Elsevier

The Lancet

Volume 358, Issue 9291, 27 October 2001, Pages 1389-1399
The Lancet

Articles
Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease

https://doi.org/10.1016/S0140-6736(01)06524-2Get rights and content

Summary

Background

Women with a family history of breast cancer are at increased risk of the disease, but no study has been large enough to characterise reliably how, over women's lives, this risk is influenced by particular familial patterns of breast cancer. This report, on the relevance of breast cancer in first-degree relatives, is based on combined data from 52 epidemiological studies.

Methods

Individual data on breast cancer in first-degree relatives (mothers, sisters, and daughters) of 58 209 women with breast cancer and of 101 986 controls were collected, checked, and analysed centrally. Risk ratios for breast cancer were calculated by conditional logistic regression, stratified by study, age, menopausal status, number of sisters, parity, and age when the first child was born. Breast-cancer incidence and mortality rates for particular family histories were calculated by applying age-specific risk ratios to breast-cancer rates typical for more-developed countries.

Findings

Altogether 7496 (12·9%) women with breast cancer and 7438 (7·3%) controls reported that one or more first-degree relatives had a history of breast cancer: 12% of women with breast cancer had one affected relative and 1% had two or more. Risk ratios for breast cancer increased with increasing numbers of affected first-degree relatives: compared with women who had no affected relative, the ratios were 1·80 (99% CI 1·69–1·91), 2·93 (2·36–3·64), and 3·90 (2·03–7·49), respectively, for one, two, and three or more affected first-degree relatives (p<0·0001 each). The risk ratios were greatest at young ages, and for women of a given age, were greater the younger the relative was when diagnosed. The results did not differ substantially between women reporting an affected mother (9104) or sister (6386). Other factors, such as childbearing history, did not significantly alter the risk ratios associated with a family history of breast cancer. For women in more-developed countries with zero, one, or two affected first-degree relatives, the estimated cumulative incidence of breast cancer up to age 50 was 1·7%, 3·7%, and 8·0%, respectively; corresponding estimates for incidence up to age 80 were 7·8%, 13·3%, and 21·1%. Corresponding estimates for death from breast cancer up to age 80 were 2·3%, 4·2%, and 7·6%. The age when the relative was diagnosed had only a moderate effect on these estimates.

Interpretation

Eight out of nine women who develop breast cancer do not have an affected mother, sister, or daughter. Although women who have first-degree relatives with a history of breast cancer are at increased risk of the disease, most will never develop breast cancer, and most who do will be aged over 50 when their cancer is diagnosed. In countries where breast cancer is common, the lifetime excess incidence of breast cancer is 5·5% for women with one affected first-degree relative and 13·3% for women with two.

Introduction

A woman's risk of developing breast cancer is increased if she has a family history of the disease. However, no study has been large enough to characterise reliably how, over a woman's life, the risk of breast cancer is influenced by particular patterns of disease in first-degree relatives (mothers, sisters, or daughters). The Collaborative Group on Hormonal Factors in Breast Cancer has brought together, for central review and analysis, relevant data from 52 epidemiological studies of women with breast cancer. Findings from these studies have already been published on the relation between breast cancer and the use of hormonal contraceptives and of hormone replacement therapy.1, 2, 3 This report, which presents data on 58 209 women with breast cancer and 101 986 controls, describes the relevance of the pattern of breast cancer in first-degree female relatives to a woman's risk of developing the disease at various ages. Although estimates of absolute risk would depend on breast-cancer incidence rates, genetic background, and childbearing history in each population studied, the patterns reported here may be expected to have general application.

Section snippets

Contributing studies and collection of data

Epidemiological studies were eligible for this collaboration if they included at least 100 women with incident invasive breast cancer and sought information from each woman on reproductive and hormonal factors. Methods for identifying such studies have been described elsewhere, and we estimate that more than 80% of eligible data worldwide are included in this collaboration.1, 2, 3 Data sought from principal investigators of each study included whether or not each woman's mother, sister(s), or

Overall findings

Altogether 58 209 women with invasive breast cancer (cases) and 101 986 women without breast cancer (controls) from 52 studies were included in these analyses (table 1). The median age of the women varied substantially from one study to another, but for all studies combined it was 52 for cases and 53 for controls. The proportion of women reporting a history of breast cancer in a mother or sister also varied from one study to another, tending to increase as the median age of the study population

Discussion

This collaborative reanalysis of individual data from 52 studies confirms the well-established increased risk of breast cancer among women with a family history of the disease. It also shows, however, that most women with one or more affected first-degree relatives will never develop the disease themselves and that most women who develop breast cancer do not have an affected first-degree relative.

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    *Collaborators and collaborating centres are given on The Lancet's website (www.thelancet.com)

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