Citations 2
Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status
Lambertini, Matteo , Blondeaux, Eva , Tomasello, Loredana Maria, Agostinetto, Elisa , Hamy, Anne‐Sophie , Kim, Hee Jeong , Franzoi, Maria Alice , Bernstein‐Molho, Rinat , Hilbers, Florentine , Pogoda, Katarzyna , Bajpai, Jyoti , Phillips, Kelly‐Anne , Rousset‐Jablonski, Christine , Renaud, Tiphaine , Cui, Wanyuan , Wong, Stephanie M. , Ruddy, Kathryn J. , Marchis, Laura De , Wildiers, Hans , Bajpai, Jyoti , Ignatiadis, Michail , Moore, Halle C F , Partridge, Ann H , Phillips, Kelly-Anne , Toss, Angela , Rousset-Jablonski, Christine , Criscitiello, Carmen , Ferrari, Alberta , Fruscio, Robert , Cui, Wanda , Wong, Stephanie M , Vernieri, Claudio , Ruddy, Kathryn J , Dieci, Maria Vittoria , Matikas, Alexios , Rozenblit, Mariya , Villarreal-Garza, Cynthia , De Marchis, Laura , Puglisi, Fabio , Rodriguez-Wallberg, Kenny A , Livraghi, Luca , Bruzzone, Marco , Boni, Luca , Balmaña, Judith , Lambertini, Matteo , Hamy, Anne-Sophie , Pogoda, K. , Wildiers, Hans , Ignatiadis, Michail , Moore, Halle C. F. , Partridge, Ann H. , Paluch–Shimon, Shani , Fruscio, Robert , Dieci, Maria Vittoria , Villarreal‐Garza, Cynthia , Duhoux, François P. , Livraghi, Luca , Bruzzone, Marco , Balmañà, Judith
Journal of Clinical Oncology | February 24, 2025 | Volume: 43 | Issue: 14 | Pages: 1706-1719
PURPOSE To investigate the clinical behavior of breast cancer in young BRCA carriers according to the specific BRCA gene ( BRCA1 v BRCA2 ) and the association of the timing of genetic testing (before v at diagnosis) with prognosis. METHODS This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in BRCA1 or BRCA2 , who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306 ). RESULTS Compared with BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) had more frequently hormone receptor–negative (74.4% v 15.5%) and high-grade (77.5% v 49.1%) tumors. Similar outcomes were observed in BRCA1 and BRCA2 carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for BRCA at diagnosis (ie, between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1: 61.3% v 32.4%), less nodal involvement (N0: 65.9% v 50.8%), less frequently received chemotherapy (84.4% v 92.9%), and axillary dissection (37.5% v 47.4%). Patients tested before diagnosis had better overall survival (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 to 0.92]); however, this result lost statistical significance after adjustment for potential confounders including tumor stage (adjusted HR, 0.74 [95% CI, 0.47 to 1.15]). CONCLUSION This global study provides evidence on the different clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers. Identifying a BRCA PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.
Pregnancy After Breast Cancer in Young BRCA Carriers
Kim, Hee Jeong , Bernstein‐Molho, Rinat , Pogoda, Katarzyna , Carrasco, Estela , Bajpai, Jyoti , Phillips, Kelly‐Anne , Rousset‐Jablonski, Christine , Renaud, Tiphaine , Cui, Wanda, Wong, Stephanie M. , Ruddy, Kathryn J. , Rozenblit, Mariya, Marchis, Laura De , Mriňáková, Bela , Meister, Sarah , Livraghi, Luca , Clatot, Florian , Yerushalmi, Rinat , Angelis, Carmine De , Meattini, Icro , Cichowska-Cwalińska, Natalia, Berlière, Martine , Salama, Mahmoud , Giorgi, Ugo De , Sonnenblick, Amir , Chiodi, Camila , Maria, Camille, Azim, Hatem A. , Molinelli, Chiara , Paesmans, Marianne , Ameye, Lieveke , Hatse, Sigrid , Nevelsteen, Ines , Neven, Patrick , Rompuy, Chantal Van, Duhoux, François, Bini, Federica , Cont, Nicoletta Tomasi, Pais, Helena Luna , Mohar, Alejandro , Palacios, Tamara, Pastò, Brenno , Bonadio, Renata Colombo , Peretz‐Yablonski, Tamar , Anghelone, Chiara Annunziata Pasqualina, Valle, Angelica Della , Campanella, Maria, Bas, Raphaëlle, Talouet, Solenne de, Bonadona, Valérie, Lasset, Christine , Acheritogaray, Marion , Sénéchal, Claire , Mariño, Monica , Feldman, Didi, Pesce, Romina , Allemand, Carol, Riggi, Cecilia, Iriarte, Maria Belen, Salgado, Alfonso Cortés, Gión, María , Prat, Aleix , Hester, Anna, Dunckelmann, Sofia, Bartsch, Rupert , Mannsbarth, Constantin, Božović‐Spasojević, Ivana, Dimitrijević, Marija, Visani, Luca , Bettazzi, Beatrice, Sini, Valentina, Rognone, Alessia, Patricelli, Maria Grazia , Rabaiotti, Emanuela , Acconci, Giulia, Baldacci, Erica, Bianchini, Giulia, Kleiterp, Sieta, Moha, Daoud Ait, Sekar, Anberson, Loi, Francesco , Dessì, Mariele, O’Connor, Sarah , Nesci, Stephanie, Michael, Chris, Larson, Nicole L. , Lopetegui, Nerea M., Rocco, Roberta Di, Bengala, Carmelo , Haddad, Stephanie , Safran, Emma, Negri, Serena , Dell'Oro, Cristina, Marchetta, Liliana, Lustberg, Maryam B. , Blansky, Deanna , Ansari, Norin , Aguilar-y-Méndez, Dione, Swain, Monique , Miller, Madison , Leach, Richard E., Synowiec, Agnieszka , Hancinova, M., Tarbaj, L., Beslija, S. , Cerić, Timur , Hasanbegovic, B. , Bianchi, Manuel A., Álvaro, Laura, Bergman, Louise Eriksson, Damian, Cristina , Eriksson, Louise , Cui, Wanyuan , Prat, Aleix , De Angelis, Carmine , Meattini, Icro , Rousset-Jablonski, Christine , Phillips, Kelly-Anne , Cui, Wanda , Wong, Stephanie M , Livraghi, Luca , Lustberg, Maryam , Pogoda, K. , Lambertini, Matteo , Blondeaux, Eva , Agostinetto, Elisa , Hamy, Anne‐Sophie , Meglio, Antonio Di , Hilbers, Florentine , Punie, Kevin , Ignatiadis, Michail , Moore, Halle C. F. , Toss, Angela , Peccatori, Fedro A , Ferrari, Alberta , Paluch–Shimon, Shani , Fruscio, Robert , Vernieri, Claudio , Dieci, Maria Vittoria , Matikas, Alexios , Rozenblit, Mariya , Villarreal‐Garza, Cynthia , Mastro, Lucia Del , Puglisi, Fabio , Estevez-Diz, Maria Del Pilar , Rodriguez-Wallberg, Kenny A , Sánchez-Bayona, Rodrigo , Lee, Young‐Jin , Boni, Luca , Partridge, Ann H. , Azambuja, Evandro de , Amant, Frédéric , Brems, Hilde , Han, Sileny , Smeets, Ann , Wildiers, Hans , Giugliano, Federica , Criscitiello, Carmen , Borea, Roberto , Arecco, Luca , Chirco, Alessandra, Venturelli, Marta , Cortesi, Laura , Ponzone, Riccardo , Balmañà, Judith , Graffeo, Rossella , Ros, Lucia Da , Miolo, Gianmaria , Garutti, Mattia , Spazzapan, Simon , Viel, Alessandra , Fidalgo, José Alejandro Pérez , Guarneri, Valentina , Heudel, Pierre‐Etienne , Trédan, Olivier , Bonadona, Valérie , Córdoba, Octavi , Cortés, Javier , Saavedra, Cristina , Rodriguez, Adela R. , Adamo, Bárbara , Harbeck, Nadia , Marhold, Maximilian , POPOVIC, LAZAR S. , Krivokuća, Ana , Livi, Lorenzo , Sposetti, Caterina , Bianchini, Giampaolo , Gentilini, Oreste D , Fontana, Andrea , Pistelli, Mirco , Linn, Sabine C. , Sarin, Rajiv , Atzori, Francesco , O’Connor, Sarah, James, Paul A. , Michael, Chris, Couch, Fergus J. , Olson, Janet E. , Yadav, Siddhartha , Carey, Lisa A. , Abdou, Yara George , Zagami, Paola , Baldassarri, Margherita , Mariamidze, Elene , Graff, Stephanie L. , Matos, Leonor Vasconcelos de , Ferreira, Arlindo Rebelo , Dell’Oro, Cristina, Inzoli, Alessandra , Costa, Clarissa , Jeon, June Evelyn , Woodruff, Teresa K. , Fabi, Alessandra , Palazzo, Antonella , Paris, Ida , Kufel-Grabowska, Joanna , Sokolović, Emir , Foulkes, William D. , Bianchi, Manuel Alva, Tolosa, Pablo , Antone, Nicoleta Zenovia , Damian, Cristina
JAMA | December 7, 2023 | Volume: 331 | Issue: 1 | Pages: 49
ImportanceYoung women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.ObjectiveTo investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers.Design, Setting, and ParticipantsInternational, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.ExposurePregnancy after breast cancer.Main Outcomes and MeasuresPrimary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer–specific survival, overall survival, pregnancy, and fetal and obstetric outcomes.ResultsOf 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer–specific survival and overall survival.Conclusions and RelevanceIn this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.Trial RegistrationClinicalTrials.gov Identifier: NCT03673306