Association of family history and location of BRCA1 and BRCA2 mutations in triple-negative breast cancer patients.

e12588 Background: We assessed the prevalence of family history and its association with germline BRCA1/2mutation status/location and age at onset in triple-negative breast cancer (TNBC) patients. Methods: 266 patients with TNBC < 60 years unselected for family history of cancer were enrolled and germline DNA was sequenced to identify mutations. Family pedigrees were prospectively collected from these patients. Logistic regression was used to investigate family history and its association with mutation type/location and age at onset. ROC curves were constructed to determine good predictors of BRCAmutations. Results: BRCA mutations were identified in 18.0% of all patients (15.0% BRCA1, 3.0% BRCA2). BRCA1 carriers have a significantly earlier age at onset than non-mutation carriers (40 vs 49 years; p < .001). While 39/124 (31.4%) patients with family history of cancer carried a BRCA1/2 mutation, 9/142 (6.3%) BRCA carriers had no family history of cancer. BRCA1 carriers with ≥1BC in the family are commonly identified in the breast cancer cluster regions (53.1%). BRCA2 carriers more commonly cluster within the ovarian cancer regions. Of note, this difference was not statistically significant. Women with mutations in BRCA1 OCCR are diagnosed at a younger age. TNBC diagnosed ≤45 years with ≥1BC and ≥1OC in the family are good predictors of BRCA1 mutation (AUC 0.867). Conclusions: Young women with TNBC and a family history of BC and OC are likely to have a BRCA mutation. Specific BRCA mutation locations may add to the identification of a subgroup of TNBC patients with a relatively higher risk of subsequent ovarian cancer. Identification of high-risk TNBC patients with BRCA1 mutation will enable clinicians to optimize cancer management for this phenotype, but will require further validation in larger studies.

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THE FAMILY HISTORY OF CANCER PATIENTS.

The Lancet ◽

10.1016/s0140-6736(02)03155-0 ◽

1886 ◽

Vol 127 (3256) ◽

pp. 146-148

Author(s):

W.Roger Williams

Keyword(s):

Family History ◽

Cancer Patients ◽

Family History Of Cancer ◽

The Family ◽

History Of ◽

History Of Cancer

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Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer

Acta Oncologica ◽

10.1080/0284186x.2017.1404635 ◽

2017 ◽

Vol 57 (5) ◽

pp. 595-603 ◽

Cited By ~ 8

Author(s):

Annelie Augustinsson ◽

Carolina Ellberg ◽

Ulf Kristoffersson ◽

Åke Borg ◽

Håkan Olsson

Keyword(s):

Breast Cancer ◽

Family History ◽

Early Onset ◽

Tumor Characteristics ◽

Early Onset Breast Cancer ◽

Mutation Status ◽

Family History Of Cancer ◽

Cancer Mutation ◽

History Of ◽

History Of Cancer

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Mortality and Risk of Cancer After Prophylactic Bilateral Oophorectomy in Women With a Family History of Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pky034 ◽

2018 ◽

Vol 2 (3) ◽

Cited By ~ 1

Author(s):

Julie Abildgaard ◽

Magnus Glindvad Ahlström ◽

Gedske Daugaard ◽

Dorte Lisbet Nielsen ◽

Anette Tønnes Pedersen ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Rate Ratio ◽

Bilateral Oophorectomy ◽

Family History Of Cancer ◽

Increased Risk ◽

History Of ◽

Risk Of Cancer ◽

The Impact ◽

History Of Cancer

Abstract Background Current international guidelines recommend systemic hormone therapy (HT) to oophorectomized women until the age of natural menopause. Despite an inherited predisposition to estrogen-dependent malignancies, the guidelines also apply to women oophorectomized because of a family history of cancer. The objective of this study was to investigate the impact of HT on mortality and risk of cancer in women oophorectomized because of a family history of cancer. Methods A nationwide, population-based cohort was used to study women oophorectomized because of a family history of cancer (n = 2002). Comparison cohorts included women from the background population individually matched on age (n = 18 018). Oophorectomized women were subdivided into three groups: oophorectomized at 1) age 45 years or younger not using HT, 2) age 45 years or younger using HT, 3) older than age 45 years, and their respective population comparison cohorts. Results Women oophorectomized at age 45 years or younger using HT had increased overall mortality (mortality rate ratio [MRR] = 3.45, 95% confidence interval [CI] = 1.53 to 7.79), mortality because of cancer (MRR = 5.67, 95% CI = 1.86 to 17.34), and risk of overall cancer (incidence rate ratio [IRR] = 3.68, 95% CI = 1.93 − 6.98), primarily reflected in an increased risk of breast cancer (IRR = 4.88, 95% CI = 2.19 − 10.68). Women oophorectomized at age 45 years or younger not using HT and women oophorectomized at older than age 45 years did not have increased mortality, mortality because of cancer, or risk of overall cancer, but they had increased risk of breast cancer (IRR = 2.64, 95% CI = 1.14 to 6.13, and IRR = 1.72, 95% CI = 1.14 to 2.59, respectively). Conclusions Use of HT in women oophorectomized at age 45 years or younger with a family history of cancer is associated with increased mortality and risk of overall cancer and breast cancer. Our study warrants further investigation to establish the impact of HT on mortality and cancer risk in oophorectomized women with a family history of cancer.

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Hospital visitors as controls in case-control studies

Revista de Saúde Pública ◽

10.1590/s0034-89102001000500005 ◽

2001 ◽

Vol 35 (5) ◽

pp. 436-442 ◽

Cited By ~ 5

Author(s):

Gulnar Azevedo S Mendonça ◽

José Eluf-Neto

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Family History ◽

Case Control ◽

Breast Size ◽

Case Control Studies ◽

Family History Of Cancer ◽

History Of ◽

Incident Cases ◽

History Of Cancer

OBJECTIVE: Selecting controls is one of the most difficult tasks in the design of case-control studies. Hospital controls may be inadequate and random controls drawn from the base population may be unavailable. The aim was to assess the use of hospital visitors as controls in a case-control study on the association of organochlorinated compounds and other risk factors for breast cancer conducted in the main hospital of the "Instituto Nacional de Câncer" -- INCA (National Cancer Institute) in Rio de Janeiro (Brazil). METHODS: The study included 177 incident cases and 377 controls recruited among female visitors. Three different models of control group composition were compared: Model 1, with all selected visitors; Model 2, excluding women visiting relatives with breast cancer; and Model 3, excluding all women visiting relatives with any type of cancer. Odds ratios (OR) and 95% confidence intervals were calculated to test the associations. RESULTS: Age-adjusted OR for breast cancer associated with risk factors other than family history of cancer, except smoking and breast size, were similar in the three models. Regarding family history of all cancers, except for breast cancer, there was a decreased risk in Models 1 and 2, while in Model 3 there was an increased risk, but not statistically significant. Family history of breast cancer was a risk factor in Models 2 and 3, but no association was found in Model 1. In multivariate analysis a significant risk of breast cancer was found when there was a family history of breast cancer in Models 2 and 3 but not in Model 1. CONCLUSIONS: These results indicate that while investigating risk factors unrelated to family history of cancer, the use of hospital visitors as controls may be a valid and feasible alternative.

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The Family-History of Cancer-Patients

BMJ ◽

10.1136/bmj.1.1222.1039 ◽

1884 ◽

Vol 1 (1222) ◽

pp. 1039-1040 ◽

Cited By ~ 2

Author(s):

W. R. Williams

Keyword(s):

Family History ◽

Cancer Patients ◽

Family History Of Cancer ◽

The Family ◽

History Of ◽

History Of Cancer

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Germline mutations in early-onset or hereditary breast cancer from the Middle East.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.20 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 20-20 ◽

Cited By ~ 1

Author(s):

Makia J Marafie ◽

Rabea Al-Temaimi ◽

Andre Megarbane ◽

Fahd Al-Mulla

Keyword(s):

Breast Cancer ◽

Family History ◽

Middle East ◽

Middle Eastern ◽

Germline Mutations ◽

Illumina Platform ◽

Family History Of Cancer ◽

Middle Eastern Women ◽

History Of ◽

History Of Cancer

20 Background: Breast cancer is the most common cancer affecting women of Middle Eastern origin. Epidemiologically, breast cancer in the Middle East clusters in families and usually affects women a decade younger than Western women. This dilemma is compounded by the lack of curated databases and ambitious studies that address the roles genetic or genomic may play in breast cancer. Methods: We have exome sequenced 60 Middle Eastern women with moderate and strong family history of cancer or young women without significant family history of cancer. DNA extracted from peripheral blood of patients and matching normal Middle Eastern women without history of familial or sporadic cancers, were subjected to whole-exome sequencing using the HiSeq 2500 Illumina platform and MLPA to map major breast cancer–activating genetic defects. Results: Several novel BRCA1/2 mutations were identified in the minority of these women. However, other complex mutations in non-BRCA1/2 genes appear to play a more subtle role in breast cancer in the Middle Eastern women. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. Conclusions: BRCA1/2 gene mutations are not a significant cause of heritable cancers in the Middle East. The region may benefit from a well-curated region-specific database accessible to clinicians and scientists where clinical and variants information can be deposited from all over the Middle East.

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