Mammographic surveillance in women younger than 50 years who have a family history of breast cancer

tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study

Stephen W. Duffy, James Mackay, Sue Thomas, Elaine Anderson, D. Gareth Evans, Hilary Fielder, Rosemary Fox, Jonathon Gray, Gerald Gui, Douglas Macmillan, Sue Moss, Cerilan Rogers, Richard Sainsbury, Mark Sibbering, Caroline Boggis, John Burn, Jack Cuzick, Bob Haward, Anthony Howell, Robert Mansel & 31 others Hazel Marshall Cork, John Robertson, Julietta Patnick, Paul Pharoah, Anne Robinson, Stephen Sutton, Masako Kataoka, Penelope Moyle, Matthew Wallis, Ruth Warren, Ellis Louise Jones, Joan Austoker, Alison Clements, Eila Watson, Ken Young, Prue Allgood, Phil Duffy, Rhian Gabe, Lorraine Roberts, Iqbal Warsi, Jack Caunt, Adam Brentnall, Fiona Dungey, J. Ferguson, Fiona Gilbert, Zosia Miedzybrodzka, Fiona Read, C. Simpson, D. Smith, James Steel, FH01 Collaborative Teams

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background
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. 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.

Methods
In the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106¿971 women aged 40–42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25–77 years, diagnosed 1980–2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809.

Findings
6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the interval between screening events, and three (2%) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0·0094), less likely to be node positive (p=0·0083), and of more favourable grade (p=0·0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0·012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0·00079) or the Dutch study (p<0·0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1·10%) than in the control group of the UK Age Trial (1·38%), with relative risk of 0·80 (95% CI 0·66–0·96; p=0·022).

Interpretation
Yearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer.

Funding
UK National Health Service Health Technology Assessment.
Original languageEnglish
Pages (from-to)1127-1134
Number of pages8
JournalThe Lancet Oncology
Volume11
Issue number12
Early online date18 Nov 2010
DOIs
Publication statusPublished - Dec 2010

Keywords

  • randomized controlled-trial
  • BRCA2 mutation carriers
  • screening program
  • follow-up
  • age 40
  • survival
  • risk
  • susceptibility
  • impact
  • ultrasound

Cite this

Mammographic surveillance in women younger than 50 years who have a family history of breast cancer : tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study. / Duffy, Stephen W.; Mackay, James; Thomas, Sue; Anderson, Elaine; Evans, D. Gareth; Fielder, Hilary; Fox, Rosemary; Gray, Jonathon; Gui, Gerald; Macmillan, Douglas; Moss, Sue; Rogers, Cerilan; Sainsbury, Richard; Sibbering, Mark; Boggis, Caroline; Burn, John; Cuzick, Jack; Haward, Bob; Howell, Anthony; Mansel, Robert; Cork, Hazel Marshall; Robertson, John; Patnick, Julietta; Pharoah, Paul; Robinson, Anne; Sutton, Stephen; Kataoka, Masako; Moyle, Penelope; Wallis, Matthew; Warren, Ruth; Jones, Ellis Louise; Austoker, Joan; Clements, Alison; Watson, Eila; Young, Ken; Allgood, Prue; Duffy, Phil; Gabe, Rhian; Roberts, Lorraine; Warsi, Iqbal; Caunt, Jack; Brentnall, Adam; Dungey, Fiona; Ferguson, J.; Gilbert, Fiona; Miedzybrodzka, Zosia; Read, Fiona; Simpson, C.; Smith, D.; Steel, James; FH01 Collaborative Teams.

In: The Lancet Oncology, Vol. 11, No. 12, 12.2010, p. 1127-1134.

Research output: Contribution to journalArticle

Duffy, SW, Mackay, J, Thomas, S, Anderson, E, Evans, DG, Fielder, H, Fox, R, Gray, J, Gui, G, Macmillan, D, Moss, S, Rogers, C, Sainsbury, R, Sibbering, M, Boggis, C, Burn, J, Cuzick, J, Haward, B, Howell, A, Mansel, R, Cork, HM, Robertson, J, Patnick, J, Pharoah, P, Robinson, A, Sutton, S, Kataoka, M, Moyle, P, Wallis, M, Warren, R, Jones, EL, Austoker, J, Clements, A, Watson, E, Young, K, Allgood, P, Duffy, P, Gabe, R, Roberts, L, Warsi, I, Caunt, J, Brentnall, A, Dungey, F, Ferguson, J, Gilbert, F, Miedzybrodzka, Z, Read, F, Simpson, C, Smith, D, Steel, J & FH01 Collaborative Teams 2010, 'Mammographic surveillance in women younger than 50 years who have a family history of breast cancer: tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study', The Lancet Oncology, vol. 11, no. 12, pp. 1127-1134. https://doi.org/10.1016/S1470-2045(10)70263-1
Duffy, Stephen W. ; Mackay, James ; Thomas, Sue ; Anderson, Elaine ; Evans, D. Gareth ; Fielder, Hilary ; Fox, Rosemary ; Gray, Jonathon ; Gui, Gerald ; Macmillan, Douglas ; Moss, Sue ; Rogers, Cerilan ; Sainsbury, Richard ; Sibbering, Mark ; Boggis, Caroline ; Burn, John ; Cuzick, Jack ; Haward, Bob ; Howell, Anthony ; Mansel, Robert ; Cork, Hazel Marshall ; Robertson, John ; Patnick, Julietta ; Pharoah, Paul ; Robinson, Anne ; Sutton, Stephen ; Kataoka, Masako ; Moyle, Penelope ; Wallis, Matthew ; Warren, Ruth ; Jones, Ellis Louise ; Austoker, Joan ; Clements, Alison ; Watson, Eila ; Young, Ken ; Allgood, Prue ; Duffy, Phil ; Gabe, Rhian ; Roberts, Lorraine ; Warsi, Iqbal ; Caunt, Jack ; Brentnall, Adam ; Dungey, Fiona ; Ferguson, J. ; Gilbert, Fiona ; Miedzybrodzka, Zosia ; Read, Fiona ; Simpson, C. ; Smith, D. ; Steel, James ; FH01 Collaborative Teams. / Mammographic surveillance in women younger than 50 years who have a family history of breast cancer : tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study. In: The Lancet Oncology. 2010 ; Vol. 11, No. 12. pp. 1127-1134.
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abstract = "BackgroundEvidence 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. 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.MethodsIn the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106¿971 women aged 40–42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25–77 years, diagnosed 1980–2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809.Findings6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77{\%}) at screening, 28 (21{\%}) symptomatically in the interval between screening events, and three (2{\%}) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0·0094), less likely to be node positive (p=0·0083), and of more favourable grade (p=0·0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0·012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0·00079) or the Dutch study (p<0·0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1·10{\%}) than in the control group of the UK Age Trial (1·38{\%}), with relative risk of 0·80 (95{\%} CI 0·66–0·96; p=0·022).InterpretationYearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer.FundingUK National Health Service Health Technology Assessment.",
keywords = "randomized controlled-trial, BRCA2 mutation carriers, screening program, follow-up, age 40, survival, risk, susceptibility, impact, ultrasound",
author = "Duffy, {Stephen W.} and James Mackay and Sue Thomas and Elaine Anderson and Evans, {D. Gareth} and Hilary Fielder and Rosemary Fox and Jonathon Gray and Gerald Gui and Douglas Macmillan and Sue Moss and Cerilan Rogers and Richard Sainsbury and Mark Sibbering and Caroline Boggis and John Burn and Jack Cuzick and Bob Haward and Anthony Howell and Robert Mansel and Cork, {Hazel Marshall} and John Robertson and Julietta Patnick and Paul Pharoah and Anne Robinson and Stephen Sutton and Masako Kataoka and Penelope Moyle and Matthew Wallis and Ruth Warren and Jones, {Ellis Louise} and Joan Austoker and Alison Clements and Eila Watson and Ken Young and Prue Allgood and Phil Duffy and Rhian Gabe and Lorraine Roberts and Iqbal Warsi and Jack Caunt and Adam Brentnall and Fiona Dungey and J. Ferguson and Fiona Gilbert and Zosia Miedzybrodzka and Fiona Read and C. Simpson and D. Smith and James Steel and {FH01 Collaborative Teams}",
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TY - JOUR

T1 - Mammographic surveillance in women younger than 50 years who have a family history of breast cancer

T2 - tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study

AU - Duffy, Stephen W.

AU - Mackay, James

AU - Thomas, Sue

AU - Anderson, Elaine

AU - Evans, D. Gareth

AU - Fielder, Hilary

AU - Fox, Rosemary

AU - Gray, Jonathon

AU - Gui, Gerald

AU - Macmillan, Douglas

AU - Moss, Sue

AU - Rogers, Cerilan

AU - Sainsbury, Richard

AU - Sibbering, Mark

AU - Boggis, Caroline

AU - Burn, John

AU - Cuzick, Jack

AU - Haward, Bob

AU - Howell, Anthony

AU - Mansel, Robert

AU - Cork, Hazel Marshall

AU - Robertson, John

AU - Patnick, Julietta

AU - Pharoah, Paul

AU - Robinson, Anne

AU - Sutton, Stephen

AU - Kataoka, Masako

AU - Moyle, Penelope

AU - Wallis, Matthew

AU - Warren, Ruth

AU - Jones, Ellis Louise

AU - Austoker, Joan

AU - Clements, Alison

AU - Watson, Eila

AU - Young, Ken

AU - Allgood, Prue

AU - Duffy, Phil

AU - Gabe, Rhian

AU - Roberts, Lorraine

AU - Warsi, Iqbal

AU - Caunt, Jack

AU - Brentnall, Adam

AU - Dungey, Fiona

AU - Ferguson, J.

AU - Gilbert, Fiona

AU - Miedzybrodzka, Zosia

AU - Read, Fiona

AU - Simpson, C.

AU - Smith, D.

AU - Steel, James

AU - FH01 Collaborative Teams

PY - 2010/12

Y1 - 2010/12

N2 - BackgroundEvidence 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. 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.MethodsIn the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106¿971 women aged 40–42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25–77 years, diagnosed 1980–2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809.Findings6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the interval between screening events, and three (2%) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0·0094), less likely to be node positive (p=0·0083), and of more favourable grade (p=0·0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0·012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0·00079) or the Dutch study (p<0·0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1·10%) than in the control group of the UK Age Trial (1·38%), with relative risk of 0·80 (95% CI 0·66–0·96; p=0·022).InterpretationYearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer.FundingUK National Health Service Health Technology Assessment.

AB - BackgroundEvidence 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. 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.MethodsIn the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106¿971 women aged 40–42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25–77 years, diagnosed 1980–2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809.Findings6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the interval between screening events, and three (2%) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0·0094), less likely to be node positive (p=0·0083), and of more favourable grade (p=0·0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0·012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0·00079) or the Dutch study (p<0·0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1·10%) than in the control group of the UK Age Trial (1·38%), with relative risk of 0·80 (95% CI 0·66–0·96; p=0·022).InterpretationYearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer.FundingUK National Health Service Health Technology Assessment.

KW - randomized controlled-trial

KW - BRCA2 mutation carriers

KW - screening program

KW - follow-up

KW - age 40

KW - survival

KW - risk

KW - susceptibility

KW - impact

KW - ultrasound

U2 - 10.1016/S1470-2045(10)70263-1

DO - 10.1016/S1470-2045(10)70263-1

M3 - Article

VL - 11

SP - 1127

EP - 1134

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 12

ER -