Literature DB >> 31012959

The Burden of Breast Cancer Predisposition Variants Across The Age Spectrum Among 10 000 Patients.

Yanin Chavarri-Guerra1, Carolyn B Hendricks2, Sandra Brown3, Catherine Marcum4, Mary Hander5, Zdenka E Segota6, Chris Hake7, Sharon Sand8, Thomas P Slavin8, Arti Hurria8, Enrique Soto-Perez-de-Celis1, Bita Nehoray8, Kenneth B Blankstein9, Kathleen R Blazer8, Jeffrey N Weitzel8.   

Abstract

BACKGROUND/
OBJECTIVES: Women diagnosed with breast cancer (BC) at an older age are less likely to undergo genetic cancer risk assessment and genetic testing since the guidelines and referrals are biased toward earlier age at diagnosis. Thus, we determined the prevalence and type of pathogenic cancer predisposition variants among women with a history of BC diagnosed at the age of 65 years or older vs younger than 65 years.
DESIGN: Prospective registration cohort.
SETTING: The Clinical Cancer Genomics Community Research Network, including 40 community-based clinics in the United States and 5 in Latin America. PARTICIPANTS: Women with BC and genetic testing results. MEASUREMENTS: Sociodemographic characteristics, clinical variables, and genetic profiles were compared between women aged 65 years and older and those younger than 65 years at BC diagnosis.
RESULTS: Among 588 women diagnosed with BC and aged 65 years and older and 9412 diagnosed at younger than 65 years, BC-associated pathogenic variants (PVs) were detected in 5.6% of those aged 65 years and older (n = 33) and 14.2% of those younger than 65 years (n = 1340) (P < .01). PVs in high-risk genes (eg, BRCA1 and BRCA2) represented 81.1% of carriers among women aged 65 years and older (n = 27) and 93.1% of those younger than 65 years (n = 1248) (P = .01). BRCA2 PVs represented 42.4% of high-risk gene findings for those aged 65 years and older, whereas BRCA1 PVs were most common among carriers younger than 65 years (49.7%). PVs (n = 7) in moderate-risk genes represented 21.2% for carriers aged 65 years and older and 7.3% of those younger than 65 years (n = 98; P < .01). CHEK2 PVs were the most common moderate-risk gene finding in both groups.
CONCLUSION: Clinically actionable BC susceptibility PVs, particularly in BRCA2 and CHEK2, were relatively prevalent among older women undergoing genetic testing. The significant burden of PVs for older women with BC provides a critical reminder to recognize the full spectrum of eligibility and provide genetic testing for older women, rather than exclusion based on chronological age alone. J Am Geriatr Soc 67:884-888, 2019.
© 2019 The American Geriatrics Society.

Entities:  

Keywords:  breast cancer; genetics; older women

Year:  2019        PMID: 31012959      PMCID: PMC6524775          DOI: 10.1111/jgs.15937

Source DB:  PubMed          Journal:  J Am Geriatr Soc        ISSN: 0002-8614            Impact factor:   5.562


  25 in total

1.  Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer.

Authors:  Ana M Gonzalez-Angulo; Kirsten M Timms; Shuying Liu; Huiqin Chen; Jennifer K Litton; Jennifer Potter; Jerry S Lanchbury; Katherine Stemke-Hale; Bryan T Hennessy; Banu K Arun; Gabriel N Hortobagyi; Kim-Anh Do; Gordon B Mills; Funda Meric-Bernstam
Journal:  Clin Cancer Res       Date:  2011-01-13       Impact factor: 12.531

Review 2.  Genetics, genomics, and cancer risk assessment: State of the Art and Future Directions in the Era of Personalized Medicine.

Authors:  Jeffrey N Weitzel; Kathleen R Blazer; Deborah J MacDonald; Julie O Culver; Kenneth Offit
Journal:  CA Cancer J Clin       Date:  2011-08-19       Impact factor: 508.702

3.  Coming of age: breast cancer in seniors.

Authors:  Hyman B Muss
Journal:  Oncologist       Date:  2010

Review 4.  BRCA1/2 mutations and triple negative breast cancers.

Authors:  Beth N Peshkin; Michelle L Alabek; Claudine Isaacs
Journal:  Breast Dis       Date:  2010

5.  Prevalence of BRCA mutations and founder effect in high-risk Hispanic families.

Authors:  Jeffrey N Weitzel; Veronica Lagos; Kathleen R Blazer; Rebecca Nelson; Charité Ricker; Josef Herzog; Colleen McGuire; Susan Neuhausen
Journal:  Cancer Epidemiol Biomarkers Prev       Date:  2005-07       Impact factor: 4.254

6.  Limited family structure and BRCA gene mutation status in single cases of breast cancer.

Authors:  Jeffrey N Weitzel; Veronica I Lagos; Carey A Cullinane; Patricia J Gambol; Julie O Culver; Kathleen R Blazer; Melanie R Palomares; Katrina J Lowstuter; Deborah J MacDonald
Journal:  JAMA       Date:  2007-06-20       Impact factor: 56.272

7.  Future of cancer incidence in the United States: burdens upon an aging, changing nation.

Authors:  Benjamin D Smith; Grace L Smith; Arti Hurria; Gabriel N Hortobagyi; Thomas A Buchholz
Journal:  J Clin Oncol       Date:  2009-04-29       Impact factor: 44.544

8.  Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations.

Authors:  Kelly D Gonzalez; Katie A Noltner; Carolyn H Buzin; Dongqing Gu; Cindy Y Wen-Fong; Vu Q Nguyen; Jennifer H Han; Katrina Lowstuter; Jeffrey Longmate; Steve S Sommer; Jeffrey N Weitzel
Journal:  J Clin Oncol       Date:  2009-02-09       Impact factor: 44.544

9.  Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer.

Authors:  Tom Walsh; Silvia Casadei; Kathryn Hale Coats; Elizabeth Swisher; Sunday M Stray; Jake Higgins; Kevin C Roach; Jessica Mandell; Ming K Lee; Sona Ciernikova; Lenka Foretova; Pavel Soucek; Mary-Claire King
Journal:  JAMA       Date:  2006-03-22       Impact factor: 56.272

10.  BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer.

Authors:  Michael J Hall; Julia E Reid; Lynn A Burbidge; Dmitry Pruss; Amie M Deffenbaugh; Cynthia Frye; Richard J Wenstrup; Brian E Ward; Thomas A Scholl; Walter W Noll
Journal:  Cancer       Date:  2009-05-15       Impact factor: 6.860

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  5 in total

Review 1.  Genetic cancer predisposition syndromes among older adults.

Authors:  Yanin Chavarri-Guerra; Thomas P Slavin; Ossian Longoria-Lozano; Jeffrey N Weitzel
Journal:  J Geriatr Oncol       Date:  2020-01-21       Impact factor: 3.599

2.  Older breast cancer survivors may harbor hereditary cancer predisposition pathogenic variants and are at risk for clonal hematopoiesis.

Authors:  Thomas P Slavin; Can-Lan Sun; Yanin Chavarri-Guerra; Mina S Sedrak; Vani Katheria; Danielle Castillo; Josef Herzog; William Dale; Arti Hurria; Jeffrey N Weitzel
Journal:  J Geriatr Oncol       Date:  2019-09-28       Impact factor: 3.599

3.  Breast cancer associated pathogenic variants among women 61 years and older with triple negative breast cancer.

Authors:  Yanin Chávarri-Guerra; Catherine A Marcum; Carolyn B Hendricks; Deborah Wilbur; Terrence Cescon; Christopher Hake; Julio Abugattas; Yenni Rodriguez; Cynthia Villarreal-Garza; Kai Yang; Aleck Cervantes; Sharon Sand; Danielle Castillo; Joseph Herzog; Janet Mokhnatkin; Mina S Sedrak; Enrique Soto-Perez-de-Celis; Jeffrey N Weitzel
Journal:  J Geriatr Oncol       Date:  2020-12-01       Impact factor: 3.929

4.  Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer.

Authors:  Siddhartha Yadav; Chunling Hu; Steven N Hart; Nicholas Boddicker; Eric C Polley; Jie Na; Rohan Gnanaolivu; Kun Y Lee; Tricia Lindstrom; Sebastian Armasu; Patrick Fitz-Gibbon; Karthik Ghosh; Daniela L Stan; Sandhya Pruthi; Lonzetta Neal; Nicole Sandhu; Deborah J Rhodes; Christine Klassen; Prema P Peethambaram; Tufia C Haddad; Janet E Olson; Tanya L Hoskin; Matthew P Goetz; Susan M Domchek; Judy C Boughey; Kathryn J Ruddy; Fergus J Couch
Journal:  J Clin Oncol       Date:  2020-03-03       Impact factor: 44.544

Review 5.  Personalising therapy for early-stage oestrogen receptor-positive breast cancer in older women.

Authors:  Neil Carleton; Azadeh Nasrazadani; Kristine Gade; Sushil Beriwal; Parul N Barry; Adam M Brufsky; Rohit Bhargava; Wendie A Berg; Margarita L Zuley; G J van Londen; Oscar C Marroquin; Darcy L Thull; Phuong L Mai; Emilia J Diego; Michael T Lotze; Steffi Oesterreich; Priscilla F McAuliffe; Adrian V Lee
Journal:  Lancet Healthy Longev       Date:  2022-01-05
  5 in total

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