Dataset Information

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

ABSTRACT:

Background

Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.

Methods

In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.

Results

Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer.

Conclusions

This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).

SUBMITTER: Hu C

PROVIDER: S-EPMC8127622 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAbsence from work after breast cancer diagnosis may be part of the burden of disease for women with cancer, but little research has addressed this. We examined work absences of 4 weeks or more among women who had had breast cancer during the 3 years after diagnosis and compared their absences with those of women who had never had cancer.MethodsOur 2 target study groups were women in Quebec 18-59 years of age who were working when they first received therapy for breast cancer between November 1996 and August 1997 and similarly aged women randomly selected from provincial health care files who had never had cancer and were working at the time of diagnosis in women who had cancer. We interviewed 646 women who had had breast cancer (73% of those eligible) and 890 women in the comparison group (51% of those eligible) by telephone 3 years after first diagnosis.ResultsOne year after diagnosis, 85% (459/541) of breast cancer survivors who remained free of disease during the 3-year study period were absent from work for 4 weeks or more compared with 18% (156/881) of healthy women (geometric mean total duration 5.6 v. 1.7 months, p < 0.001). By the third year, disease-free women were not absent more than women in the comparison group; however, more women who had experienced any new cancer event continued to be absent from work and to be absent from work for longer periods of time. Receiving adjuvant chemotherapy prolonged absence duration (9.5 v. 5.4 months among women not receiving chemotherapy). Compared with survivors belonging to a union, those who did not belong to a union (multivariate relative risk [RR] 7.54, 95% confidence interval [CI] 3.02-18.83) and those who were self-employed (RR 13.95, 95% CI 5.53-35.21) were more likely to report no work absence.InterpretationMost of the women with breast cancer took time off work (almost 6 months on average) after receiving the diagnosis. Three years after diagnosis, breast cancer survivors who remained disease-free--a large proportion of women with nonmetastatic breast cancer--were not absent from work more often or for longer periods of time than other working women.

Project description:BackgroundBreast cancer is the most common cancer type for females and has the highest relative number of suicide cases among female-specific cancers. This study aimed to demonstrate suicide rates and changing trends and to identify risk factors for suicide among female breast cancer survivors.MethodsData were derived from the surveillance, epidemiology, and end results database for women diagnosed with breast cancer from 2000 to 2017. Mortality rate and standardized mortality ratios (SMRs) were calculated to describe the incidence rate and trend of suicide among female breast cancer survivors. Gray's test and cumulative incidence function (CIF) curves were used to assess difference of cumulative suicide incidence in subgroups. Multivariate Fine-Gray competing risk model was used to identify risk factors for individual survivors and nomogram model was used to estimate the probability of suicide.ResultThere were 414 suicide cases among 638,547 female breast cancer survivors observed for 5,079,194 person-years, and the suicide rate and SMRs gradually increased with the year of diagnosis. Female breast cancer survivors had a higher risk of suicide than the general population (SMR = 1.19; 95% CI (1.08-1.31)). Based on the result of Fine-Gray competing risk models, age group (50-70 vs <50: HR=0.65, 95% CI:0.52-0.80; >70 vs <50: HR=0.22, 95% CI:0.15-0.32), race/ethnicity (black vs white: HR= 0.20, 95% CI: 0.11-0.36; other race vs white: HR= 0.67, 95% CI: 0.46-0.97), marital status (separated vs married: HR= 1.50, 95% CI: 1.16-1.94; single vs married: HR= 1.70, 95% CI: 1.31-2.20), stage (distant vs regional: HR= 0.30, 95% CI: 0.14-0.63), radiotherapy (Yes vs No/Unknown: HR= 0.62, 95% CI: 0.49-0.77), and molecular subtypes (HER-2 vs Luminal B (HR= 2.53, 95% CI: 1.10-5.82), TNBC vs Luminal B (HR= 2.11, 95% CI: 1.01-4.42)) were independent predictors of suicide among female breast cancer patients. A nomogram was constructed to predict the suicide probability for individual survivors with a C-index of 0.62 (95%CI: 0.59-0.66).ConclusionFemale breast cancer survivors with younger age (less than 50 years old), white race, unmarried status, regional stage, HER-2 or TNBC subtype, and no radiotherapy performed were more likely to commit suicide. The clinicians and family members should pay more attention to patients with high risk factors of suicide to decrease the mortality rate.

Project description:BackgroundSmall-sized primary tumor does not always indicate a better prognosis. We hypothesized that very small primary breast tumors with extensive lymph node (LN) metastases represented an aggressive biologic behavior in stage IV disease.Materials and methodsData between 2010 and 2015 were retrieved retrospectively from the Surveillance, Epidemiology, and End Results database with inclusion criteria of female sex, unilateral, metastatic, and T1/2 invasive ductal carcinoma. Primary study variables included T stage, N stage, grade, metastatic sites, number of involved sites, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. Kaplan-Meier and adjusted Cox proportional hazards models with interaction terms were used. One-, 2- and 3-year breast cancer-specific mortality (BCSM) was examined according to tumor size.ResultsWe identified 5,340 eligible patients with breast cancer. In multivariate analysis, race, age, grade, molecular subtype, surgery, brain metastases, and liver metastases were found to be independently associated with BCSM. For T1 tumors, the N0, N1, and N2+ groups had the same BCSM. In tumors smaller than 50 mm, the 1-, 2-, and 3-year BCSM did not decline with the decrease of tumor size. For triple-negative breast cancers (TNBCs), the T1a/T1bN2+ group had significantly worse BCSM than any other group did.ConclusionPatients with stage IV cancer with small-sized tumors may have BCSM as high as those with larger tumors. In TNBCs, very small tumors with severe LN involvement are associated with the worst BCSM. Continued efforts are needed to further investigate Ta1/T1bN2 + M1 TNBCs and individualize the treatment for affected patients.Implications for practiceThis study revealed that for stage IV breast cancer, smaller primary tumors were not always associated with better breast cancer-specific mortality. This study illustrated that very small triple-negative breast cancers (TNBCs) with extensive regional lymph node involvement may be a surrogate for biologically aggressive disease. Because of poor prognosis of T1a/T1bN2+ TNBCs, there might be an urgent need of more individualized treatment for affected patients. Future correlative studies ought to focus on the genetic and molecular differences in Ta1/T1bN2+ TNBCs that contribute to the biological behavior. Clarification of the regulation mechanism of very small-sized primary TNBCs with metastatic outgrowth in nodes and distant sites will play an integral role in developing targeted therapies.