Worse Breast Cancer Prognosis of BRCA1/BRCA2 Mutation Carriers: What's the Evidence? A Systematic Review with Meta-Analysis

Broek, Alexandra J. van den; Schmidt, Marjanka K.; Veer, Laura J. van ’t; Tollenaar, Rob A.E.M.; Leeuwen, Flora E. van

doi:10.1371/journal.pone.0120189

Cited by 96 publications

(74 citation statements)

References 64 publications

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“…Mutations in BRCA are more commonly studied in the setting of breast or ovarian cancer. 22,23 Although the association between BRCA mutations and PDAC in both the familial and seemingly sporadic case is known, the rarity of the diagnosis compounded by the infrequent nature of genetic testing has led to few studies of BRCA mutation and its impact on patient survival. 24–28 In theory, BRCA mutations in PDAC may fall within the unstable genotype, representing a more mutagenic and aggressive tumor biology and subsequent worse survival.…”

Section: Discussionmentioning

confidence: 99%

BRCA1/BRCA2 Germline Mutation Carriers and Sporadic Pancreatic Ductal Adenocarcinoma

Blair

Groot

Gemenetzis

et al. 2018

Journal of the American College of Surgeons

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BACKGROUND: The outcomes of sporadic pancreatic ductal adenocarcinoma (PDAC) patients with germline mutations of BRCA1/BRCA2 remains unclear. The prognostic significance of BRCA1/BRCA2 mutations on survival is not well established. STUDY DESIGN: We performed targeted next-generation sequencing (NGS) to identify BRCA1/BRCA2 germline mutations in resected sporadic PDAC cases from 2000 to 2015. Germline BRCA mutation carriers were matched by age and tumor location to those with BRCA1/BRCA2 wild-type genes from our institutional database. Demographics, clinicopathologic features, overall survival (OS), and disease-free survival (DFS) were abstracted from medical records and compared between the 2 cohorts. RESULTS: Twenty-two patients with sporadic cancer and BRCA1 (n = 4) or BRCA2 (n = 18) germline mutations and 105 wild-type patients were identified for this case-control study. The BRCA1/ BRCA2 mutations were associated with inferior median OS (20.2 vs 27.8 months, p = 0.034) and DFS (8.4 vs 16.7 months, p < 0.001) when compared with the matched wild-type controls. On multivariable analyses, a BRCA1/BRCA2 mutation (hazard ratio [HR] 2.10, p < 0.001), positive margin status (HR 1.72, p = 0.021), and lack of adjuvant therapy (HR 2.38, p < 0.001), were all independently associated with worse survival. Within the BRCA1/BRCA2 mutated group, having had platinum-based adjuvant chemotherapy (n = 10) was associated with better survival than alternative chemotherapy (n = 8) or no adjuvant therapy (n = 4) (31.0 vs 17.8 vs 9.3 months, respectively, p < 0.001). CONCLUSIONS: Carriers of BRCA1/BRCA2 mutation with sporadic PDAC had a worse survival after pancreatectomy than their BRCA wild-type counterparts. However, platinum-based chemotherapy regimens were associated with markedly improved survival in patients with BRCA1/BRCA2 mutations,with survival differences no longer appreciated with wild-type patients.

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Section: Discussionmentioning

confidence: 99%

BRCA1/BRCA2 Germline Mutation Carriers and Sporadic Pancreatic Ductal Adenocarcinoma

Blair

Groot

Gemenetzis

et al. 2018

Journal of the American College of Surgeons

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“…However, to reduce the potential influence of this group, women younger than 49 years were excluded. A systematic review has also shown that there is no difference in the proportions of advanced stage cancers between carriers and noncarriers of the BRCA1/2 mutation . Another issue is that participation in the screening program was voluntary, which meant that several factors may have influenced attendance; in particular, it is known that women with a low SES have lower attendance rates .…”

Section: Discussionmentioning

confidence: 99%

Is the incidence of advanced‐stage breast cancer affected by whether women attend a steady‐state screening program?

Munck

Fracheboud

Bock

et al. 2018

Intl Journal of Cancer

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In this cross-sectional population-based study, we assessed the incidence of advanced breast cancer based on screening attendance. Women from the Netherlands Cancer Registry were included if aged ≥49 years and diagnosed with breast cancer between 2006 and 2011, and data were linked with the screening program. Cancers were defined as screen-related (diagnosed <24 months after screening) or nonscreened (all other breast cancers). Two cut-offs were used to define advanced breast cancer: TNM-stage (III-IV vs 0-I-II) and T-stage alone (≥15 mm vs <15 mm or DCIS). The incidence rates were adjusted for age and logistic regression was used to compare groups. Of the 72,612 included women diagnosed with breast cancer, 44,246 (61%) had screen-related breast cancer. By TNM stage, advanced cancer was almost three times as likely to be at an advanced TNM stage in the nonscreened group compared with the screen-related group (38 and 94 per 100,000, respectively; OR: 2.86, 95%CI: 2.72-3.00). By T-stage, the incidence of advanced cancer was higher overall, and in nonscreened women was significantly higher than in screened women (210 and 169 per 100,000; OR: 1.85, 95%CI: 1.78-1.93). Data on actual screening attendance showed that the incidence of advanced breast cancer was significantly higher in nonscreened women than in screened women, supporting the expectation that screening would cause a stage shift to early detection. Despite critical evaluations of breast cancer screening programs, our data show that breast cancer screening is a valuable tool that can reduce the disease burden in women.

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“…(c) that found that of 66 studies assessing the survival of BRCA1/2 mutation carriers, only 8 corrected for confounding by adjuvant treatment [32]. Current evidence suggests that contrary to currently held beliefs, if confounding by treatment is taken into account, differences in survival between BRCA1/2 mutation carriers and sporadic breast cancer patients if any are likely to be small.…”

Section: Discussionmentioning

confidence: 95%

Familial versus Sporadic Breast Cancer: Different Treatments for Similar Tumors?

Engelhardt¹,

Kriege²,

Hooning³

et al. 2015

ABCR

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Objective: It is unclear if and to what extent family history of breast/ovarian cancer or BRCA1/2-mutation carriership influences breast cancer treatment strategy. We investigated whether treatment differed between patients from BRCA1/2 families and those unselected for family history. Methods: We included 478 BRCA1/2-related patients referred for genetic testing before or after diagnosis. Two references were used: 13,498 population-based and 6896 hospital-based patients. Surgical treatment and adjuvant chemotherapy use was analyzed using logistic regression models, stratified by tumor size, nodal status, age at and period of diagnosis, and estrogen receptor status (ER). Results: BRCA1/2 cases aged 35 -52 years at diagnosis and/or with tumors < 2 cm were more likely to have undergone a modified radical mastectomy (Odd Ratios (OR) ranging from 2.8 to 5.1) compared to the references. This effect was most pronounced in patients treated after 1995 (OR 5.7 to 10.3). Compared to the reference groups, chemotherapy was more often administered to BRCA1 and ER-negative BRCA1/2-cases irrespective of age and nodal status (OR 1.9 E. G. Engelhardt et al. 88to 24.3). Conclusion: After 1995 treatment of BRCA1/2-associated patients consisted notably of more mastectomies and adjuvant chemotherapy than their population-based counterparts with the same tumor characteristics. There is a need to be aware of such differences in daily practice and interpretation of survival studies on BRCA1/2 mutation carriers.

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Worse Breast Cancer Prognosis of BRCA1/BRCA2 Mutation Carriers: What's the Evidence? A Systematic Review with Meta-Analysis

Cited by 96 publications

References 64 publications

BRCA1/BRCA2 Germline Mutation Carriers and Sporadic Pancreatic Ductal Adenocarcinoma

BRCA1/BRCA2 Germline Mutation Carriers and Sporadic Pancreatic Ductal Adenocarcinoma

Is the incidence of advanced‐stage breast cancer affected by whether women attend a steady‐state screening program?

Familial versus Sporadic Breast Cancer: Different Treatments for Similar Tumors?

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