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  1. Article ; Online: Radiothérapie et thérapie ciblée pour la prise en charge du cancer du sein : mise au point.

    Beddok, A / Cottu, P / Fourquet, A / Kirova, Y

    Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique

    2023  Volume 27, Issue 5, Page(s) 447–454

    Abstract: The purpose of this study was to review the current knowledge regarding combinations of the most commonly used targeted therapies or those under development for the management of breast cancer with radiation therapy. Several studies have shown that the ... ...

    Title translation Radiotherapy and targeted therapy for the management of breast cancer: A review.
    Abstract The purpose of this study was to review the current knowledge regarding combinations of the most commonly used targeted therapies or those under development for the management of breast cancer with radiation therapy. Several studies have shown that the combination of radiation therapy and tamoxifen increased the risk of radiation-induced lung toxicity; therefore, the two modalities are generally not given concurrently. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and radiation therapy appeared to be safe. However, trastuzumab emtansine (T-DM1) should not be given concomitantly with brain radiation therapy because this combination may increase the risk of brain radionecrosis. The combination of radiation therapy with other new targeted therapies such as new selective estrogen receptor modulators (SERDs), lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but has been mainly evaluated on retrospective or prospective studies with small numbers of patients. Moreover, there is a great heterogeneity between these studies regarding the dose and fractionation used in radiotherapy, the dosage of systemic treatments and the sequence of treatments used. Therefore, the combination of these new molecules with radiotherapy should be proposed sparingly, under close monitoring, pending the ongoing prospective studies cited in this review.
    MeSH term(s) Humans ; Female ; Prospective Studies ; Retrospective Studies ; Receptor, ErbB-2/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/radiotherapy ; Trastuzumab/therapeutic use ; Ado-Trastuzumab Emtansine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
    Chemical Substances Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK) ; Ado-Trastuzumab Emtansine (SE2KH7T06F)
    Language French
    Publishing date 2023-05-10
    Publishing country France
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 1397169-4
    ISSN 1769-6658 ; 1278-3218
    ISSN (online) 1769-6658
    ISSN 1278-3218
    DOI 10.1016/j.canrad.2023.02.002
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    Zs.A 4832: Show issues Location:
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  2. Article ; Online: Aspects biologiques, précliniques et cliniques de l’association de radiothérapie et d’inhibiteur de CDK 4/6.

    Beddok, A / Porte, B / Cottu, P / Fourquet, A / Kirova, Y

    Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique

    2023  Volume 27, Issue 3, Page(s) 240–248

    Abstract: Several clinical studies have shown that CDK4/6 inhibitors (CDK4/6i) improve survival in patients with metastatic or locally advanced HR-positive, HER-2-negative breast cancer (BC). The aim of this review was to synthesize the biological, preclinical and ...

    Title translation Biological, preclinical and clinical aspects of the association between radiation therapy and CDK4/6 inhibitors.
    Abstract Several clinical studies have shown that CDK4/6 inhibitors (CDK4/6i) improve survival in patients with metastatic or locally advanced HR-positive, HER-2-negative breast cancer (BC). The aim of this review was to synthesize the biological, preclinical and clinical aspects of the treatment of BC with CDK4/6i, with a focus on the combination of CDK4/6i and radiotherapy. The DNA damage induced after exposure of cells to ionizing radiation activates control pathways that inhibit cell progression in the G1 and G2 phases and induce a transient delay in progression in the S phase. These checkpoints are in particular mediated by cyclin-dependent kinases (CDK) 4/6 activated by cyclin D1. Several preclinical studies have shown that CDK4/6i could be used as radiosensitizers in non-small cell lung cancer, medulloblastoma, brainstem glioma and breast cancer. CDK4/6 inhibition also protected against radiation-induced intestinal toxicities by inducing redistribution of quiescent intestinal progenitor cells, making them less radiosensitive. Clinical data on the combination of CDK inhibitors and radiotherapy for both locoregional and metastatic irradiation are based on retrospective data. Nevertheless, the most optimal therapeutic sequence would be radiotherapy followed by palbociclib. Pending prospective clinical trials, the concomitant combination of the two treatments should be done under close supervision.
    MeSH term(s) Humans ; Female ; Carcinoma, Non-Small-Cell Lung/radiotherapy ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Prospective Studies ; Retrospective Studies ; Cyclin-Dependent Kinase 6/genetics ; Cyclin-Dependent Kinase 6/metabolism ; Protein Kinase Inhibitors/therapeutic use ; Lung Neoplasms/drug therapy ; Breast Neoplasms/drug therapy ; Breast Neoplasms/radiotherapy ; Cyclin-Dependent Kinase 4/therapeutic use
    Chemical Substances Cyclin-Dependent Kinase 6 (EC 2.7.11.22) ; Protein Kinase Inhibitors ; CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22)
    Language French
    Publishing date 2023-04-18
    Publishing country France
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 1397169-4
    ISSN 1769-6658 ; 1278-3218
    ISSN (online) 1769-6658
    ISSN 1278-3218
    DOI 10.1016/j.canrad.2022.11.003
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  3. Article ; Online: L’administration conjointe de pertuzumab et trastuzumab est faisable en hospitalisation à domicile.

    Pailler, Christine / Gandrille, Nicolas / Poterre, Marc / Cottu, Paul / Delaloge, Suzette

    Bulletin du cancer

    2023  Volume 110, Issue 4, Page(s) 463–466

    Title translation Co-administration of pertuzumab and trastuzumab is practical in home hospitalization.
    MeSH term(s) Humans ; Female ; Trastuzumab ; Antibodies, Monoclonal, Humanized ; Receptor, ErbB-2 ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/drug therapy
    Chemical Substances Trastuzumab (P188ANX8CK) ; pertuzumab (K16AIQ8CTM) ; Antibodies, Monoclonal, Humanized ; Receptor, ErbB-2 (EC 2.7.10.1)
    Language French
    Publishing date 2023-02-15
    Publishing country France
    Document type Letter
    ZDB-ID 213270-9
    ISSN 1769-6917 ; 0007-4551
    ISSN (online) 1769-6917
    ISSN 0007-4551
    DOI 10.1016/j.bulcan.2023.01.006
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  4. Article ; Online: Multidisciplinary management and role of reirradiation in the treatment of a breast cancer patient with four locoregional recurrences.

    Courtinat, F / Cottu, P / Féron, J-G / Jehanno, N / Fourquet, A / Kirova, Y / Beddok, A

    Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique

    2022  Volume 27, Issue 2, Page(s) 154–157

    Abstract: Breast cancer is a frequent and sometimes fatal disease. The risk of locoregional recurrence has considerably decreased since the introduction of adjuvant treatments (radiotherapy, chemotherapy, hormone therapy). Nevertheless, some patients present a ... ...

    Abstract Breast cancer is a frequent and sometimes fatal disease. The risk of locoregional recurrence has considerably decreased since the introduction of adjuvant treatments (radiotherapy, chemotherapy, hormone therapy). Nevertheless, some patients present a risk of multiple local recurrences. We report here the case of a patient who had four locoregional breast cancer recurrences. There is currently no validated biomarker that allows the prediction of recurrence. Salvage surgery, most often mastectomy, remains the recommended treatment for the management of these recurrences in the irradiated field. However, increasingly, depending on the patient's wishes and the technical possibilities of multiple surgeries, the question of a second conservative treatment and reirradiation arises. This type of management must in all cases be multidisciplinary and in specialized centers. Reirradiation must in any case try to give maximum priority to the protection of healthy tissue already irradiated.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/radiotherapy ; Breast Neoplasms/drug therapy ; Re-Irradiation ; Mastectomy ; Combined Modality Therapy ; Retreatment ; Neoplasm Recurrence, Local/radiotherapy
    Language English
    Publishing date 2022-08-27
    Publishing country France
    Document type Case Reports
    ZDB-ID 1397169-4
    ISSN 1769-6658 ; 1278-3218
    ISSN (online) 1769-6658
    ISSN 1278-3218
    DOI 10.1016/j.canrad.2022.07.013
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  5. Article ; Online: Systemic treatment for hormone receptor-positive/HER2-negative advanced/metastatic breast cancer: A review of European real-world evidence studies.

    Vieira, Cláudia / Piperis, Maria N / Sagkriotis, Alexandros / Cottu, Paul

    Critical reviews in oncology/hematology

    2022  Volume 180, Page(s) 103866

    Abstract: This review examined patterns of systemic anticancer treatment in patients with HR+ /HER2- metastatic breast cancer in real-world clinical practice in Europe since 2016 to assess whether they reflect clinical guidelines and recent changes in available ... ...

    Abstract This review examined patterns of systemic anticancer treatment in patients with HR+ /HER2- metastatic breast cancer in real-world clinical practice in Europe since 2016 to assess whether they reflect clinical guidelines and recent changes in available treatment options. We identified 30 publications for inclusion. In studies evaluating patients up to the end of 2017, endocrine therapy predominated, with endocrine monotherapy typically used in 45-65 % of patients. More recent studies suggested that use of cyclin-dependent kinase 4/6 inhibitor therapy has gained ground since European approval in late 2016, with two studies reporting first-line use in over 55 % of patients. Chemotherapy was typically used first line in 25-45 % of patients, although current guidelines recommend endocrine therapy in the absence of a visceral crisis. In conclusion, our review suggests that the most recent treatment developments for patients with HR+ /HER2 - metastatic breast cancer are being reflected in the changing treatment patterns seen in real-world practice.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Receptor, ErbB-2 ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Europe
    Chemical Substances Receptor, ErbB-2 (EC 2.7.10.1)
    Language English
    Publishing date 2022-11-03
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 605680-5
    ISSN 1879-0461 ; 0737-9587 ; 1040-8428
    ISSN (online) 1879-0461
    ISSN 0737-9587 ; 1040-8428
    DOI 10.1016/j.critrevonc.2022.103866
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  6. Article ; Online: La consultation médicale en urgence dans le parcours du patient en oncologie.

    Da Costa, Isabelle / Cottu, Paul / Bouleuc, Carole / Moreau, Pauline

    Bulletin du cancer

    2022  Volume 109, Issue 12, Page(s) 1277–1286

    Abstract: Background: Medical emergencies are defined at the medical level, whereas the use of emergency consultations is decided by the patient. Urgent oncology cares are specific due to clinical, therapeutic, technic and psychologic complexity.: Methods: ... ...

    Title translation Emergency in oncologic patient's pathway.
    Abstract Background: Medical emergencies are defined at the medical level, whereas the use of emergency consultations is decided by the patient. Urgent oncology cares are specific due to clinical, therapeutic, technic and psychologic complexity.
    Methods: This descriptive retrospective study about 142 consultations carried out at the unplanned medical unit, with an analyse of demographics, clinical characteristics, reason for medical appeal, deployed resources and oncological pathway for six months.
    Results: Breast (48 %) and lung (21 %) cancer are the most common. 68 % of patients present with a disease at a non-curative stage and 83 % have received a cancer treatment within the previous two months. Pain is the main reason for consultation (19 ). 91 % of patients benefit from diagnostic and therapeutic procedures. At three month, half of patients use an emergency system again. At six months, the tumour progression rate is 54 %. The mortality rate is 33 % regardless of the risk of immediate aggravation.
    Conclusion: The use of emergency consultation mainly concerns patients in a palliative situation, sometimes announcing the change of the trajectory towards the advanced phase. The organization of the emergency care pathway should evolve to better consider the needs of this population, by formalizing longitudinal monitoring, collaboration with palliative care teams and coordination with care providers in the city.
    MeSH term(s) Humans ; Retrospective Studies ; Medical Oncology ; Emergency Medical Services ; Palliative Care ; Referral and Consultation
    Language French
    Publishing date 2022-09-08
    Publishing country France
    Document type English Abstract ; Journal Article
    ZDB-ID 213270-9
    ISSN 1769-6917 ; 0007-4551
    ISSN (online) 1769-6917
    ISSN 0007-4551
    DOI 10.1016/j.bulcan.2022.06.012
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  7. Article ; Online: Outcomes and toxicity of concurrent CDK4/6 inhibitor and locoregional radiotherapy for patients with de novo metastatic breast cancer.

    Beddok, Arnaud / Mouren, Victoire / Cottu, Paul / Laki, Fatima / Fourquet, Alain / Kirova, Youlia

    International journal of cancer

    2023  Volume 153, Issue 7, Page(s) 1386–1396

    Abstract: The objective of the present study was to assess the outcomes and toxicity of patients treated with concurrent administration of CDK4/6 inhibitors (CDK4/6i) and locoregional radiation therapy (RT), including the breast with a boost or the thoracic wall ... ...

    Abstract The objective of the present study was to assess the outcomes and toxicity of patients treated with concurrent administration of CDK4/6 inhibitors (CDK4/6i) and locoregional radiation therapy (RT), including the breast with a boost or the thoracic wall after mastectomy and the regional lymph node areas. We retrospectively analyzed data from 27 patients with hormone receptor-positive, HER2-negative de novo metastatic breast cancer treated with CDK4/6i and concomitant locoregional RT in 2017/2022. Survival rates were calculated by Kaplan-Meier method. Prognostic factors were tested with log-rank test. CDK4/6i was used as the first systemic metastatic treatment for all the patients, and the median overall treatment time was 26 months. The median time from initiation of CDK4/6i to the start of RT was 10 months (IQR: 7-14 months). The median duration of concomitant CDK4/6i and RT administration was 21 days (IQR: 14.5-23 days). After a median follow-up of 19 months (IQR: 14-36 months), 1 patient died, 11/27 had distant metastases and 1 patient had local recurrence, respectively. The 1- and 3-years progression-free survival (PFS) were 61.4% (95% CI: 45.1%-83.7%) and 53.7% (35.8%-80.5%), respectively. The acute toxicities most observed during RT were neutropenia (44%) and dermatitis (37%). Dermatitis was significantly more frequent in patients with large target volumes (CTV > 911 cc and PTV > 1285 cc). CDK4/6i had to be discontinued in five patients during RT (due to toxicity in three cases and disease progression in two cases). One patient has developed grade 2 late pulmonary fibrosis. Finally, our study demonstrated that concurrent administration of locoregional RT and CDK4/6i did not induce severe late toxicity for most patients.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/drug therapy ; Breast Neoplasms/radiotherapy ; Mastectomy ; Retrospective Studies ; Radiotherapy, Adjuvant ; Dermatitis/etiology ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinase 6 ; Antineoplastic Combined Chemotherapy Protocols
    Chemical Substances Cyclin-Dependent Kinase 4 (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22) ; CDK4 protein, human (EC 2.7.11.22)
    Language English
    Publishing date 2023-06-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.34562
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    Zs.A 478: Show issues Location:
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  8. Article ; Online: The importance of the multidisciplinary team in the decision-making process of patients undergoing neoadjuvant chemotherapy for breast cancer.

    Fancellu, Alessandro / Pasqualitto, Valerio / Cottu, Pietrina / Giuliani, Giuliana / Grasso, Lavinia / Ariu, Maria Laura / Porcu, Alberto / Sanna, Valeria

    Updates in surgery

    2024  

    Abstract: Background and objectives: Recent literature suggests that rates of breast conservation surgery (BCS) are lower than expected in patients submitted to neoadjuvant chemotherapy (NAC) for breast cancer. The aim of this study was to underscore the role of ... ...

    Abstract Background and objectives: Recent literature suggests that rates of breast conservation surgery (BCS) are lower than expected in patients submitted to neoadjuvant chemotherapy (NAC) for breast cancer. The aim of this study was to underscore the role of the multidisciplinary team (MDT) in the decision-making process of patients who underwent breast surgery after NAC.
    Methods: We conducted a retrospective study on patients with breast cancer treated according to an algorithm developed at the Breast Unit of Northern Sardinia between January 2019 and May 2023. Data collected included demographics, tumor characteristics, upfront treatment (surgery or NAC), type of primary surgery (BCS or mastectomy [Ma]) and patients' adherence to the treatment proposed by the MDT.
    Results: Overall, 1061 women were treated during the study period, of whom 164 received NAC (Group A) and 897 upfront surgery (Group B). In group A, conversion from BCS ineligibility to BCS eligibility was observed in 47 patients (40.1%). Final surgery in patients who became BCS-eligible after NAC was BCS in 42 cases (89.3%) and Ma in 5 (10.6%). Rates of patients' adherence to the treatment proposed by the MDT were significantly better in the Group A (p = 0.02).
    Conclusions: Our results suggest that the MDT has a pivotal role in increasing the rates of breast conservation in women submitted to NAC.
    Language English
    Publishing date 2024-02-05
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2572692-4
    ISSN 2038-3312 ; 2038-131X
    ISSN (online) 2038-3312
    ISSN 2038-131X
    DOI 10.1007/s13304-024-01759-w
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  9. Article: Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management.

    Beddok, Arnaud / Cottu, Paul / Fourquet, Alain / Kirova, Youlia

    Cancers

    2021  Volume 13, Issue 24

    Abstract: Background: The objective of the present study was to review the essential knowledge about the combinations of the most commonly used or under development targeted treatments and radiation therapy (RT).: Methods: Preclinical and clinical studies ... ...

    Abstract Background: The objective of the present study was to review the essential knowledge about the combinations of the most commonly used or under development targeted treatments and radiation therapy (RT).
    Methods: Preclinical and clinical studies investigating this combination were extensively reviewed.
    Results: Several studies showed that the combination of RT and tamoxifen increased the risk of radiation-induced pulmonary toxicity; therefore, both modalities should not be given concomitantly. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and RT seems to be safe. However, trastuzumab emtansine (T-DM1) should not be administered concurrently with brain RT since this combination could increase the risk of brain radionecrosis. The combination of RT and other new target treatments such as selective estrogen receptor degradants, lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but was essentially evaluated on retrospective or prospective studies with a small number of patients. Furthermore, there is considerable heterogeneity among these studies regarding the dose and fractionation of radiation, the dosage of drugs, and the sequence of treatments used.
    Conclusions: The combination of RT with most targeted therapies for BC appears to be well-tolerated, but these results need to be confirmed in prospective randomized studies.
    Language English
    Publishing date 2021-12-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13246358
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  10. Article ; Online: Breast-conserving therapy leads to better survival outcomes compared to mastectomy in patients with early breast cancer: evidences from the recent literature.

    Fancellu, Alessandro / Porzani, Silvia / Prior, Margherita / Cottu, Pietrina / Giuliani, Giuliana / Sanna, Valeria / Porcu, Alberto

    Minerva surgery

    2023  Volume 78, Issue 2, Page(s) 183–193

    Abstract: Classical studies comparing breast-conserving therapy (BCT) and mastectomy (Mx) focused on the non-inferiority of BCT in terms of survival outcomes. However, recent large retrospective studies have provided evidence that BCT could confer a survival ... ...

    Abstract Classical studies comparing breast-conserving therapy (BCT) and mastectomy (Mx) focused on the non-inferiority of BCT in terms of survival outcomes. However, recent large retrospective studies have provided evidence that BCT could confer a survival advantage over Mx. The prognostic benefit of BCT was observed in all molecular subgroups, including triple negative breast cancer, and also in young patients affected from the disease, who are often submitted to Mx irrespective of tumor size. This new concept, regarding the prognostic importance related to the type of surgical treatment of breast cancer, is of particular relevance in current times. In fact, in the last two decades there has been a rise in Mx rates in BCT-eligible women, as well as a rise in bilateral mastectomy in patients with unilateral breast cancer. This phenomenon occurs despite lack of scientific evidence supporting the necessity of a more extensive surgery, and is primarily a patient-driven trend. The results of recent studies, demonstrating that BCT achieves better overall survival than Mx, should be incorporated in the multidisciplinary decision-making process. Patients with early breast cancer for whom either BCT or Mx are surgical options, should be properly informed that the prognosis of their disease is largely dependent from the biological behaviour of the tumor, and that Mx should not be considered equal to BCT in terms of survival. The present review underscored that BCT, when feasible, should be considered the option of choice also due to its advantage in survival outcomes.
    MeSH term(s) Humans ; Female ; Mastectomy ; Retrospective Studies ; Mastectomy, Segmental/methods ; Prognosis ; Triple Negative Breast Neoplasms/pathology
    Language English
    Publishing date 2023-01-18
    Publishing country Italy
    Document type Review ; Journal Article
    ZDB-ID 3067899-7
    ISSN 2724-5438
    ISSN (online) 2724-5438
    DOI 10.23736/S2724-5691.22.09820-3
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