Reproductive factors and specific histological types of breast cancer: prospective study and meta-analysis

Abstract

Little is known about how reproductive factors affect the risk of breast cancers of different histology. In an analysis of prospective data on 1.2 million middle-aged UK women, we used proportional hazards models to estimate the relative risks of six histological types in relation to menarche, childbearing and menopause. During 8.7 million person-years of follow-up, 17 923 ductal, 3332 lobular, 1062 tubular, 944 mixed ductal lobular, 330 mucinous and 117 medullary cancers were diagnosed. The effect of both age at menarche and age at first birth was greatest for lobular tumours; relative risks per 5-year increase in age at menarche for ductal, lobular, and tubular cancers were 0.93 (0.87 -0.99), 0.65 (0.56 -0.76), and 0.75 (0.57 -0.98), respectively (P-value for heterogeneity ¼ 0.0001); and the relative risks per 5-year increase in age at first birth were 1.10 (1.07 -1.12), 1.23 (1.17 -1.29), and 1.13 (1.03 -1.23), respectively (Pvalue for heterogeneity ¼ 0.0006). Increasing parity reduced the risk of each tumour type, except medullary cancers, but the reduction in risk was greater for mucinous cancers than for any other subtype considered (Po0.05 for comparison with each other subtype in turn). The effect of menopause did not vary significantly by tumour histology. Meta-analysis of published results on the effects of age at menarche and age at first birth on ductal and lobular cancers were in keeping with our findings. Keywords: breast cancer histology; menarche; age at first birth; parity; menopause Despite the fact that reproductive factors are among the most established risk factors for breast cancer, little is known about whether their effects differ by tumour histology. Few studies of breast cancer in relation to reproductive factors have had sufficient power to estimate reliably the risk of specific subtypes according to detailed reproductive history. We report here on the relationship between age at menarche, parity, age at first birth and age at menopause, and the risk of six histological subtypes of breast cancer in a large prospective study of women in the UK, and present meta-analyses of published results. MATERIALS AND METHODSThe Million Women Study recruited 1.3 million middle-aged women in 1996 -2001, who completed a questionnaire about reproductive factors, sociodemographic factors and other personal characteristics. They were resurveyed about 3 years after recruitment to update information on menopausal status and other factors, with a 65% response rate. Full details of the study design and methods are described elsewhere (The Million Women Study Collaborative Group, 1999) and questionnaires can be viewed at http://www.millionwomenstudy.org. All participants were flagged on the National Health Service (NHS) Central Registers so that cancer registrations and deaths are routinely notified to the study investigators. These registers provide information on the date of each such event and the cancer site and morphology codes using the 10th revision of the International Classification of Diseases (IC...

Effectiveness of population‐based service screening with mammography for women ages 40 to 49 years with a high or low risk of breast cancer: Socioeconomic status, parity, and age at birth of first child

“…According to numerous case-control studies, low parity, older age at the time of birth of the first child, and high socioeconomic status (SES) are established risk factors for breast cancer [4][5][6] for women aged 40 to 49 years, although the association between SES and breast cancer appears to be more pronounced for older/postmenopausal women. [7][8][9] Women with high SES who are diagnosed with breast cancer may have a better survival than women with low SES 10,11 and breast cancer survival appears worse among young/premenopausal and nulliparous women.…”

Characteristics of the Million Women Study participants who have and have not worked at night

“…Few other studies have reported on exogenous hormone use among night-working women, although ever use of HRT was found to be less common among rotating night shift workers in the Nurses' Health Study, particularly among long-duration night workers (15). Given the established effects of the reproductive and hormonal factors on the risk of breast cancer (16)(17)(18), the differences observed in the current study would put ever night workers, and especially long-duration night workers, at an increased risk of the disease. The differences in family structure and related factors may due to the influence of night work on family life or vice versa; it is possible that women who are not married or living with a partner or are without children are more likely to select and remain in jobs involving night work.…”

Impact of Body Mass Index on Prognostically Relevant Breast Cancer Tumor Characteristics

“…Furthermore, histological BC subtypes may differ in their associations with established BC risk factors [8,9,10,11]. The few studies exploring the association between body size and aggressive triple-negative BC (TNBC) reported largely inconsistent results [12].…”