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Low grade serous ovarian cancer: Unpicking drivers of outcome

      Low grade serous ovarian cancer (LGSOC) was first recognised as a separate entity almost two decades ago. In the first ten years since then, the number of dedicated LGSOC studies was low, reporting data from only a small number of specialist institutions. However, over the last 5 years there has been a wider, more concerted research effort that has driven substantial progress in uncovering the biological and clinical nuances of this unique disease type. This has included retrospective studies demonstrating the value of endocrine therapy [
      • Fader A.N.
      • Bergstrom J.
      • Jernigan A.
      • Tanner 3rd, E.J.
      • Roche K.L.
      • Stone R.L.
      • et al.
      Primary cytoreductive surgery and adjuvant hormonal monotherapy in women with advanced low-grade serous ovarian carcinoma: reducing overtreatment without compromising survival?.
      ,
      • Gershenson D.M.
      • Bodurka D.C.
      • Coleman R.L.
      • Lu K.H.
      • Malpica A.
      • Sun C.C.
      Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum.
      ] which have informed clinical guidelines and first-line trial design [
      • Armstrong D.K.
      • Alvarez R.D.
      • Backes F.J.
      • Bakkum-Gamez J.N.
      • Barroilhet L.
      • Behbakht K.
      • et al.
      NCCN guidelines® insights: ovarian cancer, version 3.2022: featured updates to the NCCN guidelines.
      ], randomised phase III trials demonstrating the value of MEK inhibitors in the relapsed disease setting [
      • Monk B.J.
      • Grisham R.N.
      • Banerjee S.
      • Kalbacher E.
      • Mirza M.R.
      • Romero I.
      • et al.
      MILO/ENGOT-ov11: Binimetinib versus physician's choice chemotherapy in recurrent or persistent low-grade serous carcinomas of the ovary, fallopian tube, or primary peritoneum.
      ,
      • Gershenson D.M.
      • Miller A.
      • Brady W.E.
      • Paul J.
      • Carty K.
      • Rodgers W.
      • et al.
      Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial.
      ] and most recently, a number of investigations that have painted a more detailed picture of the molecular landscape in LGSOC [
      • Cheasley D.
      • Nigam A.
      • Zethoven M.
      • Hunter S.
      • Etemadmoghadam D.
      • Semple T.
      • et al.
      Genomic analysis of low-grade serous ovarian carcinoma to identify key drivers and therapeutic vulnerabilities.
      ,
      • Gershenson D.M.
      • Sun C.C.
      • Westin S.N.
      • Eyada M.
      • Cobb L.P.
      • Nathan L.C.
      • et al.
      The genomic landscape of low-grade serous ovarian/peritoneal carcinoma and its impact on clinical outcomes.
      ,
      • Cheasley D.
      • Fernandez M.L.
      • Köbel M.
      • Kim H.
      • Dawson A.
      • Hoenisch J.
      • et al.
      Molecular characterization of low-grade serous ovarian carcinoma identifies genomic aberrations according to hormone receptor expression.
      ,
      • Manning-Geist B.
      • Gordhandas S.
      • Liu Y.L.
      • Zhou Q.
      • Iasonos A.
      • Da Cruz Paula A.
      • et al.
      MAPK pathway genetic alterations are associated with prolonged overall survival in low-grade serous ovarian carcinoma.
      ].
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