Family History of Breast and Ovarian Cancers and BRCA1 and BRCA2 Mutations in a Population-Based Series of Early-Onset Breast Cancer

Abstract Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

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Oral contraceptive use and the risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations

The Women s Oncology Review ◽

10.1080/14733400500235731 ◽

2005 ◽

Vol 5 (2) ◽

pp. 127-128 ◽

Cited By ~ 1

Author(s):

William Gillanders ◽

Peter Simon, Jr

Keyword(s):

Breast Cancer ◽

Oral Contraceptive ◽

Early Onset ◽

Contraceptive Use ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Oral Contraceptive Use ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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The spectrum of BRCA1 and BRCA2 mutations and clinicopathological characteristics in Chinese women with early-onset breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-020-05573-x ◽

2020 ◽

Vol 180 (3) ◽

pp. 759-766

Author(s):

Lili Chen ◽

Fangmeng Fu ◽

Meng Huang ◽

Jinxing Lv ◽

Wenzhe Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Chinese Women ◽

Clinicopathological Characteristics ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

BMC Cancer ◽

10.1186/1471-2407-8-203 ◽

2008 ◽

Vol 8 (1) ◽

Cited By ~ 6

Author(s):

Geertruida H de Bock ◽

Catharina E Jacobi ◽

Caroline Seynaeve ◽

Elly MM Krol-Warmerdam ◽

Jannet Blom ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Early Onset ◽

Population Based ◽

Early Onset Breast Cancer ◽

History Of

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Risk of Asynchronous Contralateral Breast Cancer in Noncarriers of BRCA1 and BRCA2 Mutations With a Family History of Breast Cancer: A Report From the Women's Environmental Cancer and Radiation Epidemiology Study

Journal of Clinical Oncology ◽

10.1200/jco.2012.43.2013 ◽

2013 ◽

Vol 31 (4) ◽

pp. 433-439 ◽

Cited By ~ 78

Author(s):

Anne S. Reiner ◽

Esther M. John ◽

Jennifer D. Brooks ◽

Charles F. Lynch ◽

Leslie Bernstein ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Young Women ◽

Contralateral Breast Cancer ◽

Contralateral Breast ◽

Brca1 And Brca2 ◽

Bilateral Disease ◽

History Of ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

Purpose To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations. Patients and Methods From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history–specific 10-year cumulative absolute risks of CBC were estimated. Results Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%. Conclusion Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.

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Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22226 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22226-e22226

Author(s):

A. Kwong ◽

L. Wong ◽

C. Wong ◽

F. Law ◽

E. Tang ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Breast Cancers ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Mutation Carriers ◽

History Of ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

e22226 Background: Breast cancers due to underlying germline BRCA1 and BRCA2 mutations are associated with particular pathological features that may differ from sporadic breast cancers. We report clinical and pathologic characteristics of breast cancer in a clinical cohort of high risk Chinese women with BRCA mutations and those without mutations. Methods: 202 high risk women based on their age and family history were recruited from March 2007 to November 2008. Medical information was prospectively collected from the patients and medical records. BRCA1 and BRCA2 mutations were detected using full gene sequencing and multiplex ligation-dependent probe amplification (MLPA). Results: Of the 202 female probands tested, 25 (12.3 %) were BRCA mutation carriers of which 11 (44%) were BRCA1 and 14 (56%) were BRCA2 mutations. Breast cancer risk factors, other than family history, did not differ between carriers and non-carriers. Mutation carriers were more likely to have a familial history of breast cancer (p=0.07) and personal and family history of ovarian cancer (p=0.005; p=0.007). Other cancers found in carriers families included pancreatic, gastric, colon, lung, liver, and nasopharyngeal. 23% of women diagnosed with DCIS had BRCA mutations compared with 11.4% of those with invasive cancers. BRCA related tumors were more likely to be ER, PR and Her-2 negative (Triple negative, TN) (p= 0.006). Overall 9.6% of non-BRCA cancers were TN whereas 25.9% of BRCA cancers were TN. Prevalence of TN in BRCA1 carriers is 71% compared with 13.4% in BRCA2 carriers. BRCA1 mutation related cancers were significantly more likely to be ER negative than BRCA2 and this is only significant in those who are under 40 years of age (p=0.070). Conclusions: We have a high BRCA2 mutation rate in our cohort. BRCA related breast cancer is associated with families with increasing number of first degree relatives with breast and/or ovarian cancers and were higher for DCIS cancers. Prevalence of TN breast cancers was high compared to Caucasian cohorts. BRCA mutations were associated with pathologically, poor prognostic features (TN and high grade) especially in younger women. No significant financial relationships to disclose.

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