Review
Genetics & Heredity
Daria Grafodatskaya, Darren D. O'Rielly, Karine Bedard, Darci T. Butcher, Christopher J. Howlett, Alice Lytwyn, Elizabeth McCready, Jillian Parboosingh, Elizabeth L. Spriggs, Andrea K. Vaags, Tracy L. Stockley
Summary: This document provides considerations and recommendations for Canadian clinical laboratories developing, validating, and offering next-generation sequencing (NGS)-based BRCA1/2 tumor testing in ovarian cancers. It was drafted by the Canadian College of Medical Geneticists (CCMG) BRCA Ad Hoc Working Group and representatives from the Canadian Association of Pathologists, and approved by the CCMG board of directors. However, the current CCMG Practice Guidelines do not include all the information laboratories should consider when validating and using NGS for BRCA1/2 tumor testing in ovarian cancers.
JOURNAL OF MEDICAL GENETICS
(2022)
Review
Cell Biology
Xiaoyu Fu, Wei Tan, Qibin Song, Huadong Pei, Juanjuan Li
Summary: Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene involved in important physiological processes and its mutations or defects increase the risk of cancer. This review summarizes the molecular functions and regulation of BRCA1 and discusses recent insights into the detection and treatment of breast cancer associated with BRCA1 mutations.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Francesca Mateo, Zhengcheng He, Lin Mei, Gorka Ruiz de Garibay, Carmen Herranz, Nadia Garcia, Amanda Lorentzian, Alexandra Baiges, Eline Blommaert, Antonio Gomez, Oriol Mirallas, Anna Garrido-Utrilla, Luis Palomero, Roderic Espin, Ana Extremera, M. Teresa Soler-Monso, Anna Petit, Rong Li, Joan Brunet, Ke Chen, Susanna Tan, Connie J. Eaves, Curtis McCloskey, Razq Hakem, Rama Khokha, Philipp F. Lange, Conxi Lazaro, Christopher A. Maxwell, Miquel Angel Pujana
Summary: Breast cancer risk for carriers of BRCA1 pathological variants is influenced by genetic factors, with HMMR being a potential contributor. Overexpression of HMMR has been found to increase the risk of Brca1-mutant breast cancer by modulating the cancer cell phenotype and tumor microenvironment. This study provides insight into the biological basis of increased risk for BRCA1-associated breast cancer.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
Andrew N. J. Tutt, Judy E. Garber, Bella Kaufman, Giuseppe Viale, Debora Fumagalli, Priya Rastogi, Richard D. Gelber, Evandro de Azambuja, Anitra Fielding, Judith Balmana, Susan M. Domchek, Karen A. Gelmon, Simon J. Hollingsworth, Larissa A. Korde, Barbro Linderholm, Hanna Bandos, E. Senkus, Jennifer M. Suga, Z. Shao, Andrew W. Pippas, Zbigniew Nowecki, Tomasz Huzarski, Patricia A. Ganz, Peter C. Lucas, Nigel Baker, Sibylle Loibl, Robin McConnell, Martine Piccart, Rita Schmutzler, Guenther G. Steger, Joseph P. Costantino, Amal Arahmani, Norman Wolmark, Eleanor McFadden, Vassiliki Karantza, Sunil R. Lakhani, Greg Yothers, Christine Campbell, Charles E. Geyer
Summary: In patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than placebo. Olaparib had limited effects on global patient-reported quality of life.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Jenny Furlanetto, Volker Moebus, Andreas Schneeweiss, Kerstin Rhiem, Hans Tesch, Jens-Uwe Blohmer, Kristina Luebbe, Michael Untch, Christoph Salat, Jens Huober, Peter Klare, Rita Schmutzler, Fergus J. Couch, Bianca Lederer, Bernd Gerber, Dirk-Michael Zahm, Ingo Bauerfeind, Valentina Nekljudova, Claus Hanusch, Christian Jackisch, Theresa Link, Eric Hahnen, Sibylle Loibl, Peter A. Fasching
Summary: The study found that patients with germline BRCA1/2 mutations undergoing standard chemotherapy for early triple-negative breast cancer did not have a higher risk of severe hematological toxicities. However, under treatment with taxanes, patients with BRCA1/2 mutations may have a higher risk of hematological toxicities, suggesting the need for further research.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
D. Gareth Evans, Elke M. van Veen, Emma R. Woodward, Elaine F. Harkness, Jamie M. Ellingford, Naomi L. Bowers, Andrew J. Wallace, Sacha J. Howell, Anthony Howell, Fiona Lalloo, William G. Newman, Miriam J. Smith
Summary: Panel testing of extended group of genes, including BRCA1/2, in breast cancer patients revealed positive actionable variants in non-BRCA1/2 genes. PALB2, CHEK2, and ATM were the most predominant genes identified. Rates of non-BRCA actionable genes remained relatively constant across different likelihoods of BRCA1/2, but were lower in high MS score families.
Article
Oncology
Kelly A. Metcalfe, Andrea Eisen, Aletta Poll, Alexandra Candib, David McCready, Tulin Cil, Frances Wright, Jordan Lerner-Ellis, Jeanna McCuaig, Tracy Graham, Ping Sun, Mohammad Akbari, Steven A. Narod
Summary: The study showed that providing rapid genetic testing at the time of breast cancer diagnosis helps women make treatment decisions, with the majority of BRCA mutation carriers choosing to undergo bilateral mastectomy.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Oncology
Nicholas J. Boddicker, Chunling Hu, Jeffrey N. Weitzel, Peter Kraft, Katherine L. Nathanson, David E. Goldgar, Jie Na, Hongyan Huang, Rohan D. Gnanaolivu, Nicole Larson, Amal Yussuf, Song Yao, Celine M. Vachon, Amy Trentham-Dietz, Lauren Teras, Jack A. Taylor, Christopher E. Scott, Dale P. Sandler, Tina Pesaran, Alpa Patel, Julie R. Palmer, Irene M. Ong, Janet E. Olson, Katie O'Brien, Susan Neuhausen, Elena Martinez, Huiyan Ma, Sara Lindstrom, Loic Le Marchand, Charles Kooperberg, Rachid Karam, David J. Hunter, James M. Hodge, Christopher Haiman, Mia M. Gaudet, Chi Gao, Holly LaDuca, James Lacey, Jill S. Dolinsky, Elizabeth Chao, Brian D. Carter, Elizabeth S. Burnside, Kimberly A. Bertrand, Leslie Bernstein, Paul W. Auer, Christine Ambrosone, Siddhartha Yadav, Steven N. Hart, Eric C. Polley, Susan M. Domchek, Fergus J. Couch
Summary: This study identified the prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women over age 65 years. It found that women with PVs in BRCA1, BRCA2, and PALB2 have an increased risk of breast cancer. The study suggests that genetic testing should be considered for women diagnosed with triple-negative or ER-negative breast cancer, and MRI screening may be beneficial for women over age 65 with certain PVs.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Audrey Mailliez, Veronique D'Hondt, Amelie Lusque, Olivier Caron, Luc Cabel, Anthony Goncalves, Marc Debled, Laurence Gladieff, Jean-Marc Ferrero, Thierry Petit, Marie Ange Mouret-Reynier, Jean-Christophe Eymard, Christelle Levy, Lionel Uwer, Marianne Leheurteur, Isabelle Desmoulins, Thomas Bachelot, Jean-Sebastien Frenel, Thibault de la Motte Rouge, Gaetane Simon, William Jacot, Suzette Delaloge
Summary: The outcomes and treatment strategies for germline BRCA1/2 mutation carriers with metastatic breast cancer are uncertain. This study found that in the triple-negative subtype, these patients had better overall survival and progression-free survival, while in HR+/HER2 negative cancers, their progression-free survival was significantly lower.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Tauana Rodrigues Nagy, Simone Maistro, Giselly Encinas, Maria Lucia Hirata Katayama, Glaucia Fernanda de Lima Pereira, Nelson Gaburo-Junior, Lucas Augusto Moyses Franco, Ana Carolina Ribeiro Chaves de Gouvea, Maria del Pilar Estevez Diz, Luiz Antonio Senna Leite, Maria Aparecida Azevedo Koike Folgueira
Summary: The study found that the frequency of gBRCA mutations in postmenopausal Brazilian breast cancer patients was 10.2%, and the frequency of PIK3CA somatic mutations was 37% in postmenopausal patients and 17% in young patients. Additionally, 25% of both BRCA1/BRCA2 mutation carriers and non-carriers had PIK3CA somatic mutations, suggesting a potential association between the two types of mutations.
Article
Oncology
Yomali Ferreyra, Gina Rosas, Alicia M. Cock-Rada, Jhajaira Araujo, Leny Bravo, Franco Doimi, Jhoysi Casas, Maria de los Angeles Clavo, Joseph A. Pinto, Carolina Belmar-Lopez
Summary: This retrospective study describes the prevalence of pathogenic/likely pathogenic (P/LP) variants and variants of uncertain/unknown significance (VUS) in BRCA1 and BRCA2 genes in Peruvian breast and ovarian cancer patients. The study found that 14.7% of breast cancer patients and 20.7% of ovarian cancer patients carried P/LP variants in BRCA1/2. The most frequent pathogenic variants were c.2105dupT in BRCA1 and c.8023A>G in BRCA2.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Kelly A. Metcalfe, Andrea Eisen, Frances Wright, Aletta Poll, Alexandra Candib, David McCready, Tulin Cil, Susan Armel, Yael Silberman, Sarah Brennenstuhl, Steven A. Narod
Summary: For women receiving RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis, the study found that identifying a BRCA1 or BRCA2 mutation does not impair psychosocial functioning in the short or long term. Women with a BRCA1 or BRCA2 mutation had significantly lower depression scores compared to those with a negative result at one year post-testing.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Oncology
J. Jaime Alberty-Oller, Sarah Weltz, Antonio Santos, Kereeti Pisapati, Meng Ru, Christina Weltz, Hank Schmidt, Elisa Port
Summary: The study identified a significant underutilization of genetic testing in newly diagnosed breast cancer patients, with many eligible patients not receiving testing. Factors contributing to this underutilization include issues with family history assessment, patient age, ethnicity, and patient compliance. Broader peri-diagnostic testing should be considered, along with efforts to increase compliance rates among referred patients.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Review
Oncology
Zhewen Feng, Xiaobao Yang, Mingwei Tian, Na Zeng, Zhigang Bai, Wei Deng, Yanyan Zhao, Jianru Guo, Yingchi Yang, Zhongtao Zhang, Yun Yang
Summary: This study conducted a systematic review and meta-analysis to investigate the association between BRCA1 and BRCA2 gene mutations and colorectal cancer risk. The results showed a significant increase in the frequency of BRCA1 and BRCA2 mutations in colorectal cancer patients. Therefore, the study suggests that BRCA genes could be potential candidates for inclusion in colorectal cancer genetic testing panels.
Review
Cell Biology
A. Sokolova, K. J. Johnstone, A. E. McCart Reed, P. T. Simpson, S. R. Lakhani
Summary: Hereditary factors, including pathogenic variants in genes such as BRCA1, BRCA2, ATM, CHEK2, etc., play a significant role in breast cancer risk. Polygenic risk, which results from carrying multiple low-penetrance breast cancer susceptibility alleles, also contributes to the risk. This review provides an overview of established breast cancer susceptibility genes, breast cancer predisposition syndromes, and discusses the implications of molecular testing and therapy in hereditary breast cancer.
Article
Surgery
Martine A. van Huizum, J. Joris Hage, Nicola S. Russell, Emiel Rutgers, Leonie A. E. Woerdeman
Summary: This study compares the outcomes of immediate implant-based breast reconstruction (SSM-IIBR) in different scenarios. The results indicate that SSM-IIBR after mantle field radiotherapy is more favorable than after breast conserving therapy (BCT). Furthermore, the outcomes of the new method are comparable to those of non-irradiated breasts.
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY
(2022)
Editorial Material
Oncology
A. M. Moorman, E. J. Th. Rutgers, E. A. Kouwenhoven
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
A. M. Moorman, E. J. Th Rutgers, E. A. Kouwenhoven
Summary: The study aimed to establish a predictive model that can identify one-third of breast cancer patients who may not need SLNB surgery due to low axillary burden. In patients with relatively favorable characteristics, 26.8% had less than a 5% chance of macrometastases.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Lennart Kester, Danielle Seinstra, Annelot G. J. van Rossum, Claire Vennin, Marlous Hoogstraat, Daphne van der Velden, Mark Opdam, Erik van Werkhoven, Kerstin Hahn, Iris Nederlof, Ester H. Lips, Ingrid A. M. Mandjes, A. Elise Van Leeuwen-Stok, Sander Canisius, Harm van Tinteren, Alex L. T. Imholz, Johanneke E. A. Portielje, Monique E. M. M. Bos, Sandra D. Bakker, Emiel J. Rutgers, Hugo M. Horlings, Jelle Wesseling, Emile E. Voest, Lodewyk F. A. Wessels, Marleen Kok, Hendrika M. Oosterkamp, Alexander van Oudenaarden, Sabine C. Linn, Jacco van Rheenen
Summary: Extensive work in preclinical models shows that microenvironmental cells, including specific populations of immune and epithelial cells, influence cancer cell behavior and patient outcomes. By analyzing single-cell sequencing data and using deconvolution algorithms, researchers identified various cell types in the microenvironment that impact differential survival and treatment benefit in patients with breast cancer.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Josephine M. N. Lopes Cardozo, Caroline A. Drukker, Emiel J. T. Rutgers, Marjanka K. Schmidt, Annuska M. Glas, Anke Witteveen, Fatima Cardoso, Martine Piccart, Laura J. Esserman, Coralie Poncet, Laura J. van't Veer
Summary: Through studying patients with a 70-gene signature ultralow-risk breast cancer, it was found that these patients have excellent prognosis, with an 8-year breast cancer-specific survival rate above 99%, suggesting that they could be candidates for further de-escalation of treatment to avoid overtreatment and the risk of side effects.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Akke Bakker, C. Paola Tello Valverde, Geertjan van Tienhoven, M. Willemijn Kolff, H. Petra Kok, Ben J. Slotman, Inge R. H. M. Konings, Arlene L. Oei, Hester S. A. Oldenburg, Emiel J. T. Rutgers, Coen R. N. Rasch, H. J. G. Desiree van den Bongard, Hans Crezee
Summary: The study investigated the impact of hyperthermia thermal dose on locoregional control, overall survival, and toxicity in patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia. The results showed that a high thermal dose was associated with significantly higher locoregional control without increasing toxicity.
RADIOTHERAPY AND ONCOLOGY
(2022)
Article
Oncology
J. M. N. Lopes Cardozo, D. Byng, C. A. Drukker, M. K. Schmidt, M. A. Binuya, L. J. van 't Veer, F. Cardoso, M. Piccart, C. H. Smorenburg, C. Poncet, E. J. T. Rutgers
Summary: In patients with stage I low-risk breast cancer, adjuvant endocrine therapy has a limited effect on distant metastasis-free interval (DMA), but significantly reduces breast cancer events.
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Walter Paul Weber, Jane Shaw, Andrea Pusic, Lynda Wyld, Monica Morrow, Tari King, Zoltan Matrai, Joerg Heil, Florian Fitzal, Shelley Potter, Isabel T. Rubio, Maria-Joao Cardoso, Oreste Davide Gentilini, Viviana Galimberti, Virgilio Sacchini, Emiel J. T. Rutgers, John Benson, Tanir M. Allweis, Martin Haug, Regis R. Paulinelli, Tibor Kovacs, Yves Harder, Bahadir M. Gulluoglu, Eduardo Gonzalez, Andree Faridi, Elisabeth Elder, Peter Dubsky, Jens-Uwe Blohmer, Vesna Bjelic-Radisic, Mitchel Barry, Susanne Dieroff Hay, Kimberly Bowles, James French, Roland Reitsamer, Rupert Koller, Peter Schrenk, Daniela Kauer-Dorner, Jorge Biazus, Fabricio Brenelli, Jaime Letzkus, Ramon Saccilotto, Sarianna Joukainen, Susanna Kauhanen, Ulla Karhunen-Enckell, Juergen Hoffmann, Ulrich Kneser, Thorsten Kuhn, Michalis Kontos, Ekaterini Christina Tampaki, Moshe Carmon, Tal Hadar, Giuseppe Catanuto, Carlos A. Garcia-Etienne, Linetta Koppert, Pedro F. Gouveia, Jakob Lagergren, Tor Svensjoe, Nadia Maggi, Elisabeth A. Kappos, Fabienne D. Schwab, Liliana Castrezana, Daniel Steffens, Janna Krol, Christoph Tausch, Andreas Gunthert, Michael Knauer, Maria C. Katapodi, Susanne Bucher, Nik Hauser, Christian Kurzeder, Rosine Mucklow, Pelagia G. Tsoutsou, Atakan Sezer, Guldeniz Karadeniz Cakmak, Hasan Karanlik, Patricia Fairbrother, Laszlo Romics, Giacomo Montagna, Cicero Urban, Melanie Walker, Silvia C. Formenti, Guenther Gruber, Frank Zimmermann, Daniel Rudolf Zwahlen, Sherko Kuemmel, Mahmoud El-Tamer, Marie Jeanne Vrancken Peeters, Orit Kaidar-Person, Michael Gnant, Philip Poortmans, Jana de Boniface
Summary: The aim of this article is to discuss the demand for nipple-and skin-sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) and present clinical practice recommendations in the context of expanded indications for post-mastectomy radiation therapy (PMRT). The panel agrees that surgical technique for NSM/SSM should not be modified when PMRT is planned, with preference for autologous over implant-based BR. However, no specific recommendations are made regarding implant positioning, use of mesh or timing. The use of patient-reported outcomes in clinical practice is endorsed. The article emphasizes the importance of prospective randomized phase III studies and interdisciplinary collaboration for determining optimal sequencing and techniques for PMRT in the context of BR.
Article
Oncology
Sanne A. L. Bartels, Mila Donker, Coralie Poncet, Nicolas Sauve, Marieke E. E. Straver, Cornelis J. H. van de Velde, Robert E. E. Mansel, Charlotte Blanken, Lorenzo Orzalesi, Jean H. G. Klinkenbijl, Huub C. J. van der Mijle, Grard A. P. Nieuwenhuijzen, Sanne C. C. Veltkamp, Thijs van Dalen, Andreas Marinelli, Herman Rijna, Marko Snoj, Nigel J. J. Bundred, Jos W. S. Merkus, Yazid Belkacemi, Patrick Petignat, Dominic A. X. Schinagl, Corneel Coens, Geertjan van Tienhoven, Frederieke van Duijnhoven, Emiel J. T. Rutgers
Summary: This clinical trial compared axillary lymph node dissection (ALND) with axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer. The study found that both modalities had comparable axillary control, but ART was associated with less morbidity. Additionally, patients in the ART group had a higher risk of developing second primary cancers.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Josephine M. N. L. Cardozo, Irene L. E. Andrulis, Stig E. Bojesen, Thilo M. Doerk, Diana M. A. Eccles, Peter A. J. Fasching, Maartje J. Hooning, Renske Keeman, Heli Nevanlinna, Emiel J. T. F. Rutgers, Douglas F. Easton, Per Hall, Paul D. P. J. Pharoah, Laura J. K. van't Veer, Marjanka K. Schmidt
Summary: A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer. The results showed that PRS313 is associated with favorable tumor characteristics but not independently associated with prognosis. Rating: 8/10.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Surgery
Martine A. van Huizum, J. Joris Hage, Astrid N. Scholten, Emiel J. Rutgers
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY
(2023)
Article
Oncology
Annemiek K. E. van Hemert, Josefien P. P. van Olmen, Liesbeth J. J. Boersma, John H. H. Maduro, Nicola S. S. Russell, Jolien Tol, Ellen G. G. Engelhardt, Emiel J. Th. Rutgers, Marie-Jeanne T. F. D. Vrancken Peeters, Frederieke H. H. van Duijnhoven
Summary: The purpose of this study is to show that omitting adjuvant radiotherapy in breast cancer patients with pCR after NST can result in low rates of local recurrence and good quality of life.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Review
Oncology
Marjanka K. Schmidt, Jennifer E. Kelly, Anne Bredart, David A. Cameron, Jana de Boniface, Douglas F. Easton, Birgitte Offersen, Fiorita Poulakaki, Isabel T. Rubio, Francesco Sardanelli, Rita Schmutzler, Tanja Spanic, Britta Weigelt, Emiel J. T. Rutgers
Summary: After a unilateral breast cancer diagnosis, more and more patients are choosing to have contralateral prophylactic mastectomy (CPM), the removal of the healthy breast. Breast cancer specialists need to provide guidance to women considering CPM. This manifesto discusses the challenges of CPM and offers recommendations to improve outcomes for women with unilateral breast cancer.
EUROPEAN JOURNAL OF CANCER
(2023)
Meeting Abstract
Oncology
Josephine Lopes Cardozo, Irene L. Andrulis, Devilee Peter, Thilo Doerk, Caroline Drukker, Peter A. Fasching, Maartje J. Hooning, Renske Keeman, Heli Nevanlinna, Emiel J. Rutgers, Laura van 't Veer, Per Hall, Stig Egil Bojesen, Easton Douglas, Diana Eccles, Paul Pharoah, Marjanka Schmidt
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
A. Bakker, C. P. Tello Valverde, G. van Tienhoven, M. W. Kolff, H. P. Kok, B. J. Slotman, I. R. Konings, A. L. Oei, H. S. Oldenburg, E. J. Rutgers, C. R. Rasch, H. D. van den Bongard, H. Crezee
RADIOTHERAPY AND ONCOLOGY
(2022)