Breast Cancer Survival of BRCA1/BRCA2 Mutation Carriers in a Hospital-Based Cohort of Young Women

Schmidt, Marjanka K.; Broek, Alexandra J. van den; Tollenaar, Rob A.E.M.; Smit, Vincent T.H.B.M.; Westenend, Pieter J.; Brinkhuis, Mariël; Oosterhuis, Wolter; Wesseling, Jelle; Janssen‐Heijnen, M.L.G.; Jobsen, Jan J.; Jager, Agnes; Voogd, Adri C.; Leeuwen, Flora E. van; Veer, Laura J. van ’t

doi:10.1093/jnci/djw329

Cited by 65 publications

(67 citation statements)

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“…In our study, we screened all coding regions and exon–intron boundaries of BRCA1/2 and PALB2 genes in 2769 unselected Chinese women with breast cancer using next‐generation sequencing assays. The findings of our study showed that the overall prevalence of BRCA1 and BRCA2 mutations was 5.4%, which is similar to those reported in unselected patients in China (5.3%) and Malaysia (6.0%) recently . However, this prevalence is lowered than that detected in the unselected Ashkenazi Jewish population (mutation rates range from10.3 to 12%) …”

Section: Discussionsupporting

confidence: 84%

“…However, whether the germline mutations in BRCA1/2 or in PALB2 genes have independent prognostic influence on breast cancer patients remains unclear. Some previous studies reported that BRCA1/2 mutation carriers had a better survival outcome when compared to control groups, while other studies suggested that the prognosis was worse or no different, and most of them were based on patients with breast cancer selected for family history or age at diagnosis. More importantly, to date, few studies have estimated the survival rate in women with a PALB2 mutation and breast cancer …”

Section: Introductionmentioning

confidence: 99%

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Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China

Deng

Chen

Zhu

et al. 2019

Intl Journal of Cancer

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To gain more information on the prevalence of germline mutations in BRCA1/2 and PALB2 genes in the Chinese population, and to explore the effects of the mutation status of these genes on clinical outcomes in patients with breast cancer, we performed a screening for BRCA1/2 and PALB2 mutations in a consecutive series of unselected breast cancer patients in the Chinese population. A total of 2,769 cases were enrolled between June 1993 and September 2017. All of the exons and exon-intron boundaries of the BRCA1/2 and PALB2 genes were screened with next-generation sequencing. Of the 2,769 breast cancer patients, BRCA1, BRCA2 and PALB2 mutations accounted for 2.7% (n = 74), 2.7% (n = 76), and 0.9% (n = 24), respectively. The BRCA1 gene had the highest mutation frequency in patients with triple-negative breast cancer (TNBC), which was 9.6% (n = 42), while the BRCA2 gene had the highest mutation frequency in patients with Luminal, which was 3.2% (n = 58). The disease-free survival (DFS) of BRCA1 mutation carriers was significantly lower than that of noncarriers (adjusted HR = 2.20, 95% CI = 1.15-4.18, p = 0.017). The mutation status of the PALB2 gene was significantly associated with the decline in overall survival (OS) (adjusted HR = 8.38, 95% CI = 2.19-32.11, p = 0.002). No significant difference was found between BRCA2 pathogenic mutation carriers and noncarriers. These results demonstrate that BRCA1 mutation status may be associated with a worse disease progression in patients with breast cancer, and women who harbored a PALB2 mutation might be at a higher risk of death due to breast cancer compared to noncarriers.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China

Deng

Chen

Zhu

et al. 2019

Intl Journal of Cancer

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“…Our results were in broad agreement with more recent studies, although others had reported conflicting results. [27][28][29][30][31][32] The percentage of BRCA-associated patients in our study (12.6%) was similar to a prior prospective cohort study, 33 The bold values derived from univariated analysis indicate that BRCA-mutation status and menopausal status might attribute to risk of contralateral breast cancer (CBC), however, only BRCA-mutation status confer to the independent risk factor of CBC.…”

Section: Discussionsupporting

confidence: 85%

Outcomes and risk of subsequent breast events in breast‐conserving surgery patients with BRCA1 and BRCA2 mutation

Huang

Lang

et al. 2020

Cancer Medicine

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Purpose Previous studies provide inconsistent interpretations of the effect of inherited genetic factors on the survival and prognosis of patients with breast cancer. The aim of this study was to examine the effect of germline BRCA1 and BRCA2 mutation on survival and subsequent breast events in Chinese women who underwent breast‐conserving surgery. Methods A retrospective review of the clinical and pathological records was performed in patients diagnosed with primary invasive breast cancer between 2005 and 2018 in the cancer registry database. Clinicopathological data and data regarding treatment and outcomes, including date and site of disease progression, were collected. The survival outcomes and independent risk factors were conducted using SPSS. Results Overall, a total of 501 patients who underwent breast‐conserving surgery were identified and subjected to analyses, of which 63 cases with BRCA1 or BRCA2 mutation. The median age at diagnosis was 41 (range, 24‐74) for carriers and 37 (range, 17‐84) for noncarriers. After a median follow‐up time of 61 months (range, 8‐161) and 70 months (range, 0‐153), respectively, in carriers and noncarriers, the overall survival (P = .173) and disease‐free survival (P = .424) were not significantly different. Analogously, there was no significant difference between the two groups about the outcomes of ipsilateral breast tumor recurrence (P = .348), yet the contralateral breast cancer (CBC) was overt worse than noncarriers (P < .001). When adjusted to confounding factors, BRCA mutation was the only independent risk factors to CBC (HR = 7.89, P = .01). Conclusion In this study, BRCA mutation carriers have higher risk of CBC. And, BRCA mutation is the only independent risk factor to CBC. Therefore, intensive surveillance and follow‐up as well as more effective individual prevention are urgent. Decisions on alternatively effective prevention, especially the prevention of CBC, are urgent and should take into account patient prognosis and preferences.

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“…Published studies and meta-analyses have reported better, worse, and similar outcomes for patients with a BRCA1 or BRCA2 mutation compared with patients with sporadic breast cancer. 8 , 9 , 10 , 11 , 12 , 13 , 14 A comprehensive meta-analysis of 66 studies of breast cancer survival in patients with a BRCA1 or BRCA2 mutation compared with non-carrier patients or the general breast cancer population, which assessed study quality as well as outcome data, concluded that “it is not yet possible to draw evidence based conclusions about the association between BRCA1 [or] BRCA2 mutation carriership and breast cancer prognosis”. 12 We undertook the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study, the primary aim of which was to determine the effect of inherited BRCA1 or BRCA2 mutations on outcomes in patients with young-onset breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study

Copson

Maishman

Tapper

et al. 2018

The Lancet Oncology

342

256

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SummaryBackgroundRetrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer.MethodsWe did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing.FindingsBetween Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0–9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% [95% CI 94·5–98·4] vs 96·6% [95·8–97·3]; at 5 years: 83·8% [79·3–87·5] vs 85·0% [83·5–86·4]; at 10 years: 73·4% [67·4–78·5] vs 70·1% [67·7–72·3]; hazard ratio [HR] 0·96 [95% CI 0·76–1·22]; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% [95% CI 89–97] vs 91% [88–94]; HR 0·59 [95% CI 0·35–0·99]; p=0·047) but not 5 years (81% [73–87] vs 74% [70–78]; HR 1·13 [0·70–1·84]; p=0·62) or 10 years (72% [62–80] vs 69% [63–74]; HR 2·12 [0·82–5·49]; p= 0·12).InterpretationPatients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences.FundingCancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.

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Breast Cancer Survival of BRCA1/BRCA2 Mutation Carriers in a Hospital-Based Cohort of Young Women

Abstract: BRCA1/2 mutation carriers diagnosed with breast cancer before age 50 years are prone to a worse survival, which is partly explained by differences in tumor characteristics, treatment response, and second ovarian cancers.

Cited by 65 publications

References 44 publications

Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China

Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China

Outcomes and risk of subsequent breast events in breast‐conserving surgery patients with BRCA1 and BRCA2 mutation

Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study

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