and metastatic lesions.

High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis.

Xeroderma pigmentosum (XP, OMIM 278700-278780) is a group of autosomal recessive diseases characterized by hypersensitivity to UV rays. There are seven complementation groups of XP (XPA to XPG) and XPV. Among them, the XP group C (XP-C) is the most prevalent type in Western Europe and in the United States. We report here on the clinical and genetic investigation of XP-C patients in 14 Tunisian families. As the XPC V548A fs X572 mutation has been identified in Algerian and Moroccan populations, Tunisian patients were first screened for this mutation by a direct sequencing of exon 9 of the XPC gene. All patients with a severe clinical form had this mutation, thus showing the homogeneity of the mutational spectrum of XPC in Tunisia. A potential founder effect was searched and confirmed by haplotype analysis. Taking into account the similarity of the genetic background, we propose a direct screening of this mutation as a rapid and cost-effective tool for the diagnosis of XP-C in North Africa.

[Primary adenoid cystic carcinoma in breast]. / Carcinome adénoïde kystique primitif du sein.

Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm. We report two observations occurring in female patients, 54 and 65 years old, who consulted for a mastodynia. Clinical examination showed limited painful breast nodules. On ultrasound and mammography they are well-limited bulky mass without microcalcifications. Diagnosis was based on final histopathological exam completed by immunohistochemistry or after slides review. The two patients were treated by mammectomy plus adjuvant radiotherapy and remain alive in remission with a follow-up of 29 and 36 months.

[Estimation of years of life gained within the pilot screening program of the Ariana area of Tunisia]. / Estimation du nombre potentiel d'années de vie sauvées à travers l'expérience pilote de dépistage de masse du cancer du sein à l'Ariana.

Breast cancer is the principle cancer among female cancer in Tunisia. It represents 30% of the woman's cancers with about 1000 new cases per year. The main intervention control is mass screening using mammography in to reduce breast cancer mortality. Breast cancer screening efficacy in term of breast cancer mortality reduction is closely related to incidence and survival of this cancer. National Office of Family and Population (ONFP) conducted a pilot experience of breast cancer mass screening using the mammography in place. The main objective of this study is to calculate the potential number of life years saved through this pilot experience of the ONFP. For the methodology, we used the software Dismod (Disease Model) for the evaluation of the prevalence and the duration of the cancer of the breast in the governorate, as well as to estimate the number of life years saved. The potential breast cancer mortality reduction is 30% for women aged of 50 at 69 years, and 10% for those aged of 40 at 49 years. Breast cancer incidence in Ariana according to age for the period 1995-1998, has been calculated from the data base of cancer registry of the North of Tunisia. According to Dismod, mean duration in the absence of screening, is 11.12 years for the age group 40 to 49 years and 9.57 for the age group 50 at 69 years. Screening would increase these duration means of 2.22 years and 1.71 years, respectively for age groups 40 to 49 years and 50 at 69 years. The number of life years saved for 1000 women is of 2.97 years. In conclusion breast cancer screening using mammography would be actually little benefit in Tunisia. Mammography should be reserved for the diagnosis of the suspected cases and screening for high risk women.

[Practice of large scale mammography in the Ariana area of Tunisia: prelude to a mass screening?]. / Pratique de la mammographie à grande échelle dans le gouvernorat de l'Ariana en Tunisie: un préalable à un dépistage de masse organisé?

OBJECTIVE: To study and analyse the results of breast cancer mammography screening program in the Ariana state and to try to determinate its feasibility and reproducibility on a broader scale. MATERIALS AND METHODS: A pilot study on the mammography feasibility of screening with large scales was initiated, by Family and Population National Office, in September 2003. The duration of the study was fixed at 5 years. The adopted protocol takes account of epidemiologic and socialcultural specificities of Tunisian environment that is in the selection and in the mode of recruitment of the target population as well as in the choice of the adopted radiological protocol. RESULTS: 8244 women were screened in the first round. The majority of sensitized women was recruited in residence and in the reproductive and health centers. Nevertheless, recruitment in residence was proved to be heavy, not very effective and no reproducible in a broader scale. The participation rate was weak (9.6%). The channels of sensitizing used made it possible to touch in manner more important the "young" women (Middle Age 48.6 years). The absence of radiologist on the spot involved the recall of 18.1% of the women for which a complementary assessment was necessary, has to contribute to increase the stress among certain women and to increase the average time of reading which was, in this case, 61.7 days. The majority of the women profited from the double reading of the tests (99.4%). On the whole 50 women presented a cancer including 40 detected by the program and 10 interval cancers. CONCLUSIONS: This study has permitted to study the feasibility of mammography study. Except the topic of the cost, the two hand conditions of his feasibility binds in the systematic invitation of the women as well as in the wider uses of sensitization and information ways of the population.

[Primary breast lymphoma: a case report]. / Lymphome primitif du sein: à propos d'un cas infraclinique.

BACKGROUND: Non-hodgkinian's lymphoma (NHL) represents 0.04 to 0.53% of all breast cancers. The clinical aspects and therapeutic models of the disease are a subject of debate. AIM: The purpose of this paper is to report the clinical, imaging (sonographic, mammographic and MRI) and pathological features of breast lymphoma, a rare but aggressive tumor, based on a case report review. CASE REPORT: We report a case of primary non-hodgkinian's lymphoma of the breast in one patient aged of 52 years. The patient went to a systematic screening of breast cancer. Physical examen was normal. Mammography showed breast with transitional density, BIRADS type 2, micro-calcifications behind the.... but sometimes it had linear...., neither not distorsion were identified. Ultrasonography did not show a tumor. The disease was revealed by breast MRI. The additional value of MRI in diagnosis is validated in our patient. In fact, when cancer is occult, size evaluation is difficult at standard imaging (7 mm). The diagnosis of non-hodgkinian's lymphoma was confirmed on histological examination of tumor biopsies. It was a B-cell non-Hodgkins-type lymphoma. The clinical features have been reviewed and the tumor have been evaluated both on a morphologic and an immunohistochemical basis. With chemotherapy, the course was favourable. CONCLUSION: The breast is an uncommon site of development of malignant lymphomas. Secondary disease is more common than the primitive form. Primary breast lymphoma is a difficult diagnosis because it is very rare. The diagnosis is mainly histological. Chemotherapy is the principal therapeutic mean. Treatment combines radiotherapy and chemotherapy. Prognosis is generally bad.

[Breast cancer in Tunisia: epidemiologic characteristics and trends in incidence]. / Cancer du sein en Tunisie: caracteristiques epidemiologiques et tendance evolutive de l'incidence.

The goal of this study is to analyze certain epidemiologic characteristics of breast cancer in Tunisia and to foresee the consequences that will arise from the trends in incidence of this cancer. Data obtained from the North-Tunisia Cancer Registry (NTCR) and from the Salah AZAIZ Institute (SAI) Registry is used to estimate the different incidence rates and to compare these rates with those of other countries. In 15 years the crude incidence rate for breast cancer in the North Tunisia almost doubled to reach 21.5 cases/100,000 women per year during 1994-1998. The high rate of this cancer among women younger than 35 years (11%) could be related to a relatively low incidence among post-menopausal women. The clinical profile of breast cancer remains quite alarming: 40.2% of cases have a tumor with a clinical diameter equal or greater than 5 cm. Birth cohort effect, also know as the generation effect, is expected to lead to an increase of cancer incidence in the future. The rather high number of young cases is a source of additional cost on social and financial level. The priority is now to solve the problem of late diagnosis it has aggravated the prognosis of this cancer in Tunisia.

[Results and evaluation of 3 years of a large scale mammography program in the Ariana area of Tunisia]. / Résultats et évaluation de 3 années de pratique mammographique à grande échelle dans le gouvernorat de l'Ariana en Tunisie.

OBJECTIVE: To asses and analyse the results of 3 years large scale mammography screening of breast cancer in Ariana state in Tunisia. MATERIALS AND METHODS: This program, managed by the Family and Population National Office, was addressing to women aged from 49 to 69 years old residing in a area with adds up a population of 459 700 inhabitants including 52,729 women in the target age population. The screening was including a breast clinical examination and a mammography with two incidences face and external profile. The women was invited at their residence or were sensitized in the reproductive health centers, care and base health centers or by a close relation which heard of the program. An enlightened assent was submitted to the women who wished to profit from the screening. RESULTS: In three years, 9093 mammography were carried out of which 8244 were retained in the analyses, that is to say a rate participation of 9.6%. The rate of women recalled for suspect test was of 18.1% and it was of 13.1% among women of more than 50 years. The rate of practiced surgical biopsies was of 0.5% and the positive predictive value was of 45.5%. The average time between the date of screening and the result of the screening was 9.7 days, more important in the event of tests requiring a complementary assessment (61.7 days). On the whole 40 cancers were detected by the program, that is to say a rough rate of detected cancers, of 4.9 per thousand, in conformity with the recommendations. The percentage of invasive cancers < or = 10 mm was of 24.3 whereas percentages of in situ cancers and of cancers without ganglionic invasion were respectively of 7.7% and of 50.0%. CONCLUSIONS: The weakness of our study lay primarily in the rate of participation which remained weak. The methodology adopted for the sensitizing of the women is proven not very effective and did not allow inviting all eligible women. Results of the study are encouraging in spite of its limited impact and made it possible to detect an important rate of cancers of which cancers infra-private clinics.

[Preliminary results and analysis of the feasibility of mammographic breast cancer screening in women younger than 50 years of the Ariana area in Tunisia]. / Résultats préliminaires et faisabilité du dépistage mammographique du cancer du sein chez les femmes de moins de 50 ans du gouvernorat de l'Ariana en Tunisie.

OBJECTIVE: To report the preliminary results of the feasibility of breast cancer mammographic screening among women younger than 50 years from the l'Ariana state of Tunisia. MATERIAL AND METHODS: The National office of the Family and Population (ONFP) launched a protocol on feasibility of breast cancer mammographic screening targeting asymptomatic women aged 40-69 years, from the l'Ariana state in Tunisia. We practiced two oblique and face incidences at the mammography screening unit of the ONFP, whose equipment and control system of quality answered to the European Communitiy for breast cancer screening. RESULTS: We did 5325 mammograms between April 2004 and March 2006. Our targeted population had a 48.9 years mean age (CI 95% = [48.7-49.1]), 60.3% of them younger than 50 years. There were more young women with high breast denisty (8.2%) compared to the group from 50 to 69 years (2.1%). The women arising from the 40-49 years cohort had a socio-economic and educational level higher. The complementary rate of examination/explorations was higher in this cohort (19.5%) vs 11.5% for the 50-69 years. The youngest women presented a more often positive test (7.0 vs 5.2%) than the oldest women (p<0.01). CONCLUSION: The option to screen breast cancer by mammography in women younger than 40 years in Tunisia is partially justified by the relatively high frequency of this cancer in this age group. Our feasibility poorly useful in screening will be used to sensibilise females to the problematic of breast cancer to obtain a better compliance compared to the older age group of 50-59 years.

[Radio-histological correlation of microcalcifications of the breast: a Tunisian center experience]. / Corrélation radio-histologique des microcalcifications du sein. Experience d'un centre Tunisien.

PURPOSE: Evaluation of surgical biopsy for mammary microcalcifications, in Tunisian patients according to the American College of Radiology's recommandations (ACR). MATERIAL AND METHODS: [corrected] 100 patients treated in Salah Azaiez Institute from January 2005 to December 2006, who underwent surgical biopsy for breast microcalcifications The diagnosis was based on mammography associated in 60% of the cases, to ultra-sonography. We correlated biopsies results to ACR classification. RESULTS: 123 surgical biopsies are related to ACR 3 lesions in 72 cases (58.5%) ACR 4 in 39 cases (32%) and ACR 5 in 14 case (11.5%). The histological examination showed malignant lesions in 4 cas/72 ACR3 (5.5%), 19/39 ACR4 (48.7%) and 10 among the ACR5 (71.4%). CONCLUSION: Our preliminary study introduces a diagnostic approach of mammary microcalcifications, that are usually infra-clinic lesions, in a general context of breast tumors detected with an average size of more than 3 cm.

[Surgical treatment of breast lesions: preliminary results of the screening program of the Ariana area]. / Traitement chirurgical des lésions mammaires infracliniques: résultats préliminaires du programme de dépistage de l'Ariana.

OBJECTIVE: To report clinical, radiological and histological characteristics of the infraclinical breast lesions patients recruited via the large scale mammography breast cancer screening of l'Ariana state in Tunisia. MATERIALS AND METHODS: Retrospective study over a period of 2 years. The recruitment of patients made on the occasion of the program of breast cancer screening. RESULTS: During this period, 22 patients in our unity had had a surgical excision after wire localization. Ten patients were recruited by means of systematic breast cancer screening. In these cases, the mammographic findings were classified B.I.R.A.D.S 4 in 7 cases and BIRADS type 5 in 3 cases. Definitive histology concluded to benign disease in 4 cases and malignancy 6 cases. This collaboration enables the diagnosis an invasive ductal carcinoma in three cases. CONCLUSION: The surgical excision after wire localization for non palpable breast lesions allows diagnosis of high-risk benign lesions and low-stage breast cancer. It is a reliable technique which indications have to be based on clinical and radiological strict criteria. This procedure is at present, and in developed countries, widely outstripped with the stereotactic core needle biopsy.

[Patient satisfaction of women involved in the pilot program of large scale mammography in the Ariana area of Tunisia]. / Enquête de satisfaction auprès des femmes du projet pilote de dépistage du cancer du sein du gouvernorat de l'Ariana en Tunisie.

OBJECTIVE: Evaluate the degree of satisfaction of women included in the large scale mammography program of breast cancer screening in the state of Ariana in Tunisia. MATERIAL AND METHODS: [corrected] Within the women explored by mammography, we have contaced 112 patients who had a positif screening requiring histological checking. We have established a questionnaire concerning: the invitation, the clinical examination, the result announcement and the therapeutic management. RESULTS: The average age of patients was 49 years. 64% had a primary education level. 80 women or 71.4% were satisfied with the process of screening and the method of announcement. The main cause of dissatisfaction for patients with cancer diagnosis was delay and difficult access to adjuvant treatments. Among patients who had histological diagnosis: 47.3% had a malignant disease (53 cases) against 37.5% of benign (42 cases). 100% of patients who had a pathological result reassuring are satisfied at the end of the screening program. DISCUSSION: The psychosocial impact of screening must be considered for the development of new programs. The waiting and announcement of results are essential factors that allow us to judge the success of the project, because of patient satisfaction will depend the quality of monitoring and adherence to screening.

[Sarcomatoid carcinomas of the upper airways]. / Carcinomes sarcomatoïdes des voies aéro-digestives supérieures.

INTRODUCTION: The sarcomatoid carcinoma of the superior aerodigestive tracts is a rare malignant tumour which presents diagnostic and therapeutic challenges. MATERIAL AND METHOD: We report 11 cases of spindle cell carcinomas of the upper airways. RESULTS: Sex-ratio was 10:1 and the mean age was 57.3 years (30 - 75 years). Nine patients were smokers and 4 presented with a history of radiation exposure. Tumoral locations were as follows: larynx: 6, hypopharynx: 1, oropharynx: 1, nasopharynx: 1, oral cavity: 2. Histological diagnosis in 3 cases required the use of immunohistochemical studies. Four patients were first seen at an advanced stage. This left 9 patients and among them 7 received a curative treatment: 5 by surgery alone, 1 by surgery and radiotherapy, 1 by radiotherapy, 1 by chemo-radiotherapy for the nasopharyngeal lesion and 1 by chemotherapy alone. Two patients died from their disease before treatment. With an average delay of 15.4 months, the rates of global survival and disease-free were 5/9 and 4/9 respectively. CONCLUSION: The sarcomatoid carcinoma of the upper airways is rare, but not unusual. Its diagnosis benefits from progresses in immunohistochemistry, but also from advances in the field of molecular biology. Its treatment and natural evolution remain controversial.

[Typical medullary carcinoma of the breast: a retrospective study about 33 cases]. / Carcinome médullaire typique du sein : étude rétrospective à propos de 33 cas.

OBJECTIVE: Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. It represents less than 5% of all breast cancer. It is known for its favourable prognosis. Considering the rarity of the series we could retrieve, we aimed at underlining the particularities of this pathology. PATIENTS AND METHODS: Retrospective study about 33 cases of typical medullary carcinoma managed at the Salah-Azaïz Institute during a period of six years between 1994 and 1999. RESULTS: The mean age was 47.5 years. The left breast was concerned in about 55% of cases. Mean tumoral size was 46mm. Sixty-one percent of our patients were treated by radical surgery. Seventy-three percent undergo radiotherapy, 57% chemotherapy and 42% hormonotherapy. The five-year free-disease survival was about 85%. DISCUSSION AND CONCLUSION: Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. Its treatment is similar to the other breast cancers. Our results agree with the different published studies and confirm its favourable prognosis.