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Genomic analyses indicate left and right tumors are independent in somatic mutations and clonal phylogeny, while primary and residual disease remain closely linked across mutations and transcriptomics, linking contralateral characteristics to immunity and 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\n\n| Evolution of synchronous female bilateral breast cancersand response to treatment |  |  |\n| --- | --- | --- |\n| Received: 8 February 2022\u003Cbr>Accepted: 10 January 2023\u003Cbr>Published online: 6 March 2023  Check for updates | Anne-Sophie Hamy  1,2, Judith Abécassis2,3, Keltouma Driouch4,\u003Cbr>Lauren Darrigues5, Mathias Vandenbogaert6,7, Cecile Laurent2,\u003Cbr>Francois Zaccarini  5, Benjamin Sadacca2,7, Myriam Delomenie5, Enora Laas5, Odette Mariani8, Thanh Lam5,9, Beatriz Grandal2,5, Marick Laé8,10, Ivan Bieche4,11, Sophie Vacher  4, Jean-Yves Pierga1, Etienne Brain1, Celine Vallot6,12, Judicael Hotton13, Wilfrid Richer6,14, Dario Rocha14, Zakia Tariq4,\u003Cbr>Veronique Becette8, Didier Meseure  15, Laetitia Lesage  15,\u003Cbr>Anne Vincent-Salomon  15, Natalie Filmann16, Jenny Furlanetto16,\u003Cbr>Sibylle Loibl16,17, Elise Dumas2, Joshua J. Waterfall  6,7  & Fabien Reyal  2,5 \u003Cbr>Synchronous bilateral breast cancer (sBBC) occurs after both breasts have been affected by the same germline genetics and environmental exposures. Little evidence exists regarding immune infiltration and response to treatment insBBCs. Here we showthatthe impact of the subtype of breast cancer on levels of tumor infiltrating lymphocytes (TILs, n = 277) and on pathologic complete response (pCR) rates (n = 140) differed according to the concordant or discordant subtype of breast cancer of the contralateral tumor: luminal breast tumors with a discordant contralateral tumor had higher TIL levels and higher pCR rates than those with a concordant contralateral tumor. Tumor sequencing revealed that left and right tumors (n = 20) were independent regarding somatic mutations, copy number alterationsand clonal phylogeny, whereas primary tumor and residual disease were closely related both from the somatic mutation and from the transcriptomic point of view. Our study indicates that tumor-intrinsic characteristics may have a rolein the association of tumor immunity and pCRand demonstrates that the characteristics of the contralateral tumor are also associated with immune infiltration and response to treatment. |  |\n| Bilateral breast cancers (BBCs) represent 2–11% of breast cancers1–3, and their incidence is increasing owing to advances in breast cancer imaging4. This entity includes both synchronous bilateral breast cancers (sBBCs)—that is, occurring synchronously in both breasts—and metachronous bilateral breast cancers (mBBCs)—that is, a tumor occurring in the contralateral breast ata later time period from the primary index cancer. In several studies, sBBCs are associated with poorer survival than unilateral cancer2,5,6. Neither synchronous nor metachronous breast cancer is associated with strong genetic determinants, and only 5% of patients with BBC carry BRCA1 orBRCA2mutations5. |  | From the genomic point of view, several studies7–14, although with old technologies, investigated clonal relationships among BBCs, with most reaching the conclusion that most, if not all, of BBCs were independent events7,9,10,13,15–17. Recently, analyzing a targeted sequencing panel of 254 genes, Begget al.18 investigated the clonality of BBC pairs and found that only one pair of 39 sBBCs was interpreted as clonally related (two shared mutations out of three mutations identified), leaving the question of the independence among sBBCs unresolved. The immune microenvironment, and especially the role of tumor-infiltrating lymphocytes (TILs), in breast cancer has been |\n| A full list of affiliations appears at the end of the paper. [e-mail:](e-mail: joshua.waterfall@curie.fr)[ joshua.waterfall@curie.fr](e-mail: joshua.waterfall@curie.fr); [fabien.reyal@curie.fr](fabien.reyal@curie.fr) |  |  |\n\nNature Medicine | Volume 29 | March 2023 | 646–655 646  \nstudied extensively in the last decade. The drivers of the immunosurveillance of breast cancer derive from both (1) tumor-intrinsic charact","cbCainCsT1e4Vosi","https://ap.wps.com/l/cbCainCsT1e4Vosi","pdf",12408366,29,"English","# Overview\n# Background: bilateral breast cancer and immune microenvironment\n# Neoadjuvant chemotherapy and predictive immune markers\n# Study design and cohort\n# Results: patient and tumor characteristics","[{\"question\":\"What question does the study address about synchronous bilateral breast cancer?\",\"answer\":\"It evaluates how immune infiltration and response to treatment differ between synchronous bilateral breast cancers, focusing on tumor-infiltrating lymphocytes and pathological complete response.\"},{\"question\":\"How does the study define concordant versus discordant contralateral breast cancer subtypes?\",\"answer\":\"It compares cases where the contralateral tumor subtype matches the primary tumor subtype (concordant) versus cases with different subtypes (discordant) to assess associations with immune and response metrics.\"},{\"question\":\"What did genomic analyses reveal about the relationship between left and right tumors versus primary and residual disease?\",\"answer\":\"Left and right tumors showed independence regarding somatic mutations, copy number alterations, and clonal phylogeny, whereas primary tumor and residual disease were closely related in somatic mutations and transcriptomic profiles.\"}]","Evolution of synchronous female bilateral breast cancers and response to treatment | PDF",1790256780,73]