Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL): The French Lymphoma Study Association (LYSA) Registry Data
Authors: Le Bras Fabien , Laurent Camille , Bosc Romain , Tortelano Lionel , Dao Tu Ha , Itti Emmanuel , Malhaire Caroline , Schiano de Collela Jean Marc , Bannier Marie , Bachy Emmanuel , Slama Bohrane , Fornecker Luc Matthieu , Oberic Lucie , Traverse-Glehen Alexandra , Kirova Youlia , Fabien Reyal , Tilly Herve , Nicolas-Virelizier Emmanuelle , Xerri Luc , Gaulard Philippe , Haioun Corinne 
Published: October 2019

Abstract
Background: BIA-ALCL has recently been recognized as a distinct entity among T cell lymphomas. In the French Lymphopath network which has registered almost 60 000 lymphomas since 2010, 50 cases of BIA-ALCL were identified so far. Little is known about the causes, and prognostic factors of this disease.
Methods: since 2016, a WebEx national multidisciplinary meeting has been implemented by the French Cancer Agency in order to better define therapeutic strategies for newly diagnosed cases after histologic confirmation. In the same time, BIA-ALCL registry was funded by LYSA in order to collect ambispectively patient clinical data including reasons for breast implantation (breast augmentation, reconstruction), implant manufacturer, treatments and outcome.
Results: Thirty nine BIA-ALCL have been analyzed so far. Median age was 61 years (range 29-82) at diagnosis. In 20 out of 39 patients (pts) (51.3%) the first implant followed a mastectomy for breast cancer. Twelve pts were implanted twice (33%) and thirteen pts (36%) 3 times or more. The median delay between first implant and BIA-ALCL diagnosis was 11.9 years (range 4-37), and median delay from last implant to diagnosis was 3.6 years (range 0-26). The two clinical presentations i.e. seroma (n = 26 - 67%) and breast tumor mass with or without seroma (n = 9 - 23%) were most often correlated with the two distinct histological subtypes (in situ or infiltrative). The majority of pts (76.9%) were stage IE (n=30; 77%), and nine (23%) pts were stage IV. One hundred and thirty five implants have been used for these 39 patients. Considering available informations regarding the type of implants, almost all patients had at least one silicone-filled (n=35) and at least one textured implant (n=31). No patient had only smooth implant. Implant removal with total capsulectomy was performed in 33 patients and 13 underwent chemotherapy based mostly on CHOP or CHOP-like chemotherapy regimens (n=11; 85%). After 24 months of median follow-up, 33 pts are alive and free of evolutive disease. Two patients have not been evaluated. Four pts have died, either from lymphoma progression alone (n=2), or associated with concomitant breast cancer (n=2). All had an infiltrative histology, 3 were stage IV and one had a localized bulky disease. All but one received systemic chemotherapy and one received palliative care only due to concomitant breast cancer. One of these patients early relapsed after a first complete remission.
Conclusions: In situ BIA-ALCLs have an indolent clinical course and remain in complete remission mainly after implant removal. Infiltrative BIA-ALCLs have a more aggressive clinical course. It is therefore critical to perform a rigorous staging using multi-imaging modality including TEP at baseline. Multiple implants could favor the occurrence of BIA-ALCL. New insights into the biology of BIA-ALCL might translate into more targeted and effective therapies in refractory or relapsed patients. The modalities of breast monitoring and reconstruction remain open questions for those patients.

Disclosures
Le Bras: Amgen: Consultancy. Bachy:Roche: Research Funding; Celgene: Consultancy; Amgen: Honoraria; Takeda: Research Funding; Janssen: Honoraria; Gilead Sciences: Honoraria; Sandoz: Consultancy. Fornecker:Servier: Honoraria; Takeda: Honoraria. Traverse-Glehen:Takeda: Research Funding; Astra Zeneca: Other: Travel. Tilly:Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees. Xerri:Janssen: Other: Travel. Gaulard:Celgene: Research Funding; Roche: Honoraria; Takeda: Consultancy, Honoraria, Research Funding. Haioun:Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Sciences: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.