Annual Mammogram Could Save Lives in Women With Family History of Breast Cancer

Laurie Barclay, MD

November 23, 2010

November 23, 2010 — Annual mammography could save lives for women younger than 50 years with a family history of breast cancer, according to findings of the prospective, single-group, Family History 01 (FH01) study reported online November 18 in Lancet Oncology.

"Evidence supports a reduction in mortality from breast cancer with mammographic screening in the general population of women aged 40–49 years, but the effect of family history is not clear," write Stephen W. Duffy, from the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom, and colleagues from the FH01 collaborative teams. "We aimed to establish whether screening affects the disease stage and projected mortality of women younger than 50 years who have a clinically significant family history of breast cancer."

Between January 16, 2003, and February 28, 2007, at 76 UK centers, 6710 women younger than 50 years at intermediate familial risk were enrolled in the single-group FH01 study. Although women with BRCA mutations were eligible, they were estimated to be rare in this population. The investigators compared the FH01 cohort vs women not receiving screening using 2 external comparison groups.

The first comparison group was the control group of the UK Age Trial, consisting of 106,971 women from the general population, assumed to be at average risk. These women were 40 to 42 years old at enrollment and were followed up for 10 years. The second comparison group was from a Dutch study of women with a family history of breast cancer (cancer cases aged 25 - 77 years, diagnosed between 1980 and 2004).

Primary study outcomes were size, node status, and histologic grade of invasive tumors, as well as estimated mortality rate determined from the Nottingham prognostic index score and adjusted for underlying risk differences between the FH01 cohort and the control group of the UK Age Trial.

Participants in FH01 received yearly mammography for a mean of 4 ± 2 years until November 30, 2009, with ongoing surveillance and cancer reporting. Of 136 women diagnosed with breast cancer, 105 (77%) were diagnosed at screening, 28 (21%) because they developed symptoms between screening events, and 3 (2%) because they developed symptoms after missing their latest scheduled mammogram.

Compared with tumors in the control group of the UK Age Trial, invasive tumors in the FH01 study were smaller (P = .0094), less likely to be node positive (P = .0083), and of more favorable histologic grade (P = .0072). They were also less likely to be node positive vs tumors in the Dutch study (P = .012).

The FH01 cohort also had a lower mean Nottingham prognostic index score vs the control group of the UK Age Trial (P = .00079) or the Dutch study (P < .0001). Predicted 10-year mortality rate, after adjustment for underlying risk, was lower in the FH01 cohort (1.10%) vs the control group of the UK Age Trial (1.38%; relative risk, 0.80; 95% confidence interval, 0.66 - 0.96; P = .022).

"Yearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer," the study authors write. "...We recorded significantly fewer cases of node-positive disease and tumours larger than 20 mm in women offered screening than in those who were not. Screening was also associated with lower predicted mortality and higher 10-year survival from invasive cancer than were tumours in the control group of the UK Age Trial."

Limitations of this study include the absence of randomization or a control group, age ranges of the comparison groups differing from that in the FH01 cohort, epoch of diagnosis earlier in both comparison groups vs the FH01 cohort, and possible confounding by characteristics of tumors other than size, node status, and grade.

"We have shown evidence of a reduction in advanced stage disease with mammographic surveillance in women aged 40–49 years who have a family history of breast cancer," the study authors conclude. "On the basis of validated predictors of death from breast cancer, future mortality could be significantly reduced as a result of this intervention."

FH01 was funded by the UK National Health Service Health Technology Assessment. One of the study authors is a clinical consultant for Diagenic (Oslo, Norway). The other study authors have disclosed no relevant financial relationships.

Lancet Oncol. Published online November 18, 2010.

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