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Morphological predictors of BRCA1 germline mutations in young women with breast cancer.

Southey MC, Ramus SJ, Dowty JG, Smith LD, Tesoriero AA, Wong EE, Dite GS, Jenkins MA, Byrnes GB, Winship I, Phillips KA, Giles GG, Hopper JL - Br. J. Cancer (2011)

Bottom Line: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status.Predictors of mutation status were identified using multiple logistic regression.Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Genetic Epidemiology Laboratory, Victoria, Carlton, Australia.

ABSTRACT

Background: Knowing a young woman with newly diagnosed breast cancer has a germline BRCA1 mutation informs her clinical management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer morphology and hormone receptor status data.

Methods: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation.

Results: The probability of being a BRCA1 mutation carrier increased with number of selected histology features even after adjusting for family history and ER and PR status (P<0.0001). From the most parsimonious multivariate model, the odds ratio for being a carrier were: 9.7 (95% confidence interval: 2.6-47.0) for trabecular growth pattern (P=0.001); 7.8 (2.7-25.7) for mitotic index over 50 mitoses per 10 high-powered field (P=0.0003); and 2.7 (1.3-5.9) for each first-degree relative with breast cancer diagnosed before age 60 years (P=0.01).The area under the ROC curve was 0.87 (0.83-0.90).

Conclusion: Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost all BRCA1 germline mutation carriers among women with early-onset breast cancer without taking into account family history.

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Related in: MedlinePlus

Levels of association between the features listed in Table 1. Each row and column corresponds to a feature (in the same order as in Table 1) and the shading represents different levels of odds ratios (ORs), as indicated in the figure. Odds ratios that were <1 were shaded the same as their reciprocals.
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fig2: Levels of association between the features listed in Table 1. Each row and column corresponds to a feature (in the same order as in Table 1) and the shading represents different levels of odds ratios (ORs), as indicated in the figure. Odds ratios that were <1 were shaded the same as their reciprocals.

Mentions: Figure 2 shows that the features within each of the three categories (family history, morphology and immunohistochemistry) were strongly associated with each other. The morphology features and ER and PR status were generally associated with each other but not with the family history features.


Morphological predictors of BRCA1 germline mutations in young women with breast cancer.

Southey MC, Ramus SJ, Dowty JG, Smith LD, Tesoriero AA, Wong EE, Dite GS, Jenkins MA, Byrnes GB, Winship I, Phillips KA, Giles GG, Hopper JL - Br. J. Cancer (2011)

Levels of association between the features listed in Table 1. Each row and column corresponds to a feature (in the same order as in Table 1) and the shading represents different levels of odds ratios (ORs), as indicated in the figure. Odds ratios that were <1 were shaded the same as their reciprocals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065278&req=5

fig2: Levels of association between the features listed in Table 1. Each row and column corresponds to a feature (in the same order as in Table 1) and the shading represents different levels of odds ratios (ORs), as indicated in the figure. Odds ratios that were <1 were shaded the same as their reciprocals.
Mentions: Figure 2 shows that the features within each of the three categories (family history, morphology and immunohistochemistry) were strongly associated with each other. The morphology features and ER and PR status were generally associated with each other but not with the family history features.

Bottom Line: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status.Predictors of mutation status were identified using multiple logistic regression.Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Genetic Epidemiology Laboratory, Victoria, Carlton, Australia.

ABSTRACT

Background: Knowing a young woman with newly diagnosed breast cancer has a germline BRCA1 mutation informs her clinical management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer morphology and hormone receptor status data.

Methods: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation.

Results: The probability of being a BRCA1 mutation carrier increased with number of selected histology features even after adjusting for family history and ER and PR status (P<0.0001). From the most parsimonious multivariate model, the odds ratio for being a carrier were: 9.7 (95% confidence interval: 2.6-47.0) for trabecular growth pattern (P=0.001); 7.8 (2.7-25.7) for mitotic index over 50 mitoses per 10 high-powered field (P=0.0003); and 2.7 (1.3-5.9) for each first-degree relative with breast cancer diagnosed before age 60 years (P=0.01).The area under the ROC curve was 0.87 (0.83-0.90).

Conclusion: Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost all BRCA1 germline mutation carriers among women with early-onset breast cancer without taking into account family history.

Show MeSH
Related in: MedlinePlus